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Huang L, Xu W, Fu Y, Yang Z, Mo R, Ding Y, Xie T. RARB genetic variants might contribute to the risk of chronic obstructive pulmonary disease based on a case-control study. Ann Med 2025; 57:2445195. [PMID: 39723714 DOI: 10.1080/07853890.2024.2445195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that severely impairs patients' respiratory function and quality of life. RARB is involved in COPD progression by affecting inflammatory reactions, cell proliferation, and apoptosis. The impact of single nucleotide polymorphisms (SNPs) within RARB on COPD susceptibility remains unclear. Here, we aimed to evaluate the association between RARB SNPs and COPD risk. METHODS A total of 270 COPD patients and 271 healthy controls were enrolled. The MassARRAY iPLEX platform tested the genotype of the SNPs. The association was analyzed using logistic regression analysis. The false-positive report probability (FPRP) analysis was performed to validate the significant findings. The relationship between SNPs and RARB expression was evaluated using the GTEx database. RESULTS Our study found a significant association between rs6799734 and COPD susceptibility (OR 1.88, p = 0.008, p (FDR) = 0.047). The stratified analysis revealed that this association was particularly pronounced among individuals aged ≤ 71 years (OR 2.34, p = 0.011, p (FDR) = 0.045), males (OR 2.60, p = 0.002, p (FDR) = 0.013), those with a BMI ≥ 24 (OR 3.95, p = 0.018, p (FDR) = 0.108), and smokers (OR 2.48, p = 0.020, p (FDR) = 0.120). Additionally, rs1286641 and rs1881706 showed significant associations with COPD risk in females and smokers. These associations were further validated by FPRP analysis. Preliminary mechanism studies indicated that rs1286641 and rs1881706 were related to RARB expression. CONCLUSION Our findings suggest a potential role of RARB SNPs in influencing COPD risk.
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Affiliation(s)
- Linhui Huang
- Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Wenya Xu
- Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yihui Fu
- Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Zehua Yang
- Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Rubing Mo
- Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yipeng Ding
- Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
- Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou,China
| | - Tian Xie
- Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
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Liu C, Song Q, Peng YT, Cheng W, Lin L, Li T, Li XS, Zeng YQ, Zhou AY, Chen Y, Cai S, Chen P. Clinical characteristics and outcomes of chronic obstructive pulmonary disease patients with family history of chronic airway disease. Ann Med 2025; 57:2477299. [PMID: 40074698 PMCID: PMC11905302 DOI: 10.1080/07853890.2025.2477299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition with different risk factors, including family history. This study aimed to explore association between a family history of chronic airway disease and features and outcomes of COPD. METHODS Participants were obtained from the RealDTC study between December 2016 and December 2022. Data on demographics, pulmonary function, history of exacerbation at baseline, acute exacerbation during 1-year follow-up and survival status during 3-years follow-up were collected. RESULTS 5020 patients were enrolled, with 1307 patients (26.0%) having a family history of chronic airway diseases. Compared with patients without a family history of chronic airway diseases, patients with a family history had a lower forced expiratory Volume in one second (FEV1), higher Modified Medical Research Council (mMRC) score and COPD Assessment Test (CAT) score, higher rate of acute exacerbation and hospitalization in the past year (p < 0.05) and rate of acute exacerbation and hospitalization during 1 year follow-up period (p < 0.05). It was an independent risk factor for acute exacerbation (OR = 2.196; 95% CI =1.873-2.576) and hospitalization (OR = 2.199; 95% CI =1.812-2.670). Over 3 years of follow-up, there were no significant differences in mortality rates and annual changes in FEV1 between two groups. CONCLUSION COPD patients with a family history of chronic airway disease are not rare, and they tend to have more severe symptoms and a higher risk of future deterioration. In the management of COPD, special attention should be paid to patients with a family history of chronic airway disease.
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Affiliation(s)
- Cong Liu
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Qing Song
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Ya-Ting Peng
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Wei Cheng
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Ling Lin
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Tao Li
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Xue-Shan Li
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Yu-Qin Zeng
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Ai-Yuan Zhou
- Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Chen
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Shan Cai
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
| | - Ping Chen
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China
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Li J, Xie Y, Wang Y, Wu L, Yu X, Bai L, Shao S, Zhou M, Zhang M, Yu X, Han W, Li X, Chen T. Effect of acupuncture on patients with chronic obstructive pulmonary disease: A multicenter randomized controlled trial. Complement Ther Med 2025; 89:103146. [PMID: 39956529 DOI: 10.1016/j.ctim.2025.103146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 01/28/2025] [Accepted: 02/06/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a common and frequently occurring disease that seriously endangers health, causing a heavy economic burden on patients and society. Acupuncture has been reported to have a therapeutic effect on patients with chronic obstructive pulmonary disease (COPD). However, compared with medications, it is difficult to identify a superior therapy. Therefore, the aim of this study was to evaluate the efficacy and safety of acupuncture, conventional drug and acupuncture plus conventional drug in the treatment of COPD. METHODS This was a multicenter, open-label randomized controlled trial (RCT) through a central randomization system. A total of 150 COPD patients were randomly assigned at a 1:1:1 ratio to the acupuncture group, conventional drug group or acupuncture plus conventional drug group for 12 weeks of treatment, followed by 12 weeks of untreated follow-up. The primary outcomes included the six-minute walk distance (6MWD) and St. George's Respiratory Questionnaire (SGRQ), and the secondary outcomes included the modified Medical Research Council dyspnea scale (mMRC), acute exacerbation, lung function, and quality of life (COPD assessment test). Statistical analysis was conducted via SPSS software (version 26.0). RESULTS A total of 150 patients were included in the study, and 143 patients completed the trial. There were time effects, group effects and interaction effects in the three groups (P < 0.05). Compared with that in the conventional drug group, the 6MWD in the acupuncture plus conventional drug group increased significantly at 4, 8, and 12 weeks of treatment and at 12 weeks of follow-up. The difference was statistically significant (P < 0.05). The symptom scores, motor scores, impact scores and total SGRQ scores at different time points in the three groups tended to change with time, with a time effect (P < 0.05), and there was no group or interaction effect (P > 0.05). Among the secondary outcomes, there were time effects on the number of acute exacerbations, forced expiratory volume in one second (FEV1) and forced expiratory volume in one second/forced vital capacity (FEV1/FVC) at different time points in the three groups (P < 0.05). mMRC had time and group effects (P < 0.05). CAT had time effects, group effects and interaction effects (P < 0.05). CONCLUSIONS Compared with the acupuncture group and the conventional drug group, the acupuncture plus conventional drug group was better at improving exercise ability, improving quality of life, and reducing dyspnea. It is safe and effective for the treatment of chronic obstructive pulmonary disease in the stable period, which can provide a reference for further related research. TRIAL REGISTRATION ClinicalTrials.gov, NCT03169504. Registered on 30 May 2017.
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Affiliation(s)
- Jiansheng Li
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, No.156 Jin-shui East Road, Zhengzhou, Henan 450046, China; Henan International Joint Laboratory of Evidence-based Evaluation for Respiratory Diseases, Henan Province Clinical Research Center for Respiratory Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, China.
| | - Yang Xie
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, No.19 Ren-min Road, Zhengzhou, Henan 450000, China; Henan International Joint Laboratory of Evidence-based Evaluation for Respiratory Diseases, Henan Province Clinical Research Center for Respiratory Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, China.
| | - Yanjun Wang
- Acupuncture and Moxibustion, Hebei Province Hospital of Traditional Chinese Medicine, No.389 Zhong-shan East Road, Shijiazhuang, Hebei 050011, China.
| | - Lei Wu
- Department of Respiratory Diseases, Hebei Province Hospital of Traditional Chinese Medicine, No.389 Zhong-shan East Road, Shijiazhuang, Hebei 050011, China.
| | - Xuefeng Yu
- Department of Respiratory Diseases, the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No.60 Huang-he North Road, Shenyang, Liaoning 110034, China.
| | - Li Bai
- Department of Respiratory Diseases, Shanxi Hospital of Integrated Traditional and Western Medicine, No.13 Fu-dong Road 63, Taiyuan, Shanxi 030013, China.
| | - Suju Shao
- Acupuncture and Moxibustion, The Third Affiliated Hospital of Henan University of Chinese Medicine, No.63 Dong-ming Road, Zhengzhou, Henan 450000, China.
| | - Miao Zhou
- Department of Respiratory Diseases, The Third Affiliated Hospital of Henan University of Chinese Medicine, No.63 Dong-ming Road, Zhengzhou, Henan 450000, China.
| | - Mingli Zhang
- Department of Respiratory Diseases, Henan Integrative Medicine Hospital, No.7 Cheng-bei Road, Zhengzhou, Henan 450003, China.
| | - Xueqing Yu
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, No.156 Jin-shui East Road, Zhengzhou, Henan 450046, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, No.156 Jin-shui East Road, Zhengzhou, Henan 450046, China; Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, No.19 Ren-min Road, Zhengzhou, Henan 450000, China.
| | - Weihong Han
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, No.156 Jin-shui East Road, Zhengzhou, Henan 450046, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, No.156 Jin-shui East Road, Zhengzhou, Henan 450046, China.
| | - Xuanlin Li
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, No.156 Jin-shui East Road, Zhengzhou, Henan 450046, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, No.156 Jin-shui East Road, Zhengzhou, Henan 450046, China.
| | - Tao Chen
- Henan International Joint Laboratory of Evidence-based Evaluation for Respiratory Diseases, Henan Province Clinical Research Center for Respiratory Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, China; Global Health Trials Unit, Liverpool School of Tropical Medicine, Liverpool, UK.
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Zhang XL, Li SS, Qin JQ, Han XY, Su XH, Qin LM, Pan C. Correlation between self-management, psychological cognitive impairment, and quality of life in elderly chronic obstructive pulmonary disease patients. World J Psychiatry 2025; 15:102494. [DOI: 10.5498/wjp.v15.i4.102494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 01/01/2025] [Accepted: 02/17/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND The correlation conclusions between self-management, frailty, and quality of life (QoL) of chronic obstructive pulmonary disease (COPD) patients are inconsistent.
AIM To comprehensively assess the current status of self-management, psychological cognitive impairment, and QoL in elderly patients with COPD.
METHODS Convenient sampling was employed to select 312 elderly patients with COPD who were receiving treatment in the respiratory and critical care medicine department of a tertiary grade A hospital from November 2023 to February 2024. The study utilized demographic information and clinical characteristics, self-management behavior, occurrence of psychological cognitive impairment, and QoL as evaluated through general information questionnaires, the COPD patient self-management scale, simple frailty scale, simple mental status scale, clinical dementia assessment scale, and the clinical COPD assessment test questionnaire. This research aims to describe the current status and correlations among self-management behavior, cognitive impairment occurrence, and QoL.
RESULTS The average score for self-management behavior in elderly COPD patients was 136.00 (119.00, 164.50), indicating a moderate level overall. There were 98 cases of cognitive impairment, accounting for 31.4%, with a mental status score of 3 (2, 3.75). The average QoL score was 24 (19, 28), indicating a low level. Additionally, there was a negative correlation between total self-management behavior score and cognitive impairment occurrence (r = -0.589, P < 0.001), and QoL total score (r = -0.409, P < 0.001). Cognitive impairment occurrence was positively correlated with QoL total score (r = 0.345, P < 0.001). Disease course and self-management behavior score were independent factors affecting the total QoL score in elderly COPD patients (P < 0.05).
CONCLUSION The self-management behavior of elderly patients with COPD is at a moderate level. However, the occurrence of cognitive impairment is high and significantly influenced by disease course, level of self-management, and mental status. The QoL is low, emphasizing the urgent need to intervene in the self-management behaviors of elderly COPD patients, actively reduce the occurrence of cognitive impairment, and mitigate the impact of the disease on QoL.
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Affiliation(s)
- Xiao-Li Zhang
- Respiratory and Critical Care Medicine, Ward 1, Liuzhou Traditional Chinese Medical Hospital (Liujcouh Si Ywcuengh Yihyen), Liuzhou 545000, Guangxi Zhuang Autonomous Region, China
| | - Su-Shu Li
- Respiratory and Critical Care Medicine, Ward 1, Liuzhou Traditional Chinese Medical Hospital (Liujcouh Si Ywcuengh Yihyen), Liuzhou 545000, Guangxi Zhuang Autonomous Region, China
| | - Jian-Qing Qin
- Respiratory and Critical Care Medicine, Ward 1, Liuzhou Traditional Chinese Medical Hospital (Liujcouh Si Ywcuengh Yihyen), Liuzhou 545000, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Yu Han
- Respiratory and Critical Care Medicine, Ward 1, Liuzhou Traditional Chinese Medical Hospital (Liujcouh Si Ywcuengh Yihyen), Liuzhou 545000, Guangxi Zhuang Autonomous Region, China
| | - Xing-Hui Su
- Respiratory and Critical Care Medicine, Ward 1, Liuzhou Traditional Chinese Medical Hospital (Liujcouh Si Ywcuengh Yihyen), Liuzhou 545000, Guangxi Zhuang Autonomous Region, China
| | - Liu-Mei Qin
- Respiratory and Critical Care Medicine, Ward 1, Liuzhou Traditional Chinese Medical Hospital (Liujcouh Si Ywcuengh Yihyen), Liuzhou 545000, Guangxi Zhuang Autonomous Region, China
| | - Chang Pan
- Department of Nursing, Liuzhou Traditional Chinese Medical Hospital (Liujcouh Si Ywcuengh Yihyen), Liuzhou 545000, Guangxi Zhuang Autonomous Region, China
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Li X, Li Z, Ye J, Ye W. Association of dietary calcium intake with chronic bronchitis and emphysema. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:102. [PMID: 40176178 DOI: 10.1186/s41043-025-00843-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 03/21/2025] [Indexed: 04/04/2025]
Abstract
OBJECTIVE Chronic bronchitis and emphysema (CBE) are two main types of chronic obstructive pulmonary disease (COPD). We aimed to investigate the relationship between dietary calcium intake and the risk of CBE. METHODS Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. The ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) < 0.7 was used to define airflow obstruction. Multivariate logistic regression was performed to assess the effects of dietary calcium intake on CBE and airflow obstruction. Dietary calcium intake was divided into quartiles, with the lowest quartile set as the reference group. Linear regression models were applied to explore the association between dietary calcium intake and lung function. RESULTS A total of 10,143 participants were enrolled in the study, including 594 CBE and 9549 non-CBE individuals. The average dietary calcium intake was 908.5 ± 636.1 mg/day in the CBE group and 951.9 ± 599.7 mg/day in the non-CBE group. When using the lowest quartile of dietary calcium intake as a reference, the second, third, and fourth quartiles reduced the risk of CBE by 0.803 [95% confidence interval (CI): 0.802-0.804; P < 0.001], 0.659 (95% CI: 0.659-0.660; P < 0.001) and 0.644 (95% CI: 0.643-0.644; P < 0.001) times, respectively. Increased dietary calcium intake was correlated with reduced risk of airflow obstruction. Dietary calcium intake positively predicts FEV1 (β = 0.225, P < 0.001) and FVC (β = 0.232, P < 0.001). CONCLUSION Increased intake of dietary calcium may contribute to higher lung function, a lower risk of CBE and airflow obstruction. Since the cross-sectional design makes it difficult to determine a causal relationship, further research is needed to confirm these findings and explore the underlying mechanisms.
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Affiliation(s)
- Xuefang Li
- Department of Infectious Diseases, Zhejiang Hospital, 1229 Gudun Road, Xihu District, Hangzhou, 310013, Zhejiang Province, People's Republic of China
| | - Zhijun Li
- Department of Respiratory Diseases, Zhejiang Hospital, 1229 Gudun Road, Xihu District, Hangzhou, 310013, Zhejiang Province, People's Republic of China
| | - Jian Ye
- Department of Respiratory Diseases, Zhejiang Hospital, 1229 Gudun Road, Xihu District, Hangzhou, 310013, Zhejiang Province, People's Republic of China
| | - Wu Ye
- Department of Respiratory Diseases, Zhejiang Hospital, 1229 Gudun Road, Xihu District, Hangzhou, 310013, Zhejiang Province, People's Republic of China.
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Pollock J, Polverino E, Dhar R, Dimakou K, Traversi L, Bossios A, Haworth C, Loebinger MR, De Soyza A, Vendrell M, Burgel PR, Mertsch P, McDonnell MJ, Skgrat S, Maiz-Carro L, Sibila O, van der Eerden M, Kauppi P, Hill AT, Wilson R, Milenkovic B, Menéndez R, Murris M, Crichton ML, Borecki S, Obradovic D, Irfan M, Eshenkulova V, Nowinski A, Amorim A, Torres A, Lorent N, Welte T, Blasi F, Van Braeckel E, Altenburg J, Shteinberg M, Boersma W, Elborn JS, Aliberti S, Ringshausen FC, Goeminne P, Chalmers JD. Use of inhaled corticosteroids in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC). Thorax 2025:thorax-2024-221825. [PMID: 40122611 DOI: 10.1136/thorax-2024-221825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 01/23/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION Current bronchiectasis guidelines advise against the use of inhaled corticosteroids (ICS) except in patients with associated asthma, allergic bronchopulmonary aspergillosis (ABPA) and/or chronic obstructive pulmonary disease (COPD). This study aimed to describe the use of ICS in patients with bronchiectasis across Europe. METHODS Patients with bronchiectasis were enrolled into the European Bronchiectasis Registry from 2015 to 2022. Patients were grouped into ICS users and non-users at baseline and clinical characteristics associated with ICS use were investigated. Patients were followed up for clinical outcomes of exacerbation, hospitalisation and mortality for up to 5 years. We evaluated if elevated blood eosinophil counts (above the laboratory upper limit of normal) modified the effect of ICS on exacerbations. RESULTS 19 324 patients were included for analysis and 10 109 (52.3%) were recorded as being prescribed ICS at baseline. After exclusion of patients with a history of asthma, COPD and/or ABPA, 3174/9715 (32.7%) patients with bronchiectasis were prescribed ICS. Frequency of ICS use varied across countries, ranging from 17% to 85% of included patients. ICS users had more severe disease, with significantly worse lung function, higher Bronchiectasis Severity Index scores and more frequent exacerbations at baseline (p<0.0001). Overall, ICS users did not have a reduced risk of exacerbation or hospitalisation during follow-up, but a significant reduction in exacerbation frequency was observed in the subgroup of ICS users with elevated blood eosinophil counts (relative risk 0.70, 95% CI 0.59 to 0.84, p<0.001). CONCLUSION ICS use is common in bronchiectasis, including in those not currently recommended ICS according to bronchiectasis guidelines. ICS use may be associated with reduced exacerbation frequency in patients with elevated blood eosinophils.
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Affiliation(s)
- Jennifer Pollock
- Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK
| | - Eva Polverino
- Pneumology Department, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | | | - Katerina Dimakou
- 5th Pulmonary Department, "Sotiria" Chest Hospital, Athens, Greece
| | - Letizia Traversi
- Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | | | - Charles Haworth
- Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, UK
| | - Michael R Loebinger
- Host Defence Unit, Division of Respiratory Medicine, Royal Brompton Hospital, London, UK
- Imperial College London, National Heart and Lung Institute, London, UK
| | - Anthony De Soyza
- Lung Biology and Transplantation Group, University of Newcastle, Heaton, UK
| | | | | | | | | | - Sabina Skgrat
- Pulmonary Diseases and Allergy, University of Ljubljana Faculty of Medicine, Ljubljana, Slovenia
| | - Luis Maiz-Carro
- Chronic Bronchial Infection Unit, Pneumology Service, Ramón y Cajal Hospital, Universidad de Alcalá, Madrid, Spain
| | - Oriol Sibila
- University of Barcelona, Barcelona, Spain
- ISCIII, Madrid, Spain
| | | | - Paula Kauppi
- Allergology, Skin and Allergy Hospital, Helsinki, Finland
| | - Adam T Hill
- Respiratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
| | | | | | - Rosario Menéndez
- Pulmonology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
| | | | - Megan L Crichton
- School of Dentistry Public Health Team, University of Dundee, Dundee, UK
| | - Sermin Borecki
- Department of Pulmonology Diseases, Istanbul University, Fatih, Turkey
| | | | | | - Venera Eshenkulova
- National Centre for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan
| | - Adam Nowinski
- Department of Epidemiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Adelina Amorim
- Serviço de Pneumologia, Centro Hospitalar São João, Porto, Portugal
- Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Antoni Torres
- UVIR, Hospital Clínic, Barcelona, Spain
- Biomedical Research Center Network for Respiratory Diseases (CIBERES), Madrid, Spain
| | | | - Tobias Welte
- Respiratory Medicine, Medizinische Hochschule Hannover, Hannover, Germany
| | - Francesco Blasi
- Dipartimento Toraco-Polmonare e Cardiovascola, University of Milan, Milan, Italy
| | - Eva Van Braeckel
- Department of Internal Medicine and Pediatrics, Ghent University, Gent, Belgium
- Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Josje Altenburg
- Department of Pulmonary Diseases, AMC, Amsterdam, The Netherlands
| | - Michal Shteinberg
- Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel
- The B. Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Wim Boersma
- Department of Pulmonary Diseases, Northwest Clinics, Alkmaar, The Netherlands
| | | | - Stefano Aliberti
- Department of Biomedical Sciences, Humanitas University, Sosnowiec, Poland
- Respiratory Unit, Rozzano, Italy
| | - Felix C Ringshausen
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
| | | | - James D Chalmers
- Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK
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Kobayashi T, Murakami T, Ono H, Togashi S, Takahashi T. Segmental phase angle can predict incidence of severe exacerbation in male patients with COPD. Nutrition 2025; 132:112681. [PMID: 39826429 DOI: 10.1016/j.nut.2024.112681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/28/2024] [Accepted: 12/26/2024] [Indexed: 01/22/2025]
Abstract
OBJECTIVE To investigate whether segmental phase angle (PhA) is a useful predictor of severe chronic obstructive pulmonary disease (COPD) exacerbation. RESEARCH METHODS AND PROCEDURES This prospective cohort study enrolled consecutive patients with COPD with a follow-up period of 3 years. The primary outcome was incidence of severe exacerbation. PhA was measured for the whole body and segmental body sites (trunk and upper and lower limbs). We used receiver operating characteristic (ROC) curves to determine the cut-off values and area under the curve (AUC) for predicting exacerbation based on PhA. We applied Cox proportional hazard regression analyses to estimate the independent prognostic effect of PhA on the incidence of severe exacerbation. RESULTS We analyzed 108 male participants (mean age 75.1±7.9 years) and the median follow-up period was 1082 [643-1103] days, with an annual severe exacerbation incidence rate of 0.23 per person-year. ROC analysis revealed that the AUC for Whole-body and segmental PhA were as follows: Whole-body: AUC = 0.69 (95% confidence interval [CI] = 0.59-0.79); right arm: AUC = 0.65 (95% CI = 0.53-0.77); left arm: AUC = 0.68 (95% CI = 0.56-0.79); right leg: AUC = 0.73 (95% CI = 0.64-0.82); left leg: AUC = 0.71 (95% CI = 0.62-0.81); trunk: AUC = 0.58 (95% CI = 0.46-0.69). Cox proportional hazard analysis demonstrated that PhA of the right leg (hazard ratio [HR]=3.50, 95% CI=1.33-9.20), left leg (HR=3.26, 95% CI=1.18-9.04), and left arm (HR=2.61, 95% CI=1.17-6.80) were independently and significantly associated with incidence of severe exacerbation. Whole and trunk PhA were not significantly associated with the incidence of severe exacerbation. CONCLUSIONS Segmental PhA may serve as a valuable predictive indicator of severe exacerbation in male patients with COPD. Notably, both leg PhA were strongly associated with the occurrence of severe exacerbations. REGISTRY NUMBER UMIN000044824.
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Affiliation(s)
- Takeshi Kobayashi
- Department of Rehabilitation, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Sendai, 984-8560, Japan.
| | - Tomoyuki Murakami
- Department of Rehabilitation, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Sendai, 984-8560, Japan.
| | - Hiroto Ono
- Department of Rehabilitation, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Sendai, 984-8560, Japan.
| | - Shintaro Togashi
- Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health, Saitama, 351-0197, Japan.
| | - Tsuneyuki Takahashi
- Department of Internal Medicine, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Sendai, 984-8560, Japan.
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Olvera N, Agusti A, Vonk JM, Wang G, Hallberg J, Boezen HM, van den Berge M, Melén E, Faner R. Heterogeneity of reduced FEV 1 in early adulthood: A looking forward, looking backwards analysis. Respirology 2025; 30:326-334. [PMID: 39800892 DOI: 10.1111/resp.14876] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 12/10/2024] [Indexed: 03/17/2025]
Abstract
BACKGROUND Some individuals never achieve normal peak FEV1 in early adulthood. It is unknown if this is due to airflow limitation and/or lung restriction. METHODS To investigate this, we: (1) looked forward in 19,791 participants in the Dutch Lifelines general population cohort aged 25-35 years with 5-year follow-up; and (2) looked backwards in 2032 participants in the Swedish BAMSE birth cohort with spirometry at 24 years of age but also at 16 and/or 8 years. RESULTS (1) In Lifelines 8.5% of participants had reduced FEV1 at 25-35 years, 68% due to Preserved Ratio Impaired Spirometry ('PRISm') and 32% to airflow limitation ('low-limited'); besides, 3.8% participants with normal FEV1 showed airflow-limitation ('normal-limited'). Low-limited and normal-limited, but not PRISm, reported higher smoking exposures and asthma diagnosis than normal (p < 0.05). At 5-year follow-up, 91.2% of participants remained in the same group, and FEV1 decline was similar in normal and normal-limited participants, but statistically smaller (p < 0.05) in PRISm and low-limited; (2) these observations were largely reproduced in BAMSE at 24 years of age; and, (3) in BAMSE, low-limited or PRISm individuals were already identifiable at 8-16 years of age. CONCLUSION Low peak FEV1 in early adulthood is most often due to PRISm and results in a significant burden of respiratory symptoms. Only low-limited and normal-limited, but not PRISm, associate with a doctor diagnosis of asthma, and FEV1 decline was statistically different in PRISm indicating a need for differentiated clinical approaches. These spirometric abnormalities can be already identified in childhood and adolescence.
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Affiliation(s)
- Nuria Olvera
- Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER), Barcelona, Spain
- Cátedra Salut Respiratoria, University of Barcelona, Barcelona, Spain
| | - Alvar Agusti
- Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER), Barcelona, Spain
- Cátedra Salut Respiratoria, University of Barcelona, Barcelona, Spain
- Pulmonary Service, Respiratory Institute, Clinic Barcelona, Barcelona, Spain
| | - Judith M Vonk
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands
| | - Gang Wang
- Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden
- Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Sichuan, China
| | - Jenny Hallberg
- Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden
- Sachs' Children and Youth Hospital, Stockholm, Sweden
| | - H Marike Boezen
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands
| | - Maarten van den Berge
- University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands
- Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Erik Melén
- Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden
- Sachs' Children and Youth Hospital, Stockholm, Sweden
| | - Rosa Faner
- Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER), Barcelona, Spain
- Immunology Unit, Department of Biomedicine, University of Barcelona, Barcelona, Spain
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9
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Ma G, Dou Y, Dang S, Yu N, Guo Y, Han D, Jin C. Effect of adaptive statistical iterative reconstruction-V algorithm and deep learning image reconstruction algorithm on image quality and emphysema quantification in COPD patients under ultra-low-dose conditions. Br J Radiol 2025; 98:535-543. [PMID: 39862404 DOI: 10.1093/bjr/tqae251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 10/05/2024] [Accepted: 12/03/2024] [Indexed: 01/27/2025] Open
Abstract
PURPOSE To explore the effect of different reconstruction algorithms (ASIR-V and DLIR) on image quality and emphysema quantification in chronic obstructive pulmonary disease (COPD) patients under ultra-low-dose scanning conditions. MATERIALS AND METHODS This prospective study with patient consent included 62 COPD patients. Patients were examined by pulmonary function test (PFT), standard-dose CT (SDCT) and ultra-low-dose CT (ULDCT). SDCT images were reconstructed with filtered-back-projection (FBP), while ULDCT images were reconstructed using FBP, 30%ASIR-V, 60%ASIR-V, 90%ASIR-V, low-strength (DLIR-L), medium-strength (DLIR-M) and high-strength DLIR (DLIR-H) to form 8 image sets. Images were analysed using a commercial computer aided diagnosis (CAD) software. Parameters such as image noise, lung volume (LV), emphysema index (EI), mean lung density (MLD) and 15th percentile of lung density (PD15) were measured. Two radiologists evaluated tracheal and pulmonary artery image quality using a 5-point scale. Measurements were compared and the correlation between EI and PFT indices was analysed. RESULT ULDCT used 0.46 ± 0.22 mSv in radiation dose, 93.8% lower than SDCT (P < .001). There was no difference in LV and MLD among image groups (P > .05). ULDCT-ASIR-V90% and ULDCT-DLIR-M had similar image noise and EI and PD15 values to SDCT-FBP, and ULDCT-DLIR-M and ULDCT-DLIR-H had similar subjective scores to SDCT-FBP (all P > .05). ULDCT-DLIR-M provided the best correlation between EI and the FEV1/FVC and FEV1% indices in PFT, and the lowest deviations with SDCT-FBP in both EI and PD15. CONCLUSION DLIR-M provides the best image quality and emphysema quantification for COPD patients in ULDCT. ADVANCES IN KNOWLEDGE Ultra-low-dose CT scanning combined with DLIR-M reconstruction is comparable to standard dose images for quantitative analysis of emphysema and image quality.
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Affiliation(s)
- Guangming Ma
- Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi 710061, China
- Department of Radiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shannxi 712000, China
| | - Yuequn Dou
- Department of Radiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shannxi 712000, China
| | - Shan Dang
- Department of Radiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shannxi 712000, China
| | - Nan Yu
- Department of Radiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shannxi 712000, China
| | - Yanbing Guo
- Department of Radiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shannxi 712000, China
| | - Dong Han
- Department of Radiology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shannxi 712000, China
| | - Chenwang Jin
- Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi 710061, China
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10
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Mohamady YK, Geudens V, De Fays C, Zapata M, Hagrass O, Aversa L, Vermant M, Jin X, Willems L, Gyselinck I, Hooft C, Vermaut A, Beeckmans H, Kerckhof P, Aerts G, Aelbrecht C, Verhaegen J, Higham A, Coudyzer W, Cortesi EE, Vanstapel A, McDonough JE, Carlon MS, Quarck R, Boone MN, Dupont L, Everaerts S, Van Raemdonck DE, Ceulemans LJ, Hackett TL, Vos R, Abuouf Y, Jacob J, Wuyts WA, Hogg JC, Filoche M, Gayan-Ramirez G, Janssens W, Vanaudenaerde BM. Computational fluid dynamics of small airway disease in chronic obstructive pulmonary disease. EBioMedicine 2025; 114:105670. [PMID: 40174553 DOI: 10.1016/j.ebiom.2025.105670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 03/06/2025] [Accepted: 03/12/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND Small airways (<2 mm diameter) are major sites of airflow obstruction in chronic obstructive pulmonary disease (COPD). This study aimed to quantify the impact of small airway disease, characterized by narrowing, occlusion, and obliteration, on airflow parameters in smokers and end-stage patients with COPDs. METHODS We performed computational fluid dynamics (CFD) simulations of inspiratory airflow in three lung groups: control non-used donor lungs (no smoking/emphysema history), non-used donor lungs with a smoking history and emphysema, and explanted end-stage COPD lungs. Each group included four lungs, with two tissue cylinders. Micro-CT-scanned small airways were segmented into 3D models for CFD simulations to quantify pressure, resistance, and shear stress. CFD results were benchmarked against simplified linear and Weibel models. FINDINGS CFD simulations showed higher pressures in COPD vs. controls (p = 0.0091) and smokers (p = 0.015), along with increased resistance (p = 0.0057 vs. controls; p = 0.0083 vs. smokers) and up to a tenfold rise in shear stress (p = 0.010 vs. controls). Narrowing and occlusion were shown to independently increase pressure, resistance, and shear stress, which were validated through segmentation corrections. Pressures and resistance assessed with simplified models were up to seven-fold higher for smokers and even 72 higher for COPD compared with CFD values. INTERPRETATION These findings show that increased airflow parameters can explain the association between small airway disease and airflow limitation in COPD, underscoring small airway vulnerability. Additionally, they highlight the limitations of theoretical models in accurately capturing small airway disease. FUNDING Supported by the KU Leuven (C16/19/005).
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Affiliation(s)
- Yousry K Mohamady
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Vincent Geudens
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Charlotte De Fays
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium; Pneumology Lab, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.
| | - Marta Zapata
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Omar Hagrass
- Department of Operations Research and Financial Engineering, Princeton University, USA.
| | - Lucia Aversa
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Marie Vermant
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Xin Jin
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Lynn Willems
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Iwein Gyselinck
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Charlotte Hooft
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Astrid Vermaut
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Hanne Beeckmans
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Pieterjan Kerckhof
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Gitte Aerts
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Celine Aelbrecht
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Janne Verhaegen
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Andrew Higham
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Manchester University, UK.
| | | | - Emanuela E Cortesi
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Arno Vanstapel
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - John E McDonough
- Firestone Institute for Respiratory Health, St Joseph's Healthcare Hamilton, McMaster University, Hamilton, Canada.
| | - Marianne S Carlon
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Rozenn Quarck
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Matthieu N Boone
- Dept of Physics and Astronomy, UGCT, Radiation Physics, Ghent University, Gent, Belgium.
| | - Lieven Dupont
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Stephanie Everaerts
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Dirk E Van Raemdonck
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Laurens J Ceulemans
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium; Translational Cell and Tissue Research, KU Leuven and UZ Leuven, Leuven, Belgium.
| | - Tillie-Louise Hackett
- Center for Heart Lung Innovation, The University of British Columbia, Vancouver, Canada.
| | - Robin Vos
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Yasser Abuouf
- Department of Mechanical Engineer, Alexandria University, Egypt.
| | - Joseph Jacob
- Hawkes Institute, Department of Computer Science, UCL, London, UK; UCL Respiratory, UCL, London, UK.
| | - Wim A Wuyts
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - James C Hogg
- Center for Heart Lung Innovation, The University of British Columbia, Vancouver, Canada.
| | - Marcel Filoche
- Physique de la Matière Condensée, Ecole Polytechnique, Palaiseau, France.
| | - Ghislaine Gayan-Ramirez
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Wim Janssens
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
| | - Bart M Vanaudenaerde
- Laboratory of Respiratory Diseases and Thoracic Surgery, BREATHE, Department of CHROMETA, KU Leuven, Leuven, Belgium.
