Microbiology

Nontypeable Haemophilus influenzae colonizes the respiratory tract of patients with COPD, often presenting with a pattern in which periods of negative sputum cultures are preceded and followed by isolation of apparently identical strains. To investigate whether the strains preceding and following episodes of negative cultures were indeed the same, Murphy and colleagues performed molecular typing on isolates of H. influenzae collected monthly in a prospective study. During a 7-year study involving 104 patients, they detected 122 episodes of negative cultures lasting 1 month or more, which were preceded and followed by isolation of an apparently identical strain of H. influenzae. Seventeen such episodes of negative cultures, lasting 6 months or more, were studied in detail to test the hypothesis that these periods of negative cultures represented continuous colonization by the same strain of H. influenzae. Molecular typing by three independent methods established that the strains preceding and following the episodes of negative cultures were indeed identical. Strain-specific H. influenzae DNA was detected in some of the sputum samples that had yielded negative cultures. These results show that some patients with COPD are persistently colonized with H. influenzae, and that sputum cultures underestimate the frequency of colonization of the respiratory tract by H. influenzae. The study also suggests that chronic bacterial colonization may significantly contribute to airway inflammation and to the course and pathogenesis of COPD.

To test the hypothesis that the immune response to the homologous (infecting) strain of H. influenzae may have limited ability to kill other (heterologous) H. influenzae strains, and thus that it may protect against recurrent exacerbations caused by homologous strains, Sethi and coworkers collected sputum and serum samples in 81 patients with COPD monthly and during exacerbations. They found that, after exacerbation, an immune response to homologous H. influenzae occurs in 61% of cases with newly acquired strains as compared with 21% of cases with preexisting strains (odds ratio 4.4; confidence interval 95%, 1.8–10.8; p = 0.001). New bactericidal antibodies developed after COPD exacerbations were highly strain-specific, showing bactericidal activity for only 12% of heterologous strains. These results suggest that, after an exacerbation of COPD associated with H. influenzae strain, serum antibodies to the infecting strain develop in the majority of cases with newly acquired but homologous strains, and that the immune response to the homologous strain may not protect against infectious exacerbations by heterologous strains of H. influenzae. These observations further support the role of H. influenzae in a large proportion of COPD exacerbations and, by showing the limited immune response to heterologous strains of H. influenzae, may explain the mechanism of recurrent exacerbations with H. influenzae in COPD. In fact, although patients produce strain-specific antibodies to homologous strains of H. influenzae after exacerbations, the immune response leaves the host susceptible to reinfections by other heterologous strains of H. influenzae.

To determine whether Pneumocystis colonization is associated with COPD and its severity, Morris and colleagues conducted a cross-sectional analysis using nested polymerase chain reaction, and examined Pneumocystis colonization rates in surgical lung biopsies from 68 smokers with a wide range of pulmonary function. Pneumocystis colonization was detected in 37% of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stage IV) as compared with 5% of smokers with normal lung function or less severe COPD (Stages 0 to III; p = 0.004) and with 9% of control subjects (p = 0.007). Subjects with Pneumocystis colonization showed more severe airway obstruction than Subjects without colonized Pneumocystis (median FEV₁, 21 vs. 62% predicted, p = 0.006). Patients with very severe COPD (GOLD IV) were the strongest predictor of Pneumocystis colonization (odds ratio 7.3, 95% confidence interval, 2.4–22.4; p < 0.001), independent of smoking history. The authors concluded that there is a strong association between Pneumocystis colonization and severity of airflow obstruction in smokers, suggesting a possible pathogenic link with COPD progression.

Citations 1-3 of 3 total displayed.

Association of Chronic Obstructive Pulmonary Disease Severity and Pneumocystis Colonization

Alison Morris, Frank C. Sciurba, Irina P. Lebedeva, Andrew Githaiga, W. Mark Elliott, James C. Hogg, Laurence Huang, and Karen A. Norris
Am. J. Respir. Crit. Care Med. 170: 408 -413. First published online as doi:10.1164/rccm.200401-094OC [Abstract] [Full text]

Persistent Colonization by Haemophilus influenzae in Chronic Obstructive Pulmonary Disease

Timothy F. Murphy, Aimee L. Brauer, Andrew T. Schiffmacher, and Sanjay Sethi
Am. J. Respir. Crit. Care Med. 170: 266 -272. First published online as doi:10.1164/rccm.200403-354OC [Abstract] [Full text]

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

Sanjay Sethi, Catherine Wrona, Brydon J. B. Grant, and Timothy F. Murphy
Am. J. Respir. Crit. Care Med. 169: 448 -453. First published online as doi:10.1164/rccm.200308-1181OC [Abstract] [Full text]

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