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.
Chronic obstructive pulmonary disease (COPD) is among the most common and costly public health problems worldwide, and chronic and recurrent infections caused by Haemophilus influenzae and other opportunistic pathogens are an important problem in these patients. While much is known about how H. influenzae persists within biofilm communities in other clinical contexts, there is a general lack of reductionist experimentation on COPD related infections that is largely due to lack of suitable animal models that faithfully reproduce the pathophysiology of this disease. In this project we will use a chronic smoke exposure model with ferrets to ask how the H. influenzae bacteria persist in the COPD lung, and the implications of bacterial infection to the host response and respiratory function that are an important determinant of wellness in patients with COPD.
