Bogaert Debby, van der Valk Paul, Ramdin Reshmi, Sluijter Marcel, Monninkhof Evelyn, Hendrix Ron, de Groot Ronald, Hermans Peter W M
Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands.
Infect Immun. 2004 Feb;72(2):818-23. doi: 10.1128/IAI.72.2.818-823.2004.
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.
急性加重是慢性阻塞性肺疾病（COPD）常见的并发症。近期研究表明，肺炎链球菌等细菌在急性加重的发生发展中起一定作用。在本研究中，我们对COPD患者进行了以下调查：（i）肺炎球菌定植和感染的流行病学情况；（ii）肺炎球菌定植对急性加重发生的影响；（iii）针对肺炎链球菌的免疫反应。我们在COPD患者病情稳定期和急性加重期采集了269例患者的痰液进行培养，并通过血清分型对115株肺炎球菌分离株进行了鉴定。此外，我们还研究了这些患者针对七种结合疫苗血清型的血清免疫球蛋白G（IgG）抗体滴度、抗体亲和力和功能性抗体滴度。仅肺炎球菌定植（单一培养）会增加急性加重的风险，风险比为2.93（95%置信区间，1.41至6.07）。最常见的肺炎球菌血清型为19F、3、14、9L/N/V、23A/B和11型。我们计算出7价和11价肺炎球菌疫苗的理论覆盖率分别为60%和73%。所有患者均检测到针对七种结合疫苗血清型的IgG水平。这些抗体滴度显著低于接种疫苗的健康成年人。最后，在急性加重期，肺炎链球菌阳性痰液培养物中血清型特异性和功能性抗体平均升高了2.5倍。我们的数据表明，COPD患者的肺炎球菌定植常由疫苗血清型菌株引起。此外，肺炎球菌定植是COPD急性加重的危险因素。最后，我们的研究结果表明，COPD患者能够对肺炎球菌感染产生显著的免疫反应。因此，COPD患者可能从肺炎球菌疫苗接种中获益。
