Department of Orthopedics and Rehabilitation, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States.
Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States.
J Neurophysiol. 2024 Nov 1;132(5):1650-1666. doi: 10.1152/jn.00301.2023. Epub 2024 Oct 9.
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 (HVR) 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 hypoxic ventilatory response (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 O 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 versus SALINE. In OVA, serum interleukin-5 levels significantly correlated with change from baseline in ventilatory responses to severe hypoxia ([Formula: see text], 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. Asthma is a risk factor for obstructive sleep apnea (OSA); however, the mechanisms are incompletely understood. In a rat model of allergic inflammation associated with asthma, we found that ventilation in normoxia and ventilatory responses to hypoxia were markedly enhanced and related with systemic inflammation. These alterations indicating carotid chemoreflex sensitization, known to promote ventilatory instability during sleep in humans, may contribute to the increased OSA risk in asthma.
阻塞性睡眠呼吸暂停（OSA）在哮喘患者中非常普遍。哮喘会随着其持续时间的增加而促进 OSA 的发生，这表明哮喘在 OSA 的发病机制中起作用。我们假设哮喘相关的炎症改变了呼吸控制机制，特别是颈动脉化学感受器。因此，我们在清醒、不受约束的卵清蛋白（OVA）致敏的褐家鼠中测量了低氧通气反应（HVR），并将其与对照的假敏化（生理盐水）进行了比较。为了将过敏炎症与支气管收缩的作用区分开来，我们在长效支气管扩张剂福莫特罗给药后重复了低氧通气反应（HVR）。收集血液和支气管肺泡灌洗液（BAL）以定量炎性细胞因子。急性低氧暴露引起的 O 诱发的通气等效物的升高在 OVA 致敏后增强，而在 SALINE 后保持稳定。这种增加是由呼吸频率增加而潮气量不变引起的。在 OVA 中也观察到正常氧合时的呼吸急促性过度通气。福莫特罗既没有影响增加的 HVR 也没有影响过度的正常通气，这表明它们不是继发于肺机械限制。BAL 液和血清中的炎性细胞因子水平在 OVA 中高于 SALINE。在 OVA 中，血清白细胞介素-5 水平与严重低氧时通气反应的基线变化显著相关（[公式：见正文]，0.09）。这些观察结果与炎症诱导的颈动脉化学感受器功能增强一致，即控制器增益增加，并表明与哮喘相关的过敏炎症可能在已知促进上呼吸道塌陷和人类睡眠呼吸暂停的通气不稳定中起作用。哮喘是阻塞性睡眠呼吸暂停（OSA）的一个危险因素；然而，其机制尚不完全清楚。在与哮喘相关的过敏炎症的大鼠模型中，我们发现正常氧合时的通气和低氧通气反应明显增强，并与全身炎症有关。这些改变表明颈动脉化学感受器敏感，已知会在人类睡眠期间促进通气不稳定，可能会增加哮喘患者的 OSA 风险。
