HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 101/1/30    most recent 01190.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Brown, R. H. Articles by Permutt, S. Search for Related Content PubMed PubMed Citation Articles by Brown, R. H. Articles by Permutt, S.

The structural basis of airways hyperresponsiveness in asthma

¹Department of Anesthesiology and Critical Care Medicine, ²Department of Environmental Health Sciences, Division of Physiology, Department of Medicine, ³Division of Pulmonary and Critical Care Medicine and ⁴Division of Allergy and Clinical Immunology, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Submitted 19 September 2005 ; accepted in final form 1 February 2006

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.

computerized tomography; residual volume; total lung capacity; forced vital capacity

This article has been cited by other articles:

				C. G. Irvin and J. H. T. Bates Physiologic Dysfunction of the Asthmatic Lung: What's Going On Down There, Anyway? Proceedings of the ATS, May 1, 2009; 6(3): 306 - 311. [Abstract] [Full Text] [PDF]

				R. E. Hyatt, C. T. Cowl, J. A. Bjoraker, and P. D. Scanlon Conditions Associated With an Abnormal Nonspecific Pattern of Pulmonary Function Tests Chest, February 1, 2009; 135(2): 419 - 424. [Abstract] [Full Text] [PDF]

				A. Busacker, J. D. Newell Jr, T. Keefe, E. A. Hoffman, J. C. Granroth, M. Castro, S. Fain, and S. Wenzel A Multivariate Analysis of Risk Factors for the Air-Trapping Asthmatic Phenotype as Measured by Quantitative CT Analysis Chest, January 1, 2009; 135(1): 48 - 56. [Abstract] [Full Text] [PDF]

				B. B. Araujo, M. Dolhnikoff, L. F. F. Silva, J. Elliot, J. H. N. Lindeman, D. S. Ferreira, A. Mulder, H. A. P. Gomes, S. M. Fernezlian, A. James, et al. Extracellular matrix components and regulators in the airway smooth muscle in asthma Eur. Respir. J., July 1, 2008; 32(1): 61 - 69. [Abstract] [Full Text] [PDF]

				R. L. Sorkness, E. R. Bleecker, W. W. Busse, W. J. Calhoun, M. Castro, K. F. Chung, D. Curran-Everett, S. C. Erzurum, B. M. Gaston, E. Israel, et al. Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation J Appl Physiol, February 1, 2008; 104(2): 394 - 403. [Abstract] [Full Text] [PDF]

				D. A. Kaminsky, C. G. Irvin, L. K. A. Lundblad, J. Thompson-Figueroa, J. Klein, M. J. Sullivan, F. Flynn, S. Lang, L. Bourassa, S. Burns, et al. Heterogeneity of bronchoconstriction does not distinguish mild asthmatic subjects from healthy controls when supine J Appl Physiol, January 1, 2008; 104(1): 10 - 19. [Abstract] [Full Text] [PDF]

				R. Pellegrino and V. Brusasco Commentary on "The role of the large airways on smooth muscle contraction in asthma" J Appl Physiol, October 1, 2007; 103(4): 1460 - 1460. [Full Text] [PDF]

				H. Mitchell, P. Noble, and P. McFawn Commentary on "The role of the large airways on smooth muscle contraction in asthma" J Appl Physiol, October 1, 2007; 103(4): 1461 - 1461. [Full Text] [PDF]

				N. Stephens Commentary on "The role of the large airways on smooth muscle contraction in asthma" J Appl Physiol, October 1, 2007; 103(4): 1462 - 1462. [Full Text] [PDF]

				H. C. Haverkamp and L. K. A. Lundblad Commentary on "The role of the large airways on smooth muscle contraction in asthma" J Appl Physiol, October 1, 2007; 103(4): 1463 - 1463. [Full Text] [PDF]

				R. Sorkness Commentary on "The role of the large airways on smooth muscle contraction in asthma" J Appl Physiol, October 1, 2007; 103(4): 1464 - 1464. [Full Text] [PDF]

				S. Permutt Last Word on Viewpoint "The role of the large airways on smooth muscle contraction in asthma" J Appl Physiol, October 1, 2007; 103(4): 1466 - 1466. [Full Text] [PDF]

				S. Permutt The role of the large airways on smooth muscle contraction in asthma J Appl Physiol, October 1, 2007; 103(4): 1457 - 1458. [Full Text] [PDF]

				T. Winkler and J. G. Venegas Complex airway behavior and paradoxical responses to bronchoprovocation J Appl Physiol, August 1, 2007; 103(2): 655 - 663. [Abstract] [Full Text] [PDF]

				R. Shaaban, B. Leynaert, D. Soussan, J. M Anto, S. Chinn, R. de Marco, J. Garcia-Aymerich, J. Heinrich, C. Janson, D. Jarvis, et al. Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II Thorax, May 1, 2007; 62(5): 403 - 410. [Abstract] [Full Text] [PDF]

				H.-Y. S. Chang, A. Togias, and R. H. Brown The Effects of Systemic Lidocaine on Airway Tone and Pulmonary Function in Asthmatic Subjects Anesth. Analg., May 1, 2007; 104(5): 1109 - 1115. [Abstract] [Full Text] [PDF]

				L. A. Whittaker and C. G. Irvin Going to extremes of lung volume J Appl Physiol, March 1, 2007; 102(3): 831 - 833. [Full Text] [PDF]

				S. S. Wagers, H. C. Haverkamp, J. H. T. Bates, R. J. Norton, J. A. Thompson-Figueroa, M. J. Sullivan, and C. G. Irvin Intrinsic and antigen-induced airway hyperresponsiveness are the result of diverse physiological mechanisms J Appl Physiol, January 1, 2007; 102(1): 221 - 230. [Abstract] [Full Text] [PDF]

				R. H. Brown, D. B. Pearse, G. Pyrgos, M. C. Liu, A. Togias, and S. Permutt REPLY FROM DRS. BROWN, PEARSE, PYRGOS, LIU, TOGIAS, AND PERMUTT J Appl Physiol, December 1, 2006; 101(6): 1813 - 1813. [Full Text] [PDF]

				D. C Stanescu J Appl Physiol, December 1, 2006; 101(6): 1812 - 1812. [Full Text] [PDF]

				C. G. Irvin Lessons from structure-function studies in asthma: myths and truths about what we teach J Appl Physiol, July 1, 2006; 101(1): 7 - 9. [Full Text] [PDF]