Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Hur, Gyu Young; Broide, David H.

Epidemiologic studies of decline in lung function over a 15-year period in asthmatics who smoked tobacco demonstrate that asthmatics who smoke tobacco have a greater decline in FEV1 compared to asthmatics who did not. 4 In addition, tobacco smoking affects asthma severity, airway inflammation, accelerated decrease in lung function and impaired responses to corticosteroid therapy. 73 Studies have also investigated airway wall thickness as a surrogate measure of airway remodeling in asthmatics who do not smoke compared to those who smoke tobacco and have an asthma-COPD overlap (ACO). 74 Multidetector chest computed tomography performed to measure airway wall thickness and airway inner luminal area revealed that patients with ACO had a thicker airway wall than those with asthma who did not smoke tobacco, suggesting that airway remodeling is more prominent in ACO than in asthma. 75 Therefore, tobacco smoking likely contributes to decline in lung function and to the development of airway remodeling in asthma. In addition to tobacco smoking affecting lung function and airway remodeling, it is possible that second-hand smoke, also called ETS, can influence remodeling and lung function in children with asthma whose parents smoke tobacco. Studies using a mouse model of allergen-induced airway remodeling showed that ETS alone did not induce airway remodeling, but chronic co-exposure to ETS and allergen significantly increased the level of airway remodeling compared to allergen alone. 76 If these studies were confirmed in human subjects, it would suggest that children with asthma who were co-exposed to mothers who smoked and to indoor allergens may have enhanced airway remodeling.