Effect of Regular Use of High-dose Nebulized β2-Agonists on Resting Energy Expenditure, Weight, and Handgrip Strength in Patients With Chronic Airflow Limitation: Outcome

Although there was a relatively large variation in the timing of the return study, there is no evidence that this affected the results as there was no relation between interval time and REE. One potential confounding factor is that, although it was the intention that nonstudy medication would not be changed, there were alterations in medication throughout the study period. Five of the patients in the nebulizer group were taking ipratropium bromide in addition to salbutamol at the time of the repeat study; however, this drug has been shown to have no effect on REE acutely. One patient discontinued theophylline therapy over the study period; again this drug has also been shown not to alter metabolic rate. In both groups, the variation in REE over time was very similar to the variation we have previously observed in four sets of six repeated measures, taken at weekly intervals, in patients with no change in medication (unpublished data).
Inhaled β2-agonists are known to raise Vo2 and Vco2 in the short term in normal subjects over 10 days, and Wilson et al, in addition, showed that tolerance develops to the acute metabolic effect of 800 (Jig of salbutamol administered via an MDI. Tolerance to β2-agonists differs according to the measured effect. For example, it develops to tachycardia but does not seem to develop to bronchodi-lation (although there is loss of a protective effect for various bronchoconstricting stimuli). Asthma inhalers other Sheidegger et al showed a rise in REE by 7.8% in fit young men after oral terbutaline for 2 weeks, but this study did not include a control group.
There are several possible mechanisms to explain the rise in Vo2 and Vco2 involving different sets of β2-receptors (increase in tremor, stimulus to ventilation, and increase in cardiac output and tissue perfusion), and they are not mutually exclusive. In addition, in patients with CAL, theoretically, these effects might be partially offset by a reduction in the work of breathing brought about by bronchodilation. The difference in results between the above studies may possibly be explained by the fact that stimulation of different sets of β2-receptors with different tolerance levels and dose responses is occurring. In addition, there were differences in the β2-agonist drug used, route of administration, and equivalent doses. In particular, it now seems important to study the effect of oral β2-agonists in a controlled trial in a patient group.