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

Abstract

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 colonization 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 pneumococci (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 frequently 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.Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in adults. According to the Global Burden of Disease Study, COPD is the fifth most common disease and fourth leading cause of death in the world. Both the prevalence and mortality rate are still expected to increase in the coming decades (11). The chronic course of this disease is frequently interrupted by acute exacerbation, which has a major impact on the morbidity and mortality of COPD patients (17). Acute exacerbation of COPD is characterized by an acute sustained worsening of the patient's condition from a stable state, beyond normal day-to-day variations, which occurs one to three times a year and may warrant additional treatment (3, 18). Bacterial infections are thought to contribute to the pathogenesis and clinical course of COPD (20). Several recent studies have shown a clear association between the isolation of bacterial species such as Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae and acute exacerbation (18). Patel et al. were the first investigators who observed a significant relation between lower ai...

Superior Immune Response to Protein-Conjugate versus Free Pneumococcal Polysaccharide Vaccine in Chronic Obstructive Pulmonary Disease

“…It is possible that protein-conjugate vaccines may elicit greater IgA antibody responses as compared with polysaccharide vaccines and this may augment the mucosal immune response and better protect against both colonization and exacerbation (26). Second, the serotypes contained within PCV7 account for only about one-third of pneumococcal isolates recovered from patients with COPD suffering an acute exacerbation (27). If the vaccine were to offer protection against cross-reactive serotypes (such as 23A/B and 9L/N) then this could be extended to about two-thirds of exacerbation-associated isolates but this would still be inferior to PPSV23, which theoretically protects against 90% of serotypes.…”

Prevention of Acute Exacerbations of COPD

“…46 Patients with COPD with persistent lowerairway bacterial colonization, those with Streptococcus pneumoniae in sputum, and those with newly acquired Streptococcus pneumonia have a signifi cantly increased risk of COPD exacerbation. 47 were noted in the time to fi rst exacerbation of COPD or in the number of exacerbations, cases of pneumonia, or hospitalizations, but the study was not powered to address these issues.…”

Determinants of Pneumococcal Vaccinationi among Patients with Chronic Obstructive Pulomonary Disease in Spain

“…18 Colonization of the respiratory tract by Streptococcus pneumoniae is frequently caused by serogroups included in 23-valent pneumococcal vaccine. 19 Different institutions such as the Centers for Disease Control and World Health Organization, recommend that this vaccine be administered to persons belonging to high-risk population groups (heart and bronchial disease sufferers, etc.) and all those over the age of 64 years.…”