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Bronchial biopsies were assessed for epithelial integrity; subepithelial basement membrane (SBM) thickness; collagen type III deposition; eosinophil, neutrophil, and fibroblast numbers; mucous gland and airway smooth muscle (ASM) areas; SBM-ASM distance; ASM hypertrophy (increased cell size); and the expression of the contractile proteins \u03b1-actin, smooth muscle myosin heavy-chain isoforms, myosin light-chain kinase, and the phosphorylated form of the regulatory light chain of myosin. Neither mucosal eosinophilia nor neutrophilia, epithelial damage, or SBM thickness reflected asthma severity. In contrast, higher numbers of fibroblasts (p &amp;lt; 0.001), an increase in collagen type III deposition (p &amp;lt; 0.020), larger mucous gland (p &amp;lt; 0.040) and ASM (p &amp;lt; 0.001) areas, augmented ASM cell size (p &amp;lt; 0.001), and myosin light-chain kinase expression (p &amp;lt; 0.005) distinguished patients with severe persistent asthma from patients with milder disease or with chronic obstructive pulmonary disease. Stepwise multivariate regression analysis established that fibroblast numbers and ASM cell size were negatively associated with prebronchodilator and postbronchodilator FEV1 values in patients with asthma. We conclude that fibroblast accumulation and ASM hypertrophy in proximal airways are selective determinants of severe persistent asthma.<\/jats:p>","DOI":"10.1164\/rccm.200209-1030oc","type":"journal-article","created":{"date-parts":[[2003,5,8]],"date-time":"2003-05-08T13:54:20Z","timestamp":1052402060000},"page":"1360-1368","source":"Crossref","is-referenced-by-count":670,"title":["Airway Structural Alterations Selectively Associated with Severe Asthma"],"prefix":"10.1093","volume":"167","author":[{"given":"Laurent","family":"Benayoun","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 408, Facult\u00e9 de M\u00e9decine Xavier Bichat and Service de Pneumologie, H\u00f4pital Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Druilhe","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 408, 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