Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease
Introduction: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there i...
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doaj-fceaef8a92cd47369e6167619ef049af2020-11-25T01:17:50ZengElsevierEBioMedicine2352-39642017-05-0119C13914510.1016/j.ebiom.2017.04.020Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary DiseaseXuan Li0Ma'en Obeidat1Guohai Zhou2Janice M. Leung3Donald Tashkin4Robert Wise5John Connett6Philippe Joubert7Yohan Bossé8Maarten van den Berge9Corry-Anke Brandsma10David C. Nickle11Ke Hao12Peter D. Paré13Don D. Sin14UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, CanadaUBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, CanadaUBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, CanadaUBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, CanadaDavid Geffen School of Medicine at UCLA, Los Angeles, CA, USAJohns Hopkins University School of Medicine, Baltimore, MD, USAUniversity of Minnesota School of Public Health, Minneapolis, MN, USAInstitut universitaire de cardiologie et de pneumologie de Québec, Québec, CanadaInstitut universitaire de cardiologie et de pneumologie de Québec, Québec, CanadaUniversity of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, The NetherlandsUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The NetherlandsMerck & Co Inc, Rahway, NJ, USADepartment of Genetics and Genomics Sciences, Mount Sinai School of Medicine, New York, NY, USA.UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, CanadaUBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, CanadaIntroduction: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there is any significant sex-related differences in FEV1 responses to ipratropium bromide. Methods: Data from the Lung Health Study (n = 5887; 37% females) were used to determine changes in FEV1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5 years. Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients. Results: After 4 months, ipratropium therapy increased FEV1 by 6.0% in female and 2.9% in male subjects from baseline values (p = 2.42 × 10−16). This effect was modified by body mass index (BMI) such that the biggest improvements in FEV1 with ipratropium were observed in thin female subjects (p for BMI ∗ sex interaction = 0.044). The sex-related changes in FEV1 related to ipratropium persisted for 2 years (p = 0.0134). Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p = 6.86 × 10−8). Conclusion: Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females. Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs. Female patients are thus more likely to benefit from ipratropium than male COPD patients.http://www.sciencedirect.com/science/article/pii/S2352396417301639SexFEV1IpratropiumCOPDGene expressionLung |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuan Li Ma'en Obeidat Guohai Zhou Janice M. Leung Donald Tashkin Robert Wise John Connett Philippe Joubert Yohan Bossé Maarten van den Berge Corry-Anke Brandsma David C. Nickle Ke Hao Peter D. Paré Don D. Sin |
spellingShingle |
Xuan Li Ma'en Obeidat Guohai Zhou Janice M. Leung Donald Tashkin Robert Wise John Connett Philippe Joubert Yohan Bossé Maarten van den Berge Corry-Anke Brandsma David C. Nickle Ke Hao Peter D. Paré Don D. Sin Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease EBioMedicine Sex FEV1 Ipratropium COPD Gene expression Lung |
author_facet |
Xuan Li Ma'en Obeidat Guohai Zhou Janice M. Leung Donald Tashkin Robert Wise John Connett Philippe Joubert Yohan Bossé Maarten van den Berge Corry-Anke Brandsma David C. Nickle Ke Hao Peter D. Paré Don D. Sin |
author_sort |
Xuan Li |
title |
Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease |
title_short |
Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease |
title_full |
Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease |
title_fullStr |
Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease |
title_full_unstemmed |
Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease |
title_sort |
responsiveness to ipratropium bromide in male and female patients with mild to moderate chronic obstructive pulmonary disease |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2017-05-01 |
description |
Introduction: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there is any significant sex-related differences in FEV1 responses to ipratropium bromide.
Methods: Data from the Lung Health Study (n = 5887; 37% females) were used to determine changes in FEV1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5 years. Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients.
Results: After 4 months, ipratropium therapy increased FEV1 by 6.0% in female and 2.9% in male subjects from baseline values (p = 2.42 × 10−16). This effect was modified by body mass index (BMI) such that the biggest improvements in FEV1 with ipratropium were observed in thin female subjects (p for BMI ∗ sex interaction = 0.044). The sex-related changes in FEV1 related to ipratropium persisted for 2 years (p = 0.0134). Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p = 6.86 × 10−8).
Conclusion: Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females. Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs. Female patients are thus more likely to benefit from ipratropium than male COPD patients. |
topic |
Sex FEV1 Ipratropium COPD Gene expression Lung |
url |
http://www.sciencedirect.com/science/article/pii/S2352396417301639 |
work_keys_str_mv |
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