title: Inflammation and functional outcome in diisocyanate-induced asthma after cessation of exposure.
abstract: BACKGROUND
  The clinical outcome of diisocyanate-induced asthma has been found to be poor despite cessation of exposure. Our aim was to study the outcome of diisocyanate-induced asthma after initiation of inhaled steroid treatment at a mean period of 7 months (range 2-60 months) after cessation of exposure by following up lung function and bronchial inflammation.
  
  
  METHODS
  Bronchoscopy was performed on 17 patients 2 days after a positive inhalation challenge test, after which budesonide 1600 mug a day was started. Bronchoscopy, spirometry, and histamine challenge tests were repeated at 6 months and on average 3 years. The results were also compared with those obtained from 15 healthy control subjects.
  
  
  RESULTS
  Nonspecific bronchial hyperreactivity diminished significantly (P = 0.006); however, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values decreased, with a median yearly reduction of FEV1 of 79 ml. The count of mast cells in bronchial mucosa decreased (P = 0.012) and that of macrophages increased (P = 0.001). Interleukin-4 level in mucosa was during the first year significantly higher than in controls but its level decreased in the follow-up. Interleukin-6, interleukin-15, and tumour necrosis factor alpha messenger-RNA levels were significantly higher in hyperreactive patients than in nonhyperreactive patients at the end of the follow-up.
  
  
  CONCLUSIONS
  Our results indicate that inflammation may persist in diisocyanate-induced asthma despite inhaled steroid medication. However, TH2-type inflammation diminished. Persistent nonspecific bronchial hyperreactivity was associated with proinflammatory acting cytokines produced mainly by macrophages. Considering the poor prognosis of the disease the findings could be utilized to develop the follow-up and treatment of diisocyanate-induced asthma.
authors.affiliation: Department of Clinical Physiology, Helsinki University Hospital, HUSLAB, Helsinki, Finland.
authors.forename: P L
authors.initials: PL
authors.lastname: Piirilä
authors.forename: A
authors.initials: A
authors.lastname: Meuronen
authors.forename: M-L
authors.initials: ML
authors.lastname: Majuri
authors.forename: R
authors.initials: R
authors.lastname: Luukkonen
authors.forename: T
authors.initials: T
authors.lastname: Mäntylä
authors.forename: H J
authors.initials: HJ
authors.lastname: Wolff
authors.forename: H
authors.initials: H
authors.lastname: Nordman
authors.forename: H
authors.initials: H
authors.lastname: Alenius
authors.forename: A
authors.initials: A
authors.lastname: Laitinen
mesh_terms: D000328:Adult; D001249:Asthma / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D001980:Bronchi / Q000276:immunology / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D001999:Bronchoscopy; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D016273:Occupational Exposure; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000473:pathology; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4