Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review

Abstract

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. The precise role of bacterial infection in the course and pathogenesis of COPD has been a source of controversy for decades. Chronic bacterial colonization of the lower airways contributes to airway inflammation; more research is needed to test the hypothesis that this bacterial colonization accelerates the progressive decline in lung function seen in COPD (the vicious circle hypothesis). The course of COPD is characterized by intermittent exacerbations of the disease. Studies of samples obtained by bronchoscopy with the protected specimen brush, analysis of the human immune response with appropriate immunoassays, and antibiotic trials reveal that approximately half of exacerbations are caused by bacteria. Nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are the most common causes of exacerbations, while Chlamydia pneumoniae causes a small proportion. The role of Haemophilus parainfluenzae and gram-negative bacilli remains to be established. Recent progress in studies of the molecular mechanisms of pathogenesis of infection in the human respiratory tract and in vaccine development guided by such studies promises to lead to novel ways to treat and prevent bacterial infections in COPD.

FIG. 1

Culture results of bronchoscopic samples obtained from patients with stable COPD and those with acute exacerbation. The number of positive samples at both pathogen concentrations was significantly greater (P < 0.05) in the exacerbation group. Data taken from the work of Monso et al. (208). PSB, protected specimen brush; CFU/ml, CFU of pathogenic bacteria per milliliter of epithelial lining fluid.

FIG. 2

Diagrammatic representation of the vicious circle hypothesis.

FIG. 3

Immunoblot assay (left panel) and whole-cell radioimmunoprecipitation (RIP) assay (right panel) with preexacerbation serum (lanes A) and postexacerbation serum (lanes B) from an adult with COPD who experienced an exacerbation due to nontypeable H. influenzae. Assays were performed with the homologous infecting strain. The positions of molecular mass standards are noted (in kilodaltons) to the left of each panel. Note that immunoblot assays detect antibodies to many bands with minimal difference between pre- and postexacerbation sera. By contrast, whole-cell radioimmunoprecipitation assays with the same sera show the development of new antibodies to P2 (arrow) and higher-molecular-mass proteins following the exacerbation.