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1 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Environmental Health Sciences/Division of Physiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Medicine/Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
2 Department of Medicine/Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
3 Department of Medicine/Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Medicine/Division of Allergy and Clinical Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: rbrown{at}jhsph.edu.
We hypothesized that structural airway remodeling contributes to airways hyperresponsiveness (AHR) in asthma. Small, medium, and large airways (<5, 5-10, >10 mm diameter) were analyzed by computed tomography in 21 asthmatic volunteers under baseline conditions (FEV1 = 64% predicted) and after maximum response to albuterol (FEV1 = 76% predicted). The difference in pulmonary function between baseline and albuterol was an estimate of AHR to the baseline smooth muscle tone (BSMT). BSMT caused an increase in RV that was 3-fold greater than the decrease in FVC because of a simultaneous increase in TLC. The decrease in FVC with BSMT was the major determinant of the baseline FEV1 (P < 0.0001). The increase in RV correlated inversely with the relaxed luminal diameter of the medium airways (P = 0.009) and directly with the wall thickness of the large airways (P = 0.001). The effect of BSMT on FRC controlled the change in TLC relative to the change in RV. When the FRC increased with RV, TLC increased and FVC was preserved. When the relaxed large airways were critically narrowed, FRC and TLC did not increase and FVC fell. With critical large airways narrowing, the FRC was already elevated from dynamic hyperinflation before BSMT and did not increase further with BSMT. FEV1/FVC in the absence of BSMT correlated directly with large airway luminal diameter and inversely with the fall in FVC with BSMT. These findings suggest that the degree of dynamic hyperinflation caused by narrowing of large airways is a major determinant of AHR in asthma.
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