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1
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Hu J, Tang S, Zhu Q, Liao H. Predictive value of six anthropometric indicators for prevalence and mortality of obstructive sleep apnoea asthma and COPD using NHANES data. Sci Rep 2025; 15:16190. [PMID: 40346342 PMCID: PMC12064750 DOI: 10.1038/s41598-025-99490-y] [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: 01/15/2025] [Accepted: 04/21/2025] [Indexed: 05/11/2025] Open
Abstract
Obesity is linked to a greater risk of respiratory diseases. Due to limitations in body mass index (BMI), alternative anthropometric indicators have been developed to reflect body fat distribution. This study compares six anthropometric measures-BMI, waist circumference (WC), the waist-to-height ratio (WHtR), the body roundness index (BRI), the body shape index (ABSI), and the weight-adjusted waist index (WWI)-and their relationships with the prevalence and mortality of obstructive sleep apnoea (OSA), asthma, and chronic obstructive pulmonary disease (COPD) in the US population. Data from four NHANES cycles were analyzed. Multivariable logistic regression assessed the cross-sectional associations between the six anthropometric measures and disease prevalence. Mortality associations were analysed via Cox proportional hazards models, and time‒dependent ROC curve was utilised to evaluate the predictive performance of the significant marker for mortality. BMI, WC, WWI, BRI, ABSI, and WHtR were positively correlated with the prevalence of OSA, and COPD. For asthma, BMI, WC, BRI, and WHtR were positively associated with prevalence, while ABSI and WWI were negatively associated. Concerning mortality, higher WC and BMI were associated with better survival in the OSA and COPD groups, whereas elevated WWI and ABSI were linked to greater mortality risk in the participants with OSA symptoms. An increase of one standard deviation (SD) in the ABSI resulted in an 18% increase in mortality (95% CI 1.09-1.27) for the OSA population. The area under the curve (AUC) for ABSI was 0.752 for 3-year, 0.755 for 5-year, and 0.744 for 10-year mortality. Novel anthropometric indicators, including WWI, BRI, ABSI, and WHtR, show positive associations with the prevalence of OSA, and COPD, alongside traditional measures like BMI and WC. However, WWI and ABSI were more limited in their association with asthma prevalence. Longitudinal analyses revealed that traditional anthropometric indicators such as BMI and WC were negatively associated with mortality risks in the OSA and COPD, supporting the "obesity paradox." ABSI, however, emerged as a significant mortality predictor for OSA, providing a more nuanced view of central obesity's impact on mortality. However, in COPD patients, routine anthropometric measurements may not fully capture the effects of obesity.
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Affiliation(s)
- Jingdi Hu
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Songwen Tang
- Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Qijiang Zhu
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Huai Liao
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
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2
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Al-Beltagi M, Bediwy AS, Saeed NK, Bediwy HA, Elbeltagi R. Diabetes-inducing effects of bronchial asthma. World J Diabetes 2025; 16:97954. [PMID: 39817208 PMCID: PMC11718464 DOI: 10.4239/wjd.v16.i1.97954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 10/12/2024] [Accepted: 11/07/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The relationship between diabetes mellitus (DM) and asthma is complex and can impact disease trajectories. AIM To explore the bidirectional influences between the two conditions on clinical outcomes and disease control. METHODS We systematically reviewed the literature on the relationship between DM and asthma, focusing on their impacts, mechanisms, and therapeutic implications. Various studies were assessed, which investigated the effect of glycemic control on asthma outcomes, lung function, and exacerbations. The study highlighted the role of specific diabetes medications in managing asthma. RESULTS The results showed that poor glycemic control in diabetes can exacerbate asthma, increase hospitalizations, and reduce lung function. Conversely, severe asthma, especially in obese individuals, can complicate diabetes management and make glycemic control more difficult. The diabetes-associated mechanisms, such as inflammation, microangiopathy, and oxidative stress, can exacerbate asthma and decrease lung function. Some diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma exacerbations. CONCLUSION The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and outcomes. Inflammation and microvascular complications associated with diabetes may worsen asthma outcomes, while asthma severity, especially in obese individuals, complicates diabetes control. However, the current research has limitations, and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 26671, Manama, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Muharraq, Bahrain
| | | | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland-Bahrain, Busiateen 15503, Muharraq, Bahrain
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Chen F, Yang Y, Yu L, Song L, Zhang C, He Y, Wu L, Ma W, Zhang B. The association between type 2 diabetes and asthma incidence: a longitudinal analysis considering genetic susceptibility. BMC Public Health 2025; 25:166. [PMID: 39815260 PMCID: PMC11734334 DOI: 10.1186/s12889-024-21266-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 12/31/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND The prevalence of type 2 diabetes (T2D) and asthma is rising, yet evidence regarding the relationship between T2D and asthma, particularly in the context of genetic predispositions, remains limited. METHODS This study utilized data from the UK Biobank longitudinal cohort, involving 388,775 participants. A polygenic risk score (PRS) for asthma was derived from genome-wide association studies summary. Cox regression models were used to assess the association between T2D and asthma, incorporating the asthma PRS. RESULTS Over a median follow-up of 13.62 years, 10,211 asthma cases were documented. After adjusting for age, sex, current smoking status, and other confounding variables, T2D was significantly associated with an increased risk of developing asthma (Hazard Ratios [HR] 1.16, 95% confidence interval [CI] 1.06-1.26). This association remained significant after further adjustments for genetic susceptibility to asthma. Furthermore, T2D increased the risk of developing asthma across both high and low genetic risk groups. CONCLUSIONS T2D is associated with an increased risk of developing asthma, irrespective of genetic susceptibility. These findings underscore the importance of incorporating glucose regulation strategies into asthma prevention efforts.
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Affiliation(s)
- Fei Chen
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Ying Yang
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Liping Yu
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Lulu Song
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Cong Zhang
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Yifan He
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Lili Wu
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Wanlu Ma
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China
| | - Bo Zhang
- Department of Endocrinology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Hepingli, Chaoyang District, 100029, Beijing, China.
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Raju S, Sierra P, Tejwani V, Staggers KA, McCormack M, Villareal DT, Rosas IO, Hanania NA, Wu TD. Association of Insulin Resistance With Radiographic Lung Abnormalities and Incident Lung Disease: The Framingham Offspring Study. Diabetes Care 2025; 48:143-148. [PMID: 39571139 PMCID: PMC11664196 DOI: 10.2337/dc24-1754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 10/28/2024] [Indexed: 12/22/2024]
Abstract
OBJECTIVE Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident lung disease was determined by a study examiner. The relationship of HOMA-IR to these outcomes was estimated in models adjusted for demographics, BMI, and lifetime smoking. RESULTS A total of 875 participants with longitudinal IR data and outcomes were identified. Their mean age was 51.5 years, and BMI was 26.7 kg/m2. HOMA-IR was temporally unstable, with a within-person SD approximately two-thirds of the between-person SD. In adjusted models, a 1 SD increase in log(HOMA-IR) z score was associated with higher odds of qualitative emphysema (odds ratio [OR] 1.33; 95% CI 1.04-1.70), ILAs (OR 1.35; 95% CI 1.05-1.74), and modest increases in airway wall thickness and wall area percentage. These radiographic findings were corroborated by a positive association of HOMA-IR with incident lung disease. CONCLUSIONS IR is associated with radiographic lung abnormalities and incident lung disease. Deeper phenotyping is necessary to define mechanisms of IR-associated lung injury.
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Affiliation(s)
- Sarath Raju
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD
| | - Paula Sierra
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
| | - Vickram Tejwani
- Department of Pulmonary Medicine, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH
- Department of Systems Biology and Genome Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Kristen A. Staggers
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX
| | - Meredith McCormack
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD
| | - Dennis T. Villareal
- Section of Endocrine, Diabetes, and Metabolism, Baylor College of Medicine, Houston, TX
- Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, TX
| | - Ivan O. Rosas
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
| | - Nicola A. Hanania
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
| | - Tianshi David Wu
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX
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Cheng C, Zhang L. Association Between Triglyceride-Glucose Index and Development of Asthma in US Adolescents: A Cross-Sectional Study. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2024; 16:640-651. [PMID: 39622688 PMCID: PMC11621484 DOI: 10.4168/aair.2024.16.6.640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 07/13/2024] [Accepted: 07/21/2024] [Indexed: 12/08/2024]
Abstract
PURPOSE Metabolic abnormalities, such as insulin resistance (IR) and dyslipidemia, have been linked to an increased risk of asthma. The triglyceride-glucose index (TyG), a metric indicating metabolic dysfunction, exhibits correlations with metabolic syndrome and IR. However, little research has been conducted on the relationship between TyG and asthma in the pediatric population. Therefore, we aimed to investigate the relationship between TyG and asthma among adolescents. METHODS Data from the National Health and Nutrition Examination Survey between 2007 and 2012 was analyzed in this cross-sectional study. The association between TyG and asthma was evaluated using various statistical methods, including multivariate logistic regression analysis, restricted cubic spline (RCS) analysis, threshold effects analysis, and subgroup analysis. RESULTS A total of 1,629 adolescent participants were enrolled in the study, consisting of 878 (53.9%) males and 751 females (46.1%), with a mean age of 15.5 years. After adjusting for all covariates in the multivariate logistic regression, the adjusted odds ratio (OR) for TyG and asthma in the highest quintile (Q5, > 8.65) was 4.26 (95% confidence interval [CI], 1.54, 11.81; P = 0.005) compared to the TyG in the second quintile (Q2, 7.68-7.96). Additionally, the multivariate RCS analysis revealed a non-linear relationship between TyG and asthma (P = 0.003). In the threshold analysis, the adjusted OR of asthma was 0.001 (95% CI, 0, 0.145; P = 0.007) in participants with a TyG < 7.78, and the adjusted OR of asthma was 3.685 (95% CI, 1.499, 9.058; P = 0.004) in participants with a TyG ≥ 7.78. Subgroup analysis did not show any interactive role for TyG and asthma. CONCLUSIONS In US adolescents, a U-shaped association was observed between asthma and the TyG, with a critical turning point identified at around 7.78.
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Affiliation(s)
- Chuhan Cheng
- School of Clinical Medicine, Fujian Medical University, Fuzhou, China
- Department of Neonatology, Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, China
- Department of Neonatology, Children's Specialty Center of Fuzhou First General Hospital Affiliated with Fujian Medical University, Fuzhou, China
| | - Liyan Zhang
- School of Clinical Medicine, Fujian Medical University, Fuzhou, China
- Department of Neonatology, Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, China
- Department of Neonatology, Children's Specialty Center of Fuzhou First General Hospital Affiliated with Fujian Medical University, Fuzhou, China.
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6
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Yang Y, Wang S, Jia B, Chen S. Association Between Triglyceride-Glucose Index and Lung Function Parameters in the General Population Undergoing Health Examinations. Diabetes Metab Syndr Obes 2024; 17:4031-4047. [PMID: 39492961 PMCID: PMC11531295 DOI: 10.2147/dmso.s487744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 10/23/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose To investigate the relationship between the triglyceride-glucose (TyG) index and pulmonary function metrics among the general population undergoing health examinations. Materials and Methods The enrollment totaled 696 participants. Fasting triglycerides and glucose levels were used to calculate the TyG index. Participants were divided into two categories according to their median TyG: one with high TyG and the other with low TyG. A portable spirometer was used to assess lung function. Fundamental clinical features and lung function indicators were compared between the two groups, and the relationship between the TyG index and lung function parameters was explored. Results Compared with the low TyG group, the high TyG group exhibited significantly reduced levels of FEV1/FVC, FVC% pred, FEV1% pred, FEV3% pred, FEV3/FVC, FEF75, FEF75% pred, FEF25-75% pred, and MVV% pred, suggesting poor pulmonary function. The TyG index was significantly inversely correlated with multiple pulmonary function metrics, including FVC% pred, FEV1% pred, FEV3% pred, FEV1/FVC, FEV3/FVC, FEF75, FEF75% pred and FEF25-75% pred, which persisted even after accounting for confounding variables. Conclusion In summary, the present study establishes a correlation between the TyG index and some lung function indicators, offering a new indicator of metabolic abnormalities related to lung functionality.
