Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine

In healthy individuals, a DI can reverse (bronchodilation) or prevent (bronchoprotection) induced airway constriction. For individuals with asthma or COPD, these effects may be attenuated or absent. Previous work showed that the size and duration of a DI affected the subsequent response of the airways. Also, increased airway tone lead to increased airway size variability. The present study examined how a DI affected the temporal variability in individual airway baseline size and after methacholine challenge in dogs using High-Resolution Computed Tomography. Dogs were anesthetized and ventilated, and on 4 separate days, HRCT scans were acquired before and after a DI at baseline and during a continuous intravenous infusion of methacholine (Mch) at 3 dose rates (17, 67, and 200 µg/min). The Coefficient of Variation was used as an index of temporal variability in airway size.

We found that at baseline and the lowest dose of Mch, variability decreased immediately and 5 minutes after the DI (P < 0.0001). In contrast, with higher doses of Mch, the DI caused a variable response. At a rate of 67 µg/min of Mch, the temporal variability increased after 5 minutes, while at a rate of 200 µg/min of Mch, the temporal variability increased immediately after the DI. Increased airway temporal variability has been shown to be associated with asthma. Although the mechanisms underlying this temporal variability are poorly understood, the beneficial effects of a DI to decrease airway temporal variability was eliminated when airway tone was increased. If this effect is absent in asthmatics, this may suggest a possible mechanism for the loss of bronchoprotective and bronchodilatory effects after a DI in asthma.