Chronic Intermittent Hypoxia Induces Airflow Limitation in a Rodent Model of Allergen‐Induced Lower Airway Inflammation

Abstract

RationaleObstructive sleep apnea (OSA) aggravates asthma, but the mechanisms are unclear. Chronic intermittent hypoxia (CIH) is one hallmark feature of OSA. We tested the effects of CIH on lower airways in an ovalbumin (OVA) rodent model.MethodsFour groups (n=5–6/group) of Brown‐Norway rats underwent CIH (10% FiO2, 30 episodes/h, 10h/day for 30 days) vs. normoxia (NORM) and OVA vs. vehicle (VEH). Lung physiology and bronchoalveolar lavage (BAL) WBC differentials were compared between groups, 2 days after last challenge.ResultsOn lung physiology: 1) CIH reduced the Forced Expiratory Volume in 0.1 second (FEV0.1) to Forced Vital Capacity (FVC) ratio (FEV0.1/FVC) (p=0.008) and peak expiratory flow (p=0.03); OVA did not affect these measures. 2) FVC was increased by CIH (p=0.0009), but reduced by OVA (p <0.0001). In the BAL: 1) CIH did not change total cell counts (p = 0.25); 2) CIH induced a 2.3‐fold reduction in % eosinophils (p = 0.001); 3) In OVA‐challenged rats, CIH increased neutrophil fraction among infiltrating granulocytes (p = 0.03, Figure).ConclusionsCIH induces airflow limitation even in the absence of inhaled allergen. CIH induces a more neutrophil‐predominant response to allergen. These findings highlight the potential of OSA to aggravate lung dysfunction in patients with pre‐existent airway inflammation.Supported by UW‐Madison Department of Medicine Pilot Funding.