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Affiliation(s)
- Yu Yang
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Shuqi Wang
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
| | - Boying Jia
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
| | - Shuchun Chen
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China
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Kaur G, Sohanur Rahman M, Shaikh S, Panda K, Chinnapaiyan S, Santiago Estevez M, Xia L, Unwalla H, Rahman I. Emerging roles of senolytics/senomorphics in HIV-related co-morbidities. Biochem Pharmacol 2024; 228:116179. [PMID: 38556028 PMCID: PMC11410549 DOI: 10.1016/j.bcp.2024.116179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/18/2024] [Accepted: 03/28/2024] [Indexed: 04/02/2024]
Abstract
Human immunodeficiency virus (HIV) is known to cause cellular senescence and inflammation among infected individuals. While the traditional antiretroviral therapies (ART) have allowed the once fatal infection to be managed effectively, the quality of life of HIV patients on prolonged ART use is still inferior. Most of these individuals suffer from life-threatening comorbidities like chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), and diabetes, to name a few. Interestingly, cellular senescence is known to play a critical role in the pathophysiology of these comorbidities as well. It is therefore important to understand the role of cellular senescence in the disease progression and co-morbidity development in HIV-infected individuals. In this respect, use of senolytic/senomorphic drugs as combination therapy with ART would be beneficial for HIV patients. This review provides a critical analysis of the current literature to determine the potential and efficacy of using senolytics/senotherapeutics in managing HIV infection, latency, and associated co-morbidities in humans. The various classes of senolytics have been studied in detail to focus on their potential to combat against HIV infections and associated pathologies with advancing age.
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Affiliation(s)
- Gagandeep Kaur
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Md Sohanur Rahman
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Sadiya Shaikh
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Kingshuk Panda
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Srinivasan Chinnapaiyan
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Maria Santiago Estevez
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Li Xia
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Hoshang Unwalla
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Irfan Rahman
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
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Pelizzo G, Calcaterra V, Baldassarre P, Marinaro M, Taranto S, Ceresola M, Capelo G, Gazzola C, Zuccotti G. The impact of hormones on lung development and function: an overlooked aspect to consider from early childhood. Front Endocrinol (Lausanne) 2024; 15:1425149. [PMID: 39371928 PMCID: PMC11449876 DOI: 10.3389/fendo.2024.1425149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 08/29/2024] [Indexed: 10/08/2024] Open
Abstract
The impact of hormones on the respiratory system constitutes a multifaceted and intricate facet of human biology. We propose a comprehensive review of recent advancements in understanding the interactions between hormones and pulmonary development and function, focusing on pediatric populations. We explore how hormones can influence ventilation, perfusion, and pulmonary function, from regulating airway muscle tone to modulating the inflammatory response. Hormones play an important role in the growth and development of lung tissues, influencing them from early stages through infancy, childhood, adolescence, and into adulthood. Glucocorticoids, thyroid hormones, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1), retinoids, cholecalciferol sex steroids, hormones derived from adipose tissue, factors like insulin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and glucagon are key players in modulating respiratory mechanics and inflammation. While ample evidence underscores the impact of hormones on lung development and function, along with sex-related differences in the prevalence of respiratory disorders, further research is needed to clarify their specific roles in these conditions. Further research into the mechanisms underlying hormonal effects is essential for the development of customizing therapeutic approaches for respiratory diseases. Understanding the impact of hormones on lung function could be valuable for developing personalized monitoring approaches in both medical and surgical pediatric settings, in order to improve outcomes and the quality of care for pediatric patients.
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Affiliation(s)
- Gloria Pelizzo
- Pediatric Surgery Department, Buzzi Children’s Hospital, Milan, Italy
- Department of Biomedical and Clinical Science, University of Milan, Milan, Italy
| | - Valeria Calcaterra
- Pediatrics and Adolescentology Unit, Department of Internal Medicine, University of Pavia, Pavia, Italy
- Pediatric Department, Buzzi Children’s Hospital, Milan, Italy
| | | | - Michela Marinaro
- Pediatric Surgery Department, Buzzi Children’s Hospital, Milan, Italy
| | - Silvia Taranto
- Pediatric Department, Buzzi Children’s Hospital, Milan, Italy
| | - Michele Ceresola
- Pediatric Surgery Department, Buzzi Children’s Hospital, Milan, Italy
| | - Gerson Capelo
- Pediatric Surgery Department, Buzzi Children’s Hospital, Milan, Italy
| | | | - Gianvincenzo Zuccotti
- Department of Biomedical and Clinical Science, University of Milan, Milan, Italy
- Pediatric Department, Buzzi Children’s Hospital, Milan, Italy
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Mathur V, Karvar M, Lo T, Raby BA, Tavakkoli A, Croteau-Chonka DC, Sheu EG. Sleeve Gastrectomy is Associated with Longitudinal Improvements in Lung Function and Patient-Reported Respiratory Outcomes. Obes Surg 2024; 34:2467-2474. [PMID: 38753264 PMCID: PMC11651307 DOI: 10.1007/s11695-024-07274-6] [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: 10/30/2023] [Revised: 05/09/2024] [Accepted: 05/09/2024] [Indexed: 07/03/2024]
Abstract
PURPOSE Obesity exerts negative effects on pulmonary function through proven mechanical and biochemical pathways. Multiple studies have suggested that bariatric surgery can improve lung function. However, the timing of these effects on lung function and its association with patient reported outcomes is not known. MATERIALS AND METHODS A prospective cohort study of patients undergoing laparoscopic sleeve gastrectomy (LSG) at a tertiary care hospital was undertaken. Spirometry tests, laboratory tests, and self-reported questionnaires on asthma symptoms and asthma control (ACQ and ACT) were administered. All data were recorded pre-operatively (T0) and every 3 months post-operatively for 1 year (T3, T6, T9, T12) and were compared using a mixed-models approach for repeated measures. RESULTS For the 23 participants, mean age was 44.2 ± 12.3 years, mean BMI was 45.2 ± 7.2 kg/m2, 18(78%) were female, 9(39%) self-reported as non-white and 6(26%) reported to have asthma. Following LSG, % total body weight loss was significant at all follow-up points (P < 0.0001). Rapid improvement in forced expiratory volume (FEV)% predicted and forced vital capacity (FVC)% predicted was seen at T3. Although the overall ACQ and ACT score remained within normal range throughout the study, shortness of breath declined significantly at 3 months post-op (P < 0.05) and wheezing resolved for all patients by twelve months. Patients also reported reduced frequency of sleep interruption and inability to exercise by the end of the study (P < 0.05). CONCLUSION Improvements in objective lung function assessments and patient-reported respiratory outcomes begin as early as 3 months and continue until 12 months after sleeve gastrectomy.
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Affiliation(s)
- Vasundhara Mathur
- Laboratory of Surgical and Metabolic Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Mehran Karvar
- Laboratory of Surgical and Metabolic Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Tammy Lo
- Laboratory of Surgical and Metabolic Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Benjamin A Raby
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pulmonary Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Ali Tavakkoli
- Laboratory of Surgical and Metabolic Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Damien C Croteau-Chonka
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Eric G Sheu
- Laboratory of Surgical and Metabolic Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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Bartziokas K, Papaioannou AI, Drakopanagiotakis F, Gouveri E, Papanas N, Steiropoulos P. Unraveling the Link between Ιnsulin Resistance and Bronchial Asthma. Biomedicines 2024; 12:437. [PMID: 38398039 PMCID: PMC10887139 DOI: 10.3390/biomedicines12020437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 02/10/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has proven to be a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.
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Affiliation(s)
| | - Andriana I. Papaioannou
- 1st University Department of Respiratory Medicine, “Sotiria” Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece;
| | - Fotios Drakopanagiotakis
- Department of Pneumonology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Evanthia Gouveri
- Diabetes Centre, 2nd Department of Internal Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (E.G.); (N.P.)
| | - Nikolaos Papanas
- Diabetes Centre, 2nd Department of Internal Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (E.G.); (N.P.)
| | - Paschalis Steiropoulos
- Department of Pneumonology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
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Vine D, Ghosh M, Wang T, Bakal J. Increased Prevalence of Adverse Health Outcomes Across the Lifespan in Those Affected by Polycystic Ovary Syndrome: A Canadian Population Cohort. CJC Open 2024; 6:314-326. [PMID: 38487056 PMCID: PMC10935704 DOI: 10.1016/j.cjco.2023.12.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 12/11/2023] [Indexed: 03/17/2024] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is the most common metabolic-endocrine disorder impacting the health and quality of life of women over the lifespan. Evidence-based data on the scope of adverse health outcomes in those affected by PCOS is critical to improve healthcare and quality of life in this population. The aim of this study was to determine the prevalence of adverse health outcomes in those with PCOS compared to age-matched controls. Methods We conducted a retrospective observational case-control study in those diagnosed with PCOS and age-matched controls using the Alberta Health Services Health Analytics database and the International Classification of Diseases, for the period from 2002-2018 in Alberta, Canada. Results The cohort consisted of n = 16,531 exposed PCOS cases and n = 49,335 age-matched un-exposed controls. The prevalences of hypertension, renal disease, gastrointestinal disease, eating disorders, mental illness, depression-anxiety, rheumatoid arthritis, respiratory infections, and all malignancies were 20%-40% (P < 0.0001) higher in those with PCOS, compared to controls. The prevalence of obesity, dyslipidemia, nonalcoholic fatty liver disease, and type 2 diabetes was 2-3 fold higher in those with PCOS (P < 0.001). Cardiovascular, cerebrovascular, and peripheral vascular disease were 30%-50% higher, and they occurred 3-4 years earlier in those with PCOS (P < 0.0001); a 2-fold higher prevalence of dementia occurred in those with PCOS, compared to controls. Conclusion These findings provide evidence that PCOS is associated with a higher prevalence of morbidities over the lifespan, and the potential scope of the healthcare burden in women affected by PCOS.
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Affiliation(s)
- Donna Vine
- Metabolic and Cardiovascular Disease Laboratory, University of Alberta, Edmonton, Alberta, Canada
| | - Mahua Ghosh
- Division of Endocrinology and Metabolism, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Ting Wang
- Alberta Strategy for Patient Orientated Research, Provincial Research Data Services, Alberta Health Services, Edmonton, Alberta, Canada
| | - Jeffrey Bakal
- Alberta Strategy for Patient Orientated Research, Provincial Research Data Services, Alberta Health Services, Edmonton, Alberta, Canada
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12
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Zhou WQ, Song X, Dong WH, Chen Z. Independent effect of the triglyceride-glucose index on all-cause mortality in critically ill patients with chronic obstructive pulmonary disease and asthma: A retrospective cohort study. Chron Respir Dis 2024; 21:14799731241245424. [PMID: 38607315 PMCID: PMC11015761 DOI: 10.1177/14799731241245424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 03/08/2024] [Indexed: 04/13/2024] Open
Abstract
BACKGROUND The triglyceride-glucose (TyG) index serves as a reliable proxy for insulin resistance (IR). IR has been linked to heightened incidence, prevalence, or severity of chronic obstructive pulmonary disease (COPD) and asthma. Prior research indicates that critically ill patients are prone to developing IR. Nevertheless, few studies have delved into the correlation between IR and all-cause mortality in critically ill patients with COPD and asthma. Therefore, the aim of this study is to explore the association between the TyG index and all-cause mortality in patients with COPD and asthma, with the goal of assessing the impact of IR on the prognosis of this patient population. METHODS This is a retrospective study, and all data are from the Medical Information Mart for Intensive Care IV (MIMIC-IV) critical care database. This study included 684 ICU patients with COPD and asthma and divided them into quartiles based on TyG index levels. The primary outcomes of this study were all-cause mortality during follow-up, encompassing mortality at 30 days, 90 days, and 180 days. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality in critically ill patients with COPD and asthma. Restricted cubic spline analysis was used to assess potential nonlinear association between the TyG index and the primary outcome. RESULTS A total of 684 patients (53.9% female) were included. The 90-days all-cause mortality rate and 180-days all-cause mortality were 11.7% and 12.3%, respectively. Kaplan-Meier analysis revealed a significant association between the TyG index and both 90-days all-cause mortality (log-rank p = .039) and 180-days all-cause mortality (log-rank p = .017). Cox proportional hazards analysis revealed a significant association between the TyG index and 90-days all-cause mortality in both the unadjusted model (HR, 1.30 [95% CI 1.08-1.57] p = .005) and the model adjusted for age, gender, and diabetes (HR, 1.38 [95% CI 1.15-1.67] p < .001). Similarly, the TyG index was associated with 180-days all-cause mortality in the unadjusted model (HR, 1.30 [95% CI 1.09-1.56] p = .004) and the model adjusted for age, sex, and diabetes (HR, 1.38 [95% CI 1.15-1.66] p < .001). The restricted cubic splines (RCS) regression model indicated a significant nonlinear association between the TyG index and both 90-days and 180-days all-cause mortality. Specifically, TyG index >4.8 was associated with an increased risk of mortality at both 90 days and 180 days. CONCLUSIONS In summary, our results extend the utility of the TyG index to critically ill patients with COPD and asthma. Our study shows that the TyG index is a potential predictor of all-cause mortality in critically ill patients with COPD and asthma. In addition, in patients with a TyG index exceeding 4.8, there was a heightened risk of mortality. Measuring the TyG index may help with risk stratification and prognosis prediction in critically ill patients with COPD and asthma. Further prospective studies are needed to confirm our findings.
