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Simon P, Török É, Szalontai K, Kari B, Neuperger P, Zavala N, Kanizsai I, Puskás LG, Török S, Szebeni GJ. Nutritional Support of Chronic Obstructive Pulmonary Disease. Nutrients 2025; 17:1149. [PMID: 40218907 PMCID: PMC11990120 DOI: 10.3390/nu17071149] [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: 02/05/2025] [Revised: 03/14/2025] [Accepted: 03/19/2025] [Indexed: 04/14/2025] Open
Abstract
Background: COPD is a heterogenous disease of the respiratory tract caused by diverse genetic factors along with environmental and lifestyle-related effects such as industrial dust inhalation and, most frequently, cigarette smoking. These factors lead to airflow obstruction and chronic respiratory symptoms. Additionally, the increased risk of infections exacerbates airway inflammation in COPD patients. As a consequence of the complex pathomechanisms and difficulty in treatment, COPD is among the leading causes of mortality both in the western countries and in the developing world. Results: The management of COPD is still a challenge for the clinicians; however, alternative interventions such as smoking cessation and lifestyle changes from a sedentary life to moderate physical activity with special attention to the diet may ameliorate patients' health. Here, we reviewed the effects of different dietary components and supplements on the conditions of COPD. Conclusions: COPD patients are continuously exposed to heavy metals, which are commonly present in cigarette smoke and polluted air. Meanwhile, they often experience significant nutrient deficiencies, which affect the detoxification of these toxic metals. This in turn can further disrupt nutritional balance by interfering with the absorption, metabolism, and utilization of essential micronutrients. Therefore, awareness and deliberate efforts should be made to check levels of micronutrients, with special attention to ensuring adequate levels of antioxidants, vitamin D, vitamin K2, magnesium, and iron, as these may be particularly important in reducing the risk of COPD development and limiting disease severity.
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Grants
- 2023-1.1.1-PIACI_FÓKUSZ-2024-00036 National Research, Development, and Innovation Office (NKFI), Hungary
- 2020-1.1.6-JÖVŐ-2021-00003 National Research, Development, and Innovation Office (NKFI), Hungary
- 2022-1.2.6-TÉT-IPARI-TR-2022-00023 National Research, Development, and Innovation Office (NKFI), Hungary
- 142877 FK22 National Research, Development, and Innovation Office (NKFI), Hungary.
- BO/00582/22/8 János Bolyai Research Scholarship of the Hungarian Academy of Sciences
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Affiliation(s)
- Péter Simon
- National Korányi Institute of Pulmonology, 1121 Budapest, Hungary;
| | - Éva Török
- Gastroenterology Center Buda, 1117 Budapest, Hungary;
| | - Klára Szalontai
- Department of Pulmonology, Szent-Györgyi Albert Medical Center, University of Szeged, 6772 Deszk, Hungary;
| | - Beáta Kari
- Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, 6726 Szeged, Hungary; (B.K.); (P.N.); (N.Z.); (L.G.P.)
| | - Patrícia Neuperger
- Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, 6726 Szeged, Hungary; (B.K.); (P.N.); (N.Z.); (L.G.P.)
| | - Norma Zavala
- Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, 6726 Szeged, Hungary; (B.K.); (P.N.); (N.Z.); (L.G.P.)
| | | | - László G. Puskás
- Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, 6726 Szeged, Hungary; (B.K.); (P.N.); (N.Z.); (L.G.P.)
- Anthelos Ltd., 6726 Szeged, Hungary
| | - Szilvia Török
- National Korányi Institute of Pulmonology, 1121 Budapest, Hungary;
| | - Gabor J. Szebeni
- Laboratory of Functional Genomics, Core Facility, HUN-REN Biological Research Centre, 6726 Szeged, Hungary; (B.K.); (P.N.); (N.Z.); (L.G.P.)
- Department of Internal Medicine, Hematology Centre, Faculty of Medicine, University of Szeged, 6725 Szeged, Hungary
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Xu J, Xiong J, Jiang X, Sun M, Chen M, Luo X. Association between body roundness index and weight-adjusted waist index with asthma prevalence among US adults: the NHANES cross-sectional study, 2005-2018. Sci Rep 2025; 15:9781. [PMID: 40118914 PMCID: PMC11928567 DOI: 10.1038/s41598-025-93604-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/07/2025] [Indexed: 03/24/2025] Open
Abstract
This study investigated the connection between asthma in US individuals and their body roundness index (BRI) and weight-adjusted waist index (WWI). According to data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), 3609 of the 25,578 persons in the survey who were 18 years of age or older reported having asthma. After adjusting for all confounders, the probability of asthma prevalence increased by 8% for every unit rise in BRI (OR = 1.08, 95% CI 1.06,1.11). The probability of asthma prevalence increased by 16% for every unit rise in WWI (OR = 1.16, 95% CI 1.08,1.25). The BRI and WWI indices were associated with prevalence and were nonlinearly correlated. The inflection points for threshold saturation effects were 4.36 and 10.69, respectively (log-likelihood ratio test, P < 0.05). Relationship subgroup analyses showed that the positive associations between BRI and WWI and asthma were generalized across populations and there was no significant interaction in most subgroups. In addition, sensitivity analyses verified the robustness of these results, further confirming the conclusion of BRI and WWI as independent risk factors for asthma. Finally, receiver operating characteristic (ROC) analysis showed that BRI outperformed WWI in predicting asthma, suggesting the potential of BRI in early asthma screening. Overall, BRI and WWI are independent risk factors for asthma with important clinical applications.
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Affiliation(s)
- Jie Xu
- Department of Sports Medicine, Sichuan Provincial Orthopedics Hospital, Chengdu, China
| | | | - Xiatian Jiang
- Affiliated Sport Hospital of Chengdu Sport University, Chengdu, China
| | - Min Sun
- Department of Knee Sports Injury, Sichuan Provincial Orthopedics Hospital, Chengdu, China
| | - Meng Chen
- Department of Emergency Medicine, Nanchong Hospital of Traditional Chinese Medicine, Nanchong, China
| | - Xiaobing Luo
- Department of Sports Medicine, Sichuan Provincial Orthopedics Hospital, Chengdu, China.
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Popescu ȘO, Mihai A, Turcu-Știolică A, Lupu CE, Cismaru DM, Grecu VI, Scafa-Udriște A, Ene R, Mititelu M. Visceral Fat, Metabolic Health, and Lifestyle Factors in Obstructive Bronchial Diseases: Insights from Bioelectrical Impedance Analysis. Nutrients 2025; 17:1024. [PMID: 40290050 PMCID: PMC11945945 DOI: 10.3390/nu17061024] [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: 02/21/2025] [Revised: 03/05/2025] [Accepted: 03/13/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objectives: This study examines the relationship between visceral fat (VF), metabolic health, and dietary patterns in patients with obstructive bronchial diseases (OBDs) using bioelectrical impedance analysis (BIA). Methods: A total of 75 patients diagnosed with OBD, including chronic obstructive pulmonary disease (COPD) and/or asthma, were assessed for VF levels via BIA. Dietary habits were evaluated using a structured questionnaire to explore their correlation with VF accumulation. Results: The study cohort comprised predominantly male participants (66.7%), with the majority aged between 61 and 70 years (46.7%). Significant gender differences in VF distribution were observed, with 60% of females maintaining normal VF levels (1-9) compared to only 28% of males, while 38% of males exhibited very high VF levels (15-30; p = 0.003). Body mass index (BMI) showed a strong correlation with VF (p < 0.0001), as overweight and obese individuals predominantly displayed elevated VF levels (≥10). Moreover, metabolic syndrome (MS) was present in 66.7% of participants, with these individuals exhibiting significantly higher VF levels compared to those without MS (p = 0.001). Dietary analysis revealed that frequent consumption of fast food (r = 0.717, p < 0.001), carbonated drinks (r = 0.366, p = 0.001), and refined carbohydrates (r = 0.438, p < 0.001) was significantly associated with increased VF accumulation. Conversely, higher intake of water (r = -0.551, p < 0.001), fruits (r = -0.581, p < 0.001), and vegetables (r = -0.482, p < 0.001) correlated with lower VF levels. Lack of physical activity was also strongly linked to VF accumulation (r = 0.481, p < 0.001), further reinforcing the role of lifestyle factors in metabolic health. Conclusions: The findings underscore the significant impact of dietary habits and physical activity on VF accumulation in OBD patients. BMI and MS emerged as critical predictors of VF, while unhealthy dietary patterns and sedentary lifestyles further exacerbated VF deposition. Elevated VF levels were linked to adverse lipid profiles, reinforcing the need for dietary and lifestyle modifications in managing metabolic health among OBD patients. Although no direct association was identified between VF and forced expiratory volume in one second (FEV1), the results highlight the necessity of integrated nutritional and metabolic interventions in the management of chronic respiratory diseases.
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Affiliation(s)
- Ștefana-Oana Popescu
- Department of Biochemistry, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | | | - Adina Turcu-Știolică
- Pharmaceutical Management and Marketing, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Carmen Elena Lupu
- Department of Mathematics and Informatics, Faculty of Pharmacy, “Ovidius” University of Constanta, 900001 Constanta, Romania
| | - Diana-Maria Cismaru
- National School of Political Studies and Public Administration, College of Communication and Public Relations, 012104 Bucharest, Romania;
| | - Victor Ionel Grecu
- Victor Babeș Clinical Hospital for Infectious Diseases and Pneumophthisiology, 200515 Craiova, Romania;
| | - Alexandru Scafa-Udriște
- Department of Cardio-Thoracic Pathology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Răzvan Ene
- Clinical Department No. 14, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Magdalena Mititelu
- Department of Clinical Laboratory and Food Safety, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 020956 Bucharest, Romania;
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Zailani H, Satyanarayanan SK, Liao WC, Su KP, Chang JPC. Omega-3 Polyunsaturated Fatty Acids in Chronic Obstructive Pulmonary Disease Patients with COVID-19: A Review. Curr Nutr Rep 2025; 14:12. [PMID: 39760917 DOI: 10.1007/s13668-024-00599-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2024] [Indexed: 01/07/2025]
Abstract
PURPOSE OF THE REVIEW Mounting evidence indicates that individuals with chronic obstructive pulmonary disease (COPD) face a heightened risk of severe outcomes upon contracting coronavirus disease 2019 (COVID-19). Current medications for COVID-19 often carry side effects, necessitating alternative therapies with improved tolerance. This review explores the biological mechanisms rendering COPD patients more susceptible to severe COVID-19 and investigates the potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in mitigating the severity of COVID-19 in COPD patients. RECENT FINDINGS Current evidence indicates that COPD patients are at an increased risk of severe COVID-19 due to factors including compromised pulmonary function, dysregulated inflammation, weakened immune response, increased oxidative stress, elevated expression of angiotensin-converting enzyme (ACE2) receptors in the lungs, and genetic predispositions. Remarkably, n-3 PUFAs exhibit the potential in ameliorating the clinical outcomes of COPD patients with COVID-19 by modulating inflammation, reinforcing the body's antioxidant defenses, reducing viral entry and replication, and enhancing immunity. N-3 PUFAs hold potential for improving COVID-19 outcomes in patients with COPD. However, there has been limited investigation into the therapeutic effects of n-3 PUFAs in enhancing clinical outcomes for COPD patients. Rigorous clinical studies are essential to evaluate the impact of n-3 PUFAs on COPD patients with concurrent COVID-19 infection.
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Grants
- MOST 109-2320-B-038-057- MY3, 110-2321-B-006-004, 110-2811-B-039-507, 110-2320-B-039-048-MY2,110-2320-B-039- 047-MY3, 110-2813-C-039-327-B, 110-2314-B-039-029-MY3, 111-2321-B-006-008, and NSTC 111-2314-B-039-041-MY3 Ministry of Science and Technology, Taiwan
- MOST 109-2320-B-038-057- MY3, 110-2321-B-006-004, 110-2811-B-039-507, 110-2320-B-039-048-MY2,110-2320-B-039- 047-MY3, 110-2813-C-039-327-B, 110-2314-B-039-029-MY3, 111-2321-B-006-008, and NSTC 111-2314-B-039-041-MY3 Ministry of Science and Technology, Taiwan
- ANHRF 109-31, 109-40, 110-13, 110-26, 110-44, 110-45, 111-27, 111-28, 111-47, 111-48, and 111-52 An-Nan Hospital, China Medical University, Tainan, Taiwan
- CMRC-CMA-2 Higher Education Sprout Project by the Ministry of Education, Taiwan
- CMRC-CMA-2 Higher Education Sprout Project by the Ministry of Education, Taiwan
- CMU 110- AWARD-02, 110-N-17, 1110-SR-73 China Medical University, Taiwan
- CMU 110- AWARD-02, 110-N-17, 1110-SR-73 China Medical University, Taiwan
- DMR-106-101, 106-227, 109-102, 109-244, 110-124, 111-245, 112-097, 112-086, 112-109 and DMR-HHC-109-11, HHC-109-12, HHC-110-10, and HHC-111-8 China Medical University Hospital
- DMR-106-101, 106-227, 109-102, 109-244, 110-124, 111-245, 112-097, 112-086, 112-109 and DMR-HHC-109-11, HHC-109-12, HHC-110-10, and HHC-111-8 China Medical University Hospital
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Affiliation(s)
- Halliru Zailani
- Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Nutrition, China Medical University, Taichung, Taiwan
- Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria
| | - Senthil Kumaran Satyanarayanan
- Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
- Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Hong Kong, China
| | - Wei-Chih Liao
- Division of Pulmonary and Critical Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
- College of Medicine, China Medical University, Taichung, Taiwan.
| | - Kuan-Pin Su
- Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Jane Pei-Chen Chang
- Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
- College of Medicine, China Medical University, Taichung, Taiwan.
