# Ventilation Defect Formation in Healthy and Asthma Subjects Is Determined by Lung Inflation

 Title: Ventilation Defect Formation in Healthy and Asthma Subjects Is Determined by Lung Inflation Author: Harris, Robert Scott; Fujii-Rios, Hanae; Winkler, Tilo; Musch, Guido; Vidal Melo, Marcos Francisco; Venegas, Jose Gabriel Note: Order does not necessarily reflect citation order of authors. Citation: Harris, R. Scott, Hanae Fujii-Rios, Tilo Winkler, Guido Musch, Marcos F. Vidal Melo, and José G. Venegas. 2012. Ventilation defect formation in healthy and asthma subjects is determined by lung inflation. PLoS ONE 7(12): e53216. Full Text & Related Files: 3532117.pdf (1.100Mb; PDF) Abstract: Background: Imaging studies have demonstrated that ventilation during bronchoconstriction in subjects with asthma is patchy with large ventilation defective areas (Vdefs). Based on a theoretical model, we postulated that during bronchoconstriction, as smooth muscle force activation increases, a patchy distribution of ventilation should emerge, even in the presence of minimal heterogeneity the lung. We therefore theorized that in normal lungs, Vdefs should also emerge in regions of the lung with reduced expansion. Objective: We studied 12 healthy subjects to evaluate whether Vdefs formed during bronchoconstriction, and compared their Vdefs with those observed in 9 subjects with mild asthma. Methods: Spirometry, low frequency (0.15 Hz) lung elastance and resistance, and regional ventilation by intravenous $$^{13}$$NN-saline positron emission tomography were measured before and after a challenge with nebulized methacholine. Vdefs were defined as regions with elevated residual 13NN after a period of washout. The average location, ventilation, volume, and fractional gas content of the Vdefs, relative to those of the rest of the lung, were calculated for both groups. Results: Consistent with the predictions of the theoretical model, both healthy subjects and those with asthma developed Vdefs. These Vdefs tended to form in regions that, at baseline, had a lower degree of lung inflation and, in healthy subjects, tended to occur in more dependent locations than in subjects with asthma. Conclusion: The formation of Vdefs is determined by the state of inflation prior to bronchoconstriction. Published Version: doi:10.1371/journal.pone.0053216 Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532117/pdf/ Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11235954 Downloads of this work: