How much do we know about the pathogenic mechanism?

Professor Atsushi Nagai
First Dept. of Medicine,
Tokyo Women's Medical University

Pathogenic mechanism of COPD found in the latest research studies

COPD is well known to be a disease associated with cigarette smoking and aging. Twenty percent of smokers develop COPD, and it is known that those who have the risk factors in the beginning develop COPD with age when external factors are added.

In asthma, airway constriction occurs by thickening of the basal membrane, and swelling of the submucosa and airway smooth muscle. But in COPD, inflammation causes fibrosis and thickening of the airway wall, and hyperplasia of submucosal glands. Airway constriction in asthma occurs by abnormal airway contraction, but in the case of COPD, it occurs by dilation failure in which the airway tries to dilate but cannot.

When we compare asthma and COPD, characteristic inflammatory cells are seen in patients in the stable phase, and prognosis is known to be poor if patients who originally had asthma develop COPD. In severe COPD, alveolar collapse, peripheral airway inflammation, and thickening of the airway smooth muscle occur in the lungs of the patient, and each adversely affects the airflow (Figure 1).

COPD used to be considered an idiopathic disease in which destruction of the alveoli is caused by inhalation of harmful substances such as cigarette smoke, which destroys protein. However, the recent understanding is that COPD is a state in which cells become vulnerable to apoptosis due to activity of proteolytic enzymes (Figure 2).

In an animal model of tobacco smoke exposure, 70% of the pathogenic mechanism of emphysema can be accounted for by a TNF-α mediated pathway. Emphysema lesions are considered to be formed with the death of alveolar cells that age prematurely due to smoke stimulation, leading to cell rupture and loss.

The pathogenic mechanism has been determined to a considerable extent. However, the important thing is that smoking cessation provides the complete solution. You must understand that the pathogenic mechanism of COPD is deeply associated with smoking.