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
- Child and Adolescent Psychiatry Division, Department of Psychiatry, China Medical University Hospital, No. 2 Yu-Der Rd, North District, Taichung, 404, Taiwan.
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Li Y, Geng S, Yuan H, Ge J, Li Q, Chen X, Zhu Y, Liu Y, Guo X, Wang X, Jiang H. Multimorbidity in elderly patients with or without T2DM: A real-world cross-sectional analysis based on primary care and hospitalisation data. J Glob Health 2024; 14:04263. [PMID: 39700381 DOI: 10.7189/jogh.14.04263] [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: 12/21/2024] Open
Abstract
Background Shanghai's high level of ageing has given rise to a considerable number of elderly patients with type 2 diabetes mellitus (T2DM) who are confronted with the challenge of managing multimorbidity. We aimed to determine the prevalence of multimorbidity in elderly T2DM patients in a representative Pudong New Area community and critically evaluate current guidelines' inclusiveness in addressing major comorbidities. Methods Through the Shanghai Health Cloud platform, we extracted medical records of residents in the Huamu community (Pudong New Area, Shanghai) to screen elderly patients with at least three outpatient visits or one hospitalisation per year between 2019 and 2022. According to International Classification of Disease, 10th edition codes and personal identification number, we identified the status of T2DM and 12 other common chronic diseases, matched T2DM patients and non-T2DM patients 1:1 by age and gender, and then calculated the prevalence of multimorbidity status and annual prevalence of each comorbidity. We analysed associations between T2DM and specific chronic diseases using logistic regression models. Results More than 90% of elderly T2DM patients had at least one additional chronic disease. Multimorbidity was more frequent in women and older patients. Hyperlipidemia, hypertension, and ischaemic heart disease were the most prevalent comorbidities. The diagnosis of T2DM was significantly associated with both cardiovascular-kidney-metabolic and neuropsychiatric diseases. In addition, a higher prevalence and risk of chronic obstructive pulmonary disease (COPD) were consistently detected in elderly patients with T2DM, regardless of age and gender. Conclusions Multimorbidity in elderly patients with T2DM needs broader acknowledgement. Current guidelines focus more on cardiovascular-kidney-metabolic and neuropsychiatric diseases with inadequate guidance on COPD management. Hence, the pleiotropic effects of glucose-lowering drugs on COPD should be further investigated to optimise the comprehensive management strategy for this population.
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Affiliation(s)
- Yang Li
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shasha Geng
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Huixiao Yuan
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jianli Ge
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Qingqing Li
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xin Chen
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yingqian Zhu
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yue Liu
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaotong Guo
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaoli Wang
- Pudong Institute for Health Development, Shanghai, China
| | - Hua Jiang
- Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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Lian H, Kou L, Han X, Rui Z, Dong S, Zhang X, Zhao L, Yue Q, Hou X, Cai B. Comprehensive comorbidity assessment for the ECOPD: a long-term multi-centre retrospective study. BMC Pulm Med 2024; 24:487. [PMID: 39367367 PMCID: PMC11451238 DOI: 10.1186/s12890-024-03257-6] [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: 04/17/2024] [Accepted: 08/29/2024] [Indexed: 10/06/2024] Open
Abstract
BACKGROUND Exacerbation of chronic obstructive pulmonary disease (ECOPD) results in severe adverse outcomes and mortality. It is often associated with increased local and systemic inflammation. However, individual susceptibility to exacerbations remains largely unknown. Our study aimed to investigate the association between comorbidities and exacerbation outcomes. METHODS We included patients with the primary discharge diagnosis of exacerbation for more 10 years in China. Data on all comorbidities were collected and analysed to determine the impact of the comorbidities on 1-year exacerbation readmission, length of hospital stay, and hospital cost. Univariable and multivariable logistic regression analyses were performed, and predictive models were developed. RESULTS This extensive investigation evaluated a total of 15,708 individuals from five prominent locations in China, revealing notable variations in the prevalence of comorbidities and healthcare expenses among different regions. The study shows that there is a high rate of readmission within one year, namely 15.8%. The most common conditions among readmitted patients are hypertension (38.6%), ischemic heart disease (16.9%), and diabetes mellitus (16.6%). An extensive multivariable study revealed that age, gender, and particular comorbidities such as malnutrition and hyperlipidemia are important factors that can significantly predict greater readmission rates, longer hospital stays or increased healthcare costs. The multivariable models show a moderate to good ability to predict patient outcomes, with concordance index ranging from 0.701 to 0.752. This suggests that targeted interventions in these areas could improve patient outcomes and make better use of healthcare resources. CONCLUSIONS The results regarding the association between severe exacerbations and systemic disease status support the integration of systematic evaluation of comorbidities into the management of exacerbations and the intensification of treatment of important comorbidities as a appropriate measure for prevention of further exacerbations. Our models also provide a novel tool for clinicians to determine the risk of the 1-year recurrence of severe ECOPD in hospitalised patients.
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Affiliation(s)
- Hui Lian
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei Kou
- Individual investigator, Cleveland, OH, USA
| | | | - Zhu Rui
- Department of Medical Record, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sun Dong
- Department of Geriatrics, Geriatric Diseases Institute of Chengdu, Chengdu Fifth People's Hospital, Chengdu, China
| | - Xin Zhang
- Department of Pulmonary and Critical Care Medicine, Hebei Chest Hospital, Shijiazhuang, China
| | - Liukai Zhao
- Department of Critical Care Medicine, People's Hospital of Zhengzhou, South District, Henan, China
| | - Qianyu Yue
- Department of Pulmonary and Critical Care Medicine, First People's Hospital of Yunnan Province, Yunnan, China
| | - Xiaomeng Hou
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Baiqiang Cai
- Department of Pulmonary Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Dinakis E, O'Donnell JA, Marques FZ. The gut-immune axis during hypertension and cardiovascular diseases. Acta Physiol (Oxf) 2024; 240:e14193. [PMID: 38899764 DOI: 10.1111/apha.14193] [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: 02/02/2024] [Revised: 05/04/2024] [Accepted: 06/06/2024] [Indexed: 06/21/2024]
Abstract
The gut-immune axis is a relatively novel phenomenon that provides mechanistic links between the gut microbiome and the immune system. A growing body of evidence supports it is key in how the gut microbiome contributes to several diseases, including hypertension and cardiovascular diseases (CVDs). Evidence over the past decade supports a causal link of the gut microbiome in hypertension and its complications, including myocardial infarction, atherosclerosis, heart failure, and stroke. Perturbations in gut homeostasis such as dysbiosis (i.e., alterations in gut microbial composition) may trigger immune responses that lead to chronic low-grade inflammation and, ultimately, the development and progression of these conditions. This is unsurprising, as the gut harbors one of the largest numbers of immune cells in the body, yet is a phenomenon not entirely understood in the context of cardiometabolic disorders. In this review, we discuss the role of the gut microbiome, the immune system, and inflammation in the context of hypertension and CVD, and consolidate current evidence of this complex interplay, whilst highlighting gaps in the literature. We focus on diet as one of the major modulators of the gut microbiota, and explain key microbial-derived metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide) as potential mediators of the communication between the gut and peripheral organs such as the heart, arteries, kidneys, and the brain via the immune system. Finally, we explore the dual role of both the gut microbiome and the immune system, and how they work together to not only contribute, but also mitigate hypertension and CVD.
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Affiliation(s)
- Evany Dinakis
- Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, Victoria, Australia
| | - Joanne A O'Donnell
- Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, Victoria, Australia
| | - Francine Z Marques
- Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, Victoria, Australia
- Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Victorian Heart Institute, Monash University, Melbourne, Victoria, Australia
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8
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Biener L, Pizarro C, Skowasch D. [Chronic obstructive pulmonary disease (COPD): eosinophilia and novel drug therapies]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2024; 65:738-745. [PMID: 38831048 DOI: 10.1007/s00108-024-01725-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/08/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND The phenotyping of chronic obstructive pulmonary disease (COPD) has increasingly gained attention in recent years, as it leads to new and individualized therapeutic concepts. OBJECTIVE The aim is to provide an overview of the heterogeneity of COPD and to summarize current drug therapy concepts, particularly in the context of eosinophilic airway inflammation. DATA Several prospective, randomized, placebo-controlled studies have shown a reduction in exacerbations and overall mortality with inhaled triple therapy using an inhaled corticosteroid and dual bronchodilation. The higher the eosinophils in the blood, the greater the expected effect. In addition, a reduction in exacerbations with biologics in COPD with eosinophilia has been demonstrated for dupilumab. Eosinophil-guided therapy for acute exacerbations is the subject of current research. CONCLUSION For COPD without exacerbations, dual bronchodilation forms the basis of inhaled therapy. With exacerbations, inhaled triple therapy is indicated for patients with a blood eosinophil count of ≥ 300/µl. This type of treatment may also be useful when eosinophils are between 100 and 300/µl. Therapy with dupilumab is a possible option for the eosinophilic phenotype in the near future.
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Affiliation(s)
- L Biener
- Medizinische Klinik und Poliklinik II - Kardiologe, Pneumologie, Angiologie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland.
| | - C Pizarro
- Medizinische Klinik und Poliklinik II - Kardiologe, Pneumologie, Angiologie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland
| | - D Skowasch
- Medizinische Klinik und Poliklinik II - Kardiologe, Pneumologie, Angiologie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland
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Jesus FR, Moraes ACS, da Silva ILN, Passos FC, Salles C, Neves MCLC, Baccan GC. Analysis of Endocrine and Inflammatory Markers in Preserved Ratio Impaired Spirometry. Med Sci (Basel) 2024; 12:18. [PMID: 38651412 PMCID: PMC11036252 DOI: 10.3390/medsci12020018] [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: 02/18/2024] [Revised: 03/15/2024] [Accepted: 03/19/2024] [Indexed: 04/25/2024] Open
Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a disease of the lungs characterized by chronic airflow obstruction. Individuals with preserved ratio impaired spirometry (PRISm) may be at risk for developing COPD. This study aimed to characterize PRISm and COPD patients in terms of their immune response and endocrine profile to identify differences extending beyond lung function. The participants performed the clinical assessment, pulmonary function test, and blood collection to determine serum hormone levels and concentrations of cytokine. Differences were observed in the nutritional status, lung function, and comorbidity. There were no differences in IL-6, IL-8, IL-10, IL-12, and TNF levels between PRISm and COPD groups. Both PRISm and COPD patients have lower dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. Correlation analysis of PRISm and COPD patients revealed positive correlations between serum levels of DHEA-S and DHEA, with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), which negatively correlated with IL-8 levels. The results indicated that despite differences in lung function parameters, the PRISm and COPD groups exhibited similarities in endocrine profile alterations. This study represents the first attempt to link endocrine with immune markers and lung function in individuals with PRISm.
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Affiliation(s)
- Fabíola Ramos Jesus
- Maternidade Climério de Oliveira (MCO/EBSERH), Universidade Federal da Bahia, Salvador 40055-150, Bahia, Brazil;
| | - Anna Clara Santiago Moraes
- Departamento de Bioquímica e Biofísica, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador 40110-110, Bahia, Brazil
| | - Ingrid Lorena Neves da Silva
- Departamento de Bioquímica e Biofísica, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador 40110-110, Bahia, Brazil
| | - Fabine Correia Passos
- Departamento de Bioquímica e Biofísica, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador 40110-110, Bahia, Brazil
| | - Cristina Salles
- Unidade do Sistema Respiratório, Ambulatório Professor Francisco Magalhães Neto-Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110-200, Bahia, Brazil
| | - Margarida Célia Lima Costa Neves
- Unidade do Sistema Respiratório, Ambulatório Professor Francisco Magalhães Neto-Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110-200, Bahia, Brazil
| | - Gyselle Chrystina Baccan
- Departamento de Bioquímica e Biofísica, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador 40110-110, Bahia, Brazil
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Mariniello DF, D’Agnano V, Cennamo D, Conte S, Quarcio G, Notizia L, Pagliaro R, Schiattarella A, Salvi R, Bianco A, Perrotta F. Comorbidities in COPD: Current and Future Treatment Challenges. J Clin Med 2024; 13:743. [PMID: 38337438 PMCID: PMC10856710 DOI: 10.3390/jcm13030743] [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: 12/15/2023] [Revised: 01/24/2024] [Accepted: 01/26/2024] [Indexed: 02/12/2024] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition, primarily characterized by the presence of a limited airflow, due to abnormalities of the airways and/or alveoli, that often coexists with other chronic diseases such as lung cancer, cardiovascular diseases, and metabolic disorders. Comorbidities are known to pose a challenge in the assessment and effective management of COPD and are also acknowledged to have an important health and economic burden. Local and systemic inflammation have been proposed as having a potential role in explaining the association between COPD and these comorbidities. Considering that the number of patients with COPD is expected to rise, understanding the mechanisms linking COPD with its comorbidities may help to identify new targets for therapeutic purposes based on multi-dimensional assessments.
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Affiliation(s)
- Domenica Francesca Mariniello
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Vito D’Agnano
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Donatella Cennamo
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Stefano Conte
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Gianluca Quarcio
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Luca Notizia
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Raffaella Pagliaro
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Angela Schiattarella
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Rosario Salvi
- U.O.C. Chirurgia Toracica, Azienda Ospedaliera “S.G. Moscati”, 83100 Avellino, Italy;
| | - Andrea Bianco
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
| | - Fabio Perrotta
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80131 Naples, Italy; (D.F.M.); (V.D.); (D.C.); (S.C.); (G.Q.); (L.N.); (R.P.); (A.S.); (A.B.)
