New concepts in the pathobiology of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal persistent inflammatory response to cigarette smoke. This noxious insult leads to emphysema and airway remodeling, manifested by squamous and mucous metaplasia of the epithelium, smooth muscle hypertrophy, and airway wall fibrosis. These pathologic abnormalities interact synergistically to cause progressive airflow obstruction. Although it has been accepted that the spectrum of COPD is vast, the reasons for the development of different phenotypes from the same exposure to cigarette smoke have not been determined. Furthermore, it is becoming increasingly clear that airways disease and emphysema often coexist in many patients, even with a clear clinical phenotype of either emphysema or chronic bronchitis. Recent studies have focused on the nature of the inflammatory response to cigarette smoke, the inflammatory cell lines responsible for COPD pathogenesis, and new biomarkers for disease activity and progression. New cytokines are being discovered, and the complex interactions among them are being unraveled. The inflammatory biomarker that has received the most attention is C-reactive protein, but new ones that have caught our attention are interleukin (IL)-6, tumor necrosis factor-alpha, IL-8, and IL-10. Further research should focus on how these new concepts in lung inflammation interact to cause the various aspects of COPD pathology.

Figure 1.

Examples of airway remodeling in COPD. A represents mucous metaplasia (MM) of the epithelium and smooth muscle hypertrophy (SM). B represents peribronchial fibrosis (black arrow). C shows squamous metaplasia. D shows an inflammatory infiltrate of lymphocytes in the adventitia of a bronchiole.

Figure 2.

Periodic Acid Fluorescent Schiff stain of a small airway from a patient with advanced emphysema. The entire airway is seen at ×10 magnification in A and a quadrant of the airway at ×40 in B. Mucin granules are shown in red along the apical border of the epithelium. Note the large intralumenal mucin plug (M) in A, also noted in B (white arrow).

Figure 3.

Mechanisms of airflow obstruction in COPD. (A) Emphysema causes loss of alveolar attachments to the airway wall, predisposing it to expiratory collapse. (B) Small airway remodeling, as evidenced by epithelial thickening (E), smooth muscle hypertrophy (SM), and chronic airway inflammation (I), causes encroachment on the lumen, increased airway tone, reduced effectiveness of bronchodilators, and airway hyperresponsiveness.