ALTERED CONTROL OF BREATHING IN A RAT MODEL OF ALLERGIC LOWER AIRWAY INFLAMMATION.

Obstructive sleep apnea (OSA) is highly prevalent in patients with asthma. Asthma, dose-dependently to its duration, promotes incident OSA, suggesting that asthma plays a role in OSA pathogenesis. We hypothesized that asthma-related inflammation alters breathing control mechanisms, specifically the carotid chemoreflex. Accordingly, we measured hypoxic ventilatory responses (HRV) in awake, unrestrained, ovalbumin (OVA)-sensitized Brown Norway rats and compared them with responses in sham-sensitized (SALINE) controls. To differentiate the role of allergic inflammation from bronchoconstriction, we repeated HVR after administration of formoterol, a long-acting bronchodilator. Blood and bronchoalveolar lavage (BAL) fluid were collected for quantification of inflammatory cytokines. The rise in ventilatory equivalent for O₂ evoked by acute exposure to hypoxia was augmented following sensitization by OVA, whereas it remained stable after SALINE. This augmentation was driven by increased breathing frequency with no change in tidal volume. Tachypneic hyperventilation in normoxia was also observed with OVA. Neither the increased HVR nor excessive normoxic ventilation was affected by formoterol, suggesting that they were not secondary to lung mechanical constraints. Higher levels of inflammatory cytokines were observed in BAL fluid and serum of OVA vs. SALINE. In OVA, serum interleukin-5 correlated with change (baseline to post-sensitization) in ventilatory response to severe hypoxia (F_IO₂, 0.09). These observations are consistent with inflammation-induced enhancement of carotid chemoreflex function, i.e. increased controller gain, and they suggest a possible role for asthma-related allergic inflammation in the ventilatory instability known to promote upper airway collapse and sleep apnea in humans.