Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation

Abstract

Ventilatory instability, reflected by enhanced acute hypoxic (AHVR) and hypercapnic (AHCVR) ventilatory responses is a fundamental component of obstructive sleep apnoea (OSA) pathogenesis. Intermittent hypoxia-induced inflammation is postulated to promote AHVR enhancement in OSA, although the role of inflammation in intermittent hypoxia-induced respiratory changes in humans has not been examined. Thus, this study assessed the role of inflammation in intermittent hypoxiainduced respiratory plasticity in healthy humans.In a double-blind, placebo-controlled, randomised crossover study design, 12 males were exposed to 6 h of intermittent hypoxia on three occasions. Prior to intermittent hypoxia exposures, participants ingested (for 4 days) either placebo or the nonsteroidal anti-inflammatory drugs indomethacin (nonselective cyclooxygenase (COX) inhibitor) and celecoxib (selective COX-2 inhibitor). Pre-and post-intermittent hypoxia resting ventilation, AHVR, AHCVR and serum concentration of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α were assessed.Pre-intermittent hypoxia resting ventilation, AHVR, AHCVR and TNF-α concentrations were similar across all three conditions ( p⩾0.093). Intermittent hypoxia increased resting ventilation and the AHVR similarly across all conditions ( p=0.827), while the AHCVR was increased ( p=0.003) and TNF-α was decreased ( p=0.006) with only selective COX-2 inhibition.These findings indicate that inflammation does not contribute to human intermittent hypoxia-induced respiratory plasticity. Moreover, selective COX-2 inhibition augmented the AHCVR following intermittent hypoxia exposure, suggesting that selective COX-2 inhibition could exacerbate OSA severity by increasing ventilatory instability. @ERSpublications Nonsteroidal anti-inflammatory drugs do not prevent intermittent hypoxia-induced respiratory plasticity in humans http://ow.ly/MDiCk

A comprehensive review of respiratory, autonomic and cardiovascular responses to intermittent hypoxia in humans

“…Obstructive sleep apnea is viewed as a low-grade chronic inflammatory disease and is found to be associated with inflammatory markers including interleukin-6 and tumor necrosis factor α ( Kheirandish-Gozal and Gozal, 2019 ). Beaudin et al, 2015 , in their randomized cross-over study assessed the effect of inflammation on intermittent hypoxia-induced respiratory plasticity. This group administered two non-steroidal anti-inflammatory drugs in twelve healthy volunteers for 4 days prior to acute intermittent hypoxia exposure.…”

“…This group administered two non-steroidal anti-inflammatory drugs in twelve healthy volunteers for 4 days prior to acute intermittent hypoxia exposure. The results showed that inflammation does not impact augmentation of minute ventilation following an acute intermittent hypoxia exposure in humans ( Beaudin et al, 2015 ). However, their model of healthy humans exposed to intermittent hypoxia that matches the oxygen desaturation profile of obstructive sleep apnea is not an entirely accurate representation of the clinical condition as increased negative intrathoracic pressure, modulating carbon dioxide levels and sleep fragmentation associated with obstructive apneas were absent ( Mateika, 2019 ).…”

Generation of active expiration by serotoninergic mechanisms of the ventral medulla of rats

“…Moreover, this 5-HT 2 dependent mechanism of the RTN/pFRG is engaged during IH and is essential for the development of long-term facilitation of expiratory motor activity. Accumulating clinical and experimental evidence indicates that IH is an important risk factor for the development of cardiorespiratory dysfunctions, including sympathetic-mediated arterial hypertension, respiratory dysfunctions, and chemoreflex hyperactivity (8,43,44,48,59,66). The maintenance of higher levels of sympathetic activity after the chronic exposure to IH has been associated with strengthened respiratory-sympathetic coupling consequent to the generation of active expiration (45,66).…”

Plasma Exosomes and Improvements in Endothelial Function by Angiotensin 2 Type 1 Receptor or Cyclooxygenase 2 Blockade following Intermittent Hypoxia

“…To maintain the double-blinded nature of the study, a P tablet was included in the CEL group as the second tablet. On experimental day of IH exposures, the dosage regimen was maintained through to the end of the exposure ( 12 ). A schematic diagram of the experimental design is shown in Figure 1 .…”