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11
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Li J, Yang L, Yao Y, Gu P, Xie Y, Yin H, Xue M, Jiang Y, Dai J, Ma J. Associations between long-term night shift work and incidence of chronic obstructive pulmonary disease: a prospective cohort study of 277,059 UK Biobank participants. BMC Med 2024; 22:16. [PMID: 38225649 PMCID: PMC10790498 DOI: 10.1186/s12916-023-03240-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 12/20/2023] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition. METHODS A total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS. RESULTS The cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend < 0.001). Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of COPD was 1.28 (1.20, 1.37) for subjects with rarely/sometimes night shifts and 1.49 (1.35, 1.66) for those with permanent night shifts. Besides, the longer durations (especially in subjects with night shifts ≥ 10 years) and increasing monthly frequency of night shifts (in workers with > 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference. CONCLUSIONS Long-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.
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Affiliation(s)
- Jia Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Liangle Yang
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Yuxin Yao
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Pei Gu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Yujia Xie
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Haoyu Yin
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Mingyue Xue
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, M5T3L9, Canada
| | - Yu Jiang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Jianghong Dai
- Department of Epidemiology and Biostatistics, School of Public Health, Xinjiang Medical University, Urumqi, 830017, China.
| | - Jixuan Ma
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
- Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan, 430030, Hubei, China.
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12
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Engin A. Adipose Tissue Hypoxia in Obesity: Clinical Reappraisal of Hypoxia Hypothesis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:329-356. [PMID: 39287857 DOI: 10.1007/978-3-031-63657-8_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Obese subjects exhibit lower adipose tissue oxygen consumption in accordance with the lower adipose tissue blood flow. Thereby, compared to lean subjects, obese individuals have almost half lower capillary density and more than half lower vascular endothelial growth factor (VEGF). The VEGF expression together with hypoxia-inducible transcription factor-1 alpha (HIF-1α) activity also requires phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR)-mediated signaling. Especially HIF-1α is an important signaling molecule for hypoxia to induce the inflammatory responses. Hypoxia contributes to several biological functions, such as angiogenesis, cell proliferation, apoptosis, inflammation, and insulin resistance (IR). Pathogenesis of obesity-related comorbidities is attributed to intermittent hypoxia (IH), which is mostly observed in visceral obesity. Proinflammatory phenotype of the adipose tissue is a crucial link between IH and the development of IR. Inhibition of adaptive unfolded protein response (UPR) in hypoxia increases β cell death. Moreover, deletion of HIF-1α worsens β cell function. Oxidative stress, as well as the release of proinflammatory cytokines/adipokines in obesity, is proportional to the severity of IH. Reactive oxygen species (ROS) generation at mitochondria is responsible for propagation of the hypoxic signal; however, mitochondrial ROS production is required for hypoxic HIF-1α protein stabilization. Alterations in oxygen availability of adipose tissue directly affect the macrophage polarization and are responsible for the dysregulated adipocytokines production in obesity. Hypoxia both inhibits adipocyte differentiation from preadipocytes and macrophage migration from the hypoxic adipose tissue. Upon reaching a hypertrophic threshold beyond the adipocyte fat loading capacity, excess extracellular matrix (ECM) components are deposited, causing fibrosis. HIF-1α initiates the whole pathological process of fibrosis and inflammation in the obese adipose tissue. In addition to stressed adipocytes, hypoxia contributes to immune cell migration and activation which further aggravates adipose tissue fibrosis. Therefore, targeting HIF-1α might be an efficient way to suppress hypoxia-induced pathological changes in the ECM. The fibrosis score of adipose tissue correlates negatively with the body mass index and metabolic parameters. Inducers of browning/beiging adipocytes and adipokines, as well as modulations of matrix remodeling enzyme inhibitors, and associated gene regulators, are potential pharmacological targets for treating obesity.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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13
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Baker JG, Shaw DE. Asthma and COPD: A Focus on β-Agonists - Past, Present and Future. Handb Exp Pharmacol 2024; 285:369-451. [PMID: 37709918 DOI: 10.1007/164_2023_679] [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: 09/16/2023]
Abstract
Asthma has been recognised as a respiratory disorder for millennia and the focus of targeted drug development for the last 120 years. Asthma is one of the most common chronic non-communicable diseases worldwide. Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide, is caused by exposure to tobacco smoke and other noxious particles and exerts a substantial economic and social burden. This chapter reviews the development of the treatments of asthma and COPD particularly focussing on the β-agonists, from the isolation of adrenaline, through the development of generations of short- and long-acting β-agonists. It reviews asthma death epidemics, considers the intrinsic efficacy of clinical compounds, and charts the improvement in selectivity and duration of action that has led to our current medications. Important β2-agonist compounds no longer used are considered, including some with additional properties, and how the different pharmacological properties of current β2-agonists underpin their different places in treatment guidelines. Finally, it concludes with a look forward to future developments that could improve the β-agonists still further, including extending their availability to areas of the world with less readily accessible healthcare.
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Affiliation(s)
- Jillian G Baker
- Department of Respiratory Medicine, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
- Cell Signalling, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
| | - Dominick E Shaw
- Nottingham NIHR Respiratory Biomedical Research Centre, University of Nottingham, Nottingham, UK
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14
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Cheng X, Jiang S, Pan B, Xie W, Meng J. Ectopic and visceral fat deposition in aging, obesity, and idiopathic pulmonary fibrosis: an interconnected role. Lipids Health Dis 2023; 22:201. [PMID: 38001499 PMCID: PMC10668383 DOI: 10.1186/s12944-023-01964-3] [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: 09/25/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is considered an age-related disease. Age-related changes, along with other factors such as obesity, hormonal imbalances, and various metabolic disorders, lead to ectopic fat deposition (EFD). This accumulation of fat outside of its normal storage sites is associated with detrimental effects such as lipotoxicity, oxidative stress, inflammation, and insulin resistance. This narrative review provides an overview of the connection between ectopic and visceral fat deposition in aging, obesity, and IPF. It also elucidates the mechanism by which ectopic fat deposition in the airways and lungs, pericardium, skeletal muscles, and pancreas contributes to lung injury and fibrosis in patients with IPF, directly or indirectly. Moreover, the review discusses the impact of EFD on the severity of the disease, quality of life, presence of comorbidities, and overall prognosis in IPF patients. The review provides detailed information on recent research regarding representative lipid-lowering drugs, hypoglycemic drugs, and lipid-targeting drugs in animal experiments and clinical studies. This may offer new therapeutic directions for patients with IPF.
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Affiliation(s)
- Xiaoyun Cheng
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital of Central South University, Tongzipo Road 138, Yuelu District, Changsha, 410000, China
- Hunan Key Laboratory of Organ Fibrosis, Tongzipo Road 138, Yuelu District, Changsha, 410000, China
| | - Shuhan Jiang
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital of Central South University, Tongzipo Road 138, Yuelu District, Changsha, 410000, China
- Hunan Key Laboratory of Organ Fibrosis, Tongzipo Road 138, Yuelu District, Changsha, 410000, China
| | - Boyu Pan
- Departments of Orthopedics, The Third Hospital of Changsha, Laodong West Road 176, Tianxin District, Changsha, 410000, China
| | - Wei Xie
- Department of Cardiology, Xiangya Hospital of Central South University, Furong Middle Road 36, Kaifu District, Changsha, 410000, China
| | - Jie Meng
- Department of Pulmonary and Critical Care Medicine, The Third Xiangya Hospital of Central South University, Tongzipo Road 138, Yuelu District, Changsha, 410000, China.
- Hunan Key Laboratory of Organ Fibrosis, Tongzipo Road 138, Yuelu District, Changsha, 410000, China.
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15
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Chen J, Xu Z, Sun L, Yu K, Hersh CP, Boueiz A, Hokanson JE, Sciurba FC, Silverman EK, Castaldi PJ, Batmanghelich K. Deep Learning Integration of Chest Computed Tomography Imaging and Gene Expression Identifies Novel Aspects of COPD. CHRONIC OBSTRUCTIVE PULMONARY DISEASES (MIAMI, FLA.) 2023; 10:355-368. [PMID: 37413999 DOI: 10.15326/jcopdf.2023.0399] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/08/2023]
Abstract
Rationale Chronic obstructive pulmonary disease (COPD) is characterized by pathologic changes in the airways, lung parenchyma, and persistent inflammation, but the links between lung structural changes and blood transcriptome patterns have not been fully described. Objections The objective of this study was to identify novel relationships between lung structural changes measured by chest computed tomography (CT) and blood transcriptome patterns measured by blood RNA sequencing (RNA-seq). Methods CT scan images and blood RNA-seq gene expression from 1223 participants in the COPD Genetic Epidemiology (COPDGene®) study were jointly analyzed using deep learning to identify shared aspects of inflammation and lung structural changes that we labeled image-expression axes (IEAs). We related IEAs to COPD-related measurements and prospective health outcomes through regression and Cox proportional hazards models and tested them for biological pathway enrichment. Results We identified 2 distinct IEAs: IEAemph which captures an emphysema-predominant process with a strong positive correlation to CT emphysema and a negative correlation to forced expiratory volume in 1 second and body mass index (BMI); and IEAairway which captures an airway-predominant process with a positive correlation to BMI and airway wall thickness and a negative correlation to emphysema. Pathway enrichment analysis identified 29 and 13 pathways significantly associated with IEAemph and IEAairway, respectively (adjusted p<0.001). Conclusions Integration of CT scans and blood RNA-seq data identified 2 IEAs that capture distinct inflammatory processes associated with emphysema and airway-predominant COPD.
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Affiliation(s)
- Junxiang Chen
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Zhonghui Xu
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
| | - Li Sun
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Ke Yu
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Craig P Hersh
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
| | - Adel Boueiz
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
| | - John E Hokanson
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Frank C Sciurba
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Edwin K Silverman
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
| | - Peter J Castaldi
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, Massachusetts, United States
| | - Kayhan Batmanghelich
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
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16
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Lascano J, Riley L, Khodayari N, Brantly M. Augmentation Therapy Modulates Systemic Inflammation in Individuals with Alpha-1 Antitrypsin Deficiency and Chronic Obstructive Pulmonary Disease. CHRONIC OBSTRUCTIVE PULMONARY DISEASES (MIAMI, FLA.) 2023; 10:308-316. [PMID: 37363834 PMCID: PMC10484495 DOI: 10.15326/jcopdf.2023.0407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/11/2023] [Indexed: 06/28/2023]
Abstract
Background Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder that leads to chronic obstructive pulmonary disease (COPD) and lower circulating levels of AAT, which is a protease inhibitor with potent anti-inflammatory effects. In order to better understand the presence of systemic inflammation in AAT-deficient individuals with COPD, we investigatedthe plasma levels of C-reactive protein (CRP). Methods AAT-deficient individuals and a matched cohort with a normal AAT genotype were recruited from the Alpha-1 Foundation DNA and Tissue Bank. AAT genotypes were determined by a combination of a Taqman-based assay. AAT and CRP levels were determined by nephelometry. Comparisons were determined by unpaired t-test and standard Pearson's correlation. Results Our study included 40 control participants and 742 AAT-deficient participants, of which 498 received augmentation therapy. In the AAT-deficient participants, the plasma AAT was 20.2±11.6µM and 4.5±1.3µM (P<0.0001) with and without augmentation therapy, respectively, and the CRP was 0.32±0.53mg/dL and 0.69±1.97mg/dL (P=0.0169), respectively. There was a negative correlation between the percentage predicted of forced expiratory volume in 1 second and CRP in the group not receiving augmentation therapy (r=-0.2528, P<0.05), and there was no correlation in participants receiving augmentation therapy. Conclusion Compared to healthy individuals, AAT-deficient individuals with COPD have higher levels of circulating CRP, suggesting increased systemic inflammation. However, AAT-deficient individuals receiving augmentation therapy had lower plasma CRP levels compared to those who are not.
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Affiliation(s)
- J Lascano
- University of Florida, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Gainesville, Florida, United States
| | - L Riley
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Kansas City Veterans Affairs Medical Center, Kansas City, Missouri, United States
| | - N Khodayari
- University of Florida, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Gainesville, Florida, United States
| | - M Brantly
- University of Florida, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Gainesville, Florida, United States
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17
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Thabet RH, Massadeh NA, Badarna OB, Al-Momani OM. Highlights on molecular targets in the management of COVID-19: Possible role of pharmacogenomics. J Int Med Res 2023; 51:3000605231153764. [PMID: 36717541 PMCID: PMC9893104 DOI: 10.1177/03000605231153764] [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] [Indexed: 02/01/2023] Open
Abstract
By the end of 2022, there had been a reduction in new cases and deaths caused by coronavirus disease 2019 (COVID-19). At the same time, new variants of the severe acute respiratory syndrome coronavirus 2 virus were being discovered. Critically ill patients with COVID-19 have been found to have high serum levels of proinflammatory cytokines, especially interleukin (IL)-6. COVID-19-related mortality has been attributed in most cases to the cytokine storm caused by increased levels of inflammatory cytokines. Dexamethasone in low doses and immunomodulators such as IL-6 inhibitors are recommended to overcome the cytokine storm. This current narrative review highlights the place of other therapeutic choices such as proteasome inhibitors, protease inhibitors and nuclear factor kappa B inhibitors in the treatment of patients with COVID-19.
