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The Microbiome and Airway Disease: Role in Pathogenesis, Presentation and Response to Treatment

Boushey HA, Huang YJ.

Respiratory Drug Delivery 2014. Volume 1, 2014: 1-14.

Abstract:

Our conceptions of the role of bacteria in human health and disease have been transformed by the development of sensitive, culture-independent methods for their detection. These methods, based on amplifying and sequencing genetic material unique to prokaryotes, have established that virtually every anatomical compartment in communication with the external environment (skin, upper airway, GI tract, vagina, etc.) is colonized by a complex bacterial community characteristic to that site. Whether a distinct bacterial community is actually present in the tracheo- bronchial tree of healthy subjects is uncertain, but it has been established that the bronchial airways of patients with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma are colonized by microbial communities distinct from those in the oropharynx or upper airways. It seems likely that pathologic bacteria present in airways mediate – or at least importantly contribute to – the pathological and clinical changes of CF and COPD. For asthma, however, it is unclear whether the activity of airway bacteria themselves mediate pathologic changes, whether they are simply associated with differences in the type, abundance, or activity of other, truly pathogenic microbes (fungi, viruses), or whether their presence reflects the differences in systemic or local immune function that actually mediate the disease. But even if differences in the composition or activity of the bronchial microbiome do not play a causal role in asthma’s pathogenesis, it still seems likely that they play a role in shaping its clinical pre- sentation, its course, its response to other pathogens (e.g., respiratory viruses), and its response to treatment (e.g., inhaled corticosteroids). These different possible relationships between the bronchial microbiome and respiratory disease are illustrated here through brief review of selected studies of CF, COPD, and chronic rhinosinusitis, and through a more detailed review of the relationships of bacterial communities to the development and progression of asthma. A further possible relationship is illustrated through review of the growing evidence that the composition of the gastrointestinal microbiome in early infancy shapes the development of both systemic and local immune function, and thus the predisposition to diseases of altered immune function; this has obvious relevance to the development of childhood asthma, for differences in systemic immune function appear to predispose to sensitization to allergens deposited on mucosal surfaces, and possibly also to less effective defense against microbial infection of the airways. Together, these differences in immune function may result in the inflammation underlying the structural and functional abnormalities of asthma. While this concept was largely derived from associations demonstrated in clinical epidemiologic studies, recent data from studies of a murine model system is also reviewed, for they may open the pathway to the development of new therapies for prevention and treatment based on the mechanisms of action of the microbial communities present in health and disease.