Subject specific effects of hyperpnea but not hypocapnia on airway conductance
Introduction
Airway constriction causes an increase in flow resistance and may lead to dyspnea. The influence of CO2 on airway tone in individuals with heightened airway sensitivity has been widely researched. However, the specific nature of CO2, in particular hypocapnia, on airway tone in normal subjects has been examined less vigorously. The effects of hypocapnia in normal individuals may be of importance during the hyperventilation preceding breath-holding activities, the hyperventilatory phase of high intensity exercise, during experimental procedures such as that performed at the initiation of the modified rebreathing technique and the hypocapnic hyperpnea associated with hypoxia.
Past investigations in normal subjects have implicated variations in CO2 tension as a factor influencing airway tone, with hypocapnia causing either an increase (Cutillo et al., 1974, Newhouse et al., 1964, Sterling, 1968) or no change in airway resistance (van den Elshout et al., 1991). However, most experiments are accompanied by varied degrees of hyperpnea with resistance or conductance only measured over the course of a few breaths, or using maximal expiratory flow maneuvers. Further, some data provide evidence of a ‘dose–response’ with respect to airway constriction during hypocapnia (McFadden et al., 1977, Sterling, 1968).
The aims of the present study were to determine whether a ‘dose–response’ exists in the degree of bronchoconstriction, causing increased airway resistance, in response to two levels of precisely controlled hypocapnia. We further sought to examine the time-course of any changes in mechanics after abrupt decreases in end-tidal CO2 by assessing airway mechanics on a breath-by-breath basis for a prolonged duration.
To achieve these goals, and to assess the effect of in the hypocapnic range on airway resistance in normal subjects, we used dynamic end-tidal gas forcing to separate the effects of hyperpnea and hypocapnia on airway resistance while controlling air temperature and humidity. The hypothesis was that hypocapnia would be associated with an increase in airway resistance that would be evident during moderate hypocapnia, and further augmented with more severe degree of hypocapnia.
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Subjects
Eight healthy volunteers (27 ± 5 yr; 1 female) with normal spirometry and no history of asthma participated after providing written informed consent. Subjects arrived at the lab having abstained from caffeine, alcohol and strenuous exercise for 12 h prior to testing. The study was approved by the Conjoint Health Research Ethics Board at the University of Calgary.
Protocol
Preliminary testing indicated that voluntary hyperventilation of approximately 50 L min−1 was necessary to drop end-tidal .
Results
Due to technical difficulties requiring the cessation of testing, data during the H-8 protocol were not obtained in one subject. However, due to randomization, all eight subjects completed the ISO and H-15 protocols. Mean data during baseline and hyperpnea, across all three protocols, are shown in Table 1.
Subjects exhibited typical GL values preceding each protocol, (0.250 ± 0.052, 0.247 ± 0.068, and 0.240 ± 0.062 L min−1 cm H2O−1 preceding ISO, H-8 and H-15 respectively). was also typical of
Discussion
We assessed the separate effects of hypocapnia and hyperpnea on pulmonary conductance in normal healthy participants. Contrary to expectation, we found no significant effect of hypocapnic hyperpnea on pulmonary conductance. However, each individual subject exhibited consistent changes in GL in response to hyperpnea across all conditions with the heterogeneity of the direction and magnitude of changes between subjects explained by the significant inverse relationship to baseline GL.
Acknowledgements
This project was supported by a Private Donor Grant, the Alberta Heritage Foundation for Medical Research (AHFMR), and the Canada Foundation for Innovation. M.J. Poulin is an AHFMR Senior Medical Scholar.
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Cited by (1)
Rebuttal by Richard J. A. Wilson and Trevor A. Day
2013, Journal of Physiology