br Funding Sources This study was

Funding Sources This study was supported by the European Research Council (ERC FP7 grant 233015), a Chair from Asthma UK (CH11SJ), MRC Centre grant G1000758, National Institute of Healthcare Research Biomedical Research Centre (NIHR BRC) grant P26095, Predicta FP7 Collaborative Project grant 260895 by NIHR BRCs at Imperial College London and King’s College London. Novartis Institute for Biomedical Research (Horsham, UK) funded the cytokine assays and development of bronchosorption by Hunt Developments (UK) Ltd, Midhurst, UK. SLJ is an NIHR Senior Investigator. The Funders did not have a role in study design, data collection, data analysis, interpretation, and writing of the report.
Conflicts of Interest
Author Contributions
Acknowledgements
Introduction Traditionally, owing to greater cigarette smoking in men, chronic obstructive pulmonary disease (COPD) has been considered a “male disease”. However, with the marked rise in the smoking rates in women since the 1960′s, there has been a sharp increase in the burden of COPD among women throughout much of the Western world. Today, in the United States (US), there are 7 million more women than men with COPD and 10,000 more women than men die from COPD each year. Currently, the mortality rate is nearly 10 fold higher in women than in men (3.7%/year in females and 0.4%/year in males) (Ma et al., 2015). Despite this, ironically, the current management strategies for COPD (in both men and women) are largely based on therapeutic clinical trials that droperidol have recruited mostly male patients. In most therapeutic trials (even contemporary ones), female patients make up only 20%–25% of the total cohort (Calverley et al., 2007; Magnussen et al., 2014). There are some compelling biological reasons why there may be significant sex-related differences in the therapeutic responsiveness of inhaled drugs in COPD. Firstly, there are emerging data that indicate for the same severity of COPD, as measured by lung function, female patients have less emphysema and more small airways disease (Dransfield et al., 2007; Cazzola et al., 2011). Secondly, female patients with COPD demonstrate greater levels of bronchial reactivity to non-specific stimuli such as methacholine compared with male patients for the same degree of airflow limitation (Tashkin et al., 1992). Thirdly, women may have heightened xenobiotic metabolism of chemicals including those related to cigarette smoke and medications, as well different gene or protein expression (compared to men) of known drug targets and transporters which may modify the effectiveness of therapeutic drugs (Benowitz et al., 2006). Despite these considerations, it is not known whether there is any significant sexual dimorphism in the way in which men and women respond to commonly inhaled drugs in COPD (Statista, n.d.; FirstWord Pharma, 2013). The principal aim of the present study was to determine whether there are any sex-related differences in bronchodilation related to the use of inhaled ipratropium, one of the most commonly prescribed muscarinic receptor antagonist in the world, in patients with COPD (Statista, n.d.; FirstWord Pharma, 2013).
Methods
Results
Discussion Despite the high burden of COPD in women, the current therapeutic strategies for COPD have been derived from clinical trials that have largely recruited male subjects (Vogelmeier et al., 2017). Using data from the Lung Health Study (LHS), which was made up of nearly 40% female subjects, we found that on average women experienced a larger bronchodilatory benefit of ipratropium compared with male subjects. Significantly, these effects were modified by BMI such that females in the lowest BMI categories experienced the largest benefits. At 4months of therapy, 44% of the female subjects demonstrated a significant improvement in FEV1 (defined by an increase of 140ml or more in their FEV1 from baseline) from ipratropium; whereas only 37% of the male patients met this threshold.