title: Inter-relationships between airway inflammation, reticular basement membrane thickening and bronchial hyper-reactivity to methacholine in asthma; a systematic bronchoalveolar lavage and airway biopsy analysis.
abstract: BACKGROUND
  Asthma is accepted as a disease characterized by airway inflammation, with evidence that airway structural changes, or 'remodelling' occurs. There are few studies relating airway physiology, inflammation and remodelling, however. We have carried out a study of inter-relationships between airway inflammation, airway remodelling, reticular basement membrane (RBM) thickening, and bronchial hyper-reactivity (BHR), before and after high-dose inhaled corticosteroid (fluticasone propionate 750 microg b.d.), in a group of relatively mild but symptomatic, steroid naïve asthma patients.
  
  
  METHODS
  Double-blind, randomized, placebo-controlled, parallel group study of inhaled corticosteroid (ICS) in 35 asthmatics, with bronchoalveolar lavage (BAL) and airway endobronchial biopsy (EBB) for inflammatory cell profiles and EBB for airway remodelling carried out at baseline, 3 and 12 months.
  
  
  RESULTS
  At baseline RBM thickening was related to BAL mast cells and EBB eosinophil counts. In turn baseline log EBB EG2 eosinophil count, log%BAL epithelial cells and log RBM thickness explained 55% of the variability in BHR.
  
  
  CONCLUSIONS
  We provide new information that airway inflammation, remodelling, and BHR in asthma are inter-related and improved by ICS therapy. Our data potentially support the need for early and long-term intervention with ICS even in relatively mild asthmatics, and the need to further assess the potential merit of longitudinal BHR testing in management of some patients, as this may reflect both airway inflammation and remodelling.
authors.affiliation: Applied Immunobiology and Transplantation Research Group, The Freeman Hospital and University of Newcastle upon Tyne, UK. chris.ward@newcastle.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Ward
authors.forename: D W
authors.initials: DW
authors.lastname: Reid
authors.forename: B E
authors.initials: BE
authors.lastname: Orsida
authors.forename: B
authors.initials: B
authors.lastname: Feltis
authors.forename: V A
authors.initials: VA
authors.lastname: Ryan
authors.forename: D P
authors.initials: DP
authors.lastname: Johns
authors.forename: E H
authors.initials: EH
authors.lastname: Walters
mesh_terms: D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000276:immunology* / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016085:Bronchoconstrictor Agents; D016022:Case-Control Studies; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D016210:Methacholine Chloride; D012044:Regression Analysis; D012155:Reticulin / Q000276:immunology; D013147:Spirometry
chemical_list: D016085:Bronchoconstrictor Agents; D012155:Reticulin; D016210:Methacholine Chloride