Chronic Obstructive Pulmonary Disease Pneumococcal Infection in Patients with Host-Pathogen Interaction during

Acute exacerbation is a frequent complication of chronic obstructive pulmonary disease (COPD). Recent studies suggested a role for bacteria such as Streptococcus pneumoniae in the development of acute exacerbation. For this study, we investigated the following in COPD patients: (i) the epidemiology of pneumococcal coloni- zation and infection, (ii) the effect of pneumococcal colonization on the development of exacerbation, and (iii) the immunological response against S. pneumoniae . We cultured sputa of 269 COPD patients during a stable state and during exacerbation of COPD and characterized 115 pneumococcal isolates by use of serotyping. Moreover, we studied serum immunoglobulin G (IgG) antibody titers, antibody avidities, and functional antibody titers against the seven conjugate vaccine serotypes in these patients. Colonization with only pneu- mococci (monocultures) increased the risk of exacerbation, with a hazard ratio of 2.93 (95% conﬁdence interval, 1.41 to 6.07). The most prevalent pneumococcal serotypes found were serotypes 19F, 3, 14, 9L/N/V, 23A/B, and 11. We calculated the theoretical coverage for the 7- and 11-valent pneumococcal vaccines to be 60 and 73%, respectively. All patients had detectable IgG levels against the seven conjugate vaccine serotypes. These antibody titers were signiﬁcantly lower than those in vaccinated healthy adults. Finally, on average, a 2.5-fold rise in serotype-speciﬁc and functional antibodies in S. pneumoniae -positive sputum cultures was observed during exacerbation. Our data indicate that pneumococcal colonization in COPD patients is fre- quently caused by vaccine serotype strains. Moreover, pneumococcal colonization is a risk factor for exacerbation of COPD. Finally, our ﬁndings demonstrate that COPD patients are able to mount a signiﬁcant immune response to pneumococcal infection. COPD patients may therefore beneﬁt from pneumococcal vaccination. , reader (SpectraMAX; Molecular Devices, Sunnyvale, Calif.). Results were expressed as avidity index (AI) values, assigned as the percentages of antibodies remained bound to the antigens after thiocyanate treatment. The high-avidity antibody concentration was calculated by multiplying the antibody concentration by the AI value. The reproducibility of the assay was checked by including a control serum in each plate. Data analysis. The results were analyzed with the statistical software SPSS 10. The effect of pneumococcal colonization on the time to the ﬁrst exacerbation episode was assessed by using multivariate Cox proportional hazard analyses. We adjusted for potential confounding variables, including age, sex, smoking status, number of exacerbation episodes in the preceding year, and FEV 1 % predicted, as found previously (P. van der Valk, D. Bogaert, E. Monninkhof, J. van der P. Hermans, G. Zielhuis, C. van Herwaarden, and R. Hendriks, submitted for publication). The initial concentrations of antibodies are as geo- metric mean concentrations (GMC). Avidities are as the means of the AI values and high-avidity antibody concentrations. Statistical comparisons between antibody levels were performed by analysis of and independent sample t tests. Statistical