COPD and Gender

KBC: Bettina Levänen, Ernesto Silva , AnnSofi Sandberg
Divison of Respiratory Medicine: Magnus Sköld, Mikael Mikko, Magnus Löfdahl and Anders Eklund

Chronic Obstructive Pulmonary Disease (COPD) is a global health problem of pandemic proportion and a leading cause of morbidity and mortality worldwide. Recent epidemiological studies indicate significant gender differences in susceptibility, with post-menopausal women being at greatest risk. COPD is primarily an inflammatory disease of the peripheral airways, characterized by infiltration of macrophages and T lymphocytes. Besides smoking cessation, no efficacious treatments currently exist neither to prevent the inflammatory progression of COPD nor the progressive decline in lung function. The inflammation-induced tissue damage and subsequent remodelling invariably lead to impaired lung function and subsequent morbidity and mortality. Treatments with inhaled glucocorticoids, which are used to maintain most asthma patients, are largely ineffective in COPD patients. In macrophages from control subjects and healthy smokers, the release of inflammatory mediators is inhibited by corticosteroids, while corticosteroids remain inefficacious in macrophages of COPD patients.

The main objective of this project is to study gender differences critical for the pathophysiology of COPD, specifically by studying protein mediators from the lower airways. It is clear that multiple inflammatory mediators originating from several different inflammatory cell phenotypes are involved in the chronic inflammation and structural changes characteristic for COPD. However, the complex interplay between these inflammatory cells and their sequential appearance in the progression of the disease has not been elucidated. To this end, we are using proteomics profiling to identify protein mediators relevant for disease progression. Specifically, alterations in the proteomes of the individual inflammatory cell types involved in COPD as well as airway epithelial cells and airway exudates collected during fiberbronchoscopy of human volunteers are subject for investigation.The overall aim of these studies is to discover biomarkers of disease and susceptibility of COPD. Eventually, such biomarkers may result in improved techniques for early diagnosis of COPD, as well as novel pharmaceutical targets for the treatment of this debilitating disease. Most importantly, the findings from these studies will lead to the elucidation of gender-associated differences in the toxicological and pathological response to the major health hazard in our society, tobacco smoke, thus representing an important step towards personalized medicine.

Last updated: 2008-11-10