Dysbiotic Infections in Chronic Obstructive Pulmonary Disease

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PROJECT SUMMARY This project aims to use a physiologically relevant animal model to define determinants of bacterial persistence during opportunistic infections occurring in patients with chronic obstructive pulmonary disease. Haemophilus influenzae (Hi) is a common opportunistic pathogen in patients with COPD, and much evidence indicates that these infections might involve biofilms. We hypothesize that: i) biofilms are a determinant of Hi persistence in the lung during COPD-related infections, ii) bacterial infection with planktonic (non-biofilm) bacteria initiates inflammatory exacerbation and worsening of COPD disease, and iii) strains of Hi (and other bacterial opportunists) may differ in their capacity to initiate COPD exacerbations. In order to address these hypotheses, we will complete the following Specific Aims: Specific Aim 1. Define role(s) of biofilms in colonization/persistence of Hi within the lungs of smoke- exposed ferrets. Specific Aim 2. Test impact of bacterial infection in inflammatory exacerbation and severity of COPD pathophysiology. Significant gaps remain in our understanding of the means whereby bacteria persist during COPD disease, and the implications for these infections in the periodic changes in host responses that underlie exacerbations. The completion of the work outlined in this proposal will shed new light on chronic COPD-related bacterial infections and their implications for the management of this disease, which is among the leading public health problems worldwide.