To the Editors:
We read with interest the article by Wang et al. [1], which explored inflammatory phenotypes in adults and children with acute asthma. Their findings noted a striking paucity of Chlamydophyla pneumoniae organisms, even in patients with acute, neutrophilic asthma, and they concluded that: “The aetiology of neutrophilic asthma is unknown and is not explained by the presence of current active C. pneumoniae infection.” This is in direct contrast to recently published studies that used a similar cohort of patients [2]. A closer look at the results of the study by Wang et al. [1] revealed that while the authors used authentic quantitative PCR techniques to identify C. pneumoniae DNA, they utilised sputum samples for detection. It has been well established that C. pneumoniae resides primarily in the lower airway and is recovered much more reliably from bronchoalveolar lavage (BAL) fluid, as clearly demonstrated by Martin et al. [3].
Responding to a question about the future of PCR as a diagnostic tool for respiratory Chlamydia and Mycoplasma respiratory tract infection, M. Kraft, a co-author of the manuscript by Martin et al. [3] and an internationally recognised respiratory infectious disease expert, reiterated: “As demonstrated by the present study, PCR remains the only reliable way of demonstrating chronic infection. But PCR requires collecting relevant samples. The lower airway samples we need for diagnosis require invasive bronchoscopy” [4]. Indeed, viable C. pneumoniae have been successfully cultured from the BAL fluid of paediatric patients with chronic, severe asthma and the culture data correlated with the PCR (all culture-positive samples were also PCR-positive) [2]. Therefore, the absence of C. pneumoniae in the sputum samples used by Wang et al. [1] is not surprising. There is no question that under certain conditions of severe respiratory disease caused by C. pneumoniae the organism will be found in the sputum. However, in milder cases of acute infection, and in presumptive chronic infection, the chlamydial inclusions are most likely to be found in the macrophage or bronchial epithelial cells of the lower respiratory tract, making detection from induced sputum difficult and imprecise [3].
It may be that chronic, rather than acute, C. pneumoniae infection of only lung dendritic cells is a causative factor in asthma [5]. Schröder et al. [5] reported that adoptive transfer of dendritic cells from C. pneumoniae-infected mice was sufficient to induce an “asthmatic” phenotype in recipient animals. If this is found to be a relevant mechanism in human asthma, then direct microbiological diagnosis of C. pneumoniae by PCR, or by any method, will be even more difficult than has been anticipated, even by us. This, however, further strengthens the argument that asthma is a heterogeneous disease and this heterogeneity in inflammatory phenotype, as well as response to treatment, might be a direct result of the aetiology. While much work remains to be done in terms of deciphering the mechanisms underlying its involvement in the asthmatic process, the published data and ongoing work leave little doubt that C. pneumoniae plays an important role in asthma pathogenesis.
Footnotes
Statement of Interest
None declared.
- ©ERS 2011