Torchio Roberto, Gobbi Alessandro, Gulotta Carlo, Antonelli Andrea, Dellacà Raffaele, Pellegrino Giulia Michela, Pellegrino Riccardo, Brusasco Vito
Pneumologia-Fisiopatologia Respiratoria, Torino, Italy.
TechRes Lab, Dipartimento di Bioingegneria, Politecnico di Milano, Milano, Italy.
J Appl Physiol (1985). 2022 May 1;132(5):1137-1144. doi: 10.1152/japplphysiol.00763.2021. Epub 2022 Mar 31.
Inhaling carbon dioxide (CO) in humans is known to cause inconsistent effects on airway function. These could be due to direct effects of CO on airway smooth muscle or to changes in minute ventilation (V̇e). To address this issue, we examined the responses of the respiratory system to inhaled methacholine in healthy subjects and subjects with mild asthma while breathing air or gas mixtures containing 2% or 4% CO. Respiratory mechanics were measured by a forced oscillation technique at 5 Hz during tidal breathing. At baseline, respiratory resistance (R) was significantly higher in subjects with asthma (2.53 ± 0.38 cmHO·L·s) than healthy subjects (2.11 ± 0.42 cmHO·L·s) ( = 0.008) with room air. Similar values were observed with CO 2% or 4% in the two groups. V̇e, tidal volume (V), and breathing frequency (BF) significantly increased with CO-containing mixtures ( < 0.001) with insignificant differences between groups. After methacholine, the increase in R and the decrease in respiratory reactance (X) were significantly attenuated up to about 50% with CO-containing mixtures instead of room air in both asthmatic ( < 0.001) and controls ( < 0.001). Mediation analysis showed that the attenuation of methacholine-induced changes in respiratory mechanics by CO was due to the increase in V̇e ( = 0.006 for R and = 0.014 for X) independently of the increase in V or BF, rather than a direct effect of CO. These findings suggest that the increased stretching of airway smooth muscle by the CO-induced increase in V̇e is a mechanism through which hypercapnia can attenuate bronchoconstrictor responses in healthy subjects and subjects with mild asthma. The main results of the present study are as follows: ) breathing gas mixtures containing 2% or 4% CO significantly attenuated bronchoconstrictor responses to methacholine, not differently in healthy subjects and subjects with mild asthma, and ) the causal inhibitory effect of CO was significantly mediated via an indirect effect of the increment of V̇e in response to intrapulmonary hypercapnia.
已知人类吸入二氧化碳（CO）会对气道功能产生不一致的影响。这些影响可能是由于CO对气道平滑肌的直接作用，或者是由于分钟通气量（V̇e）的变化。为了解决这个问题，我们在健康受试者和轻度哮喘受试者呼吸空气或含有2%或4% CO的混合气体时，检测了呼吸系统对吸入乙酰甲胆碱的反应。在潮气呼吸期间，通过强迫振荡技术在5 Hz下测量呼吸力学。在基线时，哮喘受试者（2.53±0.38 cmH₂O·L⁻¹·s⁻¹）的呼吸阻力（R）显著高于健康受试者（2.11±0.42 cmH₂O·L⁻¹·s⁻¹）（P = 0.008），吸入室内空气时两组情况类似。两组吸入2%或4% CO时也观察到类似数值。V̇e、潮气量（V）和呼吸频率（BF）在吸入含CO混合气体时显著增加（P < 0.001），组间差异不显著。吸入乙酰甲胆碱后，在哮喘患者（P < 0.001）和对照组（P < 0.001）中，与吸入室内空气相比，含CO混合气体使R的增加和呼吸电抗（X）的降低显著减弱约50%。中介分析表明，CO对乙酰甲胆碱诱导的呼吸力学变化的减弱作用是由于V̇e的增加（R的P = 0.006，X的P = 0.014），独立于V或BF的增加，而不是CO的直接作用。这些发现表明，CO诱导的V̇e增加导致气道平滑肌拉伸增加，这是高碳酸血症减弱健康受试者和轻度哮喘受试者支气管收缩反应的一种机制。本研究的主要结果如下：1）吸入含有2%或...
