Abstract
BackgroundChlamydia pneumoniae (Cp) is an obligate intracellular human respiratory pathogen producing persisting lung infection with a plausible link to asthma pathogenesis. The population attributable risk of potentially treatable Cp infection in asthma has not been reported.MethodsThe author searched from 2000 to 2020 inclusive for previously un-reviewed and new cross sectional and prospective controlled studies of Cp biomarkers and chronic asthma in both children and adults. Qualitative descriptive results and quantitative estimates of population attributable risk for selected biomarkers (specific IgG, IgA and IgE) are presented.FindingsNo large, long-term prospective population-based studies of Cp infection and asthma were identified. About half of case-control studies reported one or more significant associations of Cp biomarkers and chronic asthma. Heterogeneity of results by age group (pediatric v adult asthma), severity category (severe/uncontrolled, moderate/partly controlled, mild/controlled) and antibody isotype (specific IgG, IgA, IgE) were suggested by the qualitative results and confirmed by meta-analyses. The population attributable risks for Cp-specific IgG and IgA were nul in children and were 6% (95% confidence interval 2%-10%, p = 0.002) and 13% (9%-18%, p<0.00001) respectively in adults. In contrast to the nul or small population attributable risks for Cp-specific IgG and IgA, the population attributable risk for C. pneumoniae-specific IgE (children and adults combined) was 47% (39%-55%, p<0.00001). In the subset of studies that reported on asthma severity categories, Cp biomarkers were positively and significantly (P<0.00001) associated with asthma severity.InterpretationC. pneumoniae-specific IgE is strongly associated with asthma and asthma severity, suggesting a possible mechanism linking chronic Cp infection with asthma in a subset of individuals with asthma. Infection biomarkers should be included in future macrolide treatment trials for severe and uncontrolled asthma.
Highlights
Macrolides are included in the Global Initiative for Asthma (GINA) [1], European Respiratory Society/American Thoracic Society (ERS/ATS) [2], and British Thoracic Society (BTS) [3] guidelines as treatment options for severe asthma
Another positive study reported that Chlamydia pneumoniae (Cp) biomarker positivity was associated with non-atopic asthma [14]
This systematic review/meta-analysis focused on chronic asthma, not asthma exacerbations, and was undertaken to update observational studies published since 2005, the date of the last review [8] and, for the first time, to estimate the population attributable risk (PAR) of Cp biomarkers in chronic asthma
Summary
Macrolides are included in the Global Initiative for Asthma (GINA) [1], European Respiratory Society/American Thoracic Society (ERS/ATS) [2], and British Thoracic Society (BTS) [3] guidelines as treatment options for severe asthma. Two subsequent reviews on associations of Cp and asthma, published in 1999 [7] and 2005 [8], reported on a growing body of evidence linking Cp biomarkers and chronic airway obstructive illnesses (asthma, chronic bronchitis and chronic obstructive pulmonary disease–COPD). Both reviews reported positive associations of infection biomarkers with asthma and highlighted the urgent need for further research to inform treatment guidelines. Chlamydia pneumoniae (Cp) is an obligate intracellular human respiratory pathogen producing persisting lung infection with a plausible link to asthma pathogenesis.
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