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Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma
Author(s) -
Yick C. Y.,
Ferreira D. S.,
Ani R.,
Thüsen J. H.,
Kunst P. W.,
Bel E. H.,
Lutter R.,
Mauad T.,
Sterk P. J.
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2011.02773.x
Subject(s) - extracellular matrix , asthma , methacholine , medicine , bronchoconstriction , fibronectin , spirometry , laminin , immunology , airway , respiratory disease , lung , chemistry , anesthesia , biochemistry
Background Altered deposition of extracellular matrix ( ECM ) in the airway smooth muscle ( ASM ) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo . Methods Our cross‐sectional study comprised 19 atopic mild asthma patients, 15 atopic and 12 nonatopic healthy subjects. Spirometry, methacholine responsiveness, deep‐breath‐induced bronchodilation (Δ R rs ) and bronchoscopy with endobronchial biopsies were performed. Positive staining of elastin, collagen I , III and IV , decorin, versican, fibronectin, laminin and tenascin in ASM was quantified as fractional area and mean density. Data were analysed using P earson's or S pearman's correlation coefficient. Results Extracellular matrix expression in ASM was not different between asthma and controls. In asthmatics, fractional area and mean density of collagen I and III were correlated with methacholine dose–response slope and Δ R rs , respectively ( r = 0.71, P < 0.01; r = 0.60, P = 0.02). Furthermore, ASM collagen III and laminin in asthma were correlated with FEV 1 reversibility ( r = −0.65, P = 0.01; r = −0.54, P = 0.04). Conclusion In asthma, ECM in ASM is related to the dynamics of airway function in the absence of differences in ECM expression between asthma and controls. This indicates that the ASM layer in its full composition is a major structural component in determining variable airways obstruction in asthma.