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Affiliation(s)
- Romany H. Thabet
- Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt,Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan,Romany H. Thabet, Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Shafiq Irshidat Street, Irbid 21163, Jordan.
| | - Noor A. Massadeh
- Internship, Princess Basma Hospital, Ministry of Health, Irbid, Jordan
| | - Omar B. Badarna
- Internship, Princess Basma Hospital, Ministry of Health, Irbid, Jordan
| | - Omar M. Al-Momani
- Internship, Princess Basma Hospital, Ministry of Health, Irbid, Jordan
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18
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Gastrointestinal consequences of lipopolysaccharide-induced lung inflammation. Inflamm Res 2023; 72:57-74. [PMID: 36322182 PMCID: PMC9628607 DOI: 10.1007/s00011-022-01657-0] [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: 01/11/2022] [Accepted: 09/15/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Respiratory inflammation is the body's response to lung infection, trauma or hypersensitivity and is often accompanied by comorbidities, including gastrointestinal (GI) symptoms. Why respiratory inflammation is accompanied by GI dysfunction remains unclear. Here, we investigate the effect of lipopolysaccharide (LPS)-induced lung inflammation on intestinal barrier integrity, tight-junctions, enteric neurons and inflammatory marker expression. METHODS Female C57bl/6 mice (6-8 weeks) were intratracheally administered LPS (5 µg) or sterile saline, and assessed after either 24 or 72 h. Total and differential cell counts in bronchoalveolar lavage fluid (BALF) were used to evaluate lung inflammation. Intestinal barrier integrity was assessed via cross sectional immunohistochemistry of tight junction markers claudin-1, claudin-4 and EpCAM. Changes in the enteric nervous system (ENS) and inflammation in the intestine were quantified immunohistochemically using neuronal markers Hu + and nNOS, glial markers GFAP and S100β and pan leukocyte marker CD45. RESULTS Intratracheal LPS significantly increased the number of neutrophils in BALF at 24 and 72 h. These changes were associated with an increase in CD45 + cells in the ileal mucosa at 24 and 72 h, increased goblet cell expression at 24 h, and increased expression of EpCAM at 72 h. LPS had no effect on the expression of GFAP, S100β, nor the number of Hu + neurons or proportion of nNOS neurons in the myenteric plexus. CONCLUSIONS Intratracheal LPS administration induces inflammation in the ileum that is associated with enhanced expression of EpCAM, decreased claudin-4 expression and increased goblet cell density, these changes may contribute to systemic inflammation that is known to accompany many inflammatory diseases of the lung.
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19
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Wang L, van Iersel LEJ, Pelgrim CE, Lu J, van Ark I, Leusink-Muis T, Gosker HR, Langen RCJ, Schols AMWJ, Argilés JM, van Helvoort A, Kraneveld AD, Garssen J, Henricks PAJ, Folkerts G, Braber S. Effects of Cigarette Smoke on Adipose and Skeletal Muscle Tissue: In Vivo and In Vitro Studies. Cells 2022; 11:cells11182893. [PMID: 36139468 PMCID: PMC9497292 DOI: 10.3390/cells11182893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/31/2022] [Accepted: 09/06/2022] [Indexed: 11/25/2022] Open
Abstract
Chronic obstructive pulmonary disease (COPD), often caused by smoking, is a chronic lung disease with systemic manifestations including metabolic comorbidities. This study investigates adaptive and pathological alterations in adipose and skeletal muscle tissue following cigarette smoke exposure using in vivo and in vitro models. Mice were exposed to cigarette smoke or air for 72 days and the pre-adipose cell line 3T3-L1 was utilized as an in vitro model. Cigarette smoke exposure decreased body weight, and the proportional loss in fat mass was more pronounced than the lean mass loss. Cigarette smoke exposure reduced adipocyte size and increased adipocyte numbers. Adipose macrophage numbers and associated cytokine levels, including interleukin-1β, interleukine-6 and tumor necrosis factor-α were elevated in smoke-exposed mice. Muscle strength and protein synthesis signaling were decreased after smoke exposure; however, muscle mass was not changed. In vitro studies demonstrated that lipolysis and fatty acid oxidation were upregulated in cigarette smoke-exposed pre-adipocytes. In conclusion, cigarette smoke exposure induces a loss of whole-body fat mass and adipose atrophy, which is likely due to enhanced lipolysis.
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Affiliation(s)
- Lei Wang
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Lieke E. J. van Iersel
- Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, 6200 MD Maastricht, The Netherlands
| | - Charlotte E. Pelgrim
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Jingyi Lu
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Ingrid van Ark
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Thea Leusink-Muis
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Harry R. Gosker
- Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, 6200 MD Maastricht, The Netherlands
| | - Ramon C. J. Langen
- Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, 6200 MD Maastricht, The Netherlands
| | - Annemie M. W. J. Schols
- Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, 6200 MD Maastricht, The Netherlands
| | - Josep M. Argilés
- Biochemistry and Molecular Biology of Cancer, Faculty of Biology, University of Barcelona, 08007 Barcelona, Spain
| | - Ardy van Helvoort
- Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, 6200 MD Maastricht, The Netherlands
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands
| | - Aletta D. Kraneveld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands
| | - Paul A. J. Henricks
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Gert Folkerts
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
| | - Saskia Braber
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands or
- Correspondence: ; Tel.: +31-0-622-483-913
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20
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Wang L, Pelgrim CE, Peralta Marzal LN, Korver S, van Ark I, Leusink-Muis T, van Helvoort A, Keshavarzian A, Kraneveld AD, Garssen J, Henricks PAJ, Folkerts G, Braber S. Changes in intestinal homeostasis and immunity in a cigarette smoke- and LPS-induced murine model for COPD: the lung-gut axis. Am J Physiol Lung Cell Mol Physiol 2022; 323:L266-L280. [PMID: 35699290 PMCID: PMC9423728 DOI: 10.1152/ajplung.00486.2021] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 05/10/2022] [Accepted: 06/01/2022] [Indexed: 12/14/2022] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is often associated with intestinal comorbidities. In this study, changes in intestinal homeostasis and immunity in a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD model were investigated. Mice were exposed to cigarette smoke or air for 72 days, except days 42, 52, and 62 on which the mice were treated with saline or LPS via intratracheal instillation. Cigarette smoke exposure increased the airway inflammatory cell numbers, mucus production, and different inflammatory mediators, including C-reactive protein (CRP) and keratinocyte-derived chemokine (KC), in bronchoalveolar lavage (BAL) fluid and serum. LPS did not further impact airway inflammatory cell numbers or mucus production but decreased inflammatory mediator levels in BAL fluid. T helper (Th) 1 cells were enhanced in the spleen after cigarette smoke exposure; however, in combination with LPS, cigarette exposure caused an increase in Th1 and Th2 cells. Histomorphological changes were observed in the proximal small intestine after cigarette smoke exposure, and addition of LPS had no effect. Cigarette smoke activated the intestinal immune network for IgA production in the distal small intestine that was associated with increased fecal sIgA levels and enlargement of Peyer's patches. Cigarette smoke plus LPS decreased fecal sIgA levels and the size of Peyer's patches. In conclusion, cigarette smoke with or without LPS affects intestinal health as observed by changes in intestinal histomorphology and immune network for IgA production. Elevated systemic mediators might play a role in the lung-gut cross talk. These findings contribute to a better understanding of intestinal disorders related to COPD.
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Affiliation(s)
- Lei Wang
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Charlotte E Pelgrim
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Lucía N Peralta Marzal
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Stephanie Korver
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Ingrid van Ark
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Thea Leusink-Muis
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Ardy van Helvoort
- Danone Nutricia Research, Utrecht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Ali Keshavarzian
- Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush Medical College, Rush University, Chicago, Illinois
| | - Aletta D Kraneveld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
- Danone Nutricia Research, Utrecht, The Netherlands
| | - Paul A J Henricks
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Gert Folkerts
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Saskia Braber
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
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21
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Botello-Manilla AE, López-Sánchez GN, Chávez-Tapia NC, Uribe M, Nuño-Lámbarri N. Hepatic steatosis and respiratory diseases: a new panorama. Ann Hepatol 2022; 24:100320. [PMID: 33549735 DOI: 10.1016/j.aohep.2021.100320] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 02/04/2023]
Abstract
Non-alcoholic fatty liver disease is defined as hepatic fat accumulation in more than 5% of hepatocytes, without other liver steatosis causes. It comprises a broad spectrum that can range from benign steatosis and progress to non-alcoholic steatohepatitis, fibrosis, and ultimately hepatocellular carcinoma. Non-alcoholic fatty liver is considered a multisystemic disease since it is related to multiple disorders, such as type 2 diabetes mellitus, polycystic ovary syndrome, chronic kidney disease, psoriasis, osteoporosis, hypothyroidism, cardiovascular diseases, and obstructive sleep apnea syndrome; it is becoming increasingly clear that it is also a risk factor for developing certain respiratory diseases. This article aims to understand the liver and chronic obstructive pulmonary disease mechanisms, obstructive sleep apnea syndrome, asthma, and lung cancer. Given that non-alcoholic fatty liver disease has a considerable impact on the patient's well-being and life quality, as well as on the costs they generate for the country's health services, it is essential to continue research, especially in areas such as the respiratory tract, as there is much misinformation about it.
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Affiliation(s)
- Alan Eduardo Botello-Manilla
- Traslational Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, C.P. 14050, Mexico City, Mexico
| | - Guillermo Nahúm López-Sánchez
- Traslational Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, C.P. 14050, Mexico City, Mexico
| | - Norberto Carlos Chávez-Tapia
- Traslational Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, C.P. 14050, Mexico City, Mexico; Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, C.P. 14050, Mexico City, Mexico
| | - Misael Uribe
- Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, C.P. 14050, Mexico City, Mexico
| | - Natalia Nuño-Lámbarri
- Traslational Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Toriello Guerra Tlalpan, C.P. 14050, Mexico City, Mexico.
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22
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Kotlyarov S. Involvement of the Innate Immune System in the Pathogenesis of Chronic Obstructive Pulmonary Disease. Int J Mol Sci 2022; 23:985. [PMID: 35055174 PMCID: PMC8778852 DOI: 10.3390/ijms23020985] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/14/2022] [Accepted: 01/15/2022] [Indexed: 01/27/2023] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a common, socially significant disease characterized by progressive airflow limitation due to chronic inflammation in the bronchi. Although the causes of COPD are considered to be known, the pathogenesis of the disease continues to be a relevant topic of study. Mechanisms of the innate immune system are involved in various links in the pathogenesis of COPD, leading to persistence of chronic inflammation in the bronchi, their bacterial colonization and disruption of lung structure and function. Bronchial epithelial cells, neutrophils, macrophages and other cells are involved in the development and progression of the disease, demonstrating multiple compromised immune mechanisms.
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Affiliation(s)
- Stanislav Kotlyarov
- Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia
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23
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Corlateanu A, Plahotniuc A, Corlateanu O, Botnaru V, Bikov A, Mathioudakis AG, Covantev S, Siafakas N. Multidimensional indices in the assessment of chronic obstructive pulmonary disease. Respir Med 2021; 185:106519. [PMID: 34175803 DOI: 10.1016/j.rmed.2021.106519] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/15/2021] [Accepted: 06/18/2021] [Indexed: 02/08/2023]
Abstract
Chronic obstructive pulmonary disease (COPD), a very common disease, is the third leading cause of death worldwide. Due to the significant heterogeneity of clinical phenotypes of COPD there is no single method suitable for predicting patients' health status and outcomes, and therefore multidimensional indices, assessing different components of the disease, were developed and are recommended for clinical practice by international guidelines. Several indices have been widely accepted: BODE and its modifications, ADO, DOSE, CODEX, COTE. They differ in their composition and aim, while they are more accurate and better validated in specific settings and populations. We review the characteristics, strengths and limitations of these indices, and we discuss their role in routine management of patients with COPD, as well as in specific clinical scenarios, such as resuscitation and ceiling of care, or decisions to offer more invasive treatments. This analysis may help clinicians to use those indexes in a more practical and appropriate way.
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Affiliation(s)
- Alexandru Corlateanu
- Department of Internal Medicine, Division of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Stefan cel Mare street 165, 2004, Republic of Moldova.
| | - Alexandra Plahotniuc
- Department of Internal Medicine, Division of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Stefan cel Mare street 165, 2004, Republic of Moldova.
| | - Olga Corlateanu
- Department of Internal Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Stefan cel Mare street 165, 2004, Republic of Moldova.
| | - Victor Botnaru
- Department of Internal Medicine, Division of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Stefan cel Mare street 165, 2004, Republic of Moldova.
| | - Andras Bikov
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, UK; North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
| | - Alexander G Mathioudakis
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, UK; North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
| | - Serghei Covantev
- Department of Internal Medicine, Division of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Stefan cel Mare street 165, 2004, Republic of Moldova.
| | - Nikolaos Siafakas
- University General Hospital, Dept. of Thoracic Medicine, Stavrakia, Heraklion, Crete, 71110 Heraklion, Greece.
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24
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Kaur G, Yogeswaran S, Muthumalage T, Rahman I. Persistently Increased Systemic ACE2 Activity Is Associated With an Increased Inflammatory Response in Smokers With COVID-19. Front Physiol 2021; 12:653045. [PMID: 34122129 PMCID: PMC8194708 DOI: 10.3389/fphys.2021.653045] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 04/30/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Tobacco smoking is known to be involved in the pathogenesis of several cardiopulmonary diseases. Additionally, smokers are highly susceptible to infectious agents due to weakened immunity. However, the progression of lung injury based on SARS-CoV-2-mediated COVID-19 pathogenesis amongst smokers and those with pre-existing pulmonary diseases is not known. We determined the systemic levels and activity of COVID-19 associated proteins, cytokine/chemokines, and lipid mediators (lipidomics) amongst COVID-19 patients with and without a history of smoking to understand the underlying susceptible factor in the pathogenesis of COVID-19. Methods: We obtained serum from healthy (CoV−), COVID-19 positive (CoV+), and COVID-19 recovered (CoV Rec) subjects with and without a history of smoking. We conducted a Luminex multiplex assay (cytokine levels), LC/MS (eicosanoids or oxylipin panel), and ACE2 enzymatic activity assays on the serum samples to determine the systemic changes in COVID-19 patients. Results: On comparing the levels of serum ACE2 amongst COVID-19 (positive and recovered) patients and healthy controls, we found a pronounced increase in serum ACE2 levels in patients with COVID-19 infection. Furthermore, ACE2 enzyme activity was significantly increased amongst COVID-19 patients with a smoking history. Also, we analyzed the levels of Angiotensin 1–7 (Ang1–7) peptide, the product of enzymatic action of ACE2, in the serum samples. We found significantly high levels of Ang1–7 in the serum of both CoV+ and CoV Rec patients. Our data further demonstrated a smoking-induced increase in serum furin and inflammatory cytokine [IFNγ(p = 0.0836), Eotaxin (p < 0.05), MCP-1 (p < 0.05), and IL-9 (p = 0.0991)] levels in COVID-19 patients as compared to non-smoking controls. Overall, our results show that smoking adversely affects the levels of systemic inflammatory markers and COVID-19 associated proteins, thus suggesting that COVID-19 infection may have severe outcomes amongst smokers.
