Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
Department of Physiology & Pharmacology and Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA.
J Physiol. 2023 Oct;601(19):4423-4440. doi: 10.1113/JP284767. Epub 2023 Aug 17.
The hypoxic ventilatory response (HVR) is the increase in breathing in response to reduced arterial oxygen pressure. Over several decades, studies have revealed substantial population-level differences in the magnitude of the HVR as well as significant inter-individual variation. In particular, low HVRs occur frequently in Andean high-altitude native populations. However, our group conducted hundreds of HVR measures over several years and commonly observed low responses in sea-level populations as well. As a result, we aimed to determine the normal HVR distribution, whether low responses were common, and to what extent variation in study protocols influence these findings. We conducted a comprehensive search of the literature and examined the distributions of HVR values across 78 studies that utilized step-down/steady-state or progressive hypoxia methods in untreated, healthy human subjects. Several studies included multiple datasets across different populations or experimental conditions. In the final analysis, 72 datasets reported mean HVR values and 60 datasets provided raw HVR datasets. Of the 60 datasets reporting raw HVR values, 35 (58.3%) were at least moderately positively skewed (skew > 0.5), and 21 (35%) were significantly positively skewed (skew > 1), indicating that lower HVR values are common. The skewness of HVR distributions does not appear to be an artifact of methodology or the unit with which the HVR is reported. Further analysis demonstrated that the use of step-down hypoxia versus progressive hypoxia methods did not have a significant impact on average HVR values, but that isocapnic protocols produced higher HVRs than poikilocapnic protocols. This work provides a reference for expected HVR values and illustrates substantial inter-individual variation in this key reflex. Finally, the prevalence of low HVRs in the general population provides insight into our understanding of blunted HVRs in high-altitude adapted groups. KEY POINTS: The hypoxic ventilatory response (HVR) plays a crucial role in determining an individual's predisposition to hypoxia-related pathologies. There is notable variability in HVR sensitivity across individuals as well as significant population-level differences. We report that the normal distribution of the HVR is positively skewed, with a significant prevalence of low HVR values amongst the general healthy population. We also find no significant impact of the experimental protocol used to induce hypoxia, although HVR is greater with isocapnic versus poikilocapnic methods. These results provide insight into the normal distribution of the HVR, which could be useful in clinical decisions of diseases related to hypoxaemia. Additionally, the low HVR values found within the general population provide insight into the genetic adaptations found in populations residing in high altitudes.
低氧通气反应（HVR）是指动脉血氧分压降低时呼吸的增加。几十年来，研究揭示了 HVR 幅度存在显著的人群水平差异，以及个体间的显著差异。特别是，在安第斯高海拔原住民人群中，低 HVR 很常见。然而，我们的团队在几年内进行了数百次 HVR 测量，通常也观察到海平面人群的反应较低。因此，我们旨在确定正常的 HVR 分布，低反应是否常见，以及研究方案的变化在多大程度上影响这些发现。我们进行了全面的文献检索，并检查了 78 项研究中使用逐步下降/稳态或渐进性低氧方法的 HVR 值分布，这些研究涉及未经治疗的健康人体受试者。一些研究包括不同人群或实验条件的多个数据集。在最后的分析中，72 个数据集报告了平均 HVR 值，60 个数据集提供了原始 HVR 数据集。在报告原始 HVR 值的 60 个数据集中，有 35 个（58.3%）至少中度正偏（偏度>0.5），21 个（35%）显著正偏（偏度>1），表明低 HVR 值很常见。HVR 分布的偏度似乎不是方法或 HVR 报告单位的人为产物。进一步的分析表明，使用逐步下降低氧与渐进性低氧方法对平均 HVR 值没有显著影响，但等张低氧方案产生的 HVR 高于变张低氧方案。这项工作为预期的 HVR 值提供了参考，并说明了该关键反射的个体间存在显著的变异性。最后，一般人群中低 HVR 的流行程度提供了对高海拔适应人群中 HVR 迟钝的理解。
低氧通气反应（HVR）在决定个体对与低氧相关的病理的易感性方面起着至关重要的作用。个体之间 HVR 敏感性存在显著差异，人群水平也存在显著差异。我们报告说，HVR 的正态分布是正偏的，在一般健康人群中，低 HVR 值的比例显著。我们还发现，用于诱导低氧的实验方案没有显著影响，尽管等张方法比变张方法的 HVR 更大。这些结果提供了对 HVR 正态分布的深入了解，这可能对与低氧血症相关疾病的临床决策有用。此外，在一般人群中发现的低 HVR 值提供了对高海拔地区人群中发现的遗传适应的深入了解。
