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Published ahead of print on November 3, 2003, doi:10.1164/rccm.200308-1181OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 448-453, (2004)
© 2004 American Thoracic Society

Strain-specific Immune Response to Haemophilus influenzae in Chronic Obstructive Pulmonary Disease

Sanjay Sethi, Catherine Wrona, Brydon J. B. Grant and Timothy F. Murphy

Division of Pulmonary and Critical Care Medicine; Division of Infectious Diseases, Department of Medicine; Department of Microbiology, University at Buffalo SUNY; and the Veterans Affairs Western New York Healthcare System, Buffalo, New York

Correspondence and requests for reprints should be addressed to Sanjay Sethi, M.D., VA WNY Healthcare System (151), 3495 Bailey Avenue, Buffalo, NY 14215. E-mail: ssethi{at}buffalo.edu

Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations.

Key Words: chronic obstructive pulmonary disease • Haemophilus influenzae • humoral immunity • exacerbation




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