title: Inflammatory cell mapping of the respiratory tract in fatal asthma.
abstract: BACKGROUND
  The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways.
  
  
  OBJECTIVE
  We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma.
  
  
  METHODS
  Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls.
  
  
  RESULTS
  Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028).
  
  
  CONCLUSIONS
  Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA.
authors.affiliation: Division of Clinical Immunology and Allergy, Department of Pathology, University of Sau Paulo, Sau Paulo, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: de Magalhães Simões
authors.forename: M A
authors.initials: MA
authors.lastname: dos Santos
authors.forename: M
authors.initials: M
authors.lastname: da Silva Oliveira
authors.forename: E S
authors.initials: ES
authors.lastname: Fontes
authors.forename: S
authors.initials: S
authors.lastname: Fernezlian
authors.forename: A L
authors.initials: AL
authors.lastname: Garippo
authors.forename: I
authors.initials: I
authors.lastname: Castro
authors.forename: F F M
authors.initials: FF
authors.lastname: Castro
authors.forename: M
authors.initials: M
authors.lastname: de Arruda Martins
authors.forename: P H N
authors.initials: PH
authors.lastname: Saldiva
authors.forename: T
authors.initials: T
authors.lastname: Mauad
authors.forename: M
authors.initials: M
authors.lastname: Dolhnikoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D001980:Bronchi / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D002648:Child; D004804:Eosinophils / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000737:chemistry / Q000276:immunology; D008875:Middle Aged; D009297:Nasal Mucosa / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology; D012137:Respiratory System / Q000276:immunology / Q000473:pathology*; D013224:Status Asthmaticus / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D014132:Trachea / Q000737:chemistry / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD