A pilot study measuring mixed venous carbon dioxide levels in students with and without a diagnosis of asthma
Introduction
Physiotherapists frequently use breathing control techniques to treat patients with symptoms of overbreathing, including asthma, chronic obstructive pulmonary disease and hyperventilation syndrome. Despite the frequency of their use, there is little published data on the physiological effects of breathing control techniques on the respiratory system. Physiotherapists use these techniques based on the hypothesis that they will result in a rise in patients’ carbon dioxide (CO2) levels [1], and that this will ‘desensitise’ patients to CO2 and hence reduce the sensation of breathlessness. This hypothesis suggests a belief that individuals with symptoms of hyperventilation are hypocapnic (have low CO2 levels) compared to the healthy population. During acute episodes of asthma, hyperventilation leading to hypocapnia is well documented [2], [3], [4], but only two studies have suggested that patients with asthma are hypocapnic when their asthma is stable [5], [6].
Animal studies have found that reduction in alveolar CO2 produces an increase in airway resistance by inducing bronchospasm and increasing the permeability of microvessels in the airway [7]. Although hypocapnia is a consistent finding in acute asthma, it is not certain whether it has any clinically relevant pathogenic role. Proponents of the Buteyko breathing technique [8] would suggest that this is the case. Also, in 1968 it was hypothesised in the New England Journal of Medicine [9] that hypocapnia during an asthma attack could perpetuate the bronchospasm and lead to a cycle of progressive hypocapnia and increasing bronchospasm. There is a body of experimental evidence that supports this hypothesis. There is in vitro animal evidence suggesting that low CO2 causes bronchoconstriction [7] while a high CO2 acts directly on the airway smooth muscle to cause bronchodilatation [10]. However, the mechanism for the bronchoconstriction is still uncertain and may relate to the degree of hypocapnia. Sterling [11] found that when end tidal CO2 was less than about 30 mmHg (4 kPa) the bronchoconstriction was mediated via the autonomic nervous system, through the vagus nerve, but that when end tidal CO2 was less than 15 mmHg (2 kPa) it was mediated by direct effect on the airway muscle.
There is also support for the association between hypocapnia and bronchoconstriction from experimental evidence from humans [5], [11], [12], [13], [14]. Elshout et al. [5] studied the effects of hypercapnia and hypocapnia on respiratory resistance in both normal and asthmatic subjects. They found that a reduction in end tidal CO2 of only 1 kPa caused an increase in resistance by 13% and a fall in reactance by 45%, while the same reduction in CO2 had no effect on healthy subjects. Conversely an increase in end tidal CO2 of only 1 kPa resulted in a significant fall in airway resistance in both asthmatic and normal subjects. Bayindir et al. [15] have reported on the adverse effects of hypocapnia during cardiopulmonary bypass, which led to an increase in airway resistance and a reduction in lung compliance.
Section snippets
Aim
The purpose of this pilot study was to trial an alternative methodology for the measurement of CO2 levels and to determine the likely values and variance using this technique. This data would then be used to assist in producing power calculations for a more definitive study to determine whether individuals with asthma have lower CO2 levels than healthy individuals. This study was presented at the World Confederation for Physical Therapy conference in 2003 [16] and is now reported more fully
Sample size
As this was a preliminary pilot study, power calculations were not appropriate to determine sample size and the aim was to recruit a convenience sample of 12 participants.
Recruitment
Participants were recruited via posters placed in student areas around the University of Southampton. Inclusion criteria were that all participants should be aged 18 or over, non-smokers, and asymptomatic from respiratory tract infections. Inclusion criteria for the asthma participants were that they considered themselves to
Results
Table 1 provides the descriptive data for the participants. On average, the healthy students were taller and heavier than those with asthma. In the students with asthma, percentage predicted FEV1 ranged from 84% to 112% (mean 98%) and mixed venous CO2 levels ranged from 5.08 to 5.71 kPa (mean 5.35 kPa). in the healthy students percentage predicted FEV1 ranged from 102% to 115% (mean 107%) and mixed venous CO2 levels ranged from 5.62 to 6.45 kPa (mean 6.01 kPa). The mean difference in mixed venous CO
Discussion
This preliminary pilot study has tested an indirect method for assessing arterial CO2 in individuals with a diagnosis of asthma. However, there was no formal determination of a diagnosis of asthma in the asthma group, or of good health in the control group. Participants’ own statements about their health status were accepted, which may have led to some participants being assigned to the ‘wrong’ group. However, there is no universally accepted objective test for the diagnosis of asthma [21], [22]
Conclusion
The gold standard measure for CO2 levels is arterial blood gas analysis, but mixed venous CO2 is an accepted alternative [19] that provides a reproducible and reliable indirect measurement of arterial CO2. This pilot study has demonstrated that a protocol using non invasive mixed venous CO2 measures is acceptable to people with asthma. It has also added to the evidence suggesting that asthmatic individuals have lower levels of CO2 than the healthy population, even when they are stable and
Acknowledgements
The authors are indebted to John Heath of the Pulmonary Function Laboratory, Southampton General Hospital for his assistance in the recording and analysing of the mixed venous carbon dioxide data.
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