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Druckrey-Fiskaaen KT, Madebo T, Daltveit JT, Vold JH, Furulund E, Chalabianloo F, Gilje Lid T, Fadnes LT. Integrated Nicotine Replacement and Behavioral Support to Reduce Smoking in Opioid Agonist Therapy: A Randomized Clinical Trial. JAMA Psychiatry 2025; 82:406-414. [PMID: 39937506 PMCID: PMC11822603 DOI: 10.1001/jamapsychiatry.2024.4801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 11/27/2024] [Indexed: 02/13/2025]
Abstract
Importance Approximately 85% of individuals receiving opioid agonist therapy for opioid dependence smoke tobacco. Despite the significant health risks associated with smoking-related diseases, there has been limited evaluation of smoking interventions tailored to this population. Objective To determine the effectiveness of an intervention combining nicotine replacement with brief behavioral support in reducing cigarette use. Design, Setting, and Participants This multicenter randomized clinical trial was conducted from April 2022 to October 2023 in 7 specialized opioid agonist therapy clinics in Bergen and Stavanger, Norway. The analyst was blinded to patient groupings. Assessors (study nurses) were not fully blinded to participant allocation. Individuals diagnosed with opioid dependency receiving opioid agonist therapy at participating clinics and smoking at least 1 cigarette per day were eligible for participation. Data analysis was performed from December 2023 through October 2024. Intervention In addition to standard opioid agonist therapy, participants in the intervention group received a 16-week integrated treatment combining nicotine replacement with brief behavioral support. Participants in the control group received only standard opioid agonist therapy. Main Outcomes and Measures The primary outcome was at least a 50% reduction in the number of cigarettes smoked, self-reported as cigarette use in the past 7 days at week 16. The analysis followed intention-to-treat principles. Cigarette use was self-reported as per the timeline-follow-back method. Results Among the 259 participants (mean [SD] age, 48.5 [10.4] years; 80 [30.9%] female), 135 were allocated to the intervention group and 124 to the control group. The odds ratio of at least halving the number of cigarettes smoked was 2.07 (95% CI, 1.14-3.75) in the intervention group compared with the control group. Conclusions and Relevance Providing integrated nicotine replacement and behavioral support at opioid agonist treatment clinics effectively helped opioid-dependent participants reduce the number of cigarettes smoked. Trial Registration ClinicalTrials.gov Identifier: NCT05290025.
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Affiliation(s)
- Karl Trygve Druckrey-Fiskaaen
- Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Norwegian Research Center for Agonist Treatment of Substance Use Disorders, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
| | - Tesfaye Madebo
- Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Respiratory Medicine, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Jan Tore Daltveit
- Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
| | - Jørn Henrik Vold
- Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
| | - Einar Furulund
- Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Centre for Alcohol and Drug Research, Stavanger University Hospital, Stavanger, Norway
- Oral Health Centre of Expertise Rogaland, Stavanger, Norway
| | - Fatemeh Chalabianloo
- Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Norwegian Research Center for Agonist Treatment of Substance Use Disorders, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
| | - Torgeir Gilje Lid
- Centre for Alcohol and Drug Research, Stavanger University Hospital, Stavanger, Norway
- Department of Public Health, University of Stavanger, Stavanger, Norway
| | - Lars Thore Fadnes
- Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
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12
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Buma AIG, Muntinghe-Wagenaar MB, van der Noort V, de Vries R, Schuurbiers MMF, Sterk PJ, Schipper S, Meurs J, Cristescu SM, Hiltermann TJN, van den Heuvel MM. Lung cancer detection by electronic nose analysis of exhaled breath: a multi-center prospective external validation study. Ann Oncol 2025:S0923-7534(25)00125-5. [PMID: 40174676 DOI: 10.1016/j.annonc.2025.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 03/12/2025] [Accepted: 03/24/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND Electronic nose (eNose) analysis of exhaled breath shows potential for accurate and timely lung cancer diagnosis, yet prospective external validation studies are lacking. Our study primarily aimed to prospectively and externally validate a published eNose model for lung cancer detection in COPD patients and assess its diagnostic performance alongside a new eNose model, specifically tailored to the target population, in a more general outpatient population. PATIENTS AND METHODS This multi-center prospective external validation study included adults with clinical and/or radiological suspicion of lung cancer who were recruited from thoracic oncology outpatient clinics of two sites in The Netherlands. Breath profiles were collected using a cloud-connected eNose (SpiroNose®). The diagnostic performance of the original and new eNose model was assessed in various population subsets based on ROC-AUC, specificity, positive predictive value (PPV), and negative predictive value (NPV), targeting 95% sensitivity. For the new eNose model, a training and validation cohort were used. RESULTS Between March 2019 and November 2023, 364 participants were included. The original eNose model detected lung cancer with a ROC-AUC of 0.92 (95% CI: 0.85-0.99) in COPD patients (n=98/116; 84%) and 0.80 (95% CI: 0.75-0.85) in all participants (n=216/364; 59%). At 95% sensitivity, the specificity, PPV, and NPV, were 72% and 51%, 95% and 74%, and 72% and 88%, respectively. In the validation cohort, the new eNose model identified lung cancer across all participants (n=72/121; 60%) with a ROC-AUC of 0.83 (95% CI: 0.75-0.91), 94% sensitivity, 63% specificity, PPV of 79%, and NPV of 89%. Notably, accurate detection was consistent across tumour characteristics, disease stage, diagnostic centers, and clinical characteristics. CONCLUSION This multi-center prospective external validation study confirms that eNose analysis of exhaled breath enables accurate lung cancer detection at thoracic oncology outpatient clinics, irrespective of tumour characteristics, disease stage, diagnostic center, and clinical characteristics.
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Affiliation(s)
- A I G Buma
- Department of Respiratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - M Benthe Muntinghe-Wagenaar
- Department of Respiratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - V van der Noort
- Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - R de Vries
- Breathomix B.V., Leiden, The Netherlands
| | - M M F Schuurbiers
- Department of Respiratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - P J Sterk
- Emeritus, University of Amsterdam, Amsterdam, The Netherlands
| | - S Schipper
- Department of Respiratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Life Science Trace Detection Laboratory, Department of Analytical Chemistry & Chemometrics, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
| | - J Meurs
- Life Science Trace Detection Laboratory, Department of Analytical Chemistry & Chemometrics, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
| | - S M Cristescu
- Life Science Trace Detection Laboratory, Department of Analytical Chemistry & Chemometrics, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
| | - T J N Hiltermann
- Department of Respiratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - M M van den Heuvel
- Department of Respiratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
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13
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Lu L, Wu F, Tang G, Wan Q, Deng Z, Peng J, Dai C, Zhou K, Wu X, Yu S, Huang Y, Yang C, Chen S, Ran P, Zhou Y. Associations of small airway dysfunction assessed by impulse oscillometry with lung function decline and exacerbations in participants with Chronic Obstructive Pulmonary Disease: a prospective cohort study in China. Respir Med 2025:108075. [PMID: 40174657 DOI: 10.1016/j.rmed.2025.108075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 03/10/2025] [Accepted: 03/28/2025] [Indexed: 04/04/2025]
Abstract
INTRODUCTION Small airway dysfunction (SAD) assessed by impulse oscillometry (IOS) was common in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the associations between IOS-defined small airway dysfunction (SAD) and the long-term prognosis of COPD. This study aimed to explore the associations between IOS-defined SAD, lung function decline and exacerbations in patients with COPD. METHODS We analyzed baseline and 2-year follow-up data from the prospective cohort study in China. We defined SAD using IOS parameters Z-score greater than the 1.645 or less than -1.645. Subsequently, these patients were divided into three groups based on the different criteria defined SAD using IOS (normal group [none IOS parameters abnormalities], inconsistent SAD [any IOS parameters abnormalities, but not all], consistent SAD [all of IOS parameters abnormalities]). Negative binomial regression was conducted to analyze the associations between SAD and exacerbations, while a multivariable linear regression model was utilized to identify associations between SAD and lung function decline. RESULTS 833 patients with COPD were enrolled in our study. SAD (defined by X5, AX, and Fres z-score) was associated with a faster decline in lung function and higher risk of exacerbation. Meanwhile, For inconsistent diagnosis of SAD, we observed that patients with consistent SAD and inconsistent SAD experienced a faster decline in FEV1 and higher risk of exacerbations than those with normal group. CONCLUSIONS IOS-defined SAD was associated with worse outcomes in patients with COPD, and Early intervention in small airway genesis may be effective in slowing the progression of COPD. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July 2019.
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Affiliation(s)
- Lifei Lu
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Fan Wu
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Gaoying Tang
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qi Wan
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhishan Deng
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jieqi Peng
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, China
| | - Cuiqiong Dai
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Kunning Zhou
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiaohui Wu
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shuqing Yu
- Lianping County People's Hospital, Heyuan, China
| | | | - Changli Yang
- Wengyuan County People's Hospital, Shaoguan, China
| | | | - Pixin Ran
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, China.
| | - Yumin Zhou
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, China.
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14
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Wang P, Wang J, Ge L, Gao B, Wang S, Jiang S. Automatically titrating oxygen system versus constant flow oxygen system during exercise in patients with COPD: a systematic review and meta-analysis. BMC Pulm Med 2025; 25:140. [PMID: 40155894 PMCID: PMC11951597 DOI: 10.1186/s12890-025-03594-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 03/11/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Hypoxemia is a common symptom among patients with chronic obstructive pulmonary disease (COPD). The constant flow oxygen system (CFOS) is often insufficient to correct this symptom. The automatically titrating oxygen system (ATOS), a new oxygen therapy mode, remains undetermined in its ability to improve exercise performance more effectively than CFOS in COPD patients. The main objective of this meta-analysis was to explore this issue. METHODS We conducted a thorough search of randomized controlled trials (RCTs) in PubMed, Embase, Web of Science (from inception to 1 November 2024). Study selection, data extraction, and risk of bias assessment were performed independently by two authors. Data synthesis was conducted using Stata software (Version 17.0). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was utilized to rate evidence quality. RESULTS Five eligible studies (n = 120) were included. Compared to CFOS, ATOS was more effective in extending the distance (MD = 180.28 m, 95%CI:133.03 to 227.52) and duration (MD = 237.63 s, 95%CI: 181.18 to 294.07) of endurance shuttle walking test (ESWT). Besides, ATOS could better prolong the percentage time of sustaining targeted SpO2 (92%-96%) (MD = 29.43%,95%CI:21.15 to 37.71) and relieve dyspnea at isotime (MD = -1.65, 95%CI -3.19 to -0.11) during ESWT. DISCUSSION ATOS may have more advantages in improving exercise tolerance, sustaining targeted SpO2, and ameliorating dyspnea during exercise in COPD patients. CLINICAL TRIAL REGISTRATION The review was registered with PROSPERO (The website is https://www.crd.york.ac.uk/prosp ero/, and the ID is CRD 42024574955) and we didn't make a protocol.
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Affiliation(s)
- Peijian Wang
- Department of Rehabilitation Medicine, China-Japan Friendship Hospital, 2 Yinghuayuan East St. Hepingli, Chaoyang District, Beijing, 100029, China
| | - Jing Wang
- Department of Radiotherapy, Xuzhou Central Hospital, Xuzhou, JiangSu Province, China
| | - Lijun Ge
- Department of Rehabilitation Medicine, China-Japan Friendship Hospital, 2 Yinghuayuan East St. Hepingli, Chaoyang District, Beijing, 100029, China
| | - Beiyao Gao
- Department of Rehabilitation Medicine, China-Japan Friendship Hospital, 2 Yinghuayuan East St. Hepingli, Chaoyang District, Beijing, 100029, China
| | - Siyuan Wang
- Department of Rehabilitation Medicine, China-Japan Friendship Hospital, 2 Yinghuayuan East St. Hepingli, Chaoyang District, Beijing, 100029, China.
| | - Shan Jiang
- Department of Rehabilitation Medicine, China-Japan Friendship Hospital, 2 Yinghuayuan East St. Hepingli, Chaoyang District, Beijing, 100029, China.
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15
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Estenne C, Pelletier Visa M, Pereira B, Usclade A, Coudeyre E, Dobija L. Mechanical Insufflation-Exsufflation in Older In-Patients With Impaired Cough. Respir Care 2025. [PMID: 40138199 DOI: 10.1089/respcare.12267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Affiliation(s)
- Claire Estenne
- Ms. Estenne, Pelletier Visa, Prof. Coudeyre, and Dr. Dobija are affiliated with Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, France
| | - Mathilde Pelletier Visa
- Ms. Estenne, Pelletier Visa, Prof. Coudeyre, and Dr. Dobija are affiliated with Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, France
| | - Bruno Pereira
- Dr. Pereira and Ms. Usclade are affiliated with Direction de la Recherche Clinique et de l'Innovation, Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, France
| | - Alexandra Usclade
- Dr. Pereira and Ms. Usclade are affiliated with Direction de la Recherche Clinique et de l'Innovation, Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, France
| | - Emmanuel Coudeyre
- Ms. Estenne, Pelletier Visa, Prof. Coudeyre, and Dr. Dobija are affiliated with Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, France
- Prof. Coudeyre and Dr. Dobija are affiliated with Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Lech Dobija
- Ms. Estenne, Pelletier Visa, Prof. Coudeyre, and Dr. Dobija are affiliated with Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, France
- Prof. Coudeyre and Dr. Dobija are affiliated with Unité de Nutrition Humaine, INRAE, Université Clermont Auvergne, Clermont-Ferrand, France
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16
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Wu J, Wang G, Gan J, Yang L, Zhang H, Xian J, Li Y, Li W. Nomogram to predict progression from preserved ratio impaired spirometry to chronic obstructive pulmonary disease. Sci Rep 2025; 15:10447. [PMID: 40140392 PMCID: PMC11947084 DOI: 10.1038/s41598-025-93359-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Preserved Ratio Impaired Spirometry (PRISm) is a specific subtype of pre-chronic obstructive pulmonary disease (pre-COPD). People with PRISm are at risk of progression to chronic obstructive pulmonary disease (COPD). We developed a model to predict progression in subjects with PRISm. We screened 188 patients whose lung function transitioned from PRISm to COPD and 173 patients with PRISm who remained stable over two years. After excluding 78 patients due to incomplete clinical or laboratory data, a total of 283 patients were included in the final analysis. These patients were randomly divided into a training cohort (227 patients) and a validation cohort (56 patients) at a 8:2 ratio. LASSO regression and multivariate logistic regression were used to identify factors influencing progression. Among the 283 patients, 134 progressed to COPD. The model developed using six variables showed good performance, with areas under the receiver operating characteristic (ROC) curves of 0.87 in the training cohort and 0.79 in the validation cohort. The model demonstrated excellent calibration and was clinically meaningful, as shown by decision curve analysis (DCA) and clinical impact curve (CIC). We developed China's first prediction model for the progression of lung function from PRISm to COPD in a real-world population. This model is conducive to early identification of high-risk groups of pulmonary function deterioration, so as to provide timely intervention and delay the occurrence and progression of the disease.
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Affiliation(s)
- Jiaxuan Wu
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China
- Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Guoqing Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Jiadi Gan
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China
- Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lan Yang
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China
- Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Huohuo Zhang
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China
- Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jinghong Xian
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China
- Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yalun Li
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Weimin Li
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China.
- Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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17
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Zhang W, Zong Y, Huang X, Liu K, Luo Z, Shan J, Di L. Cordyceps militaris alleviates COPD by regulating amino acid metabolism, gut microbiota and short chain fatty acids. JOURNAL OF ETHNOPHARMACOLOGY 2025; 346:119701. [PMID: 40147677 DOI: 10.1016/j.jep.2025.119701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 03/22/2025] [Accepted: 03/24/2025] [Indexed: 03/29/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chronic obstructive pulmonary disease (COPD) is a global health challenge with the high morbidity and mortality. Cordyceps militaris (CM) is a medicinal fungus that has been widely used in Asia for centuries. It has the effects of tonifying the lung and kidney, replenishing essence, resolving phlegm, and stopping bleeding. CM has been used clinically for alleviating COPD in China. However, the potential mechanism of CM in treating COPD remains indistinct. PURPOSE This article aimed to evaluate the efficacy and investigate the underlying mechanism of CM in treatment of COPD. METHODS The ingredients in CM were identified by LC Q/TOF-MS. The effect of CM in COPD was evaluated. Untargeted metabolomics assay and 16S rDNA sequencing were employed to examine the changes in metabolites and gut microbiota in COPD mice. Gut microbiota ablation experiment and quantification of short chain fatty acids (SCFAs) were integrated to elucidate the systematic mechanism of CM in treatment of COPD. RESULTS A total of 22 ingredients were identified in CM. CM alleviated COPD significantly by improving lung function and inhibiting pulmonary inflammation. Subsequently, 11 differential metabolites regulated by CM were mainly associated with amino acid metabolism. CM ameliorated the dysbiosis of intestinal microbiota in COPD mice, which contributed to the treatment of COPD. Moreover, CM increased the contents of SCFAs, including acetate, propionate, butyrate and isobutyrate. Spearman correlation indicated a close relationship among pulmonary function, differential metabolites, and gut microbiota. CONCLUSIONS This study revealed that CM alleviated COPD by regulating amino acid metabolism, ameliorating the imbalance of gut microbiota and increasing the SCFAs. These findings not only establish a foundation for the research of CM but also provide a basis for new treatment strategies of COPD.
