C. pneumoniae and asthma
Asthma is a chronic inflammatory condition characterised by reversible narrowing of the bronchial airways. It is diagnosed by the response to bronchodilator drugs, the measurement of the forced expiratory volume in one second and the peak expiratory flow rate, both of which show reductions and a marked diurnal variation. The cause is unknown but asthma attacks can be precipitated by a number of factors including allergens, exertion, excitement, cold air and respiratory infections.
Wheezing is a symptom of asthma and as it is also a feature of C. pneumoniae infection, it was wondered whether the two were linked. The first report of an association was published in 1991 [Hahn et al., 1991]. In this study, 365 subjects presenting with respiratory illness had throat swab samples taken for C. pneumoniae culture and blood for paired serology. The organism was isolated from only one subject, but acute infection was diagnosed in 19 on the basis of serology. It was not reported whether these 19 patients were more or less likely to develop wheezing and asthma compared with other subjects. However, it was found that subjects with an IgG antibody titre of ≥ 64 were more likely to have a wheeze on presentation than subjects who had titres of < 64. In a subset analysis, 71 subjects with an IgG titre of ≥ 64 were compared with 71 matched controls with titres of < 16. A high proportion (29.6%) of high titre patients were diagnosed as having asthma in the subsequent 6 months compared with only 7% of low titre patients (odds ratio 7.2, 95% confidence interval 2.2 to 23.4). Unfortunately, it cannot be certain that these diagnoses were accurate because pulmonary function tests were not obtained. Moreover, rather than asthma, it is likely that some of these patients had post infective bronchial hyper-reactivity, a well known clinical syndrome which usually improves by 6 months.
One other longitudinal study followed up 198 subjects between the ages of 11 and 21. It was found that subjects with high IgG titres were significantly less likely to have asthma [Mills et al., 2000]. Unfortunately, results from cross sectional studies fail to clarify the situation. Studies are just as likely to report no association [Larsen et al., 1998; Hahn, Antilla & Saikku, 1996; Cook et al., 1998; Routes et al., 2000] as to support one [Bjornsson et al., 1996; Hahn et al., 2000; von Hertzen et al., 2000; Gencay et al., 2001].
Although it is controversial as to whether or not C. pneumoniae causes asthma, it seems reasonable to believe that, like other acute infections, it can precipitate asthmatic attacks. Studies have shown that between 9.5 to 45% of subjects presenting with acute asthma attacks demonstrate an increase in C. pneumoniae antibody titres [Allegra et al., 1994; Cunningham et al., 1998; Freymuth et al., 1999; Kamesaki et al., 1998]. Furthermore, some [Miyashita et al., 1998; Emre et al., 1994] but not all controlled studies [Cook et al., 1998] have shown that seroconversion or culture confirmed infection is more frequent in cases than controls.
[MEW update at March 2002: A Cochrane collaboration systemic review and meta-analysis concluded that there was insufficient evidence to determine whether macrolide therapy (with C. pneumoniae in mind) was beneficial in asthma [Richeldi et al., 2002]. Patient numbers were small and further studies were needed. A small study from Finland again found an association between elevated IgA antibody to C. pneumoniae in asthma, but no significant association with antibody to chlamydial heat shock protein. [Von et al., 2002.]]
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Mills, G. D., Lindeman, J. A., Fawcett, J. P., Herbison, G. P. & Sears, M. R. (2000). Chlamydia pneumoniae serological status is not associated with asthma in children or young adults. International Journal of Epidemiology 29, 280 - 284.
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Richeldi, L., Ferrara, G., Fabbri, L. M. & Gibson, P. G. (2002). Macrolides for chronic asthma (Cochrane Review). Cochrane Database Systematic Reviews (1):CD002997. Cochrane Abstract (html)
Routes, J. M., Nelson, H. S., Noda, J.A. & Simon, F. T. (2000). Lack of correlation between Chlamydia pneumoniae antibody titers and adult-onset asthma. Journal of Allergy and Clinical Immunology 105, 391 - 392.
Von, H. L., Vasankari, T., Liippo, K., Wahlstrom, E. & Puolakkainen, M. (2002). Chlamydia pneumoniae and severity of asthma. Scandinavian Journal of Infectious Diseases 34, 22 - 27.