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Affiliation(s)
- Wen-Qiang Zhou
- Department of Emergency, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xin Song
- Department of Emergency, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Wei-Hua Dong
- Department of Emergency, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Zhi Chen
- Department of Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
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Shailesh H, Bhat AA, Janahi IA. Obesity-Associated Non-T2 Mechanisms in Obese Asthmatic Individuals. Biomedicines 2023; 11:2797. [PMID: 37893170 PMCID: PMC10603840 DOI: 10.3390/biomedicines11102797] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/30/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023] Open
Abstract
Obesity and asthma are two common health issues that have shown increased prevalence in recent years and have become a significant socioeconomic burden worldwide. Obesity increases asthma incidence and severity. Obese asthmatic individuals often experience increased exacerbation rates, enhanced airway remodeling, and reduced response to standard corticosteroid therapy. Recent studies indicate that obesity-associated non-T2 factors such as mechanical stress, hyperinsulinemia, systemic inflammation, adipose tissue mediators, metabolic dysregulation, microbiome dysbiosis, and high-fat-diet are responsible for increased asthma symptoms and reduced therapeutic response in obese asthmatic individuals. This manuscript reviews the recent findings highlighting the role of obesity-associated factors that contribute to airway hyper-reactivity, airway inflammation and remodeling, and immune cell dysfunction, consequently contributing to worsening asthma symptoms. Furthermore, the review also discusses the possible future therapies that might play a role in reducing asthma symptoms by diminishing the impact of obesity-associated non-T2 factors.
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Affiliation(s)
| | - Ajaz A. Bhat
- Precision Medicine in Diabetes, Obesity and Cancer Research Program, Department of Human Genetics, Sidra Medicine, Doha 26999, Qatar;
| | - Ibrahim A. Janahi
- Department of Medical Education, Sidra Medicine, Doha 26999, Qatar;
- Department of Pediatric Medicine, Sidra Medicine, Doha 26999, Qatar
- Department of Pediatrics, Weill Cornell Medicine, Doha 24144, Qatar
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Guarnieri G, Iervolino M, Cavallone S, Unfer V, Vianello A. The "Asthma-Polycystic Ovary Overlap Syndrome" and the Therapeutic Role of Myo-Inositol. Int J Mol Sci 2023; 24:ijms24086959. [PMID: 37108123 PMCID: PMC10138395 DOI: 10.3390/ijms24086959] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/03/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Asthma is a heterogeneous inflammatory disease characterized by abnormalities in immune response. Due to the inherent complexity of the disease and the presence of comorbidities, asthma control is often difficult to obtain. In asthmatic patients, an increased prevalence of irregular menstrual cycles, infertility, obesity, and insulin resistance has been reported. Given that these conditions are also common in patients with polycystic ovary syndrome (PCOS), we propose the definition of "asthma-PCOS overlap syndrome" to indicate a medical condition which shares characteristics of both diseases. The aim of this review is to analyze the links between asthma and PCOS and evaluate the therapeutic role of myo-inositol, a natural compound currently utilized in patients with PCOS, in the management of asthma patients.
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Affiliation(s)
- Gabriella Guarnieri
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
| | | | | | - Vittorio Unfer
- Systems Biology Group Laboratory, 00163 Rome, Italy
- The Experts Group on Inositol in Basic and Clinical Research (EGOI), 00161 Rome, Italy
| | - Andrea Vianello
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
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Hidden Comorbidities in Asthma: A Perspective for a Personalized Approach. J Clin Med 2023; 12:jcm12062294. [PMID: 36983294 PMCID: PMC10059265 DOI: 10.3390/jcm12062294] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/05/2023] [Accepted: 03/13/2023] [Indexed: 03/18/2023] Open
Abstract
Bronchial asthma is the most frequent inflammatory non-communicable condition affecting the airways worldwide. It is commonly associated with concomitant conditions, which substantially contribute to its burden, whether they involve the lung or other districts. The present review aims at providing an overview of the recent acquisitions in terms of asthma concomitant systemic conditions, besides the commonly known respiratory comorbidities. The most recent research has highlighted a number of pathobiological interactions between asthma and other organs in the view of a shared immunological background underling different diseases. A bi-univocal relationship between asthma and common conditions, including cardiovascular, metabolic or neurodegenerative diseases, as well as rare disorders such as sickle cell disease, α1-Antitrypsin deficiency and immunologic conditions with hyper-eosinophilia, should be considered and explored, in terms of diagnostic work-up and long-term assessment of asthma patients. The relevance of that acquisition is of utmost importance in the management of asthma patients and paves the way to a new approach in the light of a personalized medicine perspective, besides targeted therapies.
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Uppal P, Mohammed SA, Rajashekar S, Giri Ravindran S, Kakarla M, Ausaja Gambo M, Yousri Salama M, Haidar Ismail N, Tavalla P, Hamid P. Type 2 Diabetes Mellitus and Asthma: Pathomechanisms of Their Association and Clinical Implications. Cureus 2023; 15:e36047. [PMID: 37056543 PMCID: PMC10089620 DOI: 10.7759/cureus.36047] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 03/11/2023] [Indexed: 03/14/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) and asthma are chronic illnesses concomitantly present in a significant percentage of the population. Their comorbidity is associated with poor disease control and lower quality of life, thus imposing a substantial medical and economic burden worldwide. This review investigates the association between asthma and T2DM, in terms of pathogenesis, clinical outcomes, and therapeutic opportunities. Our review found an increased risk of asthma among diabetics, and vice versa. Having diabetes and poor glycemic control is associated with an increased rate of asthma exacerbations and increased mortality among those hospitalized for asthma exacerbations. The mechanisms postulated for the diabetes-asthma association include chronic low-grade inflammation, obesity, hyperinsulinemia, and possibly diabetic pneumopathy. Usage of metformin, which is the first-line drug for type 2 diabetes, was found to be associated with a decreased asthma occurrence, asthma exacerbations, and asthma-related hospitalizations. Glucagon-like peptide 1 receptor agonists were also found to be associated with a lower occurrence of asthma exacerbations. Thiazolidinediones are also associated with lower rates of asthma exacerbations, but their clinical efficacy for the same was suggested to be limited. This literature review supports a partly causative association between asthma and diabetes. This comorbidity leads to poor patient compliance, worse disease outcomes, and poor quality of life. Thus, further studies are warranted to explore the prognostic implications, therapeutic opportunities, and specific clinical practice algorithms for patients with concurrent asthma and type 2 diabetes mellitus.
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17
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Riaz F, Pan F, Wei P. Aryl hydrocarbon receptor: The master regulator of immune responses in allergic diseases. Front Immunol 2022; 13:1057555. [PMID: 36601108 PMCID: PMC9806217 DOI: 10.3389/fimmu.2022.1057555] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 12/02/2022] [Indexed: 12/23/2022] Open
Abstract
The aryl hydrocarbon receptor (AhR) is a widely studied ligand-activated cytosolic transcriptional factor that has been associated with the initiation and progression of various diseases, including autoimmune diseases, cancers, metabolic syndromes, and allergies. Generally, AhR responds and binds to environmental toxins/ligands, dietary ligands, and allergens to regulate toxicological, biological, cellular responses. In a canonical signaling manner, activation of AhR is responsible for the increase in cytochrome P450 enzymes which help individuals to degrade and metabolize these environmental toxins and ligands. However, canonical signaling cannot be applied to all the effects mediated by AhR. Recent findings indicate that activation of AhR signaling also interacts with some non-canonical factors like Kruppel-like-factor-6 (KLF6) or estrogen-receptor-alpha (Erα) to affect the expression of downstream genes. Meanwhile, enormous research has been conducted to evaluate the effect of AhR signaling on innate and adaptive immunity. It has been shown that AhR exerts numerous effects on mast cells, B cells, macrophages, antigen-presenting cells (APCs), Th1/Th2 cell balance, Th17, and regulatory T cells, thus, playing a significant role in allergens-induced diseases. This review discussed how AhR mediates immune responses in allergic diseases. Meanwhile, we believe that understanding the role of AhR in immune responses will enhance our knowledge of AhR-mediated immune regulation in allergic diseases. Also, it will help researchers to understand the role of AhR in regulating immune responses in autoimmune diseases, cancers, metabolic syndromes, and infectious diseases.
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Affiliation(s)
- Farooq Riaz
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China
| | - Fan Pan
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China,*Correspondence: Ping Wei, ; Fan Pan,
| | - Ping Wei
- Department of Otolaryngology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China,*Correspondence: Ping Wei, ; Fan Pan,
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18
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Kaplan AG, Kim JW. Asthma Exacerbations and Glucagon-Like Peptide-1 Receptor Agonists: a Review of the Current Evidence. Pulm Ther 2022; 8:343-358. [DOI: 10.1007/s41030-022-00203-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 10/17/2022] [Indexed: 11/24/2022] Open
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Bhaumik S, Lockett J, Saif Z, Lai A, Salomon C, Whitehead J, Clifton VL. The impact of obesity and uncontrolled asthma during pregnancy on metabolic and inflammatory pathways. J Asthma 2022; 60:1141-1152. [PMID: 36214455 DOI: 10.1080/02770903.2022.2134794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor perinatal outcomes. Our previous work has identified the presence of maternal asthma is associated with a proinflammatory milieu in the placenta and reduced fetal growth. The current study was designed to determine the relationships between immunomodulatory metabolic pathways and inflammation and establish whether these pathways are associated with uncontrolled asthma in obese pregnant women.Fifty-three obese (BMI >30) pregnant women were recruited prospectively. Participants were classified as having no asthma, controlled asthma, and uncontrolled asthma based on a doctor diagnosis and assessment using the Asthma Control Questionnaire (ACQ). Circulating plasma concentrations of metabolic hormones leptin, adiponectin, insulin, glucose, and extracellular vesicle (EVs) associated cytokines were measured at 18- and 36-weeks gestation.Concentrations of metabolic and inflammatory markers among obese participants with or without asthma were not significantly different throughout gestation. However total adiponectin concentrations increased as gestation progressed in obese, non-asthmatic women but did not increase in women with asthma. Plasma adiponectin and leptin levels in women with uncontrolled asthma were positively correlated with EV inflammatory markers including GM-CSF, IL-6, TNFα and IFNγ protein.This study demonstrated that most metabolic markers remain unchanged with the presence and severity of asthma in obese pregnant women. However, differences in the associations between metabolic and inflammatory pathways were observed in women with asthma and may be one of the mechanisms contributing to uncontrolled asthma in obese pregnant women.
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Affiliation(s)
- Sreeparna Bhaumik
- Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Jack Lockett
- Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia.,Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Metro South Health, Brisbane, Australia
| | - Zarqa Saif
- Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Andrew Lai
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Carlos Salomon
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Jon Whitehead
- Department of Life Sciences, The University of Lincoln, Lincoln, United Kingdom
| | - Vicki L Clifton
- Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
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20
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Carr TF, Granell R, Stern DA, Guerra S, Wright A, Halonen M, Henderson J, Martinez FD. High Insulin in Early Childhood Is Associated with Subsequent Asthma Risk Independent of Body Mass Index. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:785-792.e5. [PMID: 34656798 PMCID: PMC9059620 DOI: 10.1016/j.jaip.2021.09.047] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Asthma and obesity are major, interconnected public health challenges that usually have their origins in childhood, and for which the relationship is strengthened among those with insulin resistance. OBJECTIVE To determine whether high insulin in early life confers increased longitudinal risk for asthma independent of body mass index. METHODS The study used data from the Tucson Children's Respiratory Study (TCRS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Nonfasting insulin was measured in TCRS participants at age 6 years and fasting insulin in ALSPAC participants at age 8 years. Physician-diagnosed active asthma was determined at baseline and at subsequent assessments up to age 36 years in TCRS and 17 years in ALSPAC. RESULTS In TCRS, high insulin (upper quartile) at age 6 years was associated with increased odds of having active asthma from ages 8 to 36 years compared with low insulin (odds ratio,1.98; 95% CI, 1.28-3.05; P = .002). Similarly, in ALSPAC, high insulin was associated with a significantly higher risk of active asthma from ages 11 to 17 years compared with low insulin (odds ratio, 1.59; 95% CI, 1.12-2.27; P = .009). These findings were independent of baseline body mass index in both cohorts, and were not related to other demographic and asthma risk factors nor other tested markers of systemic inflammation and metabolic syndrome. CONCLUSIONS In 2 separate birth cohorts, higher blood insulin level in early childhood was associated with increased risk of active asthma through adolescence and adulthood, independent of body mass index. High insulin indicates a novel mechanism for asthma development, which may be a target for intervention.
