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Ovalbumin – Induced Airway Inflammation Enhances Hypoxic Ventilatory Response In Rats
Author(s) -
Broytman Oleg,
Brinkman Jacqueline,
Pegelow David,
Morgan Barbara,
Teodorescu Mihaela
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.728.9
Subject(s) - formoterol , medicine , hypoxia (environmental) , plethysmograph , ovalbumin , anesthesia , ventilation (architecture) , hypoxic ventilatory response , intermittent hypoxia , airway , endocrinology , inhalation , immunology , respiratory system , obstructive sleep apnea , chemistry , budesonide , oxygen , immune system , mechanical engineering , organic chemistry , engineering
Rationale Patients with asthma have an increased risk of developing obstructive sleep apnea (OSA). However, the underlying mechanisms are unknown. Allergen‐induced airway inflammation may affect control of breathing through cytokine signaling in the chemoreceptors or through mechanoreceptor feedback from lungs. We tested the effects of allergen induced lower airway inflammation on the hypoxic ventilatory response. Methods Brown‐Norway rats (n=4–6/group) were sensitized to ovalbumin (OVA) or saline (SAL) via subcutaneous injection. All animals were challenged with nebulized 1% OVA solution. Ventilation under room air, moderate hypoxia (12% F i O 2 ) and severe hypoxia (9% FiO2) was measured by awake/behaving plethysmography 24 hours after OVA challenge. Ventilatory oxygen (V̇ E /V̇ O 2 ) and carbon dioxide (V̇ E /V̇ CO 2 ) equivalents were calculated. Measurements were repeated after 20 minutes exposure to nebulized formoterol. Negative Pressure Forced Expiration (NPFE) maneuvers, before and after formoterol, were performed on anesthetized animals, 48 hours after OVA challenge. Serum OVA‐specific IgE levels were measured using sandwich ELISA. Two‐way (± Repeated Measures) ANOVA was used to compare the groups. Results OVA‐sensitized animals had 1) elevated V̇ E /V̇ O 2 during moderate hypoxia (p=0.003); 2) significantly higher slope of V̇ E /V̇ O 2 response to moderate hypoxia (p=0.039), compared to SAL‐sensitized animals. These effects were augmented by formoterol. 3) After formoterol administration, OVA‐sensitized rats also mounted steeper V̇ E /V̇ CO 2 responses to both moderate and severe hypoxia (p=0.012 and p=0.016, respectively), compared to SAL‐sensitized controls. 4) Formoterol significantly increased forced expiratory volume (FEV 0.1 /FVC) during NPFE measurements (p=0.04). 5) OVA‐specific IgE levels were significantly elevated in sera of OVA‐sensitized animals (p=0.036). Conclusions Our results suggest increased chemoreceptor loop gain in animals with OVA‐induced lung inflammation, which may involve the carotid body. Data suggest asthma patients may be prone to hyperventilation in response to hypoxia, which could lead to hyperventilation‐induced apneas during sleep. These effects appear mediated in part via pathways independent of alterations in lung mechanics. Further studies will be needed to understand these pathways and how to intervene to attenuate them. Support or Funding Information Supported by University of Wisconsin Department of Medicine Pilot Funding.