Abstract
BackgroundImaging 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.ObjectiveWe studied 12 healthy subjects to evaluate whether Vdefs formed during bronchoconstriction, and compared their Vdefs with those observed in 9 subjects with mild asthma.MethodsSpirometry, low frequency (0.15 Hz) lung elastance and resistance, and regional ventilation by intravenous 13NN-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.ResultsConsistent 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.ConclusionThe formation of Vdefs is determined by the state of inflation prior to bronchoconstriction.
Highlights
Using different imaging techniques, ventilation defective regions (Vdefs) have been demonstrated in asymptomatic asthma subjects [1] and after inhalation of methacholine [2,3,4,5] or after exercise [5,6]
Consistent with the predictions of the theoretical model, both healthy subjects and those with asthma developed ventilation defective areas (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
The methacholine dose to the asthmatic subjects was selected such that FEV1, was reduced by 20% (PC20 = 1.2361.24 mg/mL)
Summary
Ventilation defective regions (Vdefs) have been demonstrated in asymptomatic asthma subjects [1] and after inhalation of methacholine [2,3,4,5] or after exercise [5,6]. We found that in the prone position, where the subject’s lungs had a greater state of inflation, Vdefs tended to be smaller than in the supine position [3]. Those results were consistent with a theoretical model of bronchoconstriction that includes dynamic inter-dependence among parenchymal forces, gas pressures and airways in a tree structure [7]. The model predicts that, for a given smooth muscle activation, a reduction in forces on the airway wall, due to less expanded parenchyma, should result in the emergence of Vdefs, and these should increase in size with further reductions in lung inflation [8]. We theorized that in normal lungs, Vdefs should emerge in regions of the lung with reduced expansion
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