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Affiliation(s)
- Tara F Carr
- Asthma and Airway Disease Research Center, University of Arizona, Tucson, Ariz.
| | | | - Debra A Stern
- Asthma and Airway Disease Research Center, University of Arizona, Tucson, Ariz
| | - Stefano Guerra
- Asthma and Airway Disease Research Center, University of Arizona, Tucson, Ariz
| | - Anne Wright
- Asthma and Airway Disease Research Center, University of Arizona, Tucson, Ariz
| | - Marilyn Halonen
- Asthma and Airway Disease Research Center, University of Arizona, Tucson, Ariz
| | | | - Fernando D Martinez
- Asthma and Airway Disease Research Center, University of Arizona, Tucson, Ariz
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21
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Chen Y, Yang J, Han K, Wang Y, Zhuang C, Zhu L, Chen M. An Elevated METS-IR Index Is Associated With Higher Asthma Morbidity and Earlier Age of First Asthma in US Adults: Results Based on a Cross-Sectional Study. Front Endocrinol (Lausanne) 2022; 13:920322. [PMID: 35898458 PMCID: PMC9309520 DOI: 10.3389/fendo.2022.920322] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/09/2022] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE The purpose of this study was to evaluate whether there is a correlation between the METS-IR index and asthma among Americans. METHODS In an attempt to establish the relationship between the METS-IR index and asthma prevalence and age at first onset of asthma, we conducted a logistic regression analysis, subgroup analysis, and dose-response curve analysis using the National Health and Nutrition Examination Survey (NHANES) database. RESULTS In model 3, each unit increase in METS-IR index led to 1.5% increase in asthma prevalence (OR= 1.015, 95% CI: 1.012, 1.018) and an earlier age of onset of asthma by 0.057years (β= -0.057, 95% CI: -0.112, -0.002).Stratified analysis determined that an increase in METS-IR index was associated with asthma prevalence in almost all subgroups, except in the group where it was not known whether a blood relative had asthma, and a positive linear relationship was found between METS-IR index and asthma prevalence, as well as a linear negative relationship with age at asthma onset. CONCLUSION Despite the fact that a direct causal relationship cannot be demonstrated, a higher METS-IR index is positively related to asthma prevalence and correspondingly may result in asthma onset at younger ages.
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Affiliation(s)
- Yan Chen
- Department of General Practice, Wuhu City Second People’s Hospital, Wuhu, China
| | - Junping Yang
- Department of General Practice, Wuhu City Second People’s Hospital, Wuhu, China
| | - Kexing Han
- Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yan Wang
- Department of General Practice, Wuhu City Second People’s Hospital, Wuhu, China
| | - Cuixia Zhuang
- Department of General Practice, Wuhu City Second People’s Hospital, Wuhu, China
| | - Laxiang Zhu
- Department of General Practice, Wuhu City Second People’s Hospital, Wuhu, China
- *Correspondence: Laxiang Zhu, ; Mingwei Chen,
| | - Mingwei Chen
- Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Laxiang Zhu, ; Mingwei Chen,
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Abstract
PURPOSE OF REVIEW Disorders of glucose metabolism, including insulin resistance, prediabetes, and diabetes, have been identified as risk factors for worsened asthma. This review summarizes emerging evidence for their role as modifiable risk factors in asthma, including the potential benefit of diabetes medications on asthma outcomes. RECENT FINDINGS Experimental studies show that hyperinsulinemia associated with insulin resistance is associated with airway smooth muscle proliferation and promotes contractility. Epidemiologic studies have identified a higher prevalence of glycemic dysfunction among those with severe and uncontrolled asthma, and longitudinal studies have associated prediabetes and diabetes with higher risk of asthma exacerbations. The potential benefits of thiazolidinediones (TZDs), glucagon-like peptide-1 agonists, and metformin being investigated in asthma, but thus far interventional studies of TZDs have reported null results. On the contrary, observational studies have inconsistently controlled for relevant confounders which leaves conclusions vulnerable to misattribution of relationships due to corelated metabolic disorders, including dyslipidemia. SUMMARY Developing evidence suggests that disorders of glucose metabolism may be associated with worsening asthma. However, these conditions arise within a network of obesity-related metabolic diseases that may themselves worsen asthma. Few interventional trials have not identified a benefit, but data have been limited. Additional research is needed to define the potential independent impact of disorders of glucose metabolism in asthma.
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Casale T, Molfino NA, Silver J, Bogart M, Packnett E, McMorrow D, Wu J, Hahn B. Real-world effectiveness of mepolizumab in patients with severe asthma and associated comorbidities. Ann Allergy Asthma Immunol 2021; 127:354-362.e2. [PMID: 34038773 DOI: 10.1016/j.anai.2021.05.021] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/28/2021] [Accepted: 05/18/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Patients with severe asthma frequently have associated comorbidities, which can compound existing symptoms, complicating asthma management. OBJECTIVE To describe the real-world effectiveness of mepolizumab in patients with severe asthma stratified by common overlapping comorbidities. METHODS This was a retrospective analysis of patients with asthma from the MarketScan Commercial and Medicare Supplemental Database initiating mepolizumab treatment (index date). Eligible patients had more than or equal to 1 claim (excluding claims for diagnostic tests) with a diagnosis code for more than or equal to 1 of 7 comorbidities (atopic disease, nasal polyps, chronic sinusitis, obesity, respiratory infections, chronic obstructive pulmonary disease, and depression/anxiety) during the 12-month preindex baseline period; these were used to stratify patients into 7 nonmutually exclusive subgroups. Outcomes included asthma exacerbations and exacerbation-related health care resource utilization during the 12-month baseline and follow-up periods. Each patient acted as their own control. RESULTS Of the 639 patients included, the most common comorbidities were atopic diseases (73.2%), respiratory infections (55.6%), and chronic sinusitis (45.1%). Across all 7 comorbidity subgroups, there were significant (P < .05) reductions of 38% to 55% and 57% to 83% in exacerbations and exacerbations requiring hospitalization, respectively, during the follow-up vs baseline period, except for exacerbations requiring hospitalization in the nasal polyp subgroup, owing to the small subgroup sample size. During the follow-up vs baseline periods, mean number of oral corticosteroids claims was significantly (P < .001) reduced by 29% to 38%; 39% to 47% of patients achieved greater than or equal to 50% oral corticosteroids dose reduction. Significant reductions in exacerbation-related health care resource utilization were also observed. CONCLUSION Mepolizumab treatment provided real-world clinical benefits in patients.
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Affiliation(s)
- Thomas Casale
- Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida Health Morsani College of Medicine, Tampa, Florida
| | - Nestor A Molfino
- US Value Evidence and Outcomes, US Medical Affairs, GlaxoSmithKline, Research Triangle Park, North Carolina
| | - Jared Silver
- US Medical Affairs, GlaxoSmithKline, Research Triangle Park, North Carolina
| | - Michael Bogart
- US Value Evidence and Outcomes, US Medical Affairs, GlaxoSmithKline, Research Triangle Park, North Carolina
| | | | | | - Joanne Wu
- Life Sciences, IBM Watson Health, Cambridge, Maryland
| | - Beth Hahn
- US Value Evidence and Outcomes, US Medical Affairs, GlaxoSmithKline, Research Triangle Park, North Carolina.
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Wu TD, Fawzy A, Brigham E, McCormack MC, Rosas I, Villareal DT, Hanania NA. Association of Triglyceride-Glucose Index and Lung Health: A Population-based Study. Chest 2021; 160:1026-1034. [PMID: 33839084 DOI: 10.1016/j.chest.2021.03.056] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/24/2021] [Accepted: 03/26/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown. RESEARCH QUESTION What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function? STUDY DESIGN AND METHODS This study analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2012. Participants included fasting adults age ≥ 40 years (N = 6,893) with lung function measurements in a subset (n = 3,383). Associations of TyG with respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), and lung function (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated, adjusting for sociodemographic variables, comorbidities, and smoking. TyG was compared vs insulin resistance, represented by the homeostatic model assessment of insulin resistance (HOMA-IR), and vs the metabolic syndrome. RESULTS TyG was moderately correlated with HOMA-IR (Spearman ρ = 0.51) and had good discrimination for metabolic syndrome (area under the receiver-operating characteristic curve, 0.80). A one-unit increase in TyG was associated with higher odds of cough (adjusted OR [aOR], 1.28; 95% CI, 1.06-1.54), phlegm production (aOR, 1.20; 95% CI, 1.01-1.43), wheeze (aOR, 1.18; 95% CI, 1.03-1.35), exertional dyspnea (aOR, 1.21; 95% CI, 1.07-1.38), and a diagnosis of chronic bronchitis (aOR, 1.21; 95% CI, 1.02-1.43). TyG was associated with higher relative risk of a restrictive spirometry pattern (adjusted relative risk ratio, 1.45; 95% CI, 1.11-1.90). Many associations were maintained with additional adjustment for HOMA-IR or metabolic syndrome. INTERPRETATION TyG was associated with respiratory symptoms, chronic bronchitis, and a restrictive spirometry pattern. Associations were not fully explained by insulin resistance or metabolic syndrome. TyG is a satisfactory measure of metabolic dysfunction with relevance to pulmonary outcomes. Prospective study to define TyG as a biomarker for impaired lung health is warranted.
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Affiliation(s)
- Tianshi David Wu
- Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX; Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX.
| | - Ashraf Fawzy
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Emily Brigham
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Meredith C McCormack
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ivan Rosas
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Dennis T Villareal
- Division of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, TX
| | - Nicola A Hanania
- Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX
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Nejatifar F, Foumani AA, Poor ARG, Nejad AT. Association of Metabolic Syndrome and Asthma Status; A Prospective Study from Guilan Province-Iran. Endocr Metab Immune Disord Drug Targets 2021; 22:395-400. [PMID: 33676392 DOI: 10.2174/1871530321666210305125059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 08/22/2020] [Accepted: 10/08/2020] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Asthma is defined as a chronic inflammatory airway disease. Recent studies have shown the association between metabolic syndrome and deterioration of the lung functions in patients with asthma. The aim of this study was to evaluate the relation between metabolic syndrome and asthma status. METHODS In this prospective cross-sectional study, 160 asthmatic patients attending Razi hospital in Guilan province, were divided equally into two groups of 80 patients. The case group was contained asthmatic patient with metabolic syndrome and the control group contain asthmatic patient without metabolic syndrome. Blood pressure, height, weight, waist circumferences, fasting blood glucose and lipid profiles were measured by standard methods. Asthma severity was determined based on clinical symptoms and GINA criteria. To evaluate pulmonary function parameters, spirometry was performed for the patients. RESULTS Pulmonary function test including FEF, FVC and FEV1 were significantly lower in the case group compared to control group (P < 0.05). Also, a significant negative correlation was found between waist circumference, cardiovascular risk factors (including diabetes, hypertriglyceridemia, hypertension) with spirometric indices (P < 0.05). CONCLUSION Metabolic syndrome causes major declines of pulmonary parameters in asthma patients, thus controlling metabolic syndrome might improve symptoms of asthma.
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Affiliation(s)
- Fatemeh Nejatifar
- Inflammatory Lung Diseases Research Center, Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Alavi Foumani
- Inflammatory Lung Diseases Research Center, Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Ahmad Reza Ghorban Poor
- Inflammatory Lung Diseases Research Center, Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Azita Tangestani Nejad
- Inflammatory Lung Diseases Research Center, Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
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Kim BK, Song WJ, Seo B, Kim JY, Kim SH, Jang HC, Kim KW, Chang YS. Retinol-binding protein-4 was associated with sensitization to inhalant allergens in the elderly population. Korean J Intern Med 2021; 36:447-455. [PMID: 33045798 PMCID: PMC7969066 DOI: 10.3904/kjim.2019.348] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 03/18/2020] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND/AIMS Recent evidence suggests an association between allergic sensitization and metabolic markers. However, this association has rarely been examined in the elderly. Retinol-binding protein-4 (RBP-4) is a recently identified adipokine that acts on the muscle and liver affecting insulin sensitivity. We evaluated the association between metabolic parameters and allergic sensitization in the elderly. METHODS We analysed the database of the Korean Longitudinal Study on Health and Aging cohort study conducted during 2005 to 2006. Atopy was identified by inhalant allergen skin prick test. Metabolic conditions were assessed using anthropometric indices and serum biomarkers such as fasting glucose, lipid, adiponectin, and RBP-4. RESULTS Among the 854 elderly subjects, 17.2% had atopy. Plasma RBP-4 levels were significantly higher in the atopic elderly than nonatopic elderly (p = 0.003). When RBP-4 percentiles were categorized as under three groups, the prevalence of atopy and current rhinitis increased significantly with percentiles of RBP-4 levels (p = 0.019 and p = 0.007, respectively). Log RBP-4 was associated with atopy (odds ratio [OR], 4.10; p = 0.009) and current rhinitis (OR, 2.73; p = 0.014), but not with current asthma (OR, 1.17; p = 0.824). Higher RBP-4 level in atopic elderly was also observed in current rhinitis patients. Atopy, but not current rhinitis, showed significant relationships with log RBP-4 levels in multivariate analyses adjusted for other metabolic markers including body mass index. CONCLUSION RBP-4 positively associated with atopy in the general elderly population irrespective of other metabolic markers.
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Affiliation(s)
- Byung-Keun Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Woo-Jung Song
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bomi Seo
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea
| | - Ju-Young Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Sae-Hoon Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea
| | - Hak C. Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ki-Woong Kim
- Department of Neuropsychiatry, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon-Seok Chang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea
- Correspondence to Yoon-Seok Chang, M.D. Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: +82-31-787-7023, Fax: +82-31-787-4052, E-mail:
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Lee SE, Baek JY, Han K, Koh EH. Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women. Diabetes Metab J 2021; 45:175-182. [PMID: 32431107 PMCID: PMC8024158 DOI: 10.4093/dmj.2019.0150] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 12/10/2019] [Indexed: 11/08/2022] Open
Abstract
Background Although studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status. Methods A total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity. Results In premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups. Conclusion Increased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.
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Affiliation(s)
- Seung Eun Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Ji Yeon Baek
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyungdo Han
- Department of Biostatistics, The Catholic University of Korea, Seoul, Korea
| | - Eun Hee Koh
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Torres RM, Souza MDS, Coelho ACC, de Mello LM, Souza-Machado C. Association between Asthma and Type 2 Diabetes Mellitus: Mechanisms and Impact on Asthma Control-A Literature Review. Can Respir J 2021; 2021:8830439. [PMID: 33520042 PMCID: PMC7817304 DOI: 10.1155/2021/8830439] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 12/05/2020] [Accepted: 12/28/2020] [Indexed: 11/18/2022] Open
Abstract
The study aimed to analyze the scientific production on the association between asthma and type 2 diabetes mellitus (T2DM) in adults, the mechanisms that explain this association, and its impact on asthma control. A literature review of scientific articles indexed in the MEDLINE/PUBMED, BVS, CINAHL, Cochrane Library, and Web of Science databases was carried out, considering publications from January 2009 to December 2019, using the following descriptors: "asthma", "type 2 diabetes", "adult," and "association". Of 962 articles found, 18 were included because they met the eligibility criteria. It is suggested that the association between asthma and T2DM is caused by low-grade systemic inflammation (7 articles) or the use of corticosteroids (7 articles). It is noticed that there is a limited scientific production regarding the consequences of this association for the control of asthma (5 articles). It is concluded that asthma and T2DM are two common chronic conditions of increasing prevalence and that often coexist in the same patient. It is suggested that this coexistence worsens asthma control. Therefore, the study may support public policies and clinical health practices that value the approach of comorbidities associated with asthma such as T2DM, in order to minimize additional health risks and reduce the quality of life.
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Affiliation(s)
- Raimeyre Marques Torres
- Graduate Program of the School of Nursing at the Federal University of Bahia, Salvador (BA), Brazil
| | - Marcela Dos Santos Souza
- Graduate Program of the School of Nursing at the Federal University of Bahia, Salvador (BA), Brazil
| | | | - Luane Marques de Mello
- Department of Social Medicine, School of Medicine, University of São Paulo, Ribeirão Preto (SP), Brazil
| | - Carolina Souza-Machado
- Graduate Program of the School of Nursing at the Federal University of Bahia, Salvador (BA), Brazil
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Bantulà M, Roca-Ferrer J, Arismendi E, Picado C. Asthma and Obesity: Two Diseases on the Rise and Bridged by Inflammation. J Clin Med 2021; 10:jcm10020169. [PMID: 33418879 PMCID: PMC7825135 DOI: 10.3390/jcm10020169] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/29/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022] Open
Abstract
Asthma and obesity are two epidemics affecting the developed world. The relationship between obesity and both asthma and severe asthma appears to be weight-dependent, causal, partly genetic, and probably bidirectional. There are two distinct phenotypes: 1. Allergic asthma in children with obesity, which worsens a pre-existing asthma, and 2. An often non allergic, late-onset asthma developing as a consequence of obesity. In obesity, infiltration of adipose tissue by macrophages M1, together with an increased expression of multiple mediators that amplify and propagate inflammation, is considered as the culprit of obesity-related inflammation. Adipose tissue is an important source of adipokines, such as pro-inflammatory leptin, produced in excess in obesity, and adiponectin with anti-inflammatory effects with reduced synthesis. The inflammatory process also involves the synthesis of pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and TGFβ, which also contribute to asthma pathogenesis. In contrast, asthma pro-inflammatory cytokines such as IL-4, IL-5, IL-13, and IL-33 contribute to maintain the lean state. The resulting regulatory effects of the immunomodulatory pathways underlying both diseases have been hypothesized to be one of the mechanisms by which obesity increases asthma risk and severity. Reduction of weight by diet, exercise, or bariatric surgery reduces inflammatory activity and improves asthma and lung function.
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Affiliation(s)
- Marina Bantulà
- Department of Internal Medicine, Hospital Clinic, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.B.); (J.R.-F.); (E.A.)
- Department of Medicine, University of Barcelona, 08036 Barcelona, Spain
| | - Jordi Roca-Ferrer
- Department of Internal Medicine, Hospital Clinic, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.B.); (J.R.-F.); (E.A.)
- Department of Medicine, University of Barcelona, 08036 Barcelona, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), 08036 Barcelona, Spain
| | - Ebymar Arismendi
- Department of Internal Medicine, Hospital Clinic, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.B.); (J.R.-F.); (E.A.)
- Department of Medicine, University of Barcelona, 08036 Barcelona, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), 08036 Barcelona, Spain
- Servei de Pneumologia, Hospital Clinic, 08036 Barcelona, Spain
| | - César Picado
- Department of Internal Medicine, Hospital Clinic, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.B.); (J.R.-F.); (E.A.)
- Department of Medicine, University of Barcelona, 08036 Barcelona, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), 08036 Barcelona, Spain
- Correspondence: ; Tel.: +34-93-227-5400
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Fu D, Zhao H, He L, Feng H. DM-induced Hypermethylation of IR and IGF1R attenuates mast cell activation and airway responsiveness in rats. J Cell Mol Med 2020; 24:14381-14391. [PMID: 33145961 PMCID: PMC7754055 DOI: 10.1111/jcmm.16059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/22/2020] [Accepted: 10/18/2020] [Indexed: 01/17/2023] Open
Abstract
Diabetes has been reported to modulate the airway smooth muscle reactivity and lead to attenuation of allergic inflammatory response in the lungs. In this study, we aimed to study the effect of insulin on cell activation and airway responsiveness in patients with diabetes mellitus (DM). The airway contraction in rat model groups including a non‐DM group, a non‐DM+INDUCTION group, a DM+INDUCTION group and a DM+INDUCTION+INSULIN group was measured to observe the effect of insulin on airway responsiveness. Radioenzymatic assay was conducted to measure the levels of histamine, and ELISA assay was conducted to measure bronchial levels of interleukin (IL)‐1b, tumour necrosis factor (TNF)‐a, cytokine‐induced neutrophil chemoattractant (CINC)‐1, P‐selectin and β‐hexosaminidase. The tension in the main and intrapulmonary bronchi of DM+INDUCTION rats was lower than that of the non‐DM+INDUCTION rats, whereas the treatment of insulin partly restored the normal airway responsiveness to OA in DM rats. The release of histamine was remarkably suppressed in DM+INDUCTION rats but was recovered by the insulin treatment. Also, OA significantly increased the levels of IL‐1b, TNF‐a, CINC‐1 and P‐selectin in non‐DM rats, whereas insulin treatment in DM+INDUCTION rats partly restored the normal levels of IL‐1b, TNF‐a, CINC‐1 and P‐selectin in DM rats. Moreover, the expression of IR and IGF1R was evidently suppressed in DM rats, with the methylation of both IR and IGF1R promoters was aggravated in DM rats. Therefore, we demonstrated that DM‐induced hypermethylation inhibited mast cell activation and airway responsiveness, which could be reversed by insulin treatment.
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Affiliation(s)
- Dan Fu
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, China
| | - Hailu Zhao
- Diabetic Systems Center, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin, China
| | - Liang He
- Department of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Huafeng Feng
- Department of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guilin, China
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Pite H, Aguiar L, Morello J, Monteiro EC, Alves AC, Bourbon M, Morais-Almeida M. Metabolic Dysfunction and Asthma: Current Perspectives. J Asthma Allergy 2020; 13:237-247. [PMID: 32801785 PMCID: PMC7394599 DOI: 10.2147/jaa.s208823] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 07/11/2020] [Indexed: 12/16/2022] Open
Abstract
The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed. The purpose of this review is to discuss current perspectives regarding metabolic dysfunction in asthma, from obesity-related asthma to other metabolic conditions and the role of current pharmacological therapeutic strategies and lifestyle interventions. Obesity is a well-recognized risk factor for asthma across the lifespan, which is generally associated with poorer response to current available treatments, rendering a more severe, refractory disease status. Besides the epidemiological and clinical link, untargeted metabolomics studies have recently supported the obesity-associated asthma phenotype at the molecular level. Not only obesity-related, but also other aspects of metabolic dysregulation can be independently linked to asthma. These include hyperinsulinemia, dyslipidemia and hypertension, which need to be taken into account, even in the non-obese patient. Untargeted metabolomics studies have further highlighted several other metabolic pathways that can be altered in asthma, namely regarding oxidative stress and systemic inflammation, and also suggesting the importance of microbiota in asthma pathogenesis. Considering the reduced response to corticosteroids, other pharmacologic treatments have been shown to be effective regardless of body mass index. Non-pharmacologic treatments (namely weight reduction and dietary changes) may bring substantial benefit to the asthmatic patient. Taken together, this evidence points towards the need to improve our knowledge in this filed and, in particular, to address the influence of environmental factors in metabolic dysfunction and asthma development. Personalized medicine is definitely needed to optimize treatment, including a holistic view of the asthmatic patient in order to set accurate pharmacologic therapy together with dietary, physical exercise and lifestyle interventions.
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Affiliation(s)
- Helena Pite
- Allergy Center, CUF Infante Santo Hospital/CUF Descobertas Hospital, Lisbon, Portugal.,CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Laura Aguiar
- Allergy Center, CUF Infante Santo Hospital/CUF Descobertas Hospital, Lisbon, Portugal
| | - Judit Morello
- CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Emília C Monteiro
- CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Ana Catarina Alves
- Department of Health Promotion and Chronic Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal.,Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisbon, Lisbon, Portugal
| | - Mafalda Bourbon
- Department of Health Promotion and Chronic Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal.,Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisbon, Lisbon, Portugal
| | - Mário Morais-Almeida
- Allergy Center, CUF Infante Santo Hospital/CUF Descobertas Hospital, Lisbon, Portugal
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Saifuddin A, Nasir UZ, Rengganis I, Shatri H. Risk factors for asthma exacerbation among Hajj pilgrims: a case study from DKI Jakarta, Indonesia. MEDICAL JOURNAL OF INDONESIA 2020. [DOI: 10.13181/mji.oa.204170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND Hajj pilgrims are prone to asthma exacerbation because of the high transmission rate of respiratory infections, severe environmental factors, and high-intensity activities during the Hajj. Well-controlled asthma status and preventive efforts prior to the Hajj could reduce such exacerbations. This research aimed to determine the risk factors of asthma exacerbation during the Hajj to help establish preventive measures.
METHODS Participants were evaluated at community health centers (puskesmas) through history taking, physical examination, and spirometry. The risk factors examined included a history of exacerbation one year before the Hajj, obesity, comorbidities (e.g., diabetes mellitus, hypertension, coronary heart disease), lung function, smoking, fitness level, and influenza vaccination. Asthma exacerbation while in Saudi Arabia was determined through direct observations by authors and physicians assigned to Hajj pilgrim groups and analysis of data obtained from questionnaires distributed to the pilgrims before their departure. Odds ratios (OR) were calculated using logistic regression.
