The structural basis of airways hyperresponsiveness in asthma.
We hypothesized that structural airway remodeling contributes to airways hyperresponsiveness (AHR) in asthma. Small, medium, and large airways 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 residual volume (RV) that was threefold greater than the decrease in forced vital capacity (FVC) because of a simultaneous increase in total lung capacity (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 functional residual capacity (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 dynamic hyperinflation caused by narrowing of large airways is a major determinant of AHR in asthma.
Brown
Robert H
RH
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. rbrown@jhsph.edu
Pearse
David B
DB
Pyrgos
George
G
Liu
Mark C
MC
Togias
Alkis
A
Permutt
Solbert
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000473:pathology* / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D012115:Residual Volume / Q000187:drug effects / Q000502:physiology; D012132:Respiratory Muscles / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D014109:Total Lung Capacity / Q000187:drug effects / Q000502:physiology; D014797:Vital Capacity / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D000420:Albuterol