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Affiliation(s)
- Wen Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China
| | - Yuqi Zong
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China
| | - Xiao Huang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China
| | - Kai Liu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China
| | - Zichen Luo
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jinjun Shan
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Liuqing Di
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China
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18
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Mo J, Zuo J, Yu L, Zhang H, Weng S, Ye L. New insights into the effects of PFOS exposure on rat lung development: morphological, functional, and single-cell sequencing analysis. Arch Toxicol 2025:10.1007/s00204-025-04014-2. [PMID: 40128328 DOI: 10.1007/s00204-025-04014-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/27/2025] [Indexed: 03/26/2025]
Abstract
Perfluorooctane sulfonate (PFOS), a widely persistent environmental pollutant, has been demonstrated to disrupt lung development in animal models. However, its cellular and molecular mechanisms remain insufficiently understood. This study examines the effects of prenatal PFOS exposure on lung development and function in offspring rats. Pregnant rats were exposed to PFOS at concentrations relevant to both environmental and occupational exposures, with doses of 0, 0.01, 0.1, and 1 mg/kg/day from gestational day 11-20. We primarily evaluated morphological changes, pulmonary function, bronchoalveolar lavage fluid composition, and alterations in trace element and fatty acid metabolism at postnatal days 0, 4, 14, 21, and 60. Single-cell RNA sequencing was employed to profile cellular and molecular responses in the lungs. Our results show that PFOS exposure leads to dose-dependent reductions in alveolar development, increased pulmonary injury, fibrosis, and impaired lung function. PFOS also changes lung cell composition, particularly affecting structural and immune cells, and shifts immune responses from innate to adaptive immunity. Differential gene expression analyses revealed the upregulation of Fam111a and downregulation of Stk35, implicating these genes in PFOS-induced lung injury and repair processes. In addition, pathway analyses demonstrated suppression of immune-related signaling pathways and disruption of cell adhesion and phagocytosis, which may exacerbate lung tissue injury. These findings provide novel insights into the developmental toxicity of PFOS and highlight its potential long-term health risks.
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Affiliation(s)
- Jiali Mo
- Department of Pediatric Pulmonology, Children's Medical Center, Peking University First Hospital, Beijing, 102627, China
| | - Jingye Zuo
- Department of Pediatric Pulmonology, Children's Medical Center, Peking University First Hospital, Beijing, 102627, China
| | - Lin Yu
- Department of Pediatric Pulmonology, Children's Medical Center, Peking University First Hospital, Beijing, 102627, China
| | - Huishan Zhang
- Department of Pediatric Pulmonology, Children's Medical Center, Peking University First Hospital, Beijing, 102627, China
- Department of Respiratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Shuting Weng
- Department of Pediatric Pulmonology, Children's Medical Center, Peking University First Hospital, Beijing, 102627, China
| | - Leping Ye
- Department of Pediatric Pulmonology, Children's Medical Center, Peking University First Hospital, Beijing, 102627, China.
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19
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Wu JH, Wu JM, Huang B, Wei LL. Exploring self-management's mediating role in health literacy and quality of life: evidence from COPD patients in Hunan, China. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:84. [PMID: 40128913 PMCID: PMC11934677 DOI: 10.1186/s41043-025-00812-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 02/27/2025] [Indexed: 03/26/2025]
Abstract
PURPOSE This study aimed to investigate the relationship between health information literacy and quality of life and to explore the mediating role of self-management in this relationship among COPD patients in Hunan, China. METHODS Following the STROBE guidelines, this cross-sectional study employed convenience sampling to recruit 432 COPD patients from six tertiary hospitals in Hunan Province, China, between December 2022 and August 2023. Data collection instruments included the Health Literacy Self-Assessment Questionnaire (HLSQ), the COPD Self-Management Scale, and the COPD Assessment Test (CAT). Descriptive statistics were used to summarize participants' characteristics. Pearson correlation analysis and SPSS 26.0's macro program for mediation analysis were used, with a significance level set at p < 0.05. RESULTS Health information literacy showed a strong positive correlation with both self-management (r = 0.742, p < 0.001) and quality of life (r = -0.748, p < 0.001). Additionally, self-management was positively associated with quality of life (r = -0.861, p < 0.001). Self-management significantly mediated the relationship between health information literacy and quality of life, accounting for 67.4% of the total effect. CONCLUSIONS The mediating effect of self-management on the relationship between health information literacy and quality of life in COPD patients is established. Measures are needed to improve health information literacy, enhance self-management, and improve health outcomes.
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Affiliation(s)
- Ji-Hong Wu
- Department of Respiratory and Critical Care, Zhuzhou Central Hospital, Zhuzhou, 412000, China.
| | - Ji-Mei Wu
- Pediatric Medical Center, Hunan Provincial People'S Hospital (the First Affiliated Hospital of Hunan Normal University), Changsha, 410005, China
| | - Bing Huang
- Department of Respiratory and Critical Care, Zhuzhou Central Hospital, Zhuzhou, 412000, China
| | - Lan-Lan Wei
- Department of Respiratory and Critical Care, Zhuzhou Central Hospital, Zhuzhou, 412000, China
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20
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Toumpanakis D, Bartziokas K, Bakakos A, Fouka E, Bakakos P, Loukides S, Steiropoulos P, Papaioannou AI. Monoclonal Antibodies for the Treatment of Chronic Obstructive Pulmonary Disease. Pulm Ther 2025:10.1007/s41030-025-00291-5. [PMID: 40123030 DOI: 10.1007/s41030-025-00291-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Accepted: 02/26/2025] [Indexed: 03/25/2025] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a common and complex disease characterized by persistent airflow limitation and the presence of exacerbations, resulting in significant morbidity and mortality. Although the pathogenesis of COPD is multifactorial, airway inflammation plays a significant role in disease progression. Despite the advantages of non-pharmaceutical and pharmaceutical interventions that have significantly improved the symptom burden and exacerbation frequency in COPD, there is a lack of disease-modifying therapies that target the underlying disease mechanisms. Monoclonal antibodies (mAbs), a drug class that has improved treatment in severe asthma by blocking mediators of the type 2 (Th2) and allergic inflammatory cascades, are currently under investigation for their efficacy in COPD. Our review summarizes the evidence for the use of monoclonal antibodies in COPD and discusses current limitations and promising advances. Although targeting Th1 inflammation has failed to improve COPD outcomes, recent clinical trials have shown beneficial effects of monoclonal antibodies targeting Th2 inflammation, providing evidence for a personalized approach in COPD treatment.
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Affiliation(s)
- Dimitrios Toumpanakis
- 2Nd Department of Critical Care, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Konstantinos Bartziokas
- 2Nd Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Agamemnon Bakakos
- 1St Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Evangelia Fouka
- Respiratory Medicine Department, Aristotle University of Thessaloniki, G Papanikolaou Hospital, Thessaloniki, Greece
| | - Petros Bakakos
- 1St Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Stelios Loukides
- 2Nd Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Paschalis Steiropoulos
- Department of Pneumonology, Medical School, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
| | - Andriana I Papaioannou
- 1St Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Sotiria Chest Diseases Hospital, Athens, Greece
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21
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Han J, Qu Y, Dagli E, Söderlund LÅ, Restrick L, Uromtah M, Williams S, Joshi S, Zadeh DA, Lam DC, Schotte K, Song Y, Rylance S. Integrating tobacco cessation in chronic respiratory disease care: a comprehensive approach to reducing the global burden. BMJ Glob Health 2025; 10:e017851. [PMID: 40118466 PMCID: PMC11931912 DOI: 10.1136/bmjgh-2024-017851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 02/17/2025] [Indexed: 03/23/2025] Open
Affiliation(s)
- Jing Han
- Department of Non-Communicable Diseases, Rehabilitation and Disability, World Health Organization, Geneva, Switzerland
| | - Yulan Qu
- Department of Pulmonary and Critical Care Medicine, Fudan University Shanghai, Shanghai, China
| | - Elif Dagli
- Health Institute Association, Istanbul, Turkey
| | | | | | | | - Sian Williams
- International Primary Care Respiratory Group, Scotland, UK
| | - Surabhi Joshi
- Department of Digital Health and Innovation, World Health Organization, Geneva, Switzerland
| | | | - David Cl Lam
- Department of Medicine, University of Hong Kong, HongKong, Hong Kong
| | - Kerstin Schotte
- Department of Health Promotion, World Health Organization, Geneva, Switzerland
| | - Yuanlin Song
- Department of Pulmonary and Critical Care Medicine, Fudan University Shanghai, Shanghai, China
| | - Sarah Rylance
- Department of Non-Communicable Diseases, Rehabilitation and Disability, World Health Organization, Geneva, Switzerland
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Heng CKM, Darlyuk-Saadon I, Liao W, Mohanam MP, Gan PXL, Gilad N, Chan CCMY, Plaschkes I, Wong WSF, Engelberg D. A combination of alveolar type 2-specific p38α activation with a high-fat diet increases inflammatory markers in mouse lungs. J Biol Chem 2025:108425. [PMID: 40118456 DOI: 10.1016/j.jbc.2025.108425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 01/25/2025] [Accepted: 01/28/2025] [Indexed: 03/23/2025] Open
Abstract
Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) afflict millions of individuals globally and are significant sources of disease mortality. While the molecular mechanisms underlying such diseases are unclear, environmental and social factors, such as cigarette smoke and obesity, increase the risk of disease development. Yet not all smokers or obese individuals will develop chronic respiratory diseases. The MAPK p38α is abnormally active in such maladies, but its contribution, if any, to disease aetiology is unknown. To assess whether p38α activation per se in the lung could impose disease symptoms, we generated a transgenic mouse model allowing controllable expression of an intrinsically active variant, p38αD176A+F327S, specifically in lung alveolar type 2 (AT2) pneumocytes. Sustained expression of p38αD176A+F327S did not appear to induce obvious pathological outcomes or to exacerbate inflammatory outcomes in mice challenged with common respiratory disease triggers. However, mice expressing p38αD176A+F327S in AT2 cells and fed with a high-fat diet (HFD) exhibited increased numbers of airway eosinophils and lymphocytes, upregulated levels of pro-inflammatory cytokines and chemokines including interleukin-1β and eotaxin, as well as a reduction in levels of leptin and adiponectin within the lung. Neither HFD nor p38αD176A+F327S alone induced such outcomes. Perhaps in obese individuals with associated respiratory diseases, elevated p38α activity which happens to occur is the factor that promotes their development.
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Affiliation(s)
- C K Matthew Heng
- Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapor; Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore
| | - Ilona Darlyuk-Saadon
- Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapor; Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore
| | - Wupeng Liao
- Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore
| | - Manju P Mohanam
- Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapor; Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore
| | - Phyllis X L Gan
- Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore
| | - Nechama Gilad
- Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore; Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
| | - Christabel C M Y Chan
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore; Drug Discovery and Optimization Platform, Yong Loo Lin School of Medicine, National University Health System, 117600, Singapore
| | - Inbar Plaschkes
- Info-CORE, Bioinformatics unit of the I-CORE, the Hebrew University of Jerusalem, Jerusalem 91120, Israel
| | - W S Fred Wong
- Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore; Drug Discovery and Optimization Platform, Yong Loo Lin School of Medicine, National University Health System, 117600, Singapore.
| | - David Engelberg
- Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapor; Singapore-HUJ Alliance for Research and Enterprise, Mechanisms of Liver Inflammatory Diseases Program, National University of Singapore, 138602, Singapore; Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
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King MT, Nielsen LB, Weinreich UM. Effects of alcohol consumption from early adolescence on lung function and development of COPD - a retrospective cohort study. Eur Clin Respir J 2025; 12:2476232. [PMID: 40125262 PMCID: PMC11926899 DOI: 10.1080/20018525.2025.2476232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 03/03/2025] [Indexed: 03/25/2025] Open
Abstract
Background Studies indicate a U-shaped relationship between alcohol consumption (AC) and chronic obstructive pulmonary disease (COPD) with low-moderate AC being protective. We investigated the influence of AC debut (ACD) at different ages on forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and COPD development. Methods In a multi-center cohort study, data on AC were collected through a questionnaire and spirometry performed at baseline and follow-up. COPD was defined as FEV1/FVC-ratio <0.7 on post-bronchodilator spirometry. Modelling determined odds ratio (OR) of COPD and mean differences in FEV1 and FVC in stratified age groups of ACD. Never drinkers were used as reference. Adjustments were made for age, sex, smoking parameters, asthma, and education. Results In total, 4,717 participated in the initial work-up and 2,751 completed follow-up. A higher FEV1 and FVC was found in all groups compared to never drinkers. Highest statistically significant difference in FEV1 and FVC was found in age group 14-16 (0.17 and 0,23 L, respectively). With rising age of ACD a smaller difference in FEV1 and FVC was observed with the smallest difference in age group >25 (0.11 L) and age group 17-18 (0.13 L), respectively. A lower, but not statistically significant OR for COPD in ACD age 14-16 (OR = 0.83) and higher OR in the remaining groups with 21-25 being highest (OR = 1.36) was indicated. Conclusion This study found higher FEV1 and FVC in all groups drinking alcohol compared to never drinkers with the highest among participants with ACD at age 14-16. The findings on risk of COPD development were not statistically significant.
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Jiang Z, Li H, Yu L, Yu Y, Zheng T, Huang L. The relationship between dyspnea-related kinesiophobia and physical activity in people with COPD: a moderated mediation model. Sci Rep 2025; 15:9190. [PMID: 40097749 PMCID: PMC11914060 DOI: 10.1038/s41598-025-94108-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 03/11/2025] [Indexed: 03/19/2025] Open
Abstract
This study aimed to assess the levels of physical activity (PA) in people with chronic obstructive pulmonary disease (COPD), investigate the impact of dyspnea-related kinesiophobia on them, and further examine the moderated mediation effects of exercise perception and exercise self-regulatory efficacy on this relationship. This cross-sectional study was conducted from December 2023 to May 2024. Data were collected using the Breathlessness Beliefs Questionnaire, International Physical Activity Questionnaire - Long Form, Exercise Benefits/Barriers Scale, and Exercise Self-Regulatory Efficacy Scale. Descriptive statistics and Process macro in the SPSS program were used for data analysis. A total of 239 patients with COPD were included, and median physical activities were 64.50 (28.00, 126.55) MET-h/week. Dyspnea-related kinesiophobia was negatively correlated with exercise perception, exercise self-regulatory efficacy, and PA (r = -0.503, -0.739, -0.657, P < 0.01). Exercise self-regulatory efficacy partially mediated the impact of dyspnea-related kinesiophobia on PA (β = -0.255, 95% CI [-0.353, -0.164]), and exercise perception moderating this mediating pathway (β = 0.100, P = 0.030; β = 0.412, P < 0.001). People with COPD commonly have dyspnea-related kinesiophobia and experienced physical inactivity. The moderated mediation model provides a better understanding of how dyspnea-related kinesiophobia, exercise self-regulatory efficacy, and exercise perception work together to influence PA. Interventions seeking to improve the levels of PA in patients with COPD should consider these elements.
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Affiliation(s)
- Zhili Jiang
- Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hanyu Li
- Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Luyao Yu
- Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yudi Yu
- Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian Zheng
- Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lihua Huang
- Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Chen TT, Wei YY, Kang JY, Zhang DW, Ye JJ, Sun XS, Hong M, Zhang WT, Wu HM, Ding ZX, Fei GH. ADAR1-HNRNPL-Mediated CircCANX Decline Promotes Autophagy in Chronic Obstructive Pulmonary Disease. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025:e2414211. [PMID: 40091520 DOI: 10.1002/advs.202414211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 03/05/2025] [Indexed: 03/19/2025]
Abstract
Chronic obstructive pulmonary disease (COPD) is a characteristic chronic airway inflammatory disease that worsens over time, however, there are currently limited clinical therapeutics to suspend its progression. Circular RNAs (circRNAs), which have emerged as functional regulators in various diseases, including COPD, may server as new pharmacological targets in COPD. Here, it is identified a nuclear circRNA, circCANX, that is preferentially decreased in COPD. The linear splicing of CANX pre-mRNA, enhanced by the ADAR1-HNRNPL interaction, is responsible for the circCANX decline. Clinically, the higher circCANX expression is associated with a worse lung function index of FEV1/FVC among patients with COPD. CircCANX suppresses autophagy and stress granule (SG) formation to strengthen inflammation of COPD in vivo and in vitro. Mechanistically, circCANX recruits the tumor suppressor protein P53 (P53) mRNA and RNA helicase upstream frameshift 1 (UPF1) to form a ternary complex, which mediates P53 mRNA degradation through nonsense-mediated mRNA decay (NMD) process. Together, this study reveals an important circCANX-mediated regulatory mechanism in COPD, and provides new insights into the potential of circRNA-based drug and biomarker development for COPD.