RESULTS Among 68 pilgrims with asthma, exacerbation occurred in 27 (40%) pilgrims. Risk of asthma exacerbation was significantly increased in the pilgrims with a history of exacerbation one year before the Hajj (OR = 4.27; 95% confidence interval [CI] = 1.156–15.829; p = 0.029) and obesity grade II (OR = 4.02; 95% CI = 1.151–14.097; p = 0.029). Other factors, including smoking, comorbidities, lung function, fitness level, obesity grade I, and influenza vaccination, were not significantly related to exacerbation.
CONCLUSIONS Obesity grade II and history of asthma exacerbation one year before the Hajj are strong factors for asthma exacerbation during Hajj pilgrims.
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Karamzad N, Izadi N, Sanaie S, Ahmadian E, Eftekhari A, Sullman MJM, Safiri S. Asthma and metabolic syndrome: a comprehensive systematic review and meta-analysis of observational studies. J Cardiovasc Thorac Res 2020; 12:120-128. [PMID: 32626552 PMCID: PMC7321001 DOI: 10.34172/jcvtr.2020.20] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 04/12/2020] [Indexed: 12/19/2022] Open
Abstract
Introduction: This study aimed to perform a meta-analysis on the prevalence of metabolic syndrome (MetS) among patients with asthma and to measure the association asthma has with MetS.
Methods: The Web of Science, Medline, Scopus, Embase and Google Scholar were searched using the "Asthma", "Metabolic Syndrome", "Dysmetabolic Syndrome", "Cardiovascular Syndrome", "Insulin Resistance Syndrome", "Prevalence", "Odds Ratio", "Cross-Sectional Studies", and "Case-Control Studies" keywords. All observational studies reporting the prevalence of MetS among people with and without asthma were included in the study. In the presence of heterogeneity, random-effects models were used to pool the prevalence and odds ratios (OR), as measures of association in cross-sectional and case-control/ cohort studies, respectively. Results: The prevalence of MetS among patients with asthma (8 studies) and the OR comparing the prevalence of MetS among patients with and without asthma (5 studies) were pooled separately. The pooled prevalence of MetS among patients with asthma was found to be 25% (95% confidence interval (CI): 13%–38%). In contrast, the overall pooled OR for MetS in patients with asthma, compared to healthy controls, was 1.34 (95% CI: 0.91–1.76), which was not statistically significant. Conclusion: The prevalence of MetS was relatively high in patients with asthma. Furthermore, the odds of MetS was higher in patients with asthma, compared to healthy controls, although this difference was not statistically significant. More original studies among different populations are needed in order to more accurately examine the association between asthma and MetS, as well as the relationship asthma has with the individual components of MetS.
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Affiliation(s)
- Nahid Karamzad
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Izadi
- Student Research Committee, Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sarvin Sanaie
- Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Ahmadian
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Aziz Eftekhari
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Mark J M Sullman
- Department of Social Sciences, University of Nicosia, Nicosia, Cyprus.,Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
| | - Saeid Safiri
- Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Rahat Breath and Sleep Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Medeiros ML, de Oliveira MG, Tavares EG, Mello GC, Anhê GF, Mónica FZ, Antunes E. Long-term methylglyoxal intake aggravates murine Th2-mediated airway eosinophil infiltration. Int Immunopharmacol 2020; 81:106254. [PMID: 32007798 DOI: 10.1016/j.intimp.2020.106254] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 01/20/2020] [Accepted: 01/24/2020] [Indexed: 01/02/2023]
Abstract
Asthma outcomes is aggravated in obese patients. Excess of methylglyoxal (MGO) in obese/diabetic patients has been associated with diverse detrimental effects on cell function. This study aimed to evaluate the effects of long-term oral intake of MGO on ovalbumin-induced eosinophil inflammation. Male C57/Bl6 mice received 0.5% MGO in the drinking water for 12 weeks. Mice were sensitized and challenged with ovalbumin (OVA), and at 48 h thereafter, bronchoalveolar lavage (BAL) fluid and lungs were collected for cell counting, morphological analysis, and ELISA, mRNA expressions and DHE assays. In MGO-treated mice, OVA challenge significantly increased the peribronchiolar infiltrations of inflammatory cells and eosinophils compared with control group. Higher levels of IL-4, IL-5, and eotaxin in BAL fluid were also detected in MGO compared with control group. In addition, lung tissue of MGO-treated mice displayed significant increases in mRNA expressions of NF-κB and iNOS whereas COX-2 expression remained unchanged. The high TNF-α mRNA expression observed in lungs of OVA-challenged control mice was not further increased by MGO treatment. In MGO group, OVA-challenge increased significantly the NOX-2 and NOX-4 mRNA expressions, without affecting the NOX-1 expression. Levels of reactive-oxygen species (ROS) were significantly higher in lungs of MGO-treated mice, and no further increase by OVA-challenge was observed. In conclusion, 12-week intake of MGO exacerbates Th2-mediated airway eosinophil infiltration by activation of NF-kB/iNOS-dependent signaling pathway and positive regulation of NOX-2 and NOX-4 in the lung tissues. Scavengers of MGO could be an option to prevent obesity-related asthma.
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Affiliation(s)
- Matheus L Medeiros
- Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Mariana G de Oliveira
- Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Edith G Tavares
- Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Glaucia C Mello
- Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Gabriel F Anhê
- Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Fabiola Z Mónica
- Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Edson Antunes
- Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil.
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35
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Xu R, Gopireddy RR, Wu Y, Wu L, Tao X, Shao J, Wang W, Li L, Jovanovic A, Xu B, Kenyon NJ, Lu Q, Xiang YK, Fu Q. Hyperinsulinemia promotes heterologous desensitization of β 2 adrenergic receptor in airway smooth muscle in obesity. FASEB J 2020; 34:3996-4008. [PMID: 31960515 DOI: 10.1096/fj.201800688rr] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 12/08/2019] [Accepted: 12/30/2019] [Indexed: 01/05/2023]
Abstract
β-Adrenergic receptor (β-AR) agonists are the most common clinical bronchodilators for asthma. Obesity influences asthma severity and may impair response to β-AR agonists. Previous studies show that in obese mice, hyperinsulinemia plays a crucial role in β-AR desensitization in the heart. We therefore investigated whether insulin promotes β-AR desensitization in airway smooth muscle (ASM) and compromises airway relaxation responsiveness to β-AR agonists. We found that human ASM cells and mouse airway tissues exposed to insulin exhibit impaired β2 AR-induced cAMP accumulation and airway relaxation. This impaired relaxation is associated with insulin-induced phosphorylation and expression of phosphodiesterase 4D (PDE4D) through transactivation of a G protein-coupled receptor kinase 2 (GRK2)-dependent β2 AR-Gi -ERK1/2 cascade. Both acute and chronic pharmacological inhibition of PDE4 effectively reversed impaired β2 AR-mediated ASM relaxation in an obesity mouse model induced by a high fat diet. Collectively, these findings reveal that cross talk between insulin and β2 AR signaling promotes ASM β2 AR desensitization in obesity through upregulation of PDE4D phosphorylation and expression. Our results identify a novel pathway of asthma pathogenesis in patients with obesity/metabolic syndrome, in which the GRK2-mediated signaling can be a potential therapeutic modality to prevent or treat β2 AR desensitization in ASM. Moreover, PDE4 inhibitors may be used as efficacious therapeutic agents for asthma in obese and diabetic subjects.
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Affiliation(s)
- Rui Xu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China
| | | | - Yudi Wu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Wu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Tao
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ji Shao
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenxin Wang
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Li
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China
| | | | - Bing Xu
- Department of Pharmacology, University of California at Davis, Davis, CA, USA.,VA northern California Healthcare System, Mather, CA, USA
| | - Nicolas J Kenyon
- Department of Medicine, University of California at Davis, Davis, CA, USA
| | - Quan Lu
- Department of Environmental Health, School of Public Health, Harvard University, Boston, MA, USA
| | - Yang K Xiang
- Department of Pharmacology, University of California at Davis, Davis, CA, USA.,VA northern California Healthcare System, Mather, CA, USA
| | - Qin Fu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China
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Abstract
Diabetes mellitus is a chronic, progressive, incompletely understood metabolic disorder whose prevalence has been increasing steadily worldwide. Even though little attention has been paid to lung disorders in the context of diabetes, its prevalence has recently been challenged by newer studies of disease development. In this review, we summarize and discuss the role of diabetes mellitus involved in the progression of pulmonary diseases, with the main focus on pulmonary fibrosis, which represents a chronic and progressive disease with high mortality and limited therapeutic options.
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Affiliation(s)
- Saeed Kolahian
- Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), Eberhard Karls University Hospitals and Clinics, Tübingen, Germany.
- Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany.
- Department of Pharmacogenomics, University of Tübingen, Wilhelmstrasse. 56, D-72074, Tübingen, Germany.
| | - Veronika Leiss
- Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), Eberhard Karls University Hospitals and Clinics, Tübingen, Germany
| | - Bernd Nürnberg
- Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), Eberhard Karls University Hospitals and Clinics, Tübingen, Germany
- Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany
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Sánchez E, Gutiérrez-Carrasquilla L, Barbé F, Betriu À, López-Cano C, Gaeta AM, Purroy F, Pamplona R, Ortega M, Fernández E, Hernández C, Lecube A, Simó R. Lung function measurements in the prediabetes stage: data from the ILERVAS Project. Acta Diabetol 2019; 56:1005-1012. [PMID: 30989377 DOI: 10.1007/s00592-019-01333-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 03/25/2019] [Indexed: 12/31/2022]
Abstract
AIMS Patients with type 2 diabetes have been considered a susceptible group for pulmonary dysfunction. Our aim was to assess pulmonary function on the prediabetes stage. METHODS Pulmonary function was assessed in 4,459 non-diabetic subjects, aged between 45 and 70 years, without cardiovascular disease or chronic pulmonary obstructive disease from the ongoing study ILERVAS. A "restrictive spirometric pattern", an "abnormal FEV1" and an "obstructive ventilatory defect" were assessed. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association criteria. RESULTS Population was composed of 52.1% women, aged 57 [53;63] years, a BMI of 28.6 [25.8;31.8] kg/m2, and with a prevalence of prediabetes of 29.9% (n = 1392). Subjects with prediabetes had lower forced vital capacity (FVC: 93 [82;105] vs. 96 [84;106], p < 0.001) and lower forced expired volume in the first second (FEV1: 94 [82;107] vs. 96 [84;108], p = 0.011), as well as a higher percentage of the restrictive spirometric pattern (16.5% vs. 13.6%, p = 0.015) and FEV1 < 80% (20.3% vs. 17.2%, p = 0.017) compared to non-prediabetes group. In the prediabetes group, HbA1c was negatively correlated with both pulmonary parameters (FVC: r = - 0.113, p < 0.001; FEV1: r = - 0.079, p = 0.003). The multivariable logistic regression model in the whole population showed that there was a significant and independent association between HbA1c with both restrictive spirometric pattern [OR = 1.42 (1.10-1.83), p = 0.008] and FEV1 < 80% [OR = 1.50 (1.19-1.90), p = 0.001]. CONCLUSIONS The deleterious effect of type 2 diabetes on pulmonary function appears to be initiated in prediabetes, and it is related to metabolic control. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03228459.
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Affiliation(s)
- Enric Sánchez
- Endocrinology and Nutrition Department, Obesity, Diabetes and Metabolism (ODIM) Research Group, IRBLleida, University Hospital Arnau de Vilanova, University of Lleida, Avda. Rovira Roure 80. 25198, Lleida, Catalonia, Spain
| | - Liliana Gutiérrez-Carrasquilla
- Endocrinology and Nutrition Department, Obesity, Diabetes and Metabolism (ODIM) Research Group, IRBLleida, University Hospital Arnau de Vilanova, University of Lleida, Avda. Rovira Roure 80. 25198, Lleida, Catalonia, Spain
| | - Ferrán Barbé
- Respiratory Department, Translational Research in Respiratory Medicine, IRBLleida, University Hospital Arnau de Vilanova-Santa María, University of Lleida, Lleida, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Àngels Betriu
- Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA V&R), Vascular and Renal Translational Research Group. IRBLleida, University Hospital Arnau de Vilanova, University of Lleida, Lleida, Catalonia, Spain
| | - Carolina López-Cano
- Endocrinology and Nutrition Department, Obesity, Diabetes and Metabolism (ODIM) Research Group, IRBLleida, University Hospital Arnau de Vilanova, University of Lleida, Avda. Rovira Roure 80. 25198, Lleida, Catalonia, Spain
| | - Anna Michela Gaeta
- Respiratory Department, Translational Research in Respiratory Medicine, IRBLleida, University Hospital Arnau de Vilanova-Santa María, University of Lleida, Lleida, Catalonia, Spain
| | - Francesc Purroy
- Stroke Unit, Clinical Neurosciences Group, IRBLleida, University Hospital Arnau de Vilanova, University of Lleida, Lleida, Catalonia, Spain
| | - Reinald Pamplona
- Department of Experimental Medicine, IRBLleida, University of Lleida, Lleida, Catalonia, Spain
| | - Marta Ortega
- Primary Health Care Unit, Lleida, Catalonia, Spain
| | - Elvira Fernández
- Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA V&R), Vascular and Renal Translational Research Group. IRBLleida, University Hospital Arnau de Vilanova, University of Lleida, Lleida, Catalonia, Spain
| | - Cristina Hernández
- Endocrinology and Nutrition Department, Hospital Universitari Vall d'Hebron, Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Albert Lecube
- Endocrinology and Nutrition Department, Obesity, Diabetes and Metabolism (ODIM) Research Group, IRBLleida, University Hospital Arnau de Vilanova, University of Lleida, Avda. Rovira Roure 80. 25198, Lleida, Catalonia, Spain.
