Inflammation and functional outcome in diisocyanate-induced asthma after cessation of exposure

Allergy. 2008 May;63(5):583-91. doi: 10.1111/j.1398-9995.2007.01606.x.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma / chemically induced*
  • Asthma / drug therapy
  • Asthma / immunology
  • Asthma / physiopathology*
  • Bronchi / immunology
  • Bronchi / pathology
  • Bronchi / physiology*
  • Bronchi / physiopathology
  • Bronchial Hyperreactivity
  • Bronchial Provocation Tests
  • Bronchoscopy
  • Female
  • Humans
  • Inflammation / immunology*
  • Interleukin-4 / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Occupational Diseases / chemically induced
  • Occupational Diseases / drug therapy
  • Occupational Diseases / immunology
  • Occupational Diseases / physiopathology
  • Occupational Exposure*
  • Respiratory Function Tests
  • Respiratory Mucosa / pathology
  • Toluene 2,4-Diisocyanate / adverse effects*
  • Tumor Necrosis Factor-alpha / metabolism


  • Tumor Necrosis Factor-alpha
  • Toluene 2,4-Diisocyanate
  • Interleukin-4