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

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&#xa0;mg/mL) on a FlexiVent system (Scireq). Maximal (or plateau) responses (reactivity) for total respiratory system Resistance (R) and Elastance (E), Newtonian airway resistance (Ra 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 Rand Ecompared to all other groups (HDM/NORM, SAL/CIH and SAL/NORM p&#x2009;<&#x2009;0.05 for all comparisons, for doses 5-7 for R, and for doses 4-7 for E). The enhanced Rresponse was due to an increase in G (doses 4-7, p&#x2009;<&#x2009;0.05 for comparisons to all other groups), whereas Rwas 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.