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Affiliation(s)
- Gagandeep Kaur
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, United States
| | - Shaiesh Yogeswaran
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, United States
| | - Thivanka Muthumalage
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, United States
| | - Irfan Rahman
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, United States
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25
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Ju S, Jeong JH, Heo M, Heo IR, Kim TH, Kim HC, Yoo JW, Cho YJ, Jeong YY, Lee JD, Lee SJ. Serum albumin is a predictor of respiratory hospitalization in patients with bronchiectasis. Chron Respir Dis 2021; 18:14799731211017548. [PMID: 34032131 PMCID: PMC8155784 DOI: 10.1177/14799731211017548] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
We evaluated serum albumin as an index for predicting respiratory hospitalization in patients with bronchiectasis. We retrospectively reviewed the medical records of 177 patients with bronchiectasis, categorized them into low and normal albumin groups, and compared their clinical characteristics. The prediction of respiratory hospitalization by factors such as serum albumin level, bronchiectasis severity index (BSI), and FACED score (an acronym derived from five variables of forced expiratory volume in 1 s; FEV1, age, chronic colonization of Pseudomonas aeruginosa, extent of bronchiectasis, and dyspnea) was assessed. There were 15 and 162 patients categorized in the low and normal albumin groups, respectively. The low albumin group had lower body mass index and forced expiratory volume in 1 s, and higher age, frequency of previous respiratory hospitalization, percentage of Pseudomonas colonization, number of affected lobes, BSI and FACED scores, and C-reactive protein (CRP) level, than the normal albumin group. The areas under the receiver operating characteristic curve of serum albumin level and BSI and FACED scores for predicting respiratory hospitalization were 0.732 (95% confidence interval (CI), 0.647-0.816), 0.873 (95% CI, 0.817-0.928), and 0.708 (95% CI, 0.618-0.799), respectively. Albumin level, CRP, modified Medical Research Council score, and chronic Pseudomonas aeruginosa (and other organisms) colonization were independent risk factors for respiratory hospitalization. Low serum albumin level was associated with worse clinical condition, higher severity scores, and respiratory hospitalization in patients with bronchiectasis.
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Affiliation(s)
- Sunmi Ju
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Jong Hwan Jeong
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Manbong Heo
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - I Re Heo
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Republic of Korea
| | - Tae Hoon Kim
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Republic of Korea
| | - Ho Cheol Kim
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Republic of Korea
| | - Jung-Wan Yoo
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Yu Ji Cho
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Yi Yeong Jeong
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Jong Deog Lee
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Seung Jun Lee
- Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
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26
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Rogliani P, Ritondo BL, Laitano R, Chetta A, Calzetta L. Advances in understanding of mechanisms related to increased cardiovascular risk in COPD. Expert Rev Respir Med 2020; 15:59-70. [PMID: 33084434 DOI: 10.1080/17476348.2021.1840982] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Chronic obstructive pulmonary disease (COPD) represents a serious global health issue that is commonly associated with cardiovascular (CV) disease (CVD). The close relationship between COPD and CVD could be explained by different factors, first and foremost a chronic low-grade systemic inflammation implicated in the pathogenesis of both diseases and several stimuli enhancing the inflammatory processes and causing a mixed condition with worse outcomes than either disorder alone. AREAS COVERED The present narrative review considers the mechanisms underlying the increased CV risk in COPD, and it provides insights on biomarkers and predictive models to predict CVD in COPD patients. EXPERT OPINION COPD patients often remain asymptomatic of CVD, with respiratory symptoms generally attributed to the preexisting pulmonary disease. It is fundamental to understand the mechanistic pathways that underpin the intimate relationship between the two disorders. However, it is still not clear what is the origin of the common background of low-grade systemic inflammation, it could be a 'spillover' or a general inflammatory state. Primary prevention, cross-collaboration between specialists and early detection via predictive biomarkers and validated models are fundamental to stratify COPD patients according to CV risk.
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Affiliation(s)
- Paola Rogliani
- Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata" , Rome, Italy
| | - Beatrice Ludovica Ritondo
- Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata" , Rome, Italy
| | - Rossella Laitano
- Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata" , Rome, Italy
| | - Alfredo Chetta
- Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma , Parma, Italy
| | - Luigino Calzetta
- Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma , Parma, Italy
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27
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Cai Y, Liu R, Lu X, Zhang Q, Wang X, Lian H, Wang H. Correlation in gene expression between the aggravation of chronic obstructive pulmonary disease and the occurrence of complications. Bioengineered 2020; 11:1245-1257. [PMID: 33108241 PMCID: PMC8291885 DOI: 10.1080/21655979.2020.1839216] [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] [Indexed: 11/05/2022] Open
Abstract
Aggravation of the chronic obstructive pulmonary disease (COPD) often leads to a slew of complications, but the correlation between COPD aggravation and the complications on the basis of molecular level remains unclear. In this study, gene expression profiles of COPD in patients at early and aggravation stages were collected and differentially-expressed genes were selected. Meanwhile, gene expression data implicated in COPD complications were analyzed to establish a regulatory network of COPD aggravation and COPD related complications. In addition, the gene enrichment function of DAVID6.7 was utilized to evaluate the similarities between COPD aggravation and COPD complications in term of biological process. By analyzing the genes of COPD aggravation and the COPD complications, we found 18 genes highly related to COPD aggravation, among which haptoglobin (HP) was correlated with 14 complications, followed by ADRB2, LCK and CA1, which were related to 13, 11 and 11 complications, respectively. As far as the complications concerned, obesity was regulated by 17 of the 18 genes, which indicated that there was a close correlation between COPD aggravation and obesity. Meanwhile, lung cancer, diabetes and heart failure were regulated by 15, 15 and 14 genes, respectively, among the 18 selected genes. This study suggested the driver genes of COPD aggravation were capable of extensively regulating COPD complications, which would provide a theoretical basis for development of cures for COPD and its complications.
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Affiliation(s)
- Yuchen Cai
- Department of Mathematics, School of Science, Hainan University , Haikou, Hainan Province, China
| | - Runhan Liu
- Department of Mathematics, School of Science, Hainan University , Haikou, Hainan Province, China
| | - Xinhe Lu
- School of Life and Pharmaceutical Science , Haikou, Hainan Province, China
| | - Qiming Zhang
- School of Electrical and Information Engineering, Anhui University of Science and Technology , Huainan, Anhui Province, China
| | - Xinwei Wang
- College of Information Science and Engineering, Ocean University of China , Qingdao, Shandong Province, China
| | - Huijing Lian
- School of Economics, Hainan University , Haikou, Hainan Province, China
| | - Haohua Wang
- Department of Mathematics, School of Science, Hainan University , Haikou, Hainan Province, China
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Lee DY, Nam SM. Association between restrictive pulmonary disease and type 2 diabetes in Koreans: A cross-sectional study. World J Diabetes 2020; 11:425-434. [PMID: 33133390 PMCID: PMC7582118 DOI: 10.4239/wjd.v11.i10.425] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 08/11/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diabetes is a progressive disease that increases glucose levels in the blood. While studies have shown that patients with pulmonary disease (both obstructive and restrictive pulmonary disease) have a higher prevalence of type 2 diabetes mellitus (T2DM), there have been more studies on restrictive patterns than chronic obstructive pulmonary disease.
AIM To assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans.
METHODS For our analysis, we used data from the Korea National Health and Nutrition Examination Survey. A total of 2830 subjects were included in this study. Spirometry results were categorized into three patterns: Normal, restrictive pulmonary disease (RPD), and obstructive pulmonary disease (OPD).
RESULTS The factors used as diabetic indicators (i.e. homeostatic model assessment of insulin resistance, homeostatic model assessment of beta-cell function, glycated hemoglobin, and fasting insulin) were among the highest in RPD but not in OPD. Based on multivariate logistic regression analysis, subjects with RPD were found with an increased odds ratio [OR: 1.907, 95% confidence interval (CI): 1.110-3.277] for T2DM compared with subjects with normal pulmonary function, whereas in patients with OPD, the OR had not increased. Model 4, which adjusted for the variables that could affect diabetes and pulmonary disease, showed a significant increase in the T2DM OR to RPD (OR: 2.025, 95%CI: 1.264-3.244). On the other hand, no statistically significant difference was shown in OPD (OR: 0.982, 95%CI: 0.634-1.519).
CONCLUSION RPD, not OPD, is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.
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Affiliation(s)
- Do Y Lee
- Department of Physical Therapy, Daegu University, Gyeongsan-si 38453, South Korea
| | - Seung M Nam
- Department of Physical Therapy, Daegu University, Gyeongsan-si 38453, South Korea
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29
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Petrakis D, Margină D, Tsarouhas K, Tekos F, Stan M, Nikitovic D, Kouretas D, Spandidos DA, Tsatsakis A. Obesity ‑ a risk factor for increased COVID‑19 prevalence, severity and lethality (Review). Mol Med Rep 2020; 22:9-19. [PMID: 32377709 PMCID: PMC7248467 DOI: 10.3892/mmr.2020.11127] [Citation(s) in RCA: 230] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 05/05/2020] [Indexed: 02/07/2023] Open
Abstract
Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the virus responsible. The global spread of COVID‑19 can be described as the worst pandemic in humanity in the last century. To date, COVID‑19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID‑19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID‑19 will affect its prognosis. Finally, pregnancy‑associated obesity needs to be studied further in connection to COVID‑19 as this infection could pose high risk both to pregnant women and the fetus.
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Affiliation(s)
- Demetrios Petrakis
- Laboratory of Toxicology, Medical School, University of Crete, 71409 Heraklion, Greece
| | - Denisa Margină
- ‘Carol Davila’ University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Biochemistry, 020956 Bucharest, Romania
| | | | - Fotios Tekos
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500 Larissa, Greece
| | - Miriana Stan
- ‘Carol Davila’ University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Toxicology, 020956 Bucharest, Romania
| | - Dragana Nikitovic
- Laboratory of Histology-Embryology, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Demetrios Kouretas
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500 Larissa, Greece
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, 71110 Heraklion, Greece
| | - Aristidis Tsatsakis
- Laboratory of Toxicology, Medical School, University of Crete, 71409 Heraklion, Greece
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30
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Mirzaei R, Karampoor S, Sholeh M, Moradi P, Ranjbar R, Ghasemi F. A contemporary review on pathogenesis and immunity of COVID-19 infection. Mol Biol Rep 2020; 47:5365-5376. [PMID: 32601923 PMCID: PMC7323602 DOI: 10.1007/s11033-020-05621-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/22/2020] [Indexed: 02/09/2023]
Abstract
Emerging of the COVID-19 pandemic has raised interests in the field of biology and pathogenesis of coronaviruses; including interactions between host immune reactions specific, and viral factors. Deep knowledge about the interaction between coronaviruses and the host factors could be useful to provide a better support for the disease sufferers and be advantageous for managing and treatment of the lung infection caused by the virus. At this study, we reviewed the updated information on the pathogenesis of the COVID-19 and the immune responses toward it, with a special focus on structure, genetics, and viral accessory proteins, viral replication, viral receptors, the human immune reactions, cytopathic effects, and host-related factors.
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Affiliation(s)
- Rasoul Mirzaei
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Sajad Karampoor
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sholeh
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Pouya Moradi
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Ranjbar
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Faezeh Ghasemi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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31
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Chiș AF, Cătană A, Sorițău O, Chiș BA, Cutaș A, Pop CM. Interleukin-6 serum level and -597 A/G gene polymorphism in moderate and severe chronic obstructive pulmonary disease. EUR J INFLAMM 2020. [DOI: 10.1177/2058739220966469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Inflammation is a major pathogenic pathway in pulmonary chronic obstructive disease (COPD). Interleukin-6 (IL-6) mediates the local and systemic immune response. The aim consisted in investigating the relationship between IL-6 serum levels and IL-6 -597A/G gene polymorphism (rs1800797) with COPD. Serum levels of IL-6 were determined using an enzyme-linked immune-sorbent assay, in 120 participants (60 COPD patients and 60 healthy subjects), from Transylvanian region. The IL-6 -597A/G gene polymorphism was investigated by high molecular weight genomic DNA extracted from the peripheral blood leukocytes, and subsequently analyzed by the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Smoking history, the severity of the disease, expressed by the GOLD stages, and arterial blood partial pressure of oxygen (PaO2) levels were also investigated. COPD patients had significantly elevated blood levels of IL-6 when compared to the control group ( p < 0.05). The frequencies of AA, AG, and GG genotypes were 61.6%, 26.6%, and 11.6% in the COPD cases and 70%, 23.3%, and 6.7% in healthy subjects, respectively. There were no statistically significant differences in IL-6 rs1800797 genotypes and allele frequencies between cases and controls ( χ2 = 0.54, OR = 1.29 and χ2 = 0.21, OR = 1.48, respectively). Higher serum levels of IL-6 were found in the GG genotype subgroup in COPD patients. IL 6 levels are higher in COPD patients, where positively correlate with pack-year index, but not with clinical features. Although COPD patients did not have statistically different rs1800797 allele distribution compared to healthy subjects, the GG genotype is associated with higher IL6 serum levels.
