TY - JOUR T1 - <em>Haemophilus influenzae</em> persists in biofilm communities in a smoke-exposed ferret model of COPD JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00200-2020 VL - 6 IS - 3 SP - 00200-2020 AU - Benjamin C. Hunt AU - Denise Stanford AU - Xin Xu AU - Jindong Li AU - Amit Gaggar AU - Steven M. Rowe AU - S. Vamsee Raju AU - W. Edward Swords Y1 - 2020/07/01 UR - http://openres.ersjournals.com/content/6/3/00200-2020.abstract N2 - Rationale Non-typeable Haemophilus influenzae (NTHi) is a common inhabitant of the human nasopharynx and upper airways that can cause opportunistic infections of the airway mucosa including bronchopulmonary infections in patients with chronic obstructive pulmonary disease (COPD). It is clear that opportunistic infections contribute significantly to inflammatory exacerbations of COPD; however, there remains much to be learned regarding specific host and microbial determinants of persistence and/or clearance in this context.Methods In this study, we used a recently described ferret model for COPD, in which animals undergo chronic long-term exposure to cigarette smoke, to define host–pathogen interactions during COPD-related NTHi infections.Results NTHi bacteria colonised the lungs of smoke-exposed animals to a greater extent than controls, and elicited acute host inflammation and neutrophilic influx and activation, along with a significant increase in airway resistance and a decrease in inspiratory capacity consistent with inflammatory exacerbation; notably, these findings were not observed in air-exposed control animals. NTHi bacteria persisted within multicellular biofilm communities within the airway lumen, as evidenced by immunofluorescent detection of bacterial aggregates encased within a sialylated matrix as is typical of NTHi biofilms and differential bacterial gene expression consistent with the biofilm mode of growth.Conclusions Based on these results, we conclude that acute infection with NTHi initiates inflammatory exacerbation of COPD disease. The data also support the widely held hypothesis that NTHi bacteria persist within multicellular biofilm communities in the lungs of patients with COPD.Infection of smoke-exposed ferrets with COPD results in mucus obstruction and respiratory symptoms as in patients, and the bacteria are in a distinct mode of growth consistent with biofilms https://bit.ly/3euXpbQ ER -