Chronic intermittent hypoxia increases airway hyperresponsiveness during house dust mites exposures in rats

Abstract

Abstract Introduction Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested effects of Chronic Intermittent Hypoxia (CIH) – a hallmark of OSA – on airway hyperresponsiveness (AHR), in a rat model of chronic allergen-induced inflammation. Methods Brown Norway rats were exposed to six weeks of CIH or normoxia (NORM) concurrent with weekly house dust mites (HDM) or saline (SAL) challenges. At endpoint, we assessed responses to seven Methacholine (Mch) doses (0, 4, 8, 16, 32, 64, 128 mg/mL) on a FlexiVent system (Scireq). Maximal (or plateau) responses (reactivity) for total respiratory system Resistance (Rrs) and Elastance (Ers), Newtonian airway resistance (RN, a measure of central airways function) and tissue damping (G, a measure of distal airways function) were plotted. Results HDM/CIH–treated animals demonstrated the highest reactivity to Mch in Rrs and Ers compared to all other groups (HDM/NORM, SAL/CIH and SAL/NORM p < 0.05 for all comparisons, for doses 5–7 for Rrs, and for doses 4–7 for Ers). The enhanced Rrs response was due to an increase in G (doses 4–7, p < 0.05 for comparisons to all other groups), whereas RN was not affected by CIH. Conclusions In rats chronically challenged with HDM, concurrent CIH exposure induces AHR primarily in the distal airways, which affects the respiratory system frequency-dependent elastic properties.