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Affiliation(s)
- Ana Florica Chiș
- Department of Pneumology, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
- “Leon Daniello” Clinical Hospital of Pneumology, Cluj-Napoca, Romania
| | - Andreea Cătană
- Department of Molecular Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Olga Sorițău
- “Ion Chiricuţă” Oncological Institute Cluj-Napoca, Cluj-Napoca, Romania
| | - Bogdan Augustin Chiș
- 2nd Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ancuța Cutaș
- Department of Medical Informatics, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Carmen Monica Pop
- Department of Pneumology, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
- “Leon Daniello” Clinical Hospital of Pneumology, Cluj-Napoca, Romania
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32
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Katsiki N, Steiropoulos P, Papanas N, Mikhailidis DP. Diabetes Mellitus and Chronic Obstructive Pulmonary Disease: An Overview. Exp Clin Endocrinol Diabetes 2019; 129:699-704. [PMID: 31739346 DOI: 10.1055/a-1038-3883] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Chronic obstructive pulmonary disease (COPD) is a common disease with an increasing prevalence, characterised by persistent respiratory symptoms and airflow limitation. Apart from cigarette smoking, certain occupational and environmental exposures, low socioeconomic status and genetic factors may contribute to the pathogenesis of COPD. Comorbidities, e. g. diabetes mellitus (DM), can negatively affect quality of life, COPD outcomes and cardiovascular risk. The present narrative review considers the potential links between COPD and DM, such as systemic inflammation, oxidative stress, hypoxaemia and hyperglycaemia. The effects of antidiabetic drugs on lung function and COPD outcomes, as well as the possibility of common therapeutic modalities are also briefly considered. Further research is needed in this field to elucidate these relationships as well as their potential clinical implications in daily practice.
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Affiliation(s)
- Niki Katsiki
- First Department of Internal Medicine, Diabetes Centre, Division of Endocrinology and Metabolism, AHEPA University Hospital, Thessaloniki, Greece
| | - Paschalis Steiropoulos
- Department of Pneumonology, Democritus University of Thrace School of Health Sciences, Alexandroupolis, Greece
| | - Nikolaos Papanas
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, University College London, Royal Free Hospital Campus, London, United Kingdom of Great Britain and Northern Ireland
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33
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Lokwani R, Wark PA, Baines KJ, Fricker M, Barker D, Simpson JL. Blood Neutrophils In COPD But Not Asthma Exhibit A Primed Phenotype With Downregulated CD62L Expression. Int J Chron Obstruct Pulmon Dis 2019; 14:2517-2525. [PMID: 31814717 PMCID: PMC6863133 DOI: 10.2147/copd.s222486] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 09/23/2019] [Indexed: 11/25/2022] Open
Abstract
Purpose To characterize neutrophils in obstructive airway disease by measuring their surface adhesion molecules and oxidative burst along with characterizing them into different subsets as per their adhesion molecule expression. Patients and methods Peripheral blood from adults with COPD (n=17), asthma (n=20), and healthy participants (n=19) was examined for expression of CD16, CD62L, CD11b, CD11c, and CD54, and analyzed by flow cytometry. For oxidative burst and CD62L shedding analysis, CD16 and CD62L stained leukocytes were loaded with Dihydrorhodamine-123 (DHR-123) and stimulated with N-Formylmethionine-leucyl-phenylalanine (fMLF). Neutrophil subsets were characterized based on CD16 and CD62L expression. Marker surface expression was recorded on CD16+ neutrophils as median fluorescence intensity (MFI). Results Neutrophil surface expression of CD62L was significantly reduced in COPD (median (IQR) MFI: 1156 (904, 1365)) compared with asthma (1865 (1157, 2408)) and healthy controls (2079 (1054, 2960)); p=0.028. COPD neutrophils also demonstrated a significant reduction in CD62L expression with and without fMLF stimulation. Asthma participants had a significantly increased proportion and number of CD62Lbright/CD16dim neutrophils (median: 5.4% and 0.14 × 109/L, respectively), in comparison with healthy (3.54% and 0.12 × 109/L, respectively); p<0.017. Conclusion Reduced CD62L expression suggests blood neutrophils have undergone priming in COPD but not in asthma, which may be the result of systemic inflammation. The increased shedding of CD62L receptor by COPD blood neutrophils suggests a high sensitivity for activation.
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Affiliation(s)
- Ravi Lokwani
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.,Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia.,School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Peter Ab Wark
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.,Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia.,School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Katherine J Baines
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.,School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Michael Fricker
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.,School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Daniel Barker
- School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Jodie L Simpson
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.,Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia.,School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia
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34
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Henry AP, Probert K, Stewart CE, Thakker D, Bhaker S, Azimi S, Hall IP, Sayers I. Defining a role for lung function associated gene GSTCD in cell homeostasis. Respir Res 2019; 20:172. [PMID: 31370853 PMCID: PMC6676530 DOI: 10.1186/s12931-019-1146-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 07/25/2019] [Indexed: 12/11/2022] Open
Abstract
Genome wide association (GWA) studies have reproducibly identified signals on chromosome 4q24 associated with lung function and COPD. GSTCD (Glutathione S-transferase C-terminal domain containing) represents a candidate causal gene in this locus, however little is currently known about the function of this protein. We set out to further our understanding of the role of GSTCD in cell functions and homeostasis using multiple molecular and cellular approaches in airway relevant cells. Recombinant expression of human GSTCD in conjunction with a GST activity assay did not identify any enzymatic activity for two GSTCD isoforms questioning the assignment of this protein to this family of enzymes. Protein structure analyses identified a potential methyltransferase domain contained within GSTCD, with these enzymes linked to cell viability and apoptosis. Targeted knockdown (siRNA) of GSTCD in bronchial epithelial cells identified a role for GSTCD in cell viability as proliferation rates were not altered. To provide greater insight we completed transcriptomic analyses on cells with GSTCD expression knocked down and identified several differentially expressed genes including those implicated in airway biology; fibrosis e.g. TGFBR1 and inflammation e.g. IL6R. Pathway based transcriptomic analyses identified an over-representation of genes related to adipogenesis which may suggest additional functions for GSTCD. These findings identify potential additional functions for GSTCD in the context of airway biology beyond the hypothesised GST activity and warrant further investigation.
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Affiliation(s)
- Amanda P Henry
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.
| | - Kelly Probert
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Ceri E Stewart
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Dhruma Thakker
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Sangita Bhaker
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Sheyda Azimi
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Ian P Hall
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Ian Sayers
- Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
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35
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Chan SMH, Selemidis S, Bozinovski S, Vlahos R. Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies. Pharmacol Ther 2019; 198:160-188. [PMID: 30822464 PMCID: PMC7112632 DOI: 10.1016/j.pharmthera.2019.02.013] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic obstructive pulmonary disease (COPD) is a major incurable global health burden and is currently the 4th largest cause of death in the world. Importantly, much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities (e.g. skeletal muscle wasting, ischemic heart disease, cognitive dysfunction) and infective viral and bacterial acute exacerbations (AECOPD). Current pharmacological treatments for COPD are relatively ineffective and the development of effective therapies has been severely hampered by the lack of understanding of the mechanisms and mediators underlying COPD. Since comorbidities have a tremendous impact on the prognosis and severity of COPD, the 2015 American Thoracic Society/European Respiratory Society (ATS/ERS) Research Statement on COPD urgently called for studies to elucidate the pathobiological mechanisms linking COPD to its comorbidities. It is now emerging that up to 50% of COPD patients have metabolic syndrome (MetS) as a comorbidity. It is currently not clear whether metabolic syndrome is an independent co-existing condition or a direct consequence of the progressive lung pathology in COPD patients. As MetS has important clinical implications on COPD outcomes, identification of disease mechanisms linking COPD to MetS is the key to effective therapy. In this comprehensive review, we discuss the potential mechanisms linking MetS to COPD and hence plausible therapeutic strategies to treat this debilitating comorbidity of COPD.
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Affiliation(s)
- Stanley M H Chan
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia
| | - Stavros Selemidis
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia
| | - Steven Bozinovski
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia
| | - Ross Vlahos
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
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36
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Gonzalez L, Novoa U, Moya J, Gabrielli L, Jalil JE, García L, Chiong M, Lavandero S, Ocaranza MP. Angiotensin-(1-9) reduces cardiovascular and renal inflammation in experimental renin-independent hypertension. Biochem Pharmacol 2018; 156:357-370. [PMID: 30179588 DOI: 10.1016/j.bcp.2018.08.045] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 08/30/2018] [Indexed: 02/06/2023]
Abstract
Hypertension-induced cardiovascular and renal damage can be mediated by activation of the renin-angiotensin-aldosterone system. There are different factors beyond renin-angiotensin-aldosterone system involved in hypertension and renal damage. Inflammation has emerged as an important mediator of hypertension and cardiovascular and kidney damage. Angiotensin-(1-9), a peptide of the renin-angiotensin system, counter-regulates both the physiological and pathological actions of angiotensin II. Recent data has shown that angiotensin-(1-9) protects the heart and blood vessels from adverse cardiovascular remodeling in experimental models of hypertension and/or heart failure and reduces cardiac fibrosis in stroke-prone, spontaneously hypertensive rats. These effects are mediated by the angiotensin II type 2 receptor (AT2R). However, it remains unknown whether angiotensin-(1-9) also has an anti-inflammatory effect. In the present study, we investigate whether angiotensin-(1-9) reduces inflammation and fibrosis in the heart, arteries, and kidney in a DOCA-salt hypertensive model and explore the mechanisms underlying the amelioration of end-organ damage. DOCA-salt hypertensive rats received: a) vehicle, b) angiotensin-(1-9), c) PD123319 (AT2R blocker), d) angiotensin-(1-9) plus A779 (a Mas receptor blocker) or e) angiotensin-(1-9) plus PD123319, and sham rats were used as a control. Our results showed that angiotensin-(1-9) decreased hypertension and increased vasodilation in DOCA-salt hypertensive rats. These actions were partially inhibited by PD123319. Moreover, angiotensin-(1-9) decreased diuresis, fibrosis, and inflammation. These beneficial effects were not mediated by Mas or AT2R blockers. We concluded that angiotensin-(1-9) protects against volume overload-induced hypertensive cardiovascular and kidney damage by decreasing inflammation in the heart, aortic wall, and kidney, through mechanisms independent of the Mas or AT2R.
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Affiliation(s)
- Leticia Gonzalez
- Advanced Center for Chronic Diseases (ACCDiS), Facultad de Medicina, Pontificia, Universidad Catolica de Chile, Santiago 8330024, Chile; Division Enfermedades Cardiovasculares, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
| | - Ulises Novoa
- Departmento de Ciencias Basicas Biomedicas, Facultad de Ciencias de la Salud, Universidad de Talca, Chile
| | - Jackeline Moya
- Division Enfermedades Cardiovasculares, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
| | - Luigi Gabrielli
- Advanced Center for Chronic Diseases (ACCDiS), Facultad de Medicina, Pontificia, Universidad Catolica de Chile, Santiago 8330024, Chile; Division Enfermedades Cardiovasculares, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
| | - Jorge E Jalil
- Division Enfermedades Cardiovasculares, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
| | - Lorena García
- Advanced Center for Chronic Diseases (ACCDiS) & Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Facultad Ciencias Quimicas y Farmaceuticas & Facultad de Medicina, Universidad de Chile, Santiago 8380492, Chile
| | - Mario Chiong
- Advanced Center for Chronic Diseases (ACCDiS) & Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Facultad Ciencias Quimicas y Farmaceuticas & Facultad de Medicina, Universidad de Chile, Santiago 8380492, Chile
| | - Sergio Lavandero
- Advanced Center for Chronic Diseases (ACCDiS) & Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Facultad Ciencias Quimicas y Farmaceuticas & Facultad de Medicina, Universidad de Chile, Santiago 8380492, Chile; Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - María Paz Ocaranza
- Advanced Center for Chronic Diseases (ACCDiS), Facultad de Medicina, Pontificia, Universidad Catolica de Chile, Santiago 8330024, Chile; Division Enfermedades Cardiovasculares, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile.
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37
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Breathlessness and inflammation: potential relationships and implications. Curr Opin Support Palliat Care 2018; 10:242-8. [PMID: 27387764 DOI: 10.1097/spc.0000000000000229] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE OF REVIEW Breathlessness and chronic inflammation both span a wide range of disease contexts and hold prognostic significance. The possibility of a causal relationship between the two has been hypothesized. The aims of this article are to review the intersections between breathlessness and inflammation in the literature, describe potential mechanisms connecting the two phenomena, and discuss the potential clinical implications of a causal relationship. RECENT FINDINGS There is a very limited literature exploring the relationship between systemic inflammation and breathlessness in chronic obstructive pulmonary disease, heart failure, and cancer. One large study in cancer patients is suggestive of a weak association between self-reported breathlessness and inflammation. Studies exploring the relationship between inflammation and Medical Research Council Dyspnoea grade in chronic obstructive pulmonary disease patients have produced inconsistent findings. Although a causal relationship has not yet been proven, there is evidence to support the existence of potential mechanisms mediating a relationship. This evidence points to a role for the skeletal muscle and stress hormone systems. SUMMARY There is much progress to be made in this area. Interventional studies, evaluating the impact of anti-inflammatory interventions on breathlessness, are needed to help determine whether a causal relationship exists. If proven, this relationship might have important implications for both the treatment and impact of breathlessness.
