The lung microbiome and asthma pathogenesis

In this issue, Huang et al. (J Allergy Clin Immunol 2011;127: 372-381.e3), reporting on behalf of the NHLBI’s Asthma Clinical Research Network [ACRN], report first-ever research findings associating the composition of airway flora with clinical features of asthma. They postulate that the airway supports a complex community of bacteria that may contribute to clinical features of asthma among asthmatics taking inhaled corticosteroids (ICS). The researchers use a microarra-based method that detects distinct 16S rRNA gene sequences permitting detection and identification of bacterial taxa without previous knowledge of their presence in the relevant sample. Huang et al. report that using this tool, taxa in the phylum Proteobacteria were the most abundant in the cohort of patients studied.

The study occurred in parallel with a clinical trial examining the effects of long-term clarithromycin therapy in subjects with sub-optimal asthma control. Bronchial brushings were obtained from 65 asthma subjects and 10 healthy subjects. The authors find that airway colonization is variable in both healthy and asthmatic subjects, but that asthmatic subjects had significantly greater bacterial diversity than controls. Further, subjects in the clarithromycin treatment group with the highest bacterial diversity pre-treatment, had the greatest improvement in airway hyperresponsiveness following treatment.

Huang et al. comment that finding an airway microbiota in asthma patients on ICS therapy may not be surprising, but in fact, is also consistent with the notion that disturbances in epithelial/mucosal-associated microbiomes are known to be associated with disease as is the case with intestinal inflammatory diseases. They suggest that colonization by specific bacteria may contribute to persistence of inflammation, disease presentation, and/or disease heterogeneity; in particular, they cite the example of bacteria in the family Comamonadaceae, which are known to have steroid degrading capacity, as potentially contributory to steroid-resistant asthma pathology. Further, Huang et al. propose that the effectiveness of macrolide therapy on reducing airway reactivity may be a combined effect of their anti-inflammatory and antibacterial properties.

The authors state that discerning whether increased bacterial burden and diversity is a function of having asthma or being on ICS therapy is an important research question in light of the widespread use of ICS in many airway diseases. Concluding, Huang et al. comment that their findings open new research paths on disease mechanisms in asthma.

We asked senior author Dr. Susan Lynch, PhD, from the University of California - San Francisco, to tell us a little more about the study:

JACI: Your findings have far-reaching implications for airway disease and systems biology research. In your opinion, what are the proximate priorities?

Dr. Lynch: Establishment of cross-disciplinary, integrated research efforts to define microbiota structure, function and host interplay in well defined cohorts of patients. Openness to the possibility that this field of research may dramatically change our long-held perceptions of chronic inflammatory disease genesis and progression.

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