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Affiliation(s)
- Ting-Ting Chen
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
| | - Yuan-Yuan Wei
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
| | - Jia-Ying Kang
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
| | - Da-Wei Zhang
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
| | - Jing-Jing Ye
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
| | - Xi-Shi Sun
- Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, 524000, China
| | - Mei Hong
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
| | - Wen-Ting Zhang
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
| | - Hui-Mei Wu
- Department of Geriatric Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
| | - Zhen-Xing Ding
- Department of Emergency Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
| | - Guang-He Fei
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China
- Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui Province, 230022, China
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Suttapanit K, Lerdpaisarn P, Charoensuksombun C, Sanguanwit P, Supatanakij P. Diaphragmatic ultrasonographic evaluation as an assessment guide for predicting noninvasive ventilation failure in acute exacerbation of chronic obstructive pulmonary disease. Am J Emerg Med 2025; 93:13-20. [PMID: 40120416 DOI: 10.1016/j.ajem.2025.03.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 03/01/2025] [Accepted: 03/13/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Dynamic hyperinflation in severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) leads to diaphragmatic fatigue and causes acute respiratory failure. Ultrasound is reliable for evaluating diaphragmatic function. In this study, we aimed to assess the ability of diaphragmatic ultrasound to predict noninvasive ventilation (NIV) failure. METHODS This prospective single-center observational cohort study was performed on patients with AECOPD who required NIV in the emergency department between October 1, 2020, and September 30, 2022, at a tertiary healthcare center. The diaphragmatic ultrasound was measured using diaphragmatic excursion (DE) before applying NIV and diaphragmatic thickening fraction (DTF) during NIV use for 2 h. The area under the receiver-operating characteristic (AUROC) curves analysis and multivariable logistic regression was performed to assess the ability of diaphragmatic ultrasound to predict NIV failure in 48 h. RESULTS 111 patients were included in this study. DTF was an independent variable associated with NIV failure, with an adjusted odds ratio of 0.91 (95 % confidence interval [CI] 0.85-0.98), with a p-value of 0.009. DE and DTF had AUROC of 0.905 (95 % CI 0.835-0.975) and 0.940 (95 % CI 0.894-0.986), respectively, to predict NIV failure within 48 h. The lower DE and DTF increased the probability of NIV failure. The cutoff value of the DTF was 20 %, with a sensitivity of 92.0 % (95 % CI 74.0 % - 99.0 %) and a specificity of 93.0 % (95 % CI 85.4 % - 97.4 %) and the cutoff of the DE was 1.2 cm, with a sensitivity of 88.0 % (95 % CI 68.8 % - 97.5 %) and a specificity of 84.9 % (95 % CI 75.5 % - 91.7 %). CONCLUSION Diaphragmatic ultrasound, especially DTF at 2 h during NIV use, is a validated tool for predicting NIV failure in patients with AECOPD. Early detection of diaphragmatic dysfunction with diaphragmatic ultrasound in AECOPD with NIV could help identify high-risk patients and guide clinical decisions. However, further benefits from its implementation in management are required.
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Affiliation(s)
- Karn Suttapanit
- Department of Emergency Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok 10400, Thailand.
| | - Peeraya Lerdpaisarn
- Department of Emergency Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok 10400, Thailand
| | - Chanakan Charoensuksombun
- Department of Emergency Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok 10400, Thailand
| | - Pitsucha Sanguanwit
- Department of Emergency Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok 10400, Thailand.
| | - Praphaphorn Supatanakij
- Department of Emergency Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok 10400, Thailand.
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Ragusa R, Bufano P, Tognetti A, Laurino M, Caselli C. Recent Evidences of Epigenetic Alterations in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review. Int J Mol Sci 2025; 26:2571. [PMID: 40141213 PMCID: PMC11942187 DOI: 10.3390/ijms26062571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/04/2025] [Accepted: 03/09/2025] [Indexed: 03/28/2025] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory condition characterized by progressive airflow limitation, which may be caused by genetic and environmental factors. Furthermore, epigenetic mechanisms could provide valuable insights into the complex interactions between environment and genes and subsequent development of the disease. The aim of this study is to provide a systematic review of the latest knowledge on epigenetic modifications that characterize COPD, summarizing epigenetic factors that could serve as potential novel biomarkers and therapeutic targets for the treatment of COPD patients. We queried the PubMed and Scopus electronic databases with specific keywords, in May 2024, according to the PRISMA guidelines, and articles were included if they met all the inclusion criteria and survived a quality assessment. We identified 5414 publications in our systematic search. Among them, only 51 articles met the criteria of COPD-associated epigenetic modifications in human patients compared to the control group. Eight studies described DNA methylation, one study histone modifications, and forty-two studies non-coding RNAs. Apoptosis and inflammatory pathways have been found to be the main mechanisms regulated by epigenetic elements in COPD patients. In addition, non-coding RNAs may be useful as biomarkers or therapeutic targets of pulmonary disease. Future studies will be needed to confirm the role of epigenetic elements associated with COPD.
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Affiliation(s)
- Rosetta Ragusa
- Institute of Clinical Physiology, CNR, 56124 Pisa, Italy; (P.B.); (M.L.)
| | - Pasquale Bufano
- Institute of Clinical Physiology, CNR, 56124 Pisa, Italy; (P.B.); (M.L.)
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy
| | | | - Marco Laurino
- Institute of Clinical Physiology, CNR, 56124 Pisa, Italy; (P.B.); (M.L.)
| | - Chiara Caselli
- Institute of Clinical Physiology, CNR, 56124 Pisa, Italy; (P.B.); (M.L.)
- Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy
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Moin EE, Seewald NJ, Halpern SD. Development and Validation of a Simple Model to Predict Patient Height. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.03.12.25323846. [PMID: 40162276 PMCID: PMC11952625 DOI: 10.1101/2025.03.12.25323846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Background Height recorded in electronic health records (EHRs) is used extensively in diagnosis and treatment, either in isolation or as a component of body-mass index (BMI), but is often falsely high because many adults overestimate their height. Statistical models to predict height could therefore improve population health, but to date models have required extensive input and have not been externally validated. Methods We used the National Health and Nutrition Examination Survey (NHANES) to develop sex-stratified predictive models for examiner-measured height based on self-reported height and age in a random 90% sample of data. We internally validated the model in a held-out 10% sample and externally validated the model in two cohorts: The National Adolescent to Adult Longitudinal Health Study (Add Health) and the University of Michigan Health and Retirement Study (HRS). We assessed discrimination with C-index, calibration by visual inspection of calibration plots, and accuracy using root mean square error (RMSE). Results Models were trained using 62,032 NHANES subjects (51.9% women, 21.7% Black, 23.9% Hispanic or Latino, with median age 48 [IQR 31 - 64]), and evaluated in the NHANES held-out test set (n=6,846), Add Health (n=5,749), and HRS (n=5,655). Models demonstrated excellent discrimination in all validation cohorts (C-index range 0.88 - 0.89). Models were well-calibrated in all validation cohorts. Model-predicted height demonstrated lower root mean square error (RMSE) compared to self-reported height in all validation cohorts and when stratified by race and ethnicity, with greatest improvements in participants aged 45 and over. Conclusions and Relevance A model requiring minimal input data improves estimation of height over self-reported height at least as much as more complex models across stratifications of sex, age, race and ethnicity in internal validation, and is the first model to improve height estimation that has demonstrated external validity.
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Affiliation(s)
- Emily E. Moin
- Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Philadelphia
- Palliative and Advanced Illness Research (PAIR) Center, University of Pennsylvania, Philadelphia
| | - Nicholas J. Seewald
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia
| | - Scott D. Halpern
- Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Philadelphia
- Palliative and Advanced Illness Research (PAIR) Center, University of Pennsylvania, Philadelphia
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia
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Shuai L, Zhou C, Zhou J, Hu H, Lai Y, Fan L, Du W, Li M. Application of Discrete Event Simulation Models for COPD Management: A Systematic Review. Int J Chron Obstruct Pulmon Dis 2025; 20:685-698. [PMID: 40092318 PMCID: PMC11910922 DOI: 10.2147/copd.s501054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 02/01/2025] [Indexed: 03/19/2025] Open
Abstract
Background This systematic review aims to comprehensively assess the current application of discrete event simulation (DES) models in managing chronic obstructive pulmonary disease (COPD). By synthesizing and analyzing multiple studies, we incorporate the latest evidence, evaluate research quality, identify gaps, and provide recommendations for the future application of DES in COPD management. Methods We systematically searched six electronic databases including PubMed, Web of Science, Embase, Cochrane, Econlit, and China National Knowledge Infrastructure (CNKI) for articles published up to August 22, 2024. Reference lists of the included articles were also manually checked. Depending on the study type, we assessed quality using either the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist or the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Practice Guidelines. Results Out of the 273 records identified, nine studies met the inclusion criteria. All of these studies focused on health economic evaluations using DES in COPD management, and were conducted in high-income countries. The studies were divided into three groups based on the modeling systems they used: cost-effectiveness analyses of different pharmacological treatments (n=3), economic evaluations of case detection strategies (n=3), and assessments of various interventions on COPD healthcare services (n=3). All studies reported model validation methods (n=9); however, only two studies performed subgroup analysis. Conclusion This review highlights the current use of DES in COPD management and suggests avenues for future research and resource allocation to enhance the effectiveness of COPD interventions.
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Affiliation(s)
- Liu Shuai
- School of Public Health, Southeast University, Nanjing, People’s Republic of China
| | - Chunni Zhou
- School of Public Health, Southeast University, Nanjing, People’s Republic of China
| | - Jinyi Zhou
- Department of Non-Communicable Chronic Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China
| | - Hao Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, People’s Republic of China
| | - Yunfeng Lai
- School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Lijun Fan
- School of Public Health, Southeast University, Nanjing, People’s Republic of China
| | - Wei Du
- School of Public Health, Southeast University, Nanjing, People’s Republic of China
| | - Meng Li
- School of Public Health, Southeast University, Nanjing, People’s Republic of China
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Li W, Guo W, Chen H, Lu W, Yu S, Wang M, Zheng F, Wu H, Yang Q. Access to single-inhaler triple medicines for chronic obstructive pulmonary disease in China: a national survey on accessibility and utilisation. J Pharm Policy Pract 2025; 18:2466215. [PMID: 40070677 PMCID: PMC11894743 DOI: 10.1080/20523211.2025.2466215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 02/07/2025] [Indexed: 03/14/2025] Open
Abstract
Background The maintenance medicines for chronic obstructive pulmonary disease (COPD) include inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting β2-agonists (LABA). Budesonide/glycopyrronium/formoterol (BUD/GLY/FOR) and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) are two representative drugs for prefixed ICS/LAMA/LABA association in a single inhaler and have shown comparable efficacy and safety with other ICS/LAMA/LABA open combination therapies in patients with moderate-to-very severe COPD. This study aimed to investigate the availability, price, affordability, and utilisation of single-inhaler triple medicines for COPD in China. Methods Quarterly data about the use of BUD/GLY/FOR and FF/UMEC/VI from 2020 to 2022 were collected from the Chinese Medicine Economic Information Network. We used the adjusted World Health Organization and Health Action International methodology to calculate the availability and affordability of the two investigated medicines in 596 tertiary general hospitals and 299 secondary general hospitals in 31 provincial administrative regions in China. Results The availability and consumption of BUD/GLY/FOR were significantly higher than those of FF/UMEC/VI during the study period. At the end of 2022, the availability of BUD/GLY/FOR and FF/UMEC/VI in tertiary general hospitals was 69.80% and 52.01% respectively, while in secondary general hospitals, it was 52.51% and 28.76% respectively. Both medications were equally affordable at 1.3 days of the minimum wage after reimbursement in 2022. In the first quarter of 2021, with the inclusion of both drugs in the Medicare catalog, their DDDc decreased significantly, which was accompanied by notable improvements in their availability, affordability and consumption. Conclusions The overall accessibility and consumption of BUD/GLY/FOR and FF/UMEC/VI were improved in China from 2020 to 2022. The implementation of the national drug price negotiation policy reduces the cost of drugs in China and plays an important role in improving the availability of the investigated drugs.
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Affiliation(s)
- Wei Li
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University,Xuzhou, People’s Republic of China
| | - Wei Guo
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China
| | - Hongdou Chen
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
| | - Wei Lu
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
| | - Shule Yu
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
| | - Menglei Wang
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
| | - Fangfang Zheng
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
| | - Huanhuan Wu
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
| | - Qingqing Yang
- Department of Pharmacy, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China
- Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, People’s Republic of China
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Bate S, Fortescue R, Fullwood C, Sperrin M, Simmonds M, Fally M, Hansel J, Miligkos M, Manohar S, Howlett E, Linnell J, Preston A, Woodcock AA, Singh D, Stewart L, Vestbo J, Mathioudakis AG. Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation-protocol of the ICS-RECODE individual participant data meta-analysis. BMJ Open 2025; 15:e095541. [PMID: 40044194 PMCID: PMC11883585 DOI: 10.1136/bmjopen-2024-095541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/03/2025] [Indexed: 03/09/2025] Open
Abstract
INTRODUCTION Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk. This protocol details an individual participant data (IPD) meta-analysis, assessing ICS safety, efficacy and treatment×covariate interactions to identify predictors of treatment response. METHODS AND ANALYSIS This meta-analysis will adhere to Cochrane, IPD handbook and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We will conduct a two-stage IPD meta-analysis of RCTs evaluating the addition of ICS to maintenance COPD treatments. Only RCTs with at least 500 participants across all eligible arms will be included, to allow for treatment×covariate interaction evaluation. Primary outcomes are severe and moderate or severe exacerbation rates; secondary outcomes assess both safety and efficacy. Data from each RCT will be reanalysed using rigorous, consistent statistical methods. Treatment×covariate interactions will be assessed at the RCT level. Trial treatment effects and the coefficients of treatment×covariate interaction analyses will be pooled using random effects model meta-analysis. Risk of bias will be appraised using RoB-2 informed by IPD, and certainty of evidence will be assessed with GRADE and the Instrument to assess the Credibility of Effect Modification Analyses.The ICS-RECODE IPD meta-analysis will make use of the best available data to define evidence-based, precision medicine approaches for ICS use in COPD. ETHICS AND DISSEMINATION The Health Research Authority approved the ICS-RECODE study, exempting it from ethics review (HRA UK, Reference: 24/HRA/0460). Our findings will be published in peer-reviewed journals and shared with the scientific and broader stakeholder communities. PROSPERO REGISTRATION NUMBER CRD42024508286.
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Affiliation(s)
- Sebastian Bate
- Research and Innovation, Manchester University NHS Foundation Trust, Manchester, UK
- Centre for Biostatistics, The University of Manchester, Manchester, UK
| | - Rebecca Fortescue
- Population Health Research Institute, St George's University of London, London, UK
| | - Catherine Fullwood
- Research and Innovation, Manchester University NHS Foundation Trust, Manchester, UK
- Centre for Biostatistics, The University of Manchester, Manchester, UK
| | - Matthew Sperrin
- Centre for Health Informatics, Imaging and Data Science, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Mark Simmonds
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Markus Fally
- Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen University Hospital, Kobenhavn, Denmark
| | - Jan Hansel
- Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
- North West School of Intensive Care Medicine, Health Education England North West, Manchester, UK
| | - Michael Miligkos
- Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Sinduja Manohar
- Vocal, Manchester University NHS Foundation Trust, Manchester, UK
| | - Emily Howlett
- Vocal, Manchester University NHS Foundation Trust, Manchester, UK
| | - John Linnell
- Vocal, Manchester University NHS Foundation Trust, Manchester, UK
- COPD Foundation, Miami, Florida, USA
| | - Alan Preston
- Vocal, Manchester University NHS Foundation Trust, Manchester, UK
| | - Ashley A Woodcock
- North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Dave Singh
- Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
- Medicines Evaluation Unit, Manchester, UK
| | - Lesley Stewart
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Joergen Vestbo
- Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
- Department of Internal Medicine, Herlev Gentofte University Hospital, Section of Respiratory Medicine, Copenhagen University Hospital, Kobenhavn, Denmark
| | - Alexander G Mathioudakis
- Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
- North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
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Rummenholl M, Sgarbossa T, Grah C, Holland A, Huebner RH. [The Lung Emphysema Registry: Improving quality of care in interventional emphysema therapy and health management for patients with advanced COPD and lung emphysema]. Pneumologie 2025. [PMID: 40032254 DOI: 10.1055/a-2532-4885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
The Lungenemphysemregister e.V. (LE-Register) offers a specialized platform for the exchange of knowledge, the promotion of research and the improvement of the quality of care in interventional endoscopic and surgical therapies as well as the consideration of other socio-economic and health aspects of pulmonary emphysema. The current focus is primarily on endoscopic and surgical treatment approaches for patients. Through the networking of experts, the development of specific quality standards and the certification of centers, the LE Registry contributes to the evidence-based further development and optimization of these highly specialized therapies and with a focus on other aspects of health promotion in the future.
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Affiliation(s)
| | - Thomas Sgarbossa
- Klinik für Pneumologie, Beatmungsmedizin und Intensivmedizin mit dem Arbeitsbereich Schlafmedizin, Charité - Universitatsmedizin Berlin, Berlin, Deutschland
| | - Christian Grah
- Klinik für Pneumologie, Gemeinschaftskrankenhaus Havelhohe gGmbH, Berlin, Deutschland
| | - Angelique Holland
- Pneumologie, Universitätsklinikum Gießen und Marburg - Standort Marburg, Marburg, Deutschland
| | - Ralf-Harto Huebner
- Medizinische Klinik m.S. Infektiologie und Pneumologie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
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Shen J, Gao C, Lou X, Pan T, Wang S, Xu Z, Wu L, Xu M. The association between emphysema detected on computed tomography and increased risk of lung cancer: a systematic review and meta-analysis. Quant Imaging Med Surg 2025; 15:2193-2208. [PMID: 40160601 PMCID: PMC11948427 DOI: 10.21037/qims-24-1879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 01/15/2025] [Indexed: 04/02/2025]
Abstract
Background Lung cancer, chronic obstructive pulmonary disease (COPD), and emphysema share common pathophysiological mechanisms, including diffuse chronic inflammation within lung tissue, oxidative stress, and lung destruction. This study aimed to evaluate the effectiveness of computed tomography (CT) imaging in predicting the risk of lung cancer development in patients with emphysema and COPD. Methods The databases of PubMed, Embase, Web of Science, and Cochrane Library were searched to identify studies examining the relationship between CT-detected emphysema, COPD, and the risk of developing lung malignancy. The severity of emphysema (from trace to severe) was assessed visually and quantitatively on CT. COPD severity was classified from Global Initiative for Chronic Obstructive Lung Disease (GOLD) I to GOLD IV. Quality Assessment of Diagnostic Accuracy Studies, version 2 (QUADAS-2) was used to assess risk of bias in the included studies. Pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were calculated for overall and stratified analyses. Results Of the 6,114 studies screened, 12 (22,190 patients) were included. The overall pooled OR for lung cancer associated with CT-defined emphysema was 2.45 (95% CI: 2.01-2.99). In studies employing CT-based evaluation methods, the pooled OR for lung cancer was comparable between visual assessment (2.37; 95% CI: 1.93-2.80) and quantitative assessment (2.38; 95% CI: 1.85-3.05). The risk of lung cancer demonstrated a positive correlation with disease severity in both emphysema and COPD cases. Conclusions CT-defined emphysema was linked to an elevated risk of lung cancer, which was observed across various assessments. Moreover, the severity of COPD was found also to be a risk factor for the development of lung cancer.