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38
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Paul T, Salazar-Degracia A, Peinado VI, Tura-Ceide O, Blanco I, Barreiro E, Barberà JA. Soluble guanylate cyclase stimulation reduces oxidative stress in experimental Chronic Obstructive Pulmonary Disease. PLoS One 2018; 13:e0190628. [PMID: 29304131 PMCID: PMC5755849 DOI: 10.1371/journal.pone.0190628] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 12/18/2017] [Indexed: 11/19/2022] Open
Abstract
Objective Soluble guanylate cyclase (sGC) is a key enzyme of the nitric oxide–cyclic guanosine 3′,5′-monophosphate (NO–cGMP) signaling pathway, and its pharmacological stimulation has been shown to prevent the development of emphysema and pulmonary vascular remodeling in animal models of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of sGC stimulation on oxidative stress in the plasma of guinea pigs chronically exposed to cigarette smoke (CS). Methods and results Guinea pigs were exposed to CS or sham for three months, and received either the sGC stimulator BAY 41–2272 or vehicle. Body weight was measured weekly; and markers of oxidative stress in plasma, and airspace size and inflammatory cell infiltrate in lung tissue were analyzed at the end of the study. Compared to sham-exposed guinea pigs, CS-exposed animals gained less body weight and showed higher plasma levels of nitrated tyrosine residues (3-NT), 4-hydroxynonenal (4-HNE), and 8-hydroxydeoxyguanosine (8-OHdG). Treatment with the sGC stimulator led to a body weight gain in the CS-exposed guinea pigs similar to non-exposed and attenuated the increase in 3-NT and 4-HNE. Plasma levels of 3-NT correlated with the severity of inflammatory cell infiltrate in the lung. Conclusion Stimulation of sGC prevents oxidative stress induced by CS exposure and is associated with an attenuated inflammatory response in the lung.
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Affiliation(s)
- Tanja Paul
- Department of Pulmonary Medicine, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Anna Salazar-Degracia
- Pulmonology Department-Lung Cancer and Muscle Research group, IMIM-Hospital del Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain
| | - Victor I. Peinado
- Department of Pulmonary Medicine, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain
- * E-mail:
| | - Olga Tura-Ceide
- Department of Pulmonary Medicine, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain
| | - Isabel Blanco
- Department of Pulmonary Medicine, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain
| | - Esther Barreiro
- Pulmonology Department-Lung Cancer and Muscle Research group, IMIM-Hospital del Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain
| | - Joan A. Barberà
- Department of Pulmonary Medicine, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain
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Jaswal S, Saini V, Kaur J, Gupta S, Kaur H, Garg K. Association of Adiponectin with Lung Function Impairment and Disease Severity in Chronic Obstructive Pulmonary Disease. Int J Appl Basic Med Res 2018; 8:14-18. [PMID: 29552529 PMCID: PMC5846212 DOI: 10.4103/ijabmr.ijabmr_65_17] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Context: Chronic obstructive pulmonary disease (COPD) is not only restricted to the pulmonary inflammation and airway obstruction but is also associated with comorbidities, which affect the therapeutic intervention and the quality of life and survival. Markers that can predict the systemic inflammation and a decline in the pulmonary function are of scientific interest. Adiponectin (APN) appears to be one such biomarker and can be used as a potential indicator of severity and response to treatment in patients of COPD. Aims: The study aims to find out the role of APN as a marker of inflammation in the pathogenesis of COPD and explore its relationship with the severity of the disease. Settings and Design: This was a cross-sectional study. Subjects and Methods: The study group consisted of 60 patients of COPD, which included 30 males admitted with acute exacerbation of COPD (AECOPD) and 30 males with stable COPD. The study group was compared with 30 healthy, age-matched males. APN was estimated by commercially available ELISA kits. Pulmonary function tests were performed on all cases and controls using standardized protocols on SPIROLAB III. Statistical Analysis Used: Statistical analysis was performed using Student's t-test and Pearson's correlation coefficient. Results: The levels of APN were found to be significantly higher in patients with COPD as compared to the controls and the levels increased with the severity of the disease were 16.10 ± 4.97 ng/ml and 11.43 ± 4.22 ng/ml, respectively, in AECOPD and COPD. A significant positive correlation was found between the levels of APN and interleukin (IL)-8 in patients of COPD, while the levels correlated negatively with percentage of forced expiratory volume in 1 s (FEV1%). Conclusions: The results reveal that APN is associated with the inflammatory process of COPD as suggested by its significant inverse relationship with FEV1% and positive correlation with a marker of inflammation such as IL-8. It can thus be used as a biomarker for disease severity and progression in patients of COPD, therefore aiding in risk stratification and therapeutic intervention.
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Affiliation(s)
- Shivani Jaswal
- Department of Biochemistry, Government Medical College and Hospital, Chandigarh, India
| | - Varinder Saini
- Department of Pulmonary Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Jasbinder Kaur
- Department of Biochemistry, Government Medical College and Hospital, Chandigarh, India
| | - Seema Gupta
- Department of Biochemistry, Government Medical College and Hospital, Chandigarh, India
| | - Harjeet Kaur
- Department of Biochemistry, Government Medical College and Hospital, Chandigarh, India
| | - Kranti Garg
- Department of Pulmonary Medicine, Government Medical College and Hospital, Chandigarh, India
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McLoughlin RF, McDonald VM, Gibson PG, Scott HA, Hensley MJ, MacDonald-Wicks L, Wood LG. The Impact of a Weight Loss Intervention on Diet Quality and Eating Behaviours in People with Obesity and COPD. Nutrients 2017; 9:nu9101147. [PMID: 29053575 PMCID: PMC5691763 DOI: 10.3390/nu9101147] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 10/16/2017] [Accepted: 10/17/2017] [Indexed: 11/16/2022] Open
Abstract
There is a paucity of evidence to guide clinicians about appropriate management strategies for people with obesity and Chronic Obstructive Pulmonary Disease (COPD). We have recently published results from the first weight loss intervention in adults (>18 years) with obesity (body mass index; BMI ≥ 30 kg/m2) and COPD, using a low-calorie diet coupled with a partial meal replacement plan and resistance exercise training, which resulted in a 6.4% reduction in weight while maintaining skeletal muscle mass and improving health status. This sub-study aims to evaluate the intervention by (a) examining changes in dietary intake and nutritional biomarkers and (b) examining predictors of weight loss. Dietary intake was evaluated using four-day food diaries, and analysis of plasma fatty acids and plasma carotenoids as biomarkers of dietary fat intake and fruit and vegetable intake, respectively. Twenty-eight obese COPD subjects (n = 17 males, n = 11 females) with a mean (standard deviation; SD) age of 67.6 (6.3) years completed the 12-week weight loss intervention. Pre-intervention, mean (SD) BMI was 36.3 (4.6) kg/m2. Micronutrient intake improved from pre- to post-intervention, with the percentage of subjects meeting the Nutrient Reference Values increased for all micronutrients. Post-intervention, significant decreases in total (p = 0.009) and saturated fat intake (p = 0.037), and corresponding decreases in total (p = 0.007) and saturated plasma fatty acids (p = 0.003) were observed. There was a trend towards higher total carotenoids post-intervention (p = 0.078). Older age (p = 0.025), higher pre-intervention uncontrolled eating (p < 0.001) and plasma carotenoids (p = 0.009) predicted weight loss. This demonstrates the efficacy of a weight loss intervention in improving diet quality of obese COPD adults.
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Affiliation(s)
- Rebecca F McLoughlin
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2305, Australia.
| | - Vanessa M McDonald
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2305, Australia.
| | - Peter G Gibson
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2305, Australia.
- Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW 2305, Australia.
| | - Hayley A Scott
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2305, Australia.
| | - Michael J Hensley
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2305, Australia.
- Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW 2305, Australia.
| | - Lesley MacDonald-Wicks
- Discipline of Nutrition and Dietetics, School of Health Sciences, University of Newcastle, Newcastle, NSW 2308, Australia.
| | - Lisa G Wood
- Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2305, Australia.
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Mantoani LC, Dell'Era S, MacNee W, Rabinovich RA. Physical activity in patients with COPD: the impact of comorbidities. Expert Rev Respir Med 2017; 11:685-698. [PMID: 28699821 DOI: 10.1080/17476348.2017.1354699] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Comorbidities are common in patients with chronic obstructive pulmonary disease (COPD) and it plays an important role on physical activity (PA) in this population. Since low PA levels have been described as a key factor to predict morbi-mortality in COPD, it seems crucial to review the current literature available on this topic. Areas covered: This review covers the most common comorbidities found in COPD, their prevalence and prognostic implications. We explore the differences in PA between COPD patients with and without comorbidities, as well as the impact of the number or type of comorbidities on activity levels of this population. The effect of different comorbidities on activities of daily living in patients with COPD is also reviewed. Finally, we discuss options for the treatment of inactivity in COPD patients considering their comorbidities and limitations. Expert commentary: Comorbidities are highly prevalent in patients with COPD and further deteriorate PA levels in this population. Despite the wide range of interventions available in COPD, the evidence in the field seems to point at PA coaching with feedback on individual goals and longer lasting PR programmes with more than 12 weeks of duration when attempting to raise the activity levels of this population.
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Affiliation(s)
- Leandro Cruz Mantoani
- a ELEGI and COLT Laboratories , Queen's Medical Research Institute, The University of Edinburgh , Edinburgh , UK
| | - Silvina Dell'Era
- a ELEGI and COLT Laboratories , Queen's Medical Research Institute, The University of Edinburgh , Edinburgh , UK.,b Sección de Rehabilitación y Cuidados Respiratorios, Servicio de Kinesiología, Hospital Italiano de Buenos Aires , Buenos Aires , Argentina
| | - William MacNee
- a ELEGI and COLT Laboratories , Queen's Medical Research Institute, The University of Edinburgh , Edinburgh , UK
| | - Roberto A Rabinovich
- a ELEGI and COLT Laboratories , Queen's Medical Research Institute, The University of Edinburgh , Edinburgh , UK
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Viglino D, Jullian-Desayes I, Minoves M, Aron-Wisnewsky J, Leroy V, Zarski JP, Tamisier R, Joyeux-Faure M, Pépin JL. Nonalcoholic fatty liver disease in chronic obstructive pulmonary disease. Eur Respir J 2017; 49:49/6/1601923. [DOI: 10.1183/13993003.01923-2016] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 02/23/2017] [Indexed: 12/18/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is independently linked to cardiometabolic morbidity and mortality. Low-grade inflammation, oxidative stress and ectopic fat, common features of chronic obstructive pulmonary disease (COPD), might contribute to the development of NAFLD.We aimed to investigate the prevalence of NAFLD and to evaluate the relationship between various types of liver damage and COPD severity, comorbidities and circulating inflammatory cytokines. Validated noninvasive tests (FibroMax: SteatoTest, NashTest and FibroTest) were used to assess steatosis, nonalcoholic steatohepatitis (NASH) and liver fibrosis. Patients underwent an objective assessment of COPD comorbidities, including sleep studies. Biological parameters included a complete lipid profile and inflammatory markers.In COPD patients the prevalence of steatosis, NASH and fibrosis were 41.4%, 36.9% and 61.3%, respectively. In multivariate analysis, SteatoTest and FibroTest were significantly associated with sex, body mass index (BMI), untreated sleep apnoea and insulin resistance, and, in addition, COPD Global Initiative for Chronic Obstructive Lung Disease stage for SteatoTest. Patients with steatosis had higher tumour necrosis factor-α levels and those with NASH or a combination of liver damage types had raised leptin levels after adjustment for age, sex and BMI.We concluded that NAFLD is highly prevalent in COPD and might contribute to cardiometabolic comorbidities.
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Montaño M, Pérez-Ramos J, Esquivel A, Rivera-Rosales R, González-Avila G, Becerril C, Checa M, Ramos C. Obesity decreases the oxidant stress induced by tobacco smoke in a rat model. Toxicol Mech Methods 2016; 26:544-553. [PMID: 27470987 DOI: 10.1080/15376516.2016.1211208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Accepted: 07/07/2016] [Indexed: 10/21/2022]
Abstract
Obesity and emphysema are associated with low-grade systemic inflammation and oxidant stress. Assuming that the oxidant stress induced by emphysema would be decreased by obesity, we analyzed the oxidant/antioxidant state in a rat model combining both diseases simultaneously. Obesity was induced using sucrose, while emphysema by exposure to tobacco smoke. End-points evaluated were: body weight, abdominal fat, plasma dyslipidemia and malondialdehyde (MDA), insulin and glucose AUC, activities of Mn-superoxide dismutase (Mn-SOD), glutathione reductase (GR), glutathione transferase (GST) and glutathione peroxidase (GPx); lung MnSOD and 3-nitrotyrosine (3-NT) immunostaining, and expression of αV and β6 integrin subunits. In rats with obesity, the body weight, abdominal fat, plasma triglyceride levels, glucose AUC, insulin levels, GST activity, and αV and β6 integrin expressions were amplified. The rats with emphysema had lower values of body weight, abdominal fat, plasma insulin, triglycerides and glucose AUC but higher values of plasma MDA, GPx activity, and the lung expression of the αV and β6 integrins. The combination of obesity and emphysema compared to either condition alone led to diminished body weight, abdominal fat, plasma insulin MDA levels, GPx and GST activities, and αV and β6 integrin expressions; these parameters were all previously increased by obesity. Immunostaining for MnSOD augmented in all experimental groups, but the staining for 3-NT only increased in rats treated with tobacco alone or combined with sucrose. Results showed that obesity reduces oxidant stress and integrin expression, increasing antioxidant enzyme activities; these changes seem to partly contribute to a protective mechanism of obesity against emphysema development.
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Affiliation(s)
- Martha Montaño
- a Departamento de Investigación en Fibrosis Pulmonar , Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México , Mexico
| | - J Pérez-Ramos
- b Departamento de Sistemas Biológicos , Universidad Autónoma Metropolitana-Xochimilco , México , Mexico
| | - A Esquivel
- b Departamento de Sistemas Biológicos , Universidad Autónoma Metropolitana-Xochimilco , México , Mexico
| | - R Rivera-Rosales
- c Departamento de Patología , Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México , Mexico
| | - G González-Avila
- d Departamento de Enfermedades Crónico Degenerativas , Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER) , México , Mexico
| | - C Becerril
- a Departamento de Investigación en Fibrosis Pulmonar , Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México , Mexico
| | - M Checa
- a Departamento de Investigación en Fibrosis Pulmonar , Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México , Mexico
| | - C Ramos
- a Departamento de Investigación en Fibrosis Pulmonar , Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México , Mexico
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The role of serum soluble urokinase-type plasminogen activator receptor in stable chronic obstructive pulmonary disease. J Investig Med 2015; 62:938-43. [PMID: 25127435 DOI: 10.1097/jim.0000000000000105] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) results from an abnormal inflammatory response of the lungs to noxious particles or gases. Serum soluble urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted during infections and inflammation. The main goal of this study was to evaluate the serum suPAR level in stable COPD patients compared with a control group. METHODS Forty-six stable COPD patients and 41 control subjects were included in the study. Blood samples were collected from 46 stable COPD patients (40 men, 6 women; mean [SD] age, 55.92 [7.91] years; the forced expiratory volume in 1 second, 45.32% [19.1%] of predicted). Forty-one healthy subjects were selected as control subjects and were matched to COPD patients with respect to age and body mass index. Serum suPAR and plasma fibrinogen levels were measured in stable COPD patients and control subjects. RESULTS Serum suPAR levels of the COPD patients were significantly higher than those of the control subjects (4.94 [2.79] and 2.40 [2.01] ng/mL, respectively; P < 0.001). Plasma fibrinogen levels of the COPD patients were significantly higher than those of the control subjects (406.77 [172.6] and 336.53 [96.1] g/L, respectively; P < 0.05). CONCLUSIONS Our study indicated that serum suPAR may play an important role in the inflammatory process of COPD, and this increase may be particularly large for patients in Global Initiative for Chronic Obstructive Lung Disease stages III and IV. Serum suPAR and plasma fibrinogen level measurements may be useful for the evaluation of stable COPD.
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Mahishale V, Mahishale A, Patil B, Sindhuri A, Eti A. Screening for diabetes mellitus in patients with chronic obstructive pulmonary disease in tertiary care hospital in India. Niger Med J 2015; 56:122-5. [PMID: 25838628 PMCID: PMC4382602 DOI: 10.4103/0300-1652.150699] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) are common and under diagnosed medical conditions in India. Prevalence of these chronic diseases are high both in rural and urban areas. However, exact prevalence of DM in Indian COPD patients in unclear. Co-morbid conditions like DM have great impact on the outcome of COPD in the form of severity, exacerbations, morbidity and mortality. Hence the present study objective was to screen COPD patients for DM. RESULTS A total of 1662 patients with COPD (Males = 1264, Female = 398) with mean age 58 ± 9.6 were screened for DM. Patients with known history of DM were 353 (21.24%) and were enrolled as Known DM cases. Remaining 1309 (78.76%) patients whose DM status was unclear were screened by random blood sugar (RBS). One-hundred and seventy-one subjects had RBS > 110 mg/dl. About 73 (4.39%) subjects had fasting blood sugar (FBS) > 126 mg/dl. They were considered as Newly Diagnosed DM cases. Total number of DM cases in the study including new and known was 426 (25.63%). Number of patients with deranged FBS (FBS between 110 mg/dl to126 mg/dl) was 84 (5.05%). Among the DM patients with COPD 168 (10.11%) had poor glycemic control with HbA1c > 8. Prevalence of DM in present study was 25.63%. CONCLUSION Prevalence of DM in COPD patients in the present study is 25.63% when actively screened in tertiary care hospital. It is feasible and imperative to screen all COPD patients for DM in all health care facilities routinely.
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Affiliation(s)
- Vinay Mahishale
- Department of Pulmonary Medicine, Karnataka Lingayat Education University's, Jawaharlal Nehru Medical College, Belgaum, India
| | - Arati Mahishale
- Department of Obstetrics and Gynaecology Physiotherapy, Karnataka Lingayat Education University's, Jawaharlal Nehru Medical College, Belgaum, India
| | - Bhagyashri Patil
- Department of Pulmonary Medicine, Karnataka Lingayat Education University's, Jawaharlal Nehru Medical College, Belgaum, India
| | - Avuthu Sindhuri
- Department of Pulmonary Medicine, Karnataka Lingayat Education University's, Jawaharlal Nehru Medical College, Belgaum, India
| | - Ajith Eti
- Department of Pulmonary Medicine, Karnataka Lingayat Education University's, Jawaharlal Nehru Medical College, Belgaum, India
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Abstract
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.
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Affiliation(s)
- Georgios Hillas
- Department of Critical Care and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece
| | - Fotis Perlikos
- Department of Critical Care and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece
| | - Ioanna Tsiligianni
- Department of Thoracic Medicine, University Hospital of Heraklion, Medical School, University of Crete, Crete, Greece
- Department of General Practice, University Medical Centre of Groningen, Groningen, The Netherlands
| | - Nikolaos Tzanakis
- Department of Thoracic Medicine, University Hospital of Heraklion, Medical School, University of Crete, Crete, Greece
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Teichert T, Vossoughi M, Vierkötter A, Sugiri D, Schikowski T, Hoffmann B, Schulte T, Roden M, Raulf-Heimsoth M, Luckhaus C, Krämer U, Herder C. Investigating the spill-over hypothesis: analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma. ENVIRONMENTAL RESEARCH 2014; 134:24-32. [PMID: 25042033 DOI: 10.1016/j.envres.2014.06.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Revised: 06/11/2014] [Accepted: 06/21/2014] [Indexed: 06/03/2023]
Abstract
Exposure to air pollutants represents a risk factor not only for respiratory diseases and lung cancer, but also for cardiometabolic diseases. It has been hypothesised that local inflammation in the lung and systemic subclinical inflammation are linked by impaired lung function and the spill-over of proinflammatory factors from the lung into the circulation which could act as intermediaries between environmental exposures and disease risk. We wanted to investigate whether local and systemic inflammatory markers are associated, which would support the spill-over hypothesis. Sputum and plasma samples were obtained from 257 women of the German SALIA cohort. We performed immunoassays to measure multiple biomarkers of airway inflammation in sputum as well as cytokines, chemokines and soluble adhesion molecules in plasma. Correlations were calculated and adjusted for potentially confounding variables. Even though several significant associations were detected between inflammatory mediators in sputum and plasma, correlation coefficients were rather low ranging from r≥-0.20 to r≤0.20. Comparatively stronger associations were observed between nitrite, eosinophil cationic protein, leukotrienes C/D/E4 and interleukin-8 in sputum. Notably, correlations were positive with all proinflammatory biomarkers and interleukin-1 receptor antagonist in plasma, whereas negative correlations were observed with the anti-inflammatory adipokine adiponectin. In conclusion, local inflammation in the lung and systemic subclinical inflammation appear mainly independently regulated in elderly women from the general population. Although we found multiple significant correlations between inflammatory biomarkers in sputum and plasma, our results do not provide clear support for the spill-over hypothesis.
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Affiliation(s)
- Tom Teichert
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany.
| | - Mohammad Vossoughi
- IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany.
| | - Andrea Vierkötter
- IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany.
| | - Dorothea Sugiri
- IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany.
| | - Tamara Schikowski
- IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany; Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
| | - Barbara Hoffmann
- IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany; Medical Faculty, Heinrich Heine University of Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
| | - Thomas Schulte
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Bergische Landstraße 2, 40629 Düsseldorf, Germany.
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany; Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany.
| | - Monika Raulf-Heimsoth
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Center of Allergology/Immunology, Bürkle-de-la-Camp Platz 1, 44789 Bochum, Germany.
| | - Christian Luckhaus
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Bergische Landstraße 2, 40629 Düsseldorf, Germany.
| | - Ursula Krämer
- IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany.
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany.
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Esquivel AL, Pérez-Ramos J, Cisneros J, Herrera I, Rivera-Rosales R, Montaño M, Ramos C. The effect of obesity and tobacco smoke exposure on inflammatory mediators and matrix metalloproteinases in rat model. Toxicol Mech Methods 2014; 24:633-43. [PMID: 25141943 DOI: 10.3109/15376516.2014.956911] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Obesity is characterized by hypertrophy of adipose tissue and chronic obstructive pulmonary disease (COPD) by lung damage; both diseases are associated with systemic low-grade inflammation. There are no animal models combining obesity and COPD; therefore, these diseases were induced simultaneously in rats to analyze their effects on the expression of inflammatory mediators and enzymes involved in lung tissue remodeling. Obesity was induced with sucrose (30%) for 4 months concomitant with tobacco smoke exposure (20 cigarettes/day, 5 days/wk) for the last 2 months. Were evaluated: body weight, abdominal fat, dyslipidemia, glucose tolerance test (GTT), histology, inflammatory mediators with qPCR and enzyme-linked immunosorbent assay, matrix metalloproteinases (MMP-2), MMP-9, MMP-12, TIMP-1 and TIMP-2 through qRT-PCR, and MMP-2 and MMP-9 by gelatin zymography. The rats on a sucrose diet exhibited increased body weight, abdominal fat, triglycerides, GTT, and plasma levels of insulin, adiponectin, leptin, resistin, IL-6, IL-1β, tumor necrosis factor-α (TNF-α) and IFN-γ, upregulated lung IL-6, IL-1β, TNF-α and IFN-γ, showing hyperplastic bronchial and alveolar epithelium. The animals exposed to sucrose and tobacco smoke exhibited decreased body weight, abdominal fat and plasma levels of leptin, resistin, IL-1β and IFN-γ, reducing inflammation but showing emphysematous lesions. Expression of gelatinases and MMP-12 augmented in the rats exposed to tobacco smoke alone or combined with sucrose. Zymography showed prominent gelatinases activity in all the experimental groups. These results suggest that simultaneous exposure to sucrose and tobacco smoke decreases inflammation but results in emphysematous lesions similar to those observed with tobacco smoke exposure, suggesting that obesity does not confer any protective effect against lung damage.
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Affiliation(s)
- Ana Laura Esquivel
- Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana Xochimilco-Iztapalapa-Cuajimalpa , Mexico, DF , Mexico
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Naik D, Joshi A, Paul TV, Thomas N. Chronic obstructive pulmonary disease and the metabolic syndrome: Consequences of a dual threat. Indian J Endocrinol Metab 2014; 18:608-616. [PMID: 25285275 PMCID: PMC4171881 DOI: 10.4103/2230-8210.139212] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The metabolic syndrome is found to be more frequent in chronic obstructive pulmonary disease (COPD). The presence of inflammatory markers in circulation, sputum, and broncho-alveolar fluid suggest systemic inflammation is one of the potential mechanisms responsible for both COPD and metabolic syndrome. Physical inactivity, skeletal muscle dysfunction, hypogonadism, and steroid use are also important causes of the metabolic syndrome in COPD. Obesity and insulin resistance is found to be more common in mild to moderate stages (I and II) of COPD. Patients with COPD and the metabolic syndrome have increase risk of morbidity and mortality due to cardiovascular disease. This review describes in details the various components of metabolic syndrome and its impact on long outcomes in COPD patients.
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Affiliation(s)
- Dukhabandhu Naik
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India
| | - Anjali Joshi
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India
- Chellaram Diabetes Institute, Bavdhan, Pune, Maharashtra, India
| | - Thomas Vizhalil Paul
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India
| | - Nihal Thomas
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India
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Dinh QN, Drummond GR, Sobey CG, Chrissobolis S. Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. BIOMED RESEARCH INTERNATIONAL 2014; 2014:406960. [PMID: 25136585 PMCID: PMC4124649 DOI: 10.1155/2014/406960] [Citation(s) in RCA: 398] [Impact Index Per Article: 36.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 06/20/2014] [Indexed: 02/07/2023]
Abstract
Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation leads to the development of hypertension, as well as the evidence for involvement of oxidative stress and endothelial dysfunction--both thought to be key steps in the development of hypertension. Other potential proinflammatory conditions that contribute to hypertension-such as activation of the sympathetic nervous system, aging, and elevated aldosterone--are also discussed. Finally, we consider the potential benefit of anti-inflammatory drugs and statins for antihypertensive therapy. The evidence reviewed suggests that inflammation can lead to the development of hypertension and that oxidative stress and endothelial dysfunction are involved in the inflammatory cascade. Aging and aldosterone may also both be involved in inflammation and hypertension. Hence, in the absence of serious side effects, anti-inflammatory drugs could potentially be used to treat hypertension in the future.
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Affiliation(s)
- Quynh N. Dinh
- Vascular Biology & Immunopharmacology Group, Department of Pharmacology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
| | - Grant R. Drummond
- Vascular Biology & Immunopharmacology Group, Department of Pharmacology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
| | - Christopher G. Sobey
- Vascular Biology & Immunopharmacology Group, Department of Pharmacology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
| | - Sophocles Chrissobolis
- Vascular Biology & Immunopharmacology Group, Department of Pharmacology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
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