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

Li, Xuan; Obeidat, Ma’en; Zhou, Guohai; Leung, Janice M.; Tashkin, Donald P.; Wise, Robert A.; Connett, John E.; Joubert, Philippe; Bossé, Yohan; Berge, Maarten van den; Brandsma, C. A.; Nickle, David C.; Hao, Ke; Paré, Peter D.; Sin, Don D.

doi:10.1016/j.ebiom.2017.04.020

Cited by 29 publications

(32 citation statements)

References 35 publications

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“…In COPD patients, this effect might be localized to less affected parts. Clinical outcomes of ipratropium bromide in COPD are presented elsewhere [19]. Ipratropium bromide had little effect in newborn CF piglets indicating that initial CF disease is acting by a different mechanism than in COPD.…”

Section: Discussionmentioning

confidence: 99%

The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation

et al. 2018

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The beneficial effect of anti-cholinergic therapy for chronic obstructive pulmonary diseases like COPD is well-documented although cholinergic stimulation paradoxically inhibits liquid absorption, increases cilia beat frequency, and increases airway surface liquid transport. Using pig tracheobronchial explants, we quantified basal mucus transport as well as after incubation with by the clinically used anti-muscarinic compound ipratropium bromide (Atrovent) and stimulation with acetylcholine. As expected the surface liquid transport was increased by acetylcholine and carbachol. In contrast, the mucus bundles secreted from the submucosal glands normally transported on the cilia were stopped from moving by acetylcholine, an effect inhibited by ipratropium bromide. Interestingly, in pigs lacking a functional CFTR channel, the mucin bundles were almost immobile. As in wild-type pigs the cystic fibrosis (CF) surface liquid transport increased after carbachol stimulation. The stagnant CF mucin bundles were trapped on the tracheal surface attached to the surface goblet cells. Pseudomonas aeruginosa bacteria were moved by the mucus bundles in wild-type, but not CF pigs. Acetylcholine thus uncouples airway surface liquid transport from transport of the surface mucin bundles as the bundles are dynamically inhibited by acetylcholine and the CFTR channel, explaining initiation of CF and COPD and opening novel therapeutic windows.

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Section: Discussionmentioning

confidence: 99%

The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation

et al. 2018

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“… 23 In addition, the human lung transcriptome has been demonstrated to have both age and gender associations, suggesting that the genes contributing to lung health and disease during adulthood will vary across the life course. 24 Gender differences in the reporting, access, or response to available treatment modalities is also a possibility, 25 , 26 although more work is needed to better understand the underlying pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Although prior results have highlighted important sex and gender differences in men and women with COPD, the modeling of age by gender interactions across the fifth through eighth decades of life is a point of novelty and highlights the clinical imperative to more effectively and thoroughly recognize and manage respiratory symptoms in women. More research is needed to fully understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted management approaches 24 , 31 to improve outcomes across the life course for both men and women with COPD.…”

Section: Discussionmentioning

confidence: 99%

Women manifest more severe COPD symptoms across the life course

DeMeo

Ramagopalan

Kavati³

et al. 2018

COPD

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BackgroundPrevious studies suggest that gender differences exist in COPD diagnosis and symptoms; these differences may be more pronounced in younger adults. Our objective was to explore age-associated gender differences across a range of COPD severities.Materials and methodsA total of 4,484 current and former smokers with COPD from the Genetic Epidemiology of COPD cohort were investigated using regression modeling to explore the association between gender, age, disease severity, and the contributing elements of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (symptoms, exacerbation risk, airflow limitation).ResultsThe age–gender interaction was observed across multiple age categories. Compared to men with COPD, younger women with COPD had a greater likelihood of more severe dyspnea, airflow limitation, greater risk for exacerbations, and categorization in GOLD groups B and D. These differences were less pronounced in older women with COPD. However, older women remained more likely to experience severe dyspnea and to manifest more severe COPD (B vs A) than older men, despite lower pack-years of smoking.ConclusionThese data demonstrate the significant symptom burden of COPD in women, especially younger women. More research is needed to understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted clinical assessment and management approaches to improve outcomes for women and men with COPD at all ages.

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“…Multiple studies suggest that it is more difficult for women to quit smoking, but data from the Lung Health Study also suggest that smoking cessation results in greater lung function improvement for women (56). Additional data from the Lung Health Study also suggest greater FEV 1 response to inhaled ipratropium for women, possibly due to greater M3 relative to M2 receptor expression in women (57), and a pooled analysis of indacaterol/glycopyrronium studies reported greater quality-of-life improvements in women (58). Taken together, the compendium of evidence suggests that gender-specific approaches to COPD are imperative.…”

Section: Copdmentioning

confidence: 99%

Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease

Han

Arteaga‐Solis

Blenis³

et al. 2018

Am J Respir Crit Care Med

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Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women's Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions.

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

Cited by 29 publications

References 35 publications

The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation

The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation

Women manifest more severe COPD symptoms across the life course

Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease

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