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - Rafael Simó
- Endocrinology and Nutrition Department, Hospital Universitari Vall d'Hebron, Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Metabolic Syndrome Biomarkers of World Trade Center Airway Hyperreactivity: A 16-Year Prospective Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16091486. [PMID: 31035527 PMCID: PMC6539892 DOI: 10.3390/ijerph16091486] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/16/2019] [Accepted: 04/18/2019] [Indexed: 12/28/2022]
Abstract
Airway hyperreactivity (AHR) related to environmental exposure is a significant public health risk worldwide. Similarly, metabolic syndrome (MetSyn), a risk factor for obstructive airway disease (OAD) and systemic inflammation, is a significant contributor to global adverse health. This prospective cohort study followed N = 7486 World Trade Center (WTC)-exposed male firefighters from 11 September 2001 (9/11) until 1 August 2017 and investigated N = 539 with newly developed AHR for clinical biomarkers of MetSyn and compared them to the non-AHR group. Male firefighters with normal lung function and no AHR pre-9/11 who had blood drawn from 9 September 2001–24 July 2002 were assessed. World Trade Center-Airway Hyperreactivity (WTC-AHR) was defined as either a positive bronchodilator response (BDR) or methacholine challenge test (MCT). The electronic medical record (EMR) was queried for their MetSyn characteristics (lipid profile, body mass index (BMI), glucose), and routine clinical biomarkers (such as complete blood counts). We modeled the association of MetSyn characteristics at the first post-9/11 exam with AHR. Those with AHR were significantly more likely to be older, have higher BMIs, have high intensity exposure, and have MetSyn. Smoking history was not associated with WTC-AHR. Those present on the morning of 9/11 had 224% increased risk of developing AHR, and those who arrived in the afternoon of 9/11 had a 75.9% increased risk. Having ≥3 MetSyn parameters increased the risk of WTC-AHR by 65.4%. Co-existing MetSyn and high WTC exposure are predictive of future AHR and suggest that systemic inflammation may be a contributor.
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Kytikova OY, Antonyuk MV, Gvozdenko TA, Novgorodtseva TР. Metabolic aspects of the relationship of asthma and obesity. OBESITY AND METABOLISM 2019. [DOI: 10.14341/omet9578] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Asthma and obesity are serious medical and social world problems, and their combined course is characterized by a decrease in the quality of life, an increase in the frequency and duration of hospitalization. The present review summarizes the current views on the mechanisms of formation of asthma phenotype combined with obesity, role of leptin and adiponectin imbalance in the development of systemic inflammation in obesity in the pathophysiology of asthma, its interrelations with metabolic syndrome. We present data that shows that syndrome is closely related not only to the debut of asthma, but also to a decrease in its control. Along with obesity, the role of other components of metabolic syndrome, in particular insulin resistance, as a predictor of asthma development is considered. Insulin resistance may be the most likely factor in the relationship between asthma and obesity, independent of other components of the metabolic syndrome. Insulin resistance associated with obesity can lead to disruption of nitric oxide synthesis. We reveal common mechanism of metabolic disorders of nitric oxide and arginine in metabolic syndrome and asthma and show that insulin resistance treatment can be therapeutically useful in patients with asthma in combination with obesity.
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40
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Khateeb J, Fuchs E, Khamaisi M. Diabetes and Lung Disease: A Neglected Relationship. Rev Diabet Stud 2019; 15:1-15. [PMID: 30489598 DOI: 10.1900/rds.2019.15.1] [Citation(s) in RCA: 117] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Diabetes mellitus is a systemic disorder associated with inflammation and oxidative stress which may target many organs such as the kidney, retina, and the vascular system. The pathophysiology, mechanisms, and consequences of diabetes on these organs have been studied widely. However, no work has been done on the concept of the lung as a target organ for diabetes and its implications for lung diseases. AIM In this review, we aimed to investigate the effects of diabetes and hypoglycemic agent on lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, pulmonary hypertension, and lung cancer. We also reviewed the potential mechanisms by which these effects may affect lung disease patients. RESULTS Our results suggest that diabetes can affect the severity and clinical course of several lung diseases. CONCLUSIONS Although the diabetes-lung association is epidemiologically and clinically well-established, especially in asthma, the underlying mechanism and pathophysiology are not been fully understood. Several mechanisms have been suggested, mainly associated with the pro-inflammatory and proliferative properties of diabetes, but also in relation to micro- and macrovascular effects of diabetes on the pulmonary vasculature. Also, hypoglycemic drugs may influence lung diseases in different ways. For example, metformin was considered a potential therapeutic agent in lung diseases, while insulin was shown to exacerbate lung diseases; this suggests that their effects extend beyond their hypoglycemic properties.
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Affiliation(s)
- Jasmin Khateeb
- Department of Internal Medicine D, Rambam Health Care Campus, Haifa, Israel
| | - Eyal Fuchs
- Pulmonary Division, Rambam Health Care Campus, Haifa, Israel
| | - Mogher Khamaisi
- Department of Internal Medicine D, Rambam Health Care Campus, Haifa, Israel
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Odessa National Medical University 2, Valikhovsky Lane, Odessa 65028, Ukraine, Bazhora YI, Romanchuk OP. Variability and Respiration Pattern of Patients with Persistent Asthma and Obesity. UKRAÏNSʹKIJ ŽURNAL MEDICINI, BÌOLOGÌÏ TA SPORTU 2018; 3:74-83. [DOI: 10.26693/jmbs03.07.074] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/01/2023]
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Song X, Li B, Wang H, Zou X, Gao R, Zhang W, Shu T, Zhao H, Liu B, Wang J. Asthma alleviates obesity in males through regulating metabolism and energy expenditure. Biochim Biophys Acta Mol Basis Dis 2018; 1865:350-359. [PMID: 30290274 DOI: 10.1016/j.bbadis.2018.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 09/06/2018] [Accepted: 10/01/2018] [Indexed: 01/31/2023]
Abstract
Many epidemiological studies suggested a correlation between obesity and asthma. However, little is known about the molecular details explaining this correlation. Here, we show that asthma decreased body weight of asthmatic male mice fed with high fat diet via increasing energy expenditure and insulin sensitivity. The increase of energy expenditure was mainly due to upregulation of pAMPK and Sirt1. The activation of AMPK/Sirt1/PGC1α signaling promoted the expression of the thermogenic genes like ucp1, PRDM16, cidea, Elovl3, PPARα, which occurred in brown adipocyte tissue and subcutaneous white adipose tissue. Besides, by activating IL33/ILC2/AAMac pathway in subcutaneous white adipose tissue, asthma promoted subcutaneous white adipose tissue into beige fat. In addition, insulin sensitivity was improved in the asthmatic male mice by decreasing the expression of G6Pase in the liver, which was recapitulated in HepG2. In human, we found that Body Mass Index (BMI) and waist circumference were significantly lower in males suffering asthma compared with the control in the National Health and Nutrition Examination Survey (NHANES) cohort. These data together suggest asthma in males decreases obesity by improving the metabolism function of brown and subcutaneous adipose tissue, and decreasing insulin resistant in the liver.
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Affiliation(s)
- Xiaomin Song
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Bolun Li
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Haoran Wang
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Xuan Zou
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Ran Gao
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Wei Zhang
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Ting Shu
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Hongmei Zhao
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China
| | - Bin Liu
- Department of Biochemistry and Biophysics, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA
| | - Jing Wang
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China.
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Kirenga BJ, Mugenyi L, de Jong C, Lucian Davis J, Katagira W, van der Molen T, Kamya MR, Boezen M. The impact of HIV on the prevalence of asthma in Uganda: a general population survey. Respir Res 2018; 19:184. [PMID: 30241519 PMCID: PMC6151019 DOI: 10.1186/s12931-018-0898-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 09/18/2018] [Indexed: 11/17/2022] Open
Abstract
Background HIV and asthma are highly prevalent diseases in Africa but few studies have assessed the impact of HIV on asthma prevalence in high HIV burden settings. The objective of this analysis was to compare the prevalence of asthma among persons living with HIV (PLHIV) and those without HIV participating in the Uganda National Asthma Survey (UNAS). Methods UNAS was a population-based survey of persons aged ≥12 years. Asthma was diagnosed based on either self-reported current wheeze concurrently or within the prior 12 months; physician diagnosis; or use of asthma medication. HIV was defined based on confidential self-report. We used Poisson regression with robust standard errors to estimate asthma prevalence and the prevalence ratio (PR) for HIV and asthma. Results Of 3416 participants, 2067 (60.5%) knew their HIV status and 103 (5.0%) were PLHIV. Asthma prevalence was 15.5% among PLHIV and 9.1% among those without HIV, PR 1.72, (95%CI 1.07–2.75, p = 0.025). HIV modified the association of asthma with the following factors, PLHIV vs. not PLHIV: tobacco smoking (12% vs. 8%, p = < 0.001), biomass use (11% vs. 7%, p = < 0.001), allergy (17% vs. 11%, p = < 0.001), family history of asthma (17% vs. 11%, p = < 0.001), and prior TB treatment (15% vs. 10%, p = < 0.001). Conclusion In Uganda the prevalence of asthma is higher in PLHIV than in those without HIV, and HIV interacts synergistically with other known asthma risk factors. Additional studies should explore the mechanisms underlying these associations. Clinicians should consider asthma as a possible diagnosis in PLHIV presenting with respiratory symptoms.
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Affiliation(s)
- Bruce J Kirenga
- Makerere University Lung Institute & Division of Pulmonary Medicine, Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
| | - Levicatus Mugenyi
- Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda
| | - Corina de Jong
- GRIAC-Primary Care, Department of General Practice and Elderly Care, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.,Groningen Research Institute for Asthma COPD (GRIAC), University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands
| | - J Lucian Davis
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, and Pulmonary, Critical Care, and Sleep Medicine Section, Yale School of Medicine, New Haven, CT, USA
| | - Winceslaus Katagira
- Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda
| | - Thys van der Molen
- GRIAC-Primary Care, Department of General Practice and Elderly Care, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.,Groningen Research Institute for Asthma COPD (GRIAC), University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands
| | - Moses R Kamya
- Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Marike Boezen
- Department of Epidemiology, University of Groningen, Groningen, The Netherlands
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44
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The Relationship Between Insulin Resistance and Pulmonary Functions in Morbidly Obese Patients. Bariatr Surg Pract Patient Care 2018. [DOI: 10.1089/bari.2017.0053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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The asthma-obesity relationship: underlying mechanisms and treatment implications. Curr Opin Pulm Med 2018; 24:42-49. [PMID: 29176481 DOI: 10.1097/mcp.0000000000000446] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE OF REVIEW Obesity is a worldwide epidemic with a prevalence that has tripled in the last two decades. Worldwide, more than 1.5 billion adults are overweight and more than 500 million obese. Obesity has been suggested to be a risk factor for the development of more difficult-to-control asthma. Although the mechanisms underlying the asthma-obesity relationship are not fully understood, several possible explanations have been put forward. These will be reviewed in this manuscript as well as the implications for the treatment of overweight and obese asthma patients. RECENT FINDINGS Insulin resistance is a possible factor contributing to the asthma-obesity relationship and the effect is independent of other components of the metabolic syndrome such as hypertriglyceridemia, hypertension, hyperglycemia, and systemic inflammation. Obesity has important effects on airway geometry, by especially reducing expiratory reserve volume causing obese asthmatics to breathe at low lung volumes. Furthermore, obesity affects the type of inflammation in asthma and is associated with reduced inhaled corticosteroids treatment responsiveness. SUMMARY Obesity induces the development of asthma with a difficult-to-control phenotype. Treatment targeting insulin resistance may be beneficial in obese asthma patients, especially when they have concomitant diabetes. Systemic corticosteroids should be avoided as much as possible as they are not very effective in obese asthma and associated with side-effects like diabetes, weight gain, and osteoporosis.
