title: Airway structural alterations selectively associated with severe asthma.
abstract: To identify airway pathologic abnormalities selectively associated with severe asthma, we examined 10 control subjects, 10 patients with intermittent asthma, 15 patients with mild-to-moderate persistent asthma, 15 patients with severe persistent asthma, and 10 patients with chronic obstructive pulmonary disease. 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 alpha-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 < 0.001), an increase in collagen type III deposition (p < 0.020), larger mucous gland (p < 0.040) and ASM (p < 0.001) areas, augmented ASM cell size (p < 0.001), and myosin light-chain kinase expression (p < 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 408, Faculté de Médecine Xavier Bichat, Service de Pneumologie, Hôpital Bichat, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Benayoun
authors.forename: Anne
authors.initials: A
authors.lastname: Druilhe
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Dombret
authors.forename: Michel
authors.initials: M
authors.lastname: Aubier
authors.forename: Marina
authors.initials: M
authors.lastname: Pretolani
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000403:Airway Resistance / Q000502:physiology; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology*; D001707:Biopsy, Needle; D016535:Bronchial Hyperreactivity / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009130:Muscle, Smooth / Q000473:pathology; D011336:Probability; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology* / Q000503:physiopathology; D012016:Reference Values; D012044:Regression Analysis; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors