title: Investigating severe and fatal asthma.
abstract: BACKGROUND
  Severe asthma continues to present a major therapeutic problem despite advances in our understanding of the disease. Innovative ideas for investigating the underlying causes and treatment of severe asthma are few, and many patients still become dependent on oral steroids. We describe two separate studies: first, a prospective investigation measuring the responses of persons with severe asthma to an allergen-free environment; second, a retrospective analysis of factors associated with eight fatalities and one near fatality caused by asthma exacerbations.
  
  
  METHODS
  In the prospective study 17 persons with severe asthma were admitted to a hospital clinical research unit containing an allergen-free room for steroid dose reduction. Peak flow measurements