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Affiliation(s)
- Jiahao Shen
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Chen Gao
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinjing Lou
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Ting Pan
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shenghan Wang
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhengnan Xu
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Linyu Wu
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Maosheng Xu
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
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Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Bafadhel M, Christenson SA, Papi A, Singh D, Laws E, Dakin P, Maloney J, Lu X, Bauer D, Bansal A, Abdulai RM, Robinson LB. Dupilumab for chronic obstructive pulmonary disease with type 2 inflammation: a pooled analysis of two phase 3, randomised, double-blind, placebo-controlled trials. THE LANCET. RESPIRATORY MEDICINE 2025; 13:234-243. [PMID: 39900091 DOI: 10.1016/s2213-2600(24)00409-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 11/26/2024] [Accepted: 12/02/2024] [Indexed: 02/05/2025]
Abstract
BACKGROUND Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, which are key drivers of type 2 inflammation. We aimed to characterise the efficacy and safety of dupilumab in patients with COPD and type 2 inflammation. METHODS For this pooled analysis, we pooled and analysed data from all patients in the intention-to-treat populations of the phase 3, randomised, double-blind, placebo-controlled BOREAS and NOTUS trials, which comprised 206 hospitals and clinics in BOREAS and 217 in NOTUS in 38 countries across Europe, Asia, North America, South America, Africa, and Australia. Eligible patients were current or former smokers with 10 pack-years or more of smoking history, were aged 40-85 years, had physician-diagnosed COPD for at least 12 months before randomisation, had a post-bronchodilator FEV1/forced vital capacity (FVC) ratio of less than 0·7, had a post-bronchodilator percentage predicted FEV1 of 30-70%, had documented evidence of two moderate or one severe exacerbations of COPD in the previous year (at least one exacerbation had to have occurred on triple therapy), and had blood eosinophil counts 300 cells per μL or more during screening. Patients had to have symptomatic COPD and a reported chronic productive cough for at least 3 months in the previous year. Key exclusion criteria were history of asthma, pulmonary disease other than COPD, or other diagnosed pulmonary or systemic disease associated with elevated blood eosinophil. In both trials, eligible patients were randomly assigned (1:1) via block randomisation with block size 4 to receive subcutaneous dupilumab 300 mg or matching placebo once every 2 weeks for 52 weeks, alongside established background therapy with inhaled corticosteroids, a long-acting β2-agonist, and a long-acting muscarinic antagonist. The primary endpoint was the annualised rate of moderate or severe exacerbations over 52 weeks. FINDINGS 1874 patients were randomly assigned in BOREAS and NOTUS from May 9, 2019, to May 23, 2023; 938 (50·1%) were randomly assigned to the dupilumab groups and 936 (49·9%) were randomly assigned to the placebo groups. Mean age across both groups was 65·1 years (SD 8·2). 622 (33·2%) of 1874 patients were female and 1252 (66·8%) were male. 1628 (86·9%) patients were White, 719 (38·4%) were from Eastern Europe, and 1316 (70·2%) were former smokers. During the 52-week treatment period, 559 moderate or severe exacerbations were reported in 338 (36·0%) of 938 patients in the dupilumab group and 774 exacerbations were reported in 394 (42·1%) of 936 patients in the placebo group. There was a reduction in the annualised rate of moderate or severe exacerbations compared with placebo (annualised exacerbation rate 0·794 in the dupilumab group and 1·156 in the placebo group; incidence rate ratio 0·687, 95% CI 0·595-0·793; p<0·0001). In the dupilumab group, the time to first severe exacerbation was longer than in the placebo group (0·611, 0·409-0·912; p=0·016). However, there was no reduction in the annualised rate of severe exacerbations (annualised exacerbation rate 0·084 in the dupilumab group and 0·124 in the placebo group; 0·674, 0·438-1·037; p=0·073). Treatment-emergent adverse events, serious adverse events, adverse events that led to permanent treatment discontinuation, and adverse events that led to death were similar between the two groups. INTERPRETATION Dupilumab, as an add-on to standard triple therapy, reduced the annualised rate of moderate or severe exacerbations compared with placebo, highlighting its potential for personalised treatment approaches in patients with COPD with specific clinical endotypes. FUNDING Sanofi and Regeneron Pharmaceuticals.
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Affiliation(s)
- Surya P Bhatt
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama, Birmingham, AL, USA.
| | - Klaus F Rabe
- Airway Research Center North, German Center for Lung Research, LungenClinic Grosshansdorf and Christian Albrechts University of Kiel, Kiel, Germany
| | - Nicola A Hanania
- Section on Pulmonary and Critical Care Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Claus F Vogelmeier
- Department of Medicine, Pulmonary, and Critical Care Medicine, German Center for Lung Research, University of Marburg, Marburg, Germany
| | - Mona Bafadhel
- Centre for Lung Health, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Stephanie A Christenson
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA
| | - Alberto Papi
- Pulmonary Division, University of Ferrara, Ferrara, Italy
| | - Dave Singh
- Medicines Evaluation Unit, Manchester University NHS Foundation Trust, University of Manchester, Manchester, UK
| | | | - Paula Dakin
- Regeneron Pharmaceuticals, Tarrytown, NY, USA
| | | | - Xin Lu
- Sanofi, Bridgewater, NJ, USA
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Lam AH, Alhajri SA, Potts J, Harrabi I, Anand MP, Janson C, Nielsen R, Agarwal D, Malinovschi A, Juvekar S, Denguezli M, Gislason T, Jõgi R, Garcia-Larsen V, Ahmed R, Nafees AA, Koul PA, Aquat-Stewart A, Burney P, Knox-Brown B, Amaral AF. Optimal spirometry thresholds for the prediction of chronic airflow obstruction: a multinational longitudinal study. ERJ Open Res 2025; 11:00624-2024. [PMID: 40040898 PMCID: PMC11873882 DOI: 10.1183/23120541.00624-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/30/2024] [Indexed: 03/06/2025] Open
Abstract
Introduction Chronic airflow obstruction is key for COPD diagnosis, but strategies for its early detection are limited. We aimed to define the optimal z-score thresholds for spirometry parameters to discriminate chronic airflow obstruction incidence. Methods The Burden of Obstructive Lung Disease study is a multinational cohort study. Information on respiratory symptoms was collected and pre- and post-bronchodilator spirometry was performed at baseline. 18 study sites were followed-up with repeat measurements after a median of 8.4 years. We converted lung function measurements into z-scores using the Third National Health and Nutrition Survey reference equations. We used the Youden index to calculate the optimal z-score thresholds for discriminating chronic airflow obstruction incidence. We further examined differences by smoking status. Results We analysed data from 3057 adults (57% female, mean age: 51 years at baseline). Spirometry parameters were good at discriminating chronic airflow obstruction incidence (area under the curve 0.80-0.84), while respiratory symptoms performed poorly. The optimal z-score threshold was identified for pre-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC) <-1.336, equivalent to the 9th percentile (sensitivity: 78%, specificity: 72%). All z-score thresholds associated with a lower post-bronchodilator FEV1/FVC and greater odds of chronic airflow obstruction at follow-up. The risk of chronic airflow obstruction was slightly greater for current smokers and, to some extent, never-smokers with a pre-bronchodilator FEV1/FVC <9th/10th percentiles at baseline, particularly among males. Conclusions Spirometry is better than respiratory symptoms at predicting chronic airflow obstruction incidence. A pre-bronchodilator FEV1/FVC <9th/10th percentiles, particularly among current smokers, could suggest early airflow obstruction or pre-COPD.
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Affiliation(s)
- Abby H.S. Lam
- National Heart and Lung Institute, Imperial College London, London, UK
- Joint first authors
| | - Sheikhah A. Alhajri
- National Heart and Lung Institute, Imperial College London, London, UK
- Royal Commission Hospital in Jubail, Jubail, Saudi Arabia
- Joint first authors
| | - James Potts
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Imed Harrabi
- Ibn El Jazzar Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia
| | | | - Christer Janson
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - Rune Nielsen
- Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Dhiraj Agarwal
- Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India
| | - Andrei Malinovschi
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - Sanjay Juvekar
- Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India
- Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Meriam Denguezli
- Laboratoire de Recherche en Physiologie de l'Exercice et Physiopathologie, de l'Intégré au Moléculaire (LR19ES09), Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia
| | - Thorarinn Gislason
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Department of Sleep, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland
| | - Rain Jõgi
- Tartu University Hospital, Lung Clinic
| | - Vanessa Garcia-Larsen
- Department of International Health, John Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Rana Ahmed
- The Epidemiological Laboratory, Khartoum, Sudan
| | - Asaad Ahmed Nafees
- Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan
| | - Parvaiz A. Koul
- Department of Pulmonary Medicine, Sheri Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | | | - Peter Burney
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Ben Knox-Brown
- National Heart and Lung Institute, Imperial College London, London, UK
- Cambridge Respiratory Physiology, Royal Papworth & Cambridge University Hospitals NHS FT, Cambridge, UK
- Joint senior authors
| | - Andre F.S. Amaral
- National Heart and Lung Institute, Imperial College London, London, UK
- NIHR Imperial Biomedical Research Centre, London
- Joint senior authors
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Tada DK, Kim GH, Goldin JG, Teng P, Vyapari K, Banola A, Abtin F, McNitt-Gray M, Brown MS. Using a fully automated, quantitative fissure integrity score extracted from chest CT scans of emphysema patients to predict endobronchial valve response. J Med Imaging (Bellingham) 2025; 12:024501. [PMID: 40093557 PMCID: PMC11906092 DOI: 10.1117/1.jmi.12.2.024501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 02/16/2025] [Accepted: 02/19/2025] [Indexed: 03/19/2025] Open
Abstract
Purpose We aim to develop and validate a prediction model using a previously developed fully automated quantitative fissure integrity score (FIS) extracted from pre-treatment CT images to identify suitable candidates for endobronchial valve (EBV) treatment. Approach We retrospectively collected 96 anonymized pre- and post-treatment chest computed tomography (CT) exams from patients with moderate to severe emphysema and who underwent EBV treatment. We used a previously developed fully automated, deep learning-based approach to quantitatively assess the completeness of each fissure by obtaining the FIS for each fissure from each patient's pre-treatment CT exam. The response to EBV treatment was recorded as the amount of targeted lobe volume reduction (TLVR) compared with target lobe volume prior to treatment as assessed on the pre- and post-treatment CT scans. EBV placement was considered successful with a TLVR of ≥ 350 cc . The dataset was split into a training set ( N = 58 ) and a test set ( N = 38 ) to train and validate a logistic regression model using fivefold cross-validation; the extracted FIS of each patient's targeted treatment lobe was the primary CT predictor. Using the training set, a receiver operating characteristic (ROC) curve analysis and predictive values were quantified over a range of FIS thresholds to determine an optimal cutoff value that would distinguish complete and incomplete fissures, which was used to evaluate predictive values of the test set cases. Results ROC analysis of the training set provided an AUC of 0.83, and the determined FIS threshold was 89.5%. Using this threshold on the test set achieved an accuracy of 81.6%, specificity (Sp) of 90.9%, sensitivity (Sn) of 77.8%, positive predictive value (PPV) of 62.5%, and negative predictive value of 95.5%. Conclusions A model using the quantified FIS shows potential as a predictive biomarker for whether a targeted lobe will achieve successful volume reduction from EBV treatment.
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Affiliation(s)
- Dallas K. Tada
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Grace H. Kim
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Jonathan G. Goldin
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Pangyu Teng
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Kalyani Vyapari
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Ashley Banola
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Fereidoun Abtin
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Michael McNitt-Gray
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
| | - Matthew S. Brown
- The University of California, Los Angeles (UCLA), David Geffen School of Medicine at UCLA, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, Los Angeles, California, United States
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Liu X, Li R, Xia M, Gao Y, Wang J, Pan L, Xie Z, Shen M, Feng G. PTX 3 (pentraxin3) is associated with lung function among people with stable-stage smoking-related chronic obstructive pulmonary disease. Heart Lung 2025; 70:197-203. [PMID: 39709666 DOI: 10.1016/j.hrtlng.2024.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 11/13/2024] [Accepted: 11/14/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a prevalent chronic respiratory illness. Pentraxin-3 (PTX3) is abnormally elevated in the plasma of patients with acute exacerbation of COPD. However, the role and significance of PTX3 in the clinical diagnosis of COPD remain unclear. OBJECTIVES This study was to explore the functional role of plasma PTX3 in COPD and its relationship with lung function metrics and influence on the severity of the disease. METHODS We prospectively recruited 170 patients with stable-stage COPD admitted to our hospital between June 2020 and May 2023 and healthy study participants as study participants. Based on their smoking history, all participants were classified into those with a history of smoking and those without a smoking history. RESULTS Stable-stage smoking-related COPD patients exhibited lower values for FEV1(% predicted) and reduced FEV1/FVC ratios, with increased values for smoking index, red cell distribution width, fibrinogen, d-dimer, white blood cell counts, neutrophil to lymphocyte ratio (NLR), Medical Research Council (mMRC) scores, COPD assessment test (CAT) score, and plasma PTX3 level. There was a positive correlation of PTX3 levels with mMRC and CAT scores and a negative correlation with FEV1 % predicted and FEV1/FVC. Increased smoking index and plasma PTX3 and NLR were independent risk factors for exacerbation in stable smoking-related COPD patients. The area under the curve (AUC) for plasma PTX3 in predicting severe COPD was 0.831. CONCLUSIONS A plasma PTX3 level > 246.2 ng/mL could be a valuable indicator for predicting exacerbations in patients with stable-stage smoking-associated COPD exacerbation.
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Affiliation(s)
- Xincheng Liu
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China
| | - Rui Li
- Clinical Research Center, Wuxi No.2 People's Hospital/Jiangnan University Medical Center, no.68 Zhongshan Road, Chongan District, Wuxi City, 214000 Jiangsu Province, PR China
| | - Maoxu Xia
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China
| | - Yuanyuan Gao
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China
| | - Jiuqi Wang
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China
| | - Li Pan
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China
| | - Zhengjin Xie
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China
| | - Mingming Shen
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China
| | - Guangcui Feng
- Department of Respiratory and Critical Care Medicine, Mingguang People's Hospital, no.379 Mingguang Avenue, Mingguang City, Chuzhou City, 239400 Anhui Province, PR China.
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Vameghestahbanati M, Wang CJ, Sin DD. Food for thought: optimal diet in patients with asthma and chronic obstructive pulmonary disease. Curr Opin Pulm Med 2025; 31:106-116. [PMID: 39607023 DOI: 10.1097/mcp.0000000000001142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
PURPOSE OF REVIEW Nutritional intake plays a major role in the management of lung health. This review provides the latest perspective on how dietary choices can modulate lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma. RECENT FINDINGS The pathophysiology of COPD and asthma is driven by oxidative stress and inflammation of the airways, which is exacerbated by modifiable risk factors such as cigarette smoking and diet. Various foods can influence patient symptoms; highly processed foods increase the production of reactive oxygen species that augment airway inflammation, whereas foods rich in antioxidants, fiber and protein combat oxidative stress and muscle wastage. Patients with COPD or asthma are at increased risk of developing metabolic comorbidities, including cachexia and obesity that complicate disease phenotypes, leading to greater symptom severity. While clinical findings suggest a role for antioxidant and macronutrient support of lung function, comprehensive translational and clinical studies are necessary to better understand the mechanisms underlying nutrient interaction and lung structure-function. SUMMARY Understanding the nutritional requirements that protect lung health and support weight management in COPD and asthma is imperative to providing personalized dietary recommendations and reducing patient morbidity.
