Small airway hyperresponsiveness is associated with impaired alveolar development in a mouse model of bronchopulmonary dysplasia

Abstract

Introduction: Bronchopulmonary dysplasia (BPD) is a chronic disease associated with pre-term birth, with serious consequences including increased asthma risk. We hypothesised that reduced alveolar development in BPD could contribute to altered airway reactivity in the peripheral lung. Aim: To characterise alveolar changes and small airway contraction in a mouse model of BPD. Methods: Pregnant C57BL/6J dams received 150 μg/kg LPS or saline i.p. at 14 d gestation. Within 24h of birth, pups and dams were randomized to normoxic (N) or hyperoxic (H) conditions (FiO 2 0.21 or 0.65). At 28d, lungs were fixed and HE H 7.2±0.2, n=7), but increased maximum with hyperoxia (% reduction in lumen area: N 44±10; H 89±10; P Discussion: This study provides the first evidence that perinatal inflammation and hyperoxia induces airway hyperresponsiveness (AHR) that is sustained ex vivo . The increased maximum small airway contraction to MCh may be due to reduced tethering to surrounding parenchyma containing fewer but larger alveoli. This model will provide the setting for exploring other potential mechanisms contributing to altered airway reactivity as well as novel approaches to target the development and treatment of BPD-associated AHR.