The structural basis of airways hyperresponsiveness in asthma

Robert Howard Brown, David B Pearse, George Pyrgos, Mark Chang Hwa Liu, Alkis Togias, Solbert Permutt

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)30-39
Number of pages10
JournalJournal of Applied Physiology
Volume101
Issue number1
DOIs
StatePublished - 2006

Fingerprint

Smooth Muscle
Vital Capacity
Asthma
Total Lung Capacity
Functional Residual Capacity
Residual Volume
Albuterol
Airway Remodeling
Volunteers
Tomography
Lung

Keywords

  • Computerized tomography
  • Forced vital capacity
  • Residual volume
  • Total lung capacity

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

The structural basis of airways hyperresponsiveness in asthma. / Brown, Robert Howard; Pearse, David B; Pyrgos, George; Liu, Mark Chang Hwa; Togias, Alkis; Permutt, Solbert.

In: Journal of Applied Physiology, Vol. 101, No. 1, 2006, p. 30-39.

Research output: Contribution to journalArticle

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