Asthma and the Risk of Invasive Pneumococcal Disease: A Meta-Analysis

To assess the risk of invasive pneumococcal disease (IPD) or pneumonia among children with asthma following the administration of pneumococcal conjugate vaccine (PCV).

All case-controlled or cohort studies of IPD and pneumonia in populations who have received the PCV (predominantly 7-valent pneumococcal conjugate) that reported data on children with asthma and healthy controls.

Two independent reviewers examined the studies for the primary outcome of IPD and pneumonia. Secondary outcomes were mortality, hospitalizations, length of stay, ICU admission, respiratory assistance, expense, and further medication utilization.

There were only 3 retrospective cohorts and 1 case control study inclusive of 3294 children that met the criteria of the meta-analysis. Children with asthma had a 90% greater odds of IPD than healthy controls (odds ratio1.90; 95% CI, 1.63–2.11) and more frequent pneumonia, with health expenses for pneumonia enhanced with the severity of asthma. This increase in IPD occurred despite vaccination with PCV7, 10-valent pneumococcal conjugate and/or PCV13, but not 23-valent pneumococcal polysaccharide vaccine (PPSV23). PPSV23 is recommended by CDC and AAP only for children after age 2 years with asthma if they are on “prolonged high dose oral corticosteroids.” The meta-analysis was based on a small number of studies, so making clinical or policy recommendations difficult because of insufficiency of evidence.

Despite vaccination with PCV, children with asthma experienced a greater risk of IPD than children without asthma. Further investigation is needed to ascertain the benefit of a PPSV23 after regular PCV vaccination for children with asthma, regardless of systemic steroid use.

This meta-analysis study is limited by the small number and size of the included pooled study data. Furthermore, there is the limitation in the failure to determine the use of inhaled steroid asthma therapy. Inhaled and/or oral steroid therapy is itself associated with increased risk of pneumococcal pneumonia due to compromise of mucosal immune response superimposed on the impaired airway clearance of asthma. Finally, there is the failure of these pooled studies to address the influence of adherence to asthma therapy. Vulnerability to IPD and pneumonia in children with asthma could be due to poorly controlled asthma attributable to lack of adherence to or inappropriate or insufficient medications for optimal asthma control. Further studies of pneumococcal disease in children with well-controlled versus uncontrolled asthma signifying the use and adherence to medication can elucidate susceptibility to pneumococcal disease predicated on control of asthma and/or immune vulnerability related to pediatric asthma.