Dataset Information

Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease.

ABSTRACT:

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 5years. 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 4months, 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 2years (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.

SUBMITTER: Li X

PROVIDER: S-EPMC5440622 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease.

Li Xuan X Obeidat Ma'en M Zhou Guohai G Leung Janice M JM Tashkin Donald D Wise Robert R Connett John J Joubert Philippe P Bossé Yohan Y van den Berge Maarten M Brandsma Corry-Anke CA Nickle David C DC Hao Ke K Paré Peter D PD Sin Don D DD

EBioMedicine 20170412

<h4>Introduction</h4>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 FEV<sub>1</sub> responses to ipratropium bromide.<h4>Methods</h4>Data from the Lung Health Study (n=5887; 37% females) were used to determine change ...[more]

PMID: 28461224

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Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with short-acting beta-2 agonists (SABA) and anticholinergic bronchodilator medications, and both are recommended in COPD guidelines. These medications have different mechanisms of action and therefore could have an additive effect when combined.ObjectivesTo compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and short- acting beta-2 agonist therapy in patients with stable COPD.Search strategyThe Cochrane Airways Group Specialised Register of Trials was searched. Bibliographies were checked to identify relevant cross-references. Drug companies were contacted for relevant trial data. The searches are current to August 2005.Selection criteriaAll randomised controlled trials comparing at least 4 weeks of treatment with an anticholinergic agent (ipratropium bromide) alone or in combination with a beta-2 agonist (short acting) versus the beta-2 agonist alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD.Data collection and analysisData extraction and study quality assessment was performed independently by three reviewers. Authors of studies and relevant manufacturers were contacted if data were missing.Main resultsEleven studies (3912 participants) met the inclusion criteria of the review. Small benefits of ipratropium over a short-acting beta-2 agonist were demonstrated on lung function outcomes. There were small benefits in favour of ipratropium on quality of life (HRQL), as well as a reduction in the requirement for oral steroids. Combination therapy with ipratropium plus a short-acting beta-2 agonist conferred benefits over a short-acting beta-2 agonist alone in terms of post-bronchodilator lung function. There was no significant benefit of combination therapy in subjective improvements in HRQL, but again there was a reduction in the requirement for oral steroids.Authors' conclusionsThe available data from the trials included in this review suggest that the advantage of regular long term use of ipratropium alone or in combination with a short-acting beta-2 agonist or over a beta-2 agonist alone are small, if the aim is to improve lung function, symptoms and exercise tolerance. Until further data are available, the strategy of providing a short-acting beta-2 agonist on a PRN basis, and then either continuing with the short-acting beta-2 agonist regularly or conducting an "n of 1" trial of regular beta-2 agonist or regular anticholinergic to determine the treatment that gives the best relief of symptoms (and continuing with it), would seem cost effective. This strategy does need formal evaluation. Patient preference is also important, as is the relative importance of avoiding the use of systemic corticosteroids.

Project description:BACKGROUND:Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. METHODS:Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. RESULTS:Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. CONCLUSION:This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota.

Dataset Information

Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease.

Introduction

Methods

Results

Conclusion

Publications

Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease.

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