| Autor: |
Torchio R; Pneumologia-Fisiopatologia Respiratoria, Torino, Italy., Gobbi A; TechRes Lab, Dipartimento di Bioingegneria, Politecnico di Milano, Milano, Italy.; Restech Srl, Milano, Italy., Gulotta C; Pneumologia-Fisiopatologia Respiratoria, Torino, Italy., Antonelli A; Allergologia e Fisiopatologia Respiratoria, Cuneo, Italy., Dellacà R; TechRes Lab, Dipartimento di Bioingegneria, Politecnico di Milano, Milano, Italy., Pellegrino GM; Respiratory Unit, ASST Santi Paolo e Carlo, Dipartimento Scienze della Salute, Università degli Studi di Milano, Milan, Italy.; Casa di Cura del Policlinico, Dipartimento di Scienze Neuroriabilitative, Milano, Italy., Pellegrino R; Centro Medico Pneumologico Torino, Torino, Italy., Brusasco V; Centro Polifunzionale di Scienze Motorie, Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy. |
| Abstrakt: |
Inhaling carbon dioxide (CO 2 ) in humans is known to cause inconsistent effects on airway function. These could be due to direct effects of CO 2 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 2 . Respiratory mechanics were measured by a forced oscillation technique at 5 Hz during tidal breathing. At baseline, respiratory resistance (R 5 ) was significantly higher in subjects with asthma (2.53 ± 0.38 cmH 2 O·L -1 ·s) than healthy subjects (2.11 ± 0.42 cmH 2 O·L -1 ·s) ( P = 0.008) with room air. Similar values were observed with CO 2 2% or 4% in the two groups. V̇e, tidal volume (V T ), and breathing frequency (BF) significantly increased with CO 2 -containing mixtures ( P < 0.001) with insignificant differences between groups. After methacholine, the increase in R 5 and the decrease in respiratory reactance (X 5 ) were significantly attenuated up to about 50% with CO 2 -containing mixtures instead of room air in both asthmatic ( P < 0.001) and controls ( P < 0.001). Mediation analysis showed that the attenuation of methacholine-induced changes in respiratory mechanics by CO 2 was due to the increase in V̇e ( P = 0.006 for R 5 and P = 0.014 for X 5 ) independently of the increase in V T or BF, rather than a direct effect of CO 2 . These findings suggest that the increased stretching of airway smooth muscle by the CO 2 -induced increase in V̇e is a mechanism through which hypercapnia can attenuate bronchoconstrictor responses in healthy subjects and subjects with mild asthma. NEW & NOTEWORTHY The main results of the present study are as follows: 1 ) breathing gas mixtures containing 2% or 4% CO 2 significantly attenuated bronchoconstrictor responses to methacholine, not differently in healthy subjects and subjects with mild asthma, and 2 ) the causal inhibitory effect of CO 2 was significantly mediated via an indirect effect of the increment of V̇e in response to intrapulmonary hypercapnia. |
