Lori Grove

Pseudomonas aeruginosa in chronic obstructive pulmonary disease.

RATIONALE Pseudomonas aeruginosa is isolated from adults with chronic obstructive pulmonary disease (COPD) in cross-sectional studies. However, patterns of carriage and the role of P. aeruginosa in COPD are unknown. OBJECTIVES To elucidate carriage patterns, phenotypes of strains, clinical manifestations, and the antibody response to P. aeruginosa in COPD. METHODS A prospective study of adults with COPD was conducted. Isolates of P. aeruginosa were subjected to genotypic and phenotypic analysis. Sputum samples were studied for P. aeruginosa DNA, and immune responses were assayed. MEASUREMENTS AND MAIN RESULTS We analyzed longitudinal clinical data, sputum cultures, pulsed-field gel electrophoresis of bacterial DNA, polymerase chain reaction of sputum, and immunoblot assays of serum. Fifty-seven episodes of acquisition of strains of P. aeruginosa were observed in 39 of 126 patients over 10 years. Acquisition of a new strain was associated with exacerbation. Thirty-one episodes of carriage were followed by clearance of the strain; 16 were of short (<1 mo) duration. Thirteen strains demonstrated persistence, and 13 strains were of indeterminate duration. Six strains were mucoid and were more likely to persist than nonmucoid strains (P = 0.005). Antibody responses developed in 53.8% of persistent carriage and in only 9.7% of short-term carriage episodes (P = 0.003). Antibiotics did not account for clearance. CONCLUSIONS Two distinct patterns of carriage by P. aeruginosa were observed: (1) short-term colonization followed by clearance and (2) long-term persistence. Mucoid strains showed persistence. Acquisition of P. aeruginosa is associated with the occurrence of an exacerbation. Serum antibody responses do not mediate clearance of P. aeruginosa.

Impaired Phagocytosis of Nontypeable Haemophilus influenzae by Human Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

BACKGROUND Interactions of nontypeable Haemophilus influenzae (NTHI) with human alveolar macrophages are implicated in the persistence of NTHI in chronic obstructive pulmonary disease (COPD). However, the immunologic mechanisms that mediate NTHI-induced macrophage responses are poorly understood. We hypothesized that immunologic responses of alveolar macrophages to NTHI are impaired in COPD. METHODS Blood and alveolar macrophages--obtained from ex-smokers with COPD (n = 14), ex-smokers without COPD (n = 15), and nonsmokers (n = 9)--were incubated with 3 distinct NTHI strains obtained from patients with COPD. Phagocytosis of 3H-NTHI, expressed as a percentage of the mean total radioactivity, and of intracellular viability, assessed as a percentage of viable cell-associated NTHI, were measured. RESULTS Alveolar macrophages from donors with COPD, compared with those from donors without COPD, had impaired phagocytosis (median [interquartile range]) for each NTHI strain: 14P13H5, 0.26 (0.08-0.61) versus 1.36 (0.69-1.95); 6P5H1, 0.92 (0.32-1.82) versus 1.90 (1.32-2.68); and 14P14H1, 0.79 (0.23-1.32) versus 2.13 (1.13-2.40) (P < or = .01 for each). However, phagocytosis of all NTHI strains by blood macrophages from donors with COPD was indistinguishable from that of blood macrophages from donors without COPD and from nonsmokers. The intracellular killing of NTHI was not impaired in alveolar macrophages from donors with COPD. CONCLUSIONS These results support a paradigm of impaired phagocytosis by alveolar macrophages, but not blood macrophages, in COPD and provide an immunologic basis for persistence of NTHI in the airways of adults with COPD.