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Normal subjects prevented from taking a deep breath show changes in airflow similar to those of asthmatics when challenged with methacholine (MCh). To confirm airway narrowing by MCh in this setting and to determine its location, we concurrently measured changes in airway lumenal area using high resolution computed tomography (HRCT) and airflow using partial spirometry in five normal subjects challenged with increasing doses of MCh under prohibition of deep breaths. In an attempt to improve imaging accuracy, we corrected for the changes in lung volume during bronchoprovocation. At every step of the provocation, scanning was performed at approximately the same lung volume. On the HRCT images, airway area decreased in response to the increasing doses of MCh to 91 +/- 2%, 88 +/- 2%, and 80 +/- 2% of baseline at the doses of MCh 0.25, 0.75, and 2.5 mg/ml, respectively (p0.001). Airway narrowing showed no predilection for particular airway sizes and occurred in a heterogeneous pattern. The changes in the mean airway lumenal area as measured by HRCT and the mean partial spirometric outcomes were highly correlated: FEV(1)p (r(2) = 0.46, p = 0.001), FVCp (r(2) = 0.20, p = 0.05), FEV(1)/FVCp (r(2) = 0.55, p = 0.002), MMEFp (r(2) = 0.31, p = 0.01), and taup (r(2) = 0.51, p = 0.0004). We conclude that in normal subjects who are prevented from taking a deep breath, the spirometric changes occurring with aerosol MCh challenge are associated with conducting airway narrowing.