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Affiliation(s)
- Motahareh Vameghestahbanati
- Department of Medicine, McGill University and McGill University Health Centre Research, Institute, Montreal, Quebec
| | | | - Don D Sin
- Centre for Heart Lung Innovation, St. Paul's Hospital
- Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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Knox-Brown B, Algharbi F, Mulhern O, Potts J, Harrabi I, Janson C, Nielsen R, Agarwal D, Malinovschi A, Juvekar S, Denguezli M, Gíslason T, Ahmed R, Nafees A, Koul PA, Obaseki D, Anand MP, Loh LC, Dias HB, Rodrigues F, Mannino D, Elbiaze M, El Rhazi K, Mejza F, Devereux G, Franssen FM, El Sony A, Wouters E, Al Ghobain M, Mortimer K, Rashid A, Osman R, Studnicka M, Cardoso J, Burney P, Amaral AF. Bronchodilator responsiveness and future chronic airflow obstruction: a multinational longitudinal study. EClinicalMedicine 2025; 81:103123. [PMID: 40083442 PMCID: PMC11905823 DOI: 10.1016/j.eclinm.2025.103123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 01/31/2025] [Accepted: 02/04/2025] [Indexed: 03/16/2025] Open
Abstract
Background Bronchodilator responsiveness testing is mainly used for diagnosing asthma. We aimed to investigate whether it is associated with progression to chronic airflow obstruction over time. Methods The multinational Burden of Obstructive Lung Disease cohort study surveyed adults, aged 40 years and above, at baseline and followed them up after a mean of 9.1 years. Recruitment took place between January 2, 2003 and December 26, 2016. Follow-up measurements were collected between January 29, 2019 and October 24, 2021. On both occasions, study participants provided information on respiratory symptoms, health status and several environmental and lifestyle exposures. They also underwent pre- and post-bronchodilator spirometry. We defined bronchodilator responsiveness at baseline using the American Thoracic Society and European Respiratory Society (ATS/ERS) 2022 definition, and the presence of chronic airflow obstruction at follow-up as a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC) less than the lower limit of normal. We used multi-level regression models to estimate the association between baseline bronchodilator responsiveness and incident chronic airflow obstruction. We stratified analyses by gender and performed a sensitivity analysis in never smokers. Findings We analysed data from 3701 adults with 56% being women. Compared to those without bronchodilator responsiveness at baseline, those with bronchodilator responsiveness had 36% increased risk of developing chronic airflow obstruction (RR: 1.36, 95%CI 1.04, 1.80). This effect was stronger in women (RR: 1.45, 95%CI 1.09, 1.91) than men (RR: 1.07, 95%CI 0.51, 2.24). Never smokers with bronchodilator responsiveness also were at greater risk of incident chronic airflow obstruction (RR: 1.48, 95%CI 1.01, 2.20). Interpretation Bronchodilator responsiveness appears to be a risk factor for incident chronic airflow obstruction. It is important that future studies in other large population-based cohorts replicate these findings. Funding National Heart and Lung Institute, UK Medical Research Council, and Wellcome Trust.
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Affiliation(s)
- Ben Knox-Brown
- National Heart and Lung Institute, Imperial College London, London, UK
- Royal Papworth Hospital NHS FT, Cambridge, UK
| | - Fahad Algharbi
- National Heart and Lung Institute, Imperial College London, London, UK
- Respiratory Services, Royal Commission Health Services Program, Jubail, Saudi Arabia
| | - Octavia Mulhern
- National Heart and Lung Institute, Imperial College London, London, UK
- Guttmacher Institute, New York, USA
| | - James Potts
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Imed Harrabi
- Ibn El Jazzar Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia
| | - Christer Janson
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - Rune Nielsen
- Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Dhiraj Agarwal
- Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India
| | - Andrei Malinovschi
- Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden
| | - Sanjay Juvekar
- Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India
- Dr. D. Y. Patil Medical College, Hospital and Research Centre, India
| | - Miriam Denguezli
- Université de Sousse, Faculté de Médecine de Sousse, LR19ES09, Sousse 4000, Tunisia
| | - Thorarinn Gíslason
- Faculty of Medicine, University of Iceland, Reykjavík, Iceland
- Department of Sleep, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland
| | - Rana Ahmed
- The Epidemiological Laboratory, Khartoum, Sudan
| | - Asaad Nafees
- Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan
| | - Parvaiz A. Koul
- Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J&K, India
| | | | | | - Li Cher Loh
- RCSI and UCD Malaysia Campus, Penang, Malaysia
| | - Hermínia Brites Dias
- Escola Superior de Tecnologia da Saúde de Lisboa, Politécnico de Lisboa (Lisbon School of Health Technology, Polytechnic of Lisbon), Lisbon, Portugal
| | - Fátima Rodrigues
- Pulmonology Department, Santa Maria Local Health Unit, Lisbon, Portugal
- Institute of Environmental Health, Lisbon Medical School, Lisbon University, Lisbon, Portugal
| | - David Mannino
- University of Kentucky, Lexington, KY, USA
- COPD Foundation, Miami, FL, USA
| | - Mohammed Elbiaze
- Faculté de Médecine et de Pharmacie et de Médecine dentaire Fès, Morocco
- Directeur du Centre de Médecine Universitaire du Sommeil et Spécialiste Pneumologie CHU Hassan II Fès, Morocco
| | - Karima El Rhazi
- Epidemiology and Research in Health Sciences Laboratory, Faculty of Medicine, Pharmacy and Dentistry, Sidi Mohamed Ben Abdillah University, Morocco
- Hassan Il University Hospital Centre of Fez, Morocco
| | - Filip Mejza
- Centre for Evidence Based Medicine, 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland
| | - Graham Devereux
- Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK
| | | | | | - Emiel Wouters
- Maastricht University Medical Centre, Maastricht, the Netherlands
- Ludwig Boltzmann Institute for Lung Health, Vienna, Austria
| | - Mohammed Al Ghobain
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
| | - Kevin Mortimer
- University of Cambridge, Cambridge, UK
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | | | | | - Michael Studnicka
- Department of Pulmonary Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Joao Cardoso
- Pulmonology Department, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
- NOVA Medical School, Nova University Lisbon, Lisboa, Portugal
| | - Peter Burney
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Andre F.S. Amaral
- National Heart and Lung Institute, Imperial College London, London, UK
- NIHR Imperial Biomedical Research Centre, London
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Wichmann J, Hoffmann M, Laudien M. [Balloon dilatation of subglottic stenoses, especially in granulomatosis with polyangiitis]. Laryngorhinootologie 2025; 104:167-176. [PMID: 38996431 DOI: 10.1055/a-2357-8895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2024]
Abstract
INTRODUCTION Subglottic stenoses (SGS) are constrictions in the region below the vocal folds, that can pose a life-threatening problem for those affected. The aim of this research project was to identify the patient group for which the treatment of SGS by balloon dilatation can lead to long-term success. METHODS 14 patients with SGS were examined (before and up to12 months after intervention) using pulmonary function tests, laryngoscopies and two questionnaires (Clinical Chronic Obstructive Pulmonary Disease Questionnaire, modified Medical Research Council Dyspnoea Scale) regarding the respiratory situation. Additionally, the number of necessary interventions, the degree of stenosis (according to Myer Cotton and measured in millimeters) were documented. RESULTS Four patients who required only one intervention with the balloon showed better pre-interventional respiratory function and a higher subjective stress level. Lung function tests and evaluation of the questionnaires showed an improvement in the respiratory situation and state of health of all 14 patients after the initial intervention. The degree of stenosis measured in millimeters shows that patients with a stenosis diameter of less than 4 mm only required one intervention. All patients who received an intervention using a 12-mm-balloon had to be treated several times. CONCLUSIONS Patients with a high degree of stenosis and a tendency towards greater subjective stress and less objective restriction of the respiratory function appear to have a higher probability of long-term successful treatment with the balloon. Furthermore, the choice of balloon size seems to be an additional decisive factor for the success of an intervention.
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Affiliation(s)
- Jeannette Wichmann
- Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
| | - Markus Hoffmann
- Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
| | - Martin Laudien
- Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
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Suissa S, Dell'Aniello S, Ernst P. Single-Inhaler Triple vs Long-Acting Beta 2-Agonist-Inhaled Corticosteroid Therapy for COPD: Comparative Safety in Real-World Clinical Practice. Chest 2025; 167:712-723. [PMID: 39461554 PMCID: PMC11882741 DOI: 10.1016/j.chest.2024.10.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 10/16/2024] [Accepted: 10/17/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUND Recent treatment guidelines for COPD have replaced the long-acting beta2-agonist (LABA) and inhaled corticosteroid (ICS) combination with single-inhaler triple therapy that adds a long-acting muscarinic antagonist (LAMA). However, the corresponding trials reported numerically higher incidences of cardiovascular adverse events with triple therapy compared with LABA-ICS. RESEARCH QUESTION Does single-inhaler triple therapy increase the incidence of major adverse cardiovascular events, compared with LABA-ICS, in a real-world clinical practice setting? STUDY DESIGN AND METHODS We identified a cohort of patients with COPD aged ≥ 40 years treated during 2017-2021 from the UK's Clinical Practice Research Datalink. Among LAMA-naive patients, initiators of single-inhaler triple therapy were matched 1:1 to LABA-ICS users on time-conditional propensity scores. They were compared on the incidence of major adverse cardiovascular events (MACEs), defined as hospitalization for myocardial infarction or stroke, or all-cause-mortality, over 1 year. RESULTS The cohort included 10,255 initiators of triple therapy and 10,255 matched users of LABA-ICS. The incidence rate of MACEs was 11.3 per 100 per year with triple therapy compared with 8.8 per 100 per year for LABA-ICS. The corresponding adjusted hazard ratio (HR) of MACEs with triple therapy was 1.28 (95% CI, 1.05-1.55), relative to LABA-ICS; however, the increase was mainly in the first 4 months (HR, 1.41; 95% CI, 1.14-1.74). The HR of all-cause death was 1.31 (95% CI, 1.06-1.62), whereas for acute myocardial infarction and stroke hospitalization it was 1.00 (95% CI, 0.56-1.79) and 1.06 (95% CI, 0.48-2.36), respectively, with triple therapy, relative to LABA-ICS. INTERPRETATION In a real-world setting of COPD treatment, patients who initiated single-inhaler triple therapy had an increased incidence of MACEs compared with similar patients treated with an LABA-ICS inhaler. This small increase was due to the all-cause mortality component, occurring mainly in the first 4 months after treatment initiation.
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Affiliation(s)
- Samy Suissa
- Centre for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital; Montreal, QC; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada.
| | - Sophie Dell'Aniello
- Centre for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital; Montreal, QC
| | - Pierre Ernst
- Centre for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital; Montreal, QC; Department of Medicine, McGill University, Montreal, QC, Canada
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Gupta YS, Simpson S, Graham R, Kumaran M, Dako F, Hota P, Dass C. Imaging of Bronchoscopic Lung Volume Reduction Using Endobronchial Valves. Radiographics 2025; 45:e240156. [PMID: 40014469 DOI: 10.1148/rg.240156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Lung volume reduction is a treatment option for patients with severe emphysema and predominant chronic obstructive pulmonary disease that is refractory to medical treatment. These patients often experience symptoms associated with hyperinflation including dyspnea and exercise limitation. In recent years, bronchoscopic lung volume reduction using endobronchial valve (EBV) therapy has emerged as a U.S. Food and Drug Administration-approved and less invasive alternative to lung volume reduction surgery. The two approved one-way valves allow air to exit the lung but prohibit air from entering, with the intended goal of reducing hyperinflation. After patients meet clinical eligibility criteria, imaging has an integral role in preprocedural and postprocedural assessment. Findings from qualitative and quantitative preprocedural thin-section CT and perfusion scintigraphic analysis provides the characterization of emphysema, degree of collateral ventilation, and lung perfusion data necessary for target lobe selection, while aiding in detection of the presence of contraindications to the procedure, including suspicious pulmonary nodules, significant bronchiectasis, large bullae, and pleural adhesions. At procedure completion, chest radiography is required for assessment of complications, most commonly pneumothorax. Subsequent imaging may determine whether the procedure has successfully induced lobar atelectasis as well as the presence of additional complications such as infection and valve malposition or migration. Knowledge of EBV therapy and pertinent imaging findings is crucial in optimizing patient selection for the procedure, identifying complications, and evaluating treatment response. ©RSNA, 2025.
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Affiliation(s)
- Yogesh S Gupta
- From the Department of Radiology, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19104 (Y.S.G., R.G., M.K., C.D.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (S.S., F.D.); and Division of Chest Imaging, Atlantic Medical Imaging, Galloway, NJ (P.H.)
| | - Scott Simpson
- From the Department of Radiology, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19104 (Y.S.G., R.G., M.K., C.D.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (S.S., F.D.); and Division of Chest Imaging, Atlantic Medical Imaging, Galloway, NJ (P.H.)
| | - Ryan Graham
- From the Department of Radiology, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19104 (Y.S.G., R.G., M.K., C.D.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (S.S., F.D.); and Division of Chest Imaging, Atlantic Medical Imaging, Galloway, NJ (P.H.)
| | - Maruti Kumaran
- From the Department of Radiology, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19104 (Y.S.G., R.G., M.K., C.D.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (S.S., F.D.); and Division of Chest Imaging, Atlantic Medical Imaging, Galloway, NJ (P.H.)
| | - Farouk Dako
- From the Department of Radiology, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19104 (Y.S.G., R.G., M.K., C.D.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (S.S., F.D.); and Division of Chest Imaging, Atlantic Medical Imaging, Galloway, NJ (P.H.)
| | - Partha Hota
- From the Department of Radiology, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19104 (Y.S.G., R.G., M.K., C.D.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (S.S., F.D.); and Division of Chest Imaging, Atlantic Medical Imaging, Galloway, NJ (P.H.)
| | - Chandra Dass
- From the Department of Radiology, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19104 (Y.S.G., R.G., M.K., C.D.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (S.S., F.D.); and Division of Chest Imaging, Atlantic Medical Imaging, Galloway, NJ (P.H.)
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Chen YF, Chang CL, Hou HH, Chien N, Lu KZ, Chen YY, Hung ZC, Hsiao YH, Sheu CC, Wang PH, Hsieh MH, Hsu WH, Chen MT, Ou WF, Wei YF, Yang TM, Lan CC, Wang CY, Lin CB, Lin MS, Wang YT, Lin CH, Liu SF, Cheng MH, Cheng WC, Peng CK, Chan MC, Chen CY, Jao LY, Wang YH, Chen CJ, Chen SP, Tsai YH, Cheng SL, Lin HC, Chien JY, Wang HC, Yu CJ. The impact of COPD-bronchiectasis association on clinical outcomes: insights from East Asian cohorts validating the ROSE criteria. ERJ Open Res 2025; 11:00626-2024. [PMID: 40071267 PMCID: PMC11895104 DOI: 10.1183/23120541.00626-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 09/13/2024] [Indexed: 03/14/2025] Open
Abstract
Background The radiology, obstruction, symptoms and exposure (ROSE) criteria provide a standardised approach for identifying the "COPD-bronchiectasis (BE) association." However, the clinical implications and outcomes of the COPD-BE association in East Asian populations remain unclear. Our study applied the ROSE criteria to assess the prevalence, clinical impact and outcomes of the COPD-BE association in an East Asian cohort, and compared that cohort with nonsmoking BE patients with fixed airflow obstruction (FAO) and those without FAO. Methods An integrated cohort analysis was conducted within a Taiwanese demographic, combining a prospective cohort of 147 participants with a multicentre retrospective cohort of 574 participants. Stratification was based on the ROSE criteria, distinguishing between nonsmoking BE, smoking BE, nonsmoking BE with FAO and BE in compliance with the ROSE criteria. Clinical, radiological and spirometric variables were assessed in conjunction with outcomes to validate the diagnostic utility of the criteria. Results Using the ROSE criteria, we found that 16.5% of participants had a COPD-BE association (22.4% in the prospective cohort and 14.9% in the retrospective cohort), predominantly in older male patients. These patients had escalated dyspnoea scores, higher COPD diagnosis rates and increased use of inhalation therapies, compared with those without FAO. Notably, patients with a COPD-BE association and nonsmoking BE with FAO displayed similar clinical symptoms, pulmonary function and disease severity, but differed slightly in airway microbiology. Furthermore, patients with a COPD-BE association had significantly higher risks of exacerbations and hospitalisations, even after adjusting for confounding factors, which highlights that they have poorer clinical outcomes than other groups. Conclusion The ROSE criteria effectively identify the COPD-BE association in East Asian populations, highlighting a significant future exacerbation risk compared with other BE groups. Future research is warranted to better understand BE progression, especially in FAO subgroups.
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Affiliation(s)
- Yen-Fu Chen
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliu, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Thoracic Medicine Center, Department of Medicine and Surgery, National Taiwan University Hospital, Yunlin Branch, Douliu, Taiwan
| | - Chia-Ling Chang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Hsin-Han Hou
- Graduate Institute of Oral Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ning Chien
- Department of Medical Imaging, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Kai-Zen Lu
- Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ying-Yin Chen
- Precision Medicine Center, National Taiwan University Hospital, Yunlin Branch, Hu-Wei, Taiwan
| | - Zheng-Ci Hung
- Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Han Hsiao
- Division of General Chest Medicine, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chau-Chyun Sheu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ping-Huai Wang
- Division of Thoracic Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Meng-heng Hsieh
- Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wu-Huei Hsu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Critical Medical Center, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Tsung Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Fan Ou
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yu-Feng Wei
- Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Tsung-Ming Yang
- Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chou-Chin Lan
- Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Chih-Bin Lin
- Division of Pulmonary Medicine, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu-Chi University, Hualien, Taiwan
| | - Ming-Shian Lin
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - Yao-Tung Wang
- Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Ching-Hsiung Lin
- Department of Internal Medicine, Division of Chest Medicine, Changhua Christian Hospital, Changhua, Taiwan
- Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan
- PhD Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Recreation and Holistic Wellness, MingDao University, Changhua, Taiwan
| | - Shih-Feng Liu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Meng-Hsuan Cheng
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Chien Cheng
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chung-Kan Peng
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ming-Cheng Chan
- Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Post Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Ching-Yi Chen
- Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Lun-Yu Jao
- Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
- School of Medicine, Tzu-Chi University, Hualien, Taiwan
| | - Ya-Hui Wang
- Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Chi-Jui Chen
- Division of Pulmonary Medicine, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Shih-Pin Chen
- Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Yi-Hsuan Tsai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Department of Pulmonary Medicine, Lee's Clinic, Pingtung, Taiwan
| | - Shih-Lung Cheng
- Division of Thoracic Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan City, Taiwan
| | - Horng-Chyuan Lin
- Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Respiratory Therapy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Jung-Yien Chien
- Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hao-Chien Wang
- Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Medicine, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
- H-C. Wang and C-J. Yu contributed equally to this article as lead authors and supervised the work
| | - Chong-Jen Yu
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- H-C. Wang and C-J. Yu contributed equally to this article as lead authors and supervised the work
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Ekström M, Lewthwaite H, Li PZ, Bourbeau J, Tan WC, Jensen D. Identifying Abnormal Exertional Breathlessness in COPD: Comparing Modified Medical Research Council and COPD Assessment Test With Cardiopulmonary Exercise Testing. Chest 2025; 167:697-711. [PMID: 39490971 PMCID: PMC11882773 DOI: 10.1016/j.chest.2024.10.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 10/11/2024] [Accepted: 10/20/2024] [Indexed: 11/05/2024] Open
Abstract
BACKGROUND COPD management is guided by the respiratory symptom burden, assessed using the modified Medical Research Council (mMRC) scale, the COPD Assessment Test (CAT), or both. RESEARCH QUESTION What are the abilities of mMRC and CAT to detect abnormally high exertional breathlessness on incremental cardiopulmonary cycle exercise testing (CPET) in people with COPD? STUDY DESIGN AND METHODS Analysis of people aged ≥ 40 years with FEV1 to FVC ratio of < 0.70 after bronchodilator administration and ≥ 10 pack-years of smoking from the Canadian Cohort Obstructive Lung Disease study. Abnormal exertional breathlessness was defined as a breathlessness (Borg scale 0-10) intensity rating more than the upper limit of normal at the symptom-limited peak of CPET using normative reference equations. RESULTS We included 318 people with COPD (40% female) with a mean (SD) age of 66.5 (9.3) years and FEV1 of 79.5% predicted (19.0% predicted); 26% showed abnormally low exercise capacity (peak oxygen uptake less than the lower limit of normal). Abnormally high exertional breathlessness was present in 24%, including 9% and 11% of people with mMRC score of 0 and CAT score of < 10, respectively. An mMRC score of ≥ 2 and CAT score of ≥ 10 was most specific (95%) to detect abnormal exertional breathlessness, but showed low sensitivity of only 12%. Accuracy for all scale cutoffs or combinations was < 65%. Compared with people with true-negatives findings, people with abnormal exertional breathlessness but low mMRC score, low CAT scores (false-negatives findings), or both showed worse self-reported and physiologic outcomes during CPET, were more likely to have physician-diagnosed COPD, but were not more likely to be taking any respiratory medication (37% vs 30%; mean difference, 6.1%; 95% CI, -7.2 to 19.4; P= .36). INTERPRETATION In COPD, mMRC and CAT showed low concordance with CPET and failed to identify many people with abnormally high exertional breathlessness. CLINICAL TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00920348; URL: www. CLINICALTRIALS gov.
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Affiliation(s)
- Magnus Ekström
- Department of Clinical Sciences Lund, Respiratory Medicine, Allergology and Palliative Medicine (M. E.), Faculty of Medicine, Lund University, Lund, Sweden.
| | - Hayley Lewthwaite
- Centre of Research Excellence Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia; Asthma and Breathing Research Program (H. L.), Hunter Medical Research Institute, Newcastle, NSW, Australia
| | - Pei Zhi Li
- Montreal Chest Institute, McGill University Health Center Research Institute, Montréal, QC, Canada
| | - Jean Bourbeau
- Montreal Chest Institute, McGill University Health Center Research Institute, Montréal, QC, Canada; Translational Research in Respiratory Diseases Program and Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre Research Institute, Montréal, QC, Canada
| | - Wan C Tan
- Centre for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Dennis Jensen
- Montreal Chest Institute, McGill University Health Center Research Institute, Montréal, QC, Canada; Translational Research in Respiratory Diseases Program and Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre Research Institute, Montréal, QC, Canada; Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, Faculty of Education, McGill University, Montréal, QC, Canada
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45
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Gao Q, Zhu H. Investigating the risk factors for the coexistence of insomnia and its exacerbation in AECOPD. Respir Med 2025; 238:107987. [PMID: 39921070 DOI: 10.1016/j.rmed.2025.107987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 01/18/2025] [Accepted: 02/04/2025] [Indexed: 02/10/2025]
Abstract
AIM Explore the risk factors contributing to insomnia and its severity in patients experiencing Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). METHODS The study included 155 patients with AECOPD from Chaohu Hospital, Anhui Medical University, treated between September 2022 and October 2023. Patients were categorized into insomnia groups (mild, moderate, severe) and a comparison group based on Insomnia Severity Index Scale (ISI) scores. Sleep quality and severity were assessed using the Pittsburgh Sleep Quality Index (PSQI), CAT score, and mMRC classification. Clinical data, pathology, and results from various laboratory tests were collected. Details of current admission treatment, including ventilator usage, medication types, and administration methods, were documented for group comparisons. RESULTS This study included 155 AECOPD patients, with over 70 % identified as high-risk for obstructive sleep apnea (OSA). Among them, 87 were in the insomnia group and 68 in the comparison group. The insomnia group comprised 46 mild, 36 moderate, and 5 severe cases. Female patients, those with lower education, shorter smoking history, higher CAT and PSQI scores, more frequent hospital admissions, and those using oral or intravenous glucocorticoids were more likely to experience insomnia. In the moderate insomnia subgroup, patients had higher CAT and PSQI scores and longer hospitalization than the mild insomnia group. No significant differences were found in the use of quinolones, glucocorticoid administration, ventilator use, or resuscitation behaviors among insomnia severity levels. CONCLUSION Insomnia coexisting with AECOPD is prevalent, with the patient's gender, educational level, smoking history, severity of clinical symptoms, and the type of treatment influencing their sleep status.
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Affiliation(s)
- Qianqian Gao
- Chaohu Hospital Affiliated with Anhui Medical University, Chaohu City, People's Republic of China
| | - Hongbin Zhu
- Department of Respiratory and Critical Care Medicine, Chaohu Hospital Affiliated with Anhui Medical University, Chaohu City, People's Republic of China.
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46
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Pianigiani T, Paggi I, Cooper GE, Staples KJ, McDonnell M, Bergantini L. Natural killer cells in the lung: novel insight and future challenge in the airway diseases. ERJ Open Res 2025; 11:00683-2024. [PMID: 40071269 PMCID: PMC11895099 DOI: 10.1183/23120541.00683-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/13/2024] [Indexed: 03/14/2025] Open
Abstract
Natural killer (NK) cells are innate lymphoid cells which are present in the lung as circulating and resident cells. They are key players both in airway surveillance and in crosstalk with (COPD) pathogenesis, and they seem to contribute to the development of bronchiectasis. In asthma, NK cell dysfunction was observed mainly in severe forms, and it can lead to a biased type-2 immune response and failure in the resolution of eosinophilic inflammation that characterise both allergic and eosinophilic phenotypes. Moreover, aberrant NK cell functions may interfere with antimicrobial immune response contributing to the frequency and severity of virus-induced exacerbations. In COPD, lung NK cells exhibit increased cytotoxicity against lung epithelium contributing to lung tissue destruction and emphysema. This cell destruction may be exacerbated by viral infections and cigarette smoke exposure through NKG2D-dependent detection of cellular stress. Lastly, in bronchiectasis, the airway NK cells might both promote neutrophil survival following stimulation by proinflammatory cytokines and promote neutrophil apoptosis. Systemic steroid treatment seemingly compromises NK activity, while biologic treatment with benralizumab could enhance NK cell proliferation, maturation and activation. This narrative review gives an overview of NK cells in airway diseases focusing on pathophysiological and clinical implications. Together, our findings emphasise the pleiotropic role of NK cells in airway diseases underscoring their possible implications as to therapeutical approaches.
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Affiliation(s)
- Tommaso Pianigiani
- Respiratory Diseases Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University Hospital, Siena, Italy
| | - Irene Paggi
- Respiratory Diseases Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University Hospital, Siena, Italy
| | - Grace E. Cooper
- Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK
| | - Karl J. Staples
- Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK
- NIHR Southampton Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK
| | - Melissa McDonnell
- Department of Respiratory Medicine, Galway University Hospital, Galway, Ireland
| | - Laura Bergantini
- Respiratory Diseases Unit, Department of Medical Sciences, Surgery and Neurosciences, Siena University Hospital, Siena, Italy
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D'Andria Ursoleo J, Bottussi A, Sullivan DR, D'Andria C, Smirnova N, Rosa WE, Nava S, Monaco F. Chronic obstructive pulmonary disease: A narrative synthesis of its hallmarks for palliative care clinicians. Eur J Intern Med 2025; 133:25-34. [PMID: 39794226 DOI: 10.1016/j.ejim.2024.12.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 12/26/2024] [Accepted: 12/30/2024] [Indexed: 01/13/2025]
Abstract
Chronic obstructive pulmonary disease (COPD) is a life-limiting condition and the third leading cause of death worldwide. People with COPD experience physical and psychological symptoms and functional limitations that impair their quality of life. Their caregivers face adverse clinical outcomes due to personal, social, and financial demands. As such, recent emphasis has been placed on early referral to palliative care services to enhance prognostic awareness, clarify goals of care, and manage symptoms. In this narrative synthesis of key aspects of COPD care, we propose practical, evidence-based strategies to integrate palliative care principles with conventional disease-directed treatments throughout the illness trajectory. We emphasize the importance of equipping clinicians caring for people with COPD with a thorough understanding of both the inherent disease complexities and the cornerstones of its multimodal management, including palliative care, to address the unique psychosocial and physical needs of this patient population.
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Affiliation(s)
- Jacopo D'Andria Ursoleo
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. https://twitter.com/JDAndriaUrsoleo
| | - Alice Bottussi
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. https://twitter.com/abottussi
| | - Donald R Sullivan
- Oregon Health & Science University, Division of Pulmonary, Allergy & Critical Care Medicine, Portland, OR, United States; Division of Oncological Sciences, Knight Cancer Institute-OHSU, Portland, OR, United States; Center to Improve Veteran Involvement in Care (CIVIC), Veterans Affairs-Portland Healthcare System, Portland, OR, United States. https://twitter.com/DSullyResearch
| | - Corrado D'Andria
- Allergy and Immunopathology Unit, Department of Internal Medicine, SS. Annunziata General Hospital, 74121 Taranto, Italy; Department of Translational Medicine and Neurosciences, School of Medicine and Surgery, Aldo Moro University of Bari, 70121 Bari, Italy
| | - Natalia Smirnova
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States. https://twitter.com/SRAnesthesiaICU
| | - William E Rosa
- Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, United States. https://twitter.com/BillyRosaPhD
| | - Stefano Nava
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; Respiratory and Critical Care Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy. https://twitter.com/md_monaco
| | - Fabrizio Monaco
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
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Kim CH, Park B, Baek MS. The effect of long-term exposure to a mixture of air pollutants on chronic obstructive pulmonary disease. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 292:117978. [PMID: 40043502 DOI: 10.1016/j.ecoenv.2025.117978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 02/17/2025] [Accepted: 02/25/2025] [Indexed: 03/17/2025]
Abstract
Chronic obstructive pulmonary disease (COPD) is a major global cause of morbidity and mortality; however, evidence on the effects of air pollutant mixtures on COPD remains limited. This study assessed the impact of long-term exposure to multiple pollutants on COPD prevalence and identified vulnerable subgroups. We analyzed Korea National Health and Nutrition Examination Survey (2010-2017) data linked to 5-year moving average concentrations of CO, NO₂, SO₂, O₃, PM₂.₅, and PM₁₀. Bayesian kernel machine regression (BKMR) estimated the combined effects of pollutants on COPD prevalence, with subgroup analyses performed according to sex, smoking status, and airflow limitation. Adjustments included age, sex, BMI, smoking status, and household income. Among 21,804 participants, 3515 had COPD. BKMR analysis showed that long-term exposure to a pollutant mixture was associated with increased COPD prevalence. O₃ and NO₂ were identified as the most influential pollutants (posterior inclusion probabilities > 0.50). Further analysis showed a significant increase in COPD risk with higher NO₂ and O₃ concentrations, particularly when other pollutants were at lower or median levels. Significant interactions were observed, particularly between SO₂ and CO, CO and O₃, and NO₂ and O₃. Subgroup analyses identified vulnerable populations, indicating stronger associations among females and never smokers and more pronounced effects in individuals with GOLD 2-4. These findings suggest that long-term exposure to multiple air pollutants could increase COPD risk, particularly for females, never smokers, and individuals with more severe COPD. Targeted interventions and policy measures are needed to reduce exposure, especially for these at-risk populations.
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Affiliation(s)
- Chung Ho Kim
- Department of Preventive Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - Bomi Park
- Department of Preventive Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
| | - Moon Seong Baek
- Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea; Biomedical Research Institute, Chung-Ang University Hospital, Seoul, Republic of Korea.
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Jin F, Lin H, Pan S. Novel therapeutic strategy: Nrf2 activation in targeting senescence-related changes in chronic obstructive pulmonary disease. J Thorac Dis 2025; 17:623-640. [PMID: 40083491 PMCID: PMC11898394 DOI: 10.21037/jtd-24-710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 01/07/2025] [Indexed: 03/16/2025]
Abstract
Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, largely driven by the accumulation of senescent bronchial epithelial cells, which contribute to inflammation and tissue remodeling. This study investigates the therapeutic potential of nuclear factor erythroid 2-related factor 2 (Nrf2) activation in targeting senescence-related changes to alleviate COPD progression. Methods Single-cell transcriptome analysis, in vitro COPD cell models, and a COPD mouse model were utilized to examine the effects of Nrf2 activation. Specifically, the study focused on the impact of Nrf2 on senescent ciliated epithelial cells and the associated secretory phenotype. Respiratory function tests and lung pathology assessments were conducted to evaluate the intervention's efficacy in the mouse model. Results The study identified a significant presence of senescent ciliated epithelial cells in COPD patients, contributing to disease progression. Nrf2 activation in vitro reduced senescence markers, enhanced cell proliferation, and decreased inflammatory cytokines. In vivo, Nrf2 activation significantly improved lung function and reduced pathological damage in the COPD mouse model. Conclusions The findings underscore the potential of Nrf2 activation as a therapeutic strategy to mitigate COPD progression by modulating the senescence-associated secretory phenotype (SASP). This study suggests that Nrf2 activators could offer a promising approach to improving clinical outcomes for COPD patients.
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Affiliation(s)
- Fenhua Jin
- Department of Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hui Lin
- Department of Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shufang Pan
- Department of Nephrology Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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50
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Zhu W, Han L, He L, Peng W, Li Y, Tian W, Qi H, Wei S, Shen J, Song Y, Shen Y, Zhu Q, Zhou J. Lsm2 is critical to club cell proliferation and its inhibition aggravates COPD progression. Respir Res 2025; 26:71. [PMID: 40022153 PMCID: PMC11871738 DOI: 10.1186/s12931-025-03126-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 01/28/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition, with its severity inversely related to the levels of Club cell 10 kDa secretory protein (CC10). The gene Lsm2, involved in RNA metabolism and cell proliferation, has an unclear role in COPD development. METHODS An in vitro COPD model was developed by stimulating 16HBE cells with cigarette smoke extract (CSE). To establish an in vivo COPD model, mice with defective Lsm2 gene expression in lung or club cells were exposed to cigarette smoke for 3 months. Multiplexed immunohistochemistry (mIHC) was employed to identify the specific cells where Lsm2 gene expression is predominant. RNA sequencing and single-nucleus RNA sequencing were conducted to investigate the role of Lsm2 in the pathogenesis of COPD. RESULTS In this study, we found that cigarette smoke extract increases Lsm2 expression, and knocking down Lsm2 in 16HBE cells significantly reduces cell viability in vitro. mIHC showed that Lsm2 is primarily expressed in Club cells. Knockout of Lsm2, either in the lungs or specifically in Club cells, exacerbated lung injury and inflammation caused by cigarette smoke exposure in vivo. Single-nucleus RNA sequencing analysis revealed that Club cell-specific knockout of Lsm2 leads to a reduction in the Club cell population, particularly those expressing Chia1+/Crb1+. This decrease in Club cells subsequently reduces the number of ciliated epithelial cells. CONCLUSION Knocking out Lsm2 in Club cells results in a significant decrease in Club cell numbers, which subsequently leads to a reduction in ciliated epithelial cells. This increased lung vulnerability to cigarette smoke and accelerating the progression of COPD. Our findings highlight that Lsm2 is critical to club cell proliferation and its inhibition aggravates COPD progression.
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Affiliation(s)
- Wensi Zhu
- Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai, 200032, China
- Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, 200032, China
| | - Linxiao Han
- Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai, 200032, China
- Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, 200032, China
| | - Ludan He
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, 200032, China
- Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai, 200032, China
- Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, 200032, China
| | - Wenjun Peng
- Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai, 200032, China
- Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, 200032, China
| | - Ying Li
- Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Weibin Tian
- Department of Respiratory and Critial Care Medicine, Shanghai Pudong Hospital, 2800 Gongwei Rd, Shanghai, 201399, China
| | - Hui Qi
- Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, 050091, Hebei, China
| | - Shuoyan Wei
- Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai, 200032, China
- Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, 200032, China
| | - Jie Shen
- Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Fudan University, Shanghai, 200540, China
| | - Yuanlin Song
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, 200032, China
- Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, 200032, China
| | - Yao Shen
- Department of Respiratory and Critial Care Medicine, Shanghai Pudong Hospital, 2800 Gongwei Rd, Shanghai, 201399, China.
| | - Qiaoliang Zhu
- Department of Thoracic Surgery, Shanghai Geriatric Medical Center, 2560 Chunshen Road, Shanghai, 201104, China.
| | - Jian Zhou
- Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China.
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, 200032, China.
- Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine, 180 Fenglin Road, Shanghai, 200032, China.
- Shanghai Key Laboratory of Lung Inflammation and Injury, 180 Fenglin Road, Shanghai, 200032, China.
- Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Fudan University, Shanghai, 200540, China.
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