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Bseikri M, McCann JC, Lal A, Fong E, Graves K, Goldrich A, Block D, Gildengoren GL, Mietus-Snyder M, Shigenaga M, Suh J, Hardy K, Ames BN. A novel nutritional intervention improves lung function in overweight/obese adolescents with poorly controlled asthma: the Supplemental Nutrition in Asthma Control (SNAC) pilot study. FASEB J 2018; 32:fj201700338. [PMID: 30024788 DOI: 10.1096/fj.201700338] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Asthma in the obese is often severe, difficult to treat, and characterized by less eosinophilic inflammation than asthma in the nonobese. Obesity-associated metabolic dysregulation may be a causal factor. We previously reported that a nutrient- and fiber-dense bar [Children's Hospital Oakland Research Institute (CHORI)-bar], which was designed to fill gaps in poor diets, improved metabolism in healthy overweight/obese (OW/OB) adults. In this pilot trial, OW/OB adolescents with poorly controlled asthma were randomized to weekly nutrition/exercise classes with or without twice-daily CHORI-bar consumption. Intent-to-treat analysis did not indicate CHORI-bar-specific effects. However, restricting the analysis to participants with acceptable compliance and a relatively low fraction of exhaled nitric oxide (FENO; <50/ ppb, a surrogate for noneosinophilic asthma; study participants: CHORI-bar, n = 16; controls, n = 15) indicated that CHORI-bar-specific, significant improvements in lung function (forced vital capacity, percent-predicted forced expiratory volume in 1 s, and percent-predicted forced expiratory flow between 25 and 75% of forced vital capacity), primarily in participants with low chronic inflammation (high-sensitivity C-reactive protein <1.5 mg/L). (We previously observed that chronic inflammation blunted CHORI-bar-induced metabolic improvements in healthy OW/OB adults.) Lung function improvement occurred without weight loss and was independent of improvements in metabolic and anthropometric end points and questionnaire-based measures of asthma control and quality of life. This study suggests that a nutritional intervention can improve lung function in OW/OB adolescents with asthma and relatively low FENO without requiring major changes in dietary habits, lifestyle, or weight loss and that this effect is blunted by chronic inflammation.-Bseikri, M., McCann, J. C., Lal, A., Fong, E., Graves, K., Goldrich, A., Block, D., Gildengoren, G. L., Mietus-Snyder, M., Shigenaga, M., Suh, J., Hardy, K., Ames, B. N. A novel nutritional intervention improves lung function in overweight/obese adolescents with poorly controlled asthma: the Supplemental Nutrition in Asthma Control (SNAC) pilot study.
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Affiliation(s)
- Mustafa Bseikri
- University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland, Oakland, California, USA
| | - Joyce C McCann
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
| | - Ashutosh Lal
- University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland, Oakland, California, USA
| | - Edward Fong
- University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland, Oakland, California, USA
| | - Kirsten Graves
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
| | - Alisa Goldrich
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
| | - Devan Block
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
| | - Ginny L Gildengoren
- University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland, Oakland, California, USA
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
| | - Michele Mietus-Snyder
- University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland, Oakland, California, USA
- Children's National Medical Center, Washington, DC, USA
| | - Mark Shigenaga
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
| | - Jung Suh
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
| | - Karen Hardy
- University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland, Oakland, California, USA
| | - Bruce N Ames
- Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute (CHORI), Oakland, California, USA
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Park S, Choi NK, Kim S, Lee CH. The relationship between metabolic syndrome and asthma in the elderly. Sci Rep 2018; 8:9378. [PMID: 29925841 PMCID: PMC6010438 DOI: 10.1038/s41598-018-26621-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 05/10/2018] [Indexed: 01/28/2023] Open
Abstract
The burden of asthma in the elderly is increasing, but the etiology of asthma in the elderly is not clearly understood. Recent studies have reported the epidemiological link between metabolic syndrome (MS) and asthma, but it has rarely been studied in the elderly. This study investigated the association between MS and asthma and the contribution of insulin resistance (IR) and systemic inflammation to this MS-asthma association in the elderly. Our study analyzed 4,060 elderly participants (≥65 years old) from a cross-sectional survey, the Korean National Health and Nutritional Examination Survey 2007–2012. Mediation analyses were performed to examine whether IR and systemic inflammation mediates the MS-asthma association. Participants with MS had significantly higher prevalence of asthma (adjusted odds ratio = 1.34; 95% confidence interval = 1.09–1.64), and those who had greater waist circumference and lower HDL-C were especially likely to have asthma. Participants with IR and systemic inflammation were associated with higher prevalence of asthma. Prevalence of IR and systemic inflammation were higher in participants with MS or with each MS component. The MS-asthma association was substantially mediated by IR and systemic inflammation. Our study showed a significant association between MS and asthma in the elderly. MS might affect asthma through both IR and systemic inflammation.
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Affiliation(s)
- Sangshin Park
- Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States.,Department of Pediatrics, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States
| | - Nam-Kyong Choi
- Department of Health Convergence, Ewha Womans University, Seoul, Republic of Korea
| | - Seungsoo Kim
- Division of Allergy and Pulmonology, Department of Internal Medicine, Catholic University of Korea Daejeon St. Mary's Hospital, Daejeon, Republic of Korea
| | - Chang-Hoon Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
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48
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Perdue AD, Cottrell LA, Lilly CL, Gower WA, Ely BA, Foringer B, Wright ML, Neal WA. Pediatric metabolic outcome comparisons based on a spectrum of obesity and asthmatic symptoms. J Asthma 2018; 56:388-394. [PMID: 29676936 DOI: 10.1080/02770903.2018.1463377] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
RATIONALE Asthma and obesity are 2 of the most prevalent public health issues for children in the U.S. Trajectories of both have roughly paralleled one another over the past several decades causing many to explore their connection to one another and to other associated health issues such as diabetes and dyslipidemia. Earlier models have commonly designated obesity as the central hub of these associations; however, more recent models have argued connections between pediatric asthma and other obesity-related metabolic conditions regardless of children's obesity risk. OBJECTIVES To examine the relationships between asthma, obesity, and abnormal metabolic indices. METHODS We conducted a cross-sectional study of 179 children ages 7 to 12 years recruited from a rural, Appalachian region. Our model controlled for children's smoke exposure, body mass index percentile, and gender to examine the association between children's asthma (based on pulmonary function tests, medical history, medications, and parent report of severity), lipids (fasting lipid profile), and measures of altered glucose metabolism (glycosylated hemoglobin and homeostatic model assessment 2-insulin resistance). RESULTS Our findings revealed a statistically significant model for low density lipids, high density lipids, log triglyceride, and homeostatic model assessment 2-insulin resistance; however, Asthma had a significant effect for the mean triglycerides. We also found an asthma-obesity interaction effect on children's glycosylated hemoglobin with asthmatic obese children revealing significantly higher glycosylated hemoglobin values than non-asthmatic obese children. CONCLUSIONS Our findings support a connection between asthma and children's glycosylated hemoglobin values; however, this association remains entwined with obesity factors.
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Affiliation(s)
- Ashley D Perdue
- a Institute for Community and Rural Health , Morgantown , WV , USA
| | - Lesley A Cottrell
- b Department of Pediatrics , West Virginia University School of Medicine , Morgantown , WV , USA
| | - Christa L Lilly
- c Department of Biostatistics , West Virginia University School of Public Health , Morgantown , WV , USA
| | - William A Gower
- d Department of Pediatrics , Wake Forest School of Medicine , Winston-Salem , NC , USA
| | - Brian A Ely
- b Department of Pediatrics , West Virginia University School of Medicine , Morgantown , WV , USA
| | - Brad Foringer
- e Division of Respiratory Therapy , West Virginia Hospital Association , Morgantown , WV , USA
| | - Melvin L Wright
- b Department of Pediatrics , West Virginia University School of Medicine , Morgantown , WV , USA
| | - William A Neal
- b Department of Pediatrics , West Virginia University School of Medicine , Morgantown , WV , USA
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DeBoer MD, Phillips BR, Mauger DT, Zein J, Erzurum SC, Fitzpatrick AM, Gaston BM, Myers R, Ross KR, Chmiel J, Lee MJ, Fahy JV, Peters M, Ly NP, Wenzel SE, Fajt ML, Holguin F, Moore WC, Peters SP, Meyers D, Bleecker ER, Castro M, Coverstone AM, Bacharier LB, Jarjour NN, Sorkness RL, Ramratnam S, Irani AM, Israel E, Levy B, Phipatanakul W, Gaffin JM, Gerald Teague W. Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma. BMC Pulm Med 2018; 18:58. [PMID: 29631584 PMCID: PMC5891903 DOI: 10.1186/s12890-018-0612-x] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 03/09/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch. METHODS To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6-18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n = 68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression. RESULTS From pre-/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. By contrast females had lower post-BD FEV1% and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV1%, pre-BD FVC %, and negatively (improved) with ACQ6. Patients treated with high-dose inhaled corticosteroids had similar levels of circulating DHEA-S. In females, estradiol levels increased by Tanner stage, and associated negatively with pre-BD FEV1% and FVC %. CONCLUSIONS These results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma. Longitudinal data are necessary to confirm these cross-sectional findings and to further elucidate hormonal mechanisms informing sex differences in asthma features with puberty. TRIAL REGISTRATION ClinicalTrials.gov registration number: NCT01748175 .
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Affiliation(s)
- Mark D DeBoer
- University of Virginia School of Medicine, Charlottesville, VA, 22908, USA
| | | | - David T Mauger
- Pennsylvania State University School of Medicine, Hershey, USA
| | - Joe Zein
- Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, USA
| | - Serpil C Erzurum
- Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, USA
| | | | | | - Ross Myers
- Rainbow Babies and Children's Hospital, Cleveland, USA
| | | | - James Chmiel
- Rainbow Babies and Children's Hospital, Cleveland, USA
| | - Min Jie Lee
- Emory University School of Medicine, Atlanta, USA
| | - John V Fahy
- San Francisco School of Medicine, University of California, San Francisco, USA
| | - Michael Peters
- San Francisco School of Medicine, University of California, San Francisco, USA
| | - Ngoc P Ly
- San Francisco School of Medicine, University of California, San Francisco, USA
| | - Sally E Wenzel
- University of Pittsburgh School of Medicine, Pittsburgh, USA
| | - Merritt L Fajt
- University of Pittsburgh School of Medicine, Pittsburgh, USA
| | | | - Wendy C Moore
- Wake Forest University School of Medicine, Winston-Salem, USA
| | | | - Deborah Meyers
- Wake Forest University School of Medicine, Winston-Salem, USA
| | | | - Mario Castro
- Washington University School of Medicine, St. Louis, USA
| | | | | | | | | | - Sima Ramratnam
- University of Wisconsin School of Medicine, Madison, USA
| | - Anne-Marie Irani
- Virginia Commonwealth University School of Medicine, Richmond, USA
| | | | - Bruce Levy
- Harvard University School of Medicine, Boston, USA
| | | | | | - W Gerald Teague
- University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
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High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol. Sci Rep 2017; 7:17296. [PMID: 29229986 PMCID: PMC5725490 DOI: 10.1038/s41598-017-17558-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 11/28/2017] [Indexed: 12/14/2022] Open
Abstract
Insulin resistance plays an important role in obesity-associated asthma exacerbations. Using a murine model of allergic airway inflammation, we evaluated the insulin signaling transmission in lungs of obese compared with lean mice. We further evaluated the effects of the polyphenol resveratrol in the pulmonary insulin signaling. In lean mice, insulin stimulation significantly increased phosphorylations of AKT, insulin receptor substrate 1 (IRS-1) and insulin receptor β (IRβ) in lung tissue and isolated bronchi (p < 0.05), which were impaired in obese group. Instead, obese mice displayed increased tyrosine nitrations of AKT, IRβ and IRS-1 (p < 0.05). Two-week therapy of obese mice with resveratrol (100 mg/kg/day) restored insulin-stimulated AKT, IRS-1 and IRβ phosphorylations, and simultaneously blunted the tyrosine nitration of these proteins. Additionally, the c-Jun N-terminal kinase (JNK) and inhibitor of NF-κB Kinase (IκK) phosphorylations were significantly increased in obese group, an effect normalized by resveratrol. In separate experiments, the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (20 mg/kg/day, three weeks) mimicked the protective effects exerted by resveratrol in lungs of obese mice. Lungs of obese mice display nitrosative-associated impairment of insulin signaling, which is reversed by resveratrol. Polyphenols may be putative drugs to attenuate asthma exacerbations in obese individuals.
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