Temporal variability in the responses of individual canine airways to methacholine

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA.
Journal of Applied Physiology (Impact Factor: 3.06). 06/2008; 104(5):1381-6. DOI: 10.1152/japplphysiol.01348.2007
Source: PubMed


Previous work showed that individual airway size, before any spasmogen, varied widely in the same animals on different days. The effect of this variable baseline size on the airway response to a subsequent challenge is unknown. The present study examined how the variability in individual airway baseline size in dogs was related to that after methacholine challenge on 4 different days using high-resolution computed tomography scans. Dogs were anesthetized and ventilated, and on 4 separate days randomly varying between 1 and 8 wk apart, baseline scans were acquired, followed by a continuous intravenous infusion of methacholine at three rates in increasing order (17, 67, and 200 microg/min). As the measure of variability, we used the coefficient of variation (CV) of the four airway luminal measurements of each airway at baseline and at each dose of methacholine. For most airways, there was wide variability both between and within dogs in the response to a given dose of methacholine (CV = 33-38%). Airways with any level of methacholine stimulation had greater variability than those at baseline. The airway variability was greatest at the lowest dose of methacholine administered but was elevated at all the doses. In conclusion, there was substantial day-to-day variability in baseline airway size. Most importantly, the same dose of methacholine to the same individual airway showed even greater variability than that at baseline. If we consider that increased heterogeneity may potentiate clinical symptoms, then airway response variability may play an important role in the manifestation of airway disease.

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Available from: David W. Kaczka
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    • "We previously demonstrated that airways with any level of Mch stimulation had greater temporal variability than without Mch.15 Our current results also demonstrate that the temporal variability of the airways decreased after the deep inspiration both at baseline and during low concentrations of Mch stimulation, but this beneficial effect of a deep inspiration was lost at higher concentrations of Mch. "
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    • "Incorporating this model into a network of ventilation simulating imaging patterns observed in asthmatics, Venegas et al. (2005) documented that local interactions between airway wall and surrounding parenchyma caused by increasing airway smooth muscle tone or decreasing ventilation yielded a bimodal ventilation distribution, with some airways closing or approaching closure while others opening at the same time. These data would suggest that the interactions between operational lung volumes, tidal breathing, and airway smooth muscle tone is so potent to generate heterogeneous bronchoconstriction that may largely overcome the effects of any other source of heterogeneity , such as anatomical, neural, functional, and distribution of the constrictor agents (Brown et al., 2008). Decrements in lung volumes and ventilation could have contributed to cause heterogeneous and thus exaggerated airway narrowing in our study by two mechanisms. "
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