Why most smokers do not get COPD

Tobacco smoking and air pollution are considered the leading causes of chronic obstructive pulmonary disease (COPD). Despite this, the disease develops in only a few smokers. ILH and DZL scientists at the Giessen/Marburg and Großhansdorf sites have researched which mechanisms prevent non-susceptible smokers from developing COPD. They found that an enzyme in the cells of the alveoli provides protection. Their findings also point to a new treatment approach for the lung disease.

Free radicals cause stress

Cigarette smoking and environmental toxins induce free radicals. When the concentration of free radicals is increased, oxidative stress occurs. This is because there is an imbalance between the body's antioxidant defense system and the reactive particles. This stress can impair numerous cell functions.

The research team studied the antioxidant defense of the cells in a novel model in the laboratory, a cell line resistant to cigarette smoke, and on blood, sputum, and lung tissue samples from healthy people and people suffering from COPD. They analysed how much 3-nitrotyrosine (3-NT) is produced, which is a marker for oxidative stress. They also investigated the antioxidant capacity and which genes are active in the cell line.

Potential biomarker for COPD

They found that in the cells that line the inside of the alveoli, the so-called alveolar epithelial cells, the enzyme haem oxygenase 1 (HO-1) protects smokers from COPD. In addition, cell adhesion molecule 6 (CEACAM6) was shown to negatively regulate how much of the protective enzyme HO-1 is present in alveolar cells. When the concentration of the cell adhesion molecule CEACAM6 was increased, the cells were more sensitive to oxidative stress.

The research results suggest that CEACAM6 could be a potential biomarker for COPD. Targeting the CEACAM6/HO-1 axis could also provide a new therapeutic strategy for COPD patients.

Original publication: Wu CY, Cilic A, Pak O, et al. CEACAM6 as a Novel Therapeutic Target to Boost HO-1-mediated Antioxidant Defense in COPD [published online ahead of print, 2023 May 23]. Am J Respir Crit Care Med. 2023;10.1164/rccm.202208-1603OC. doi: 10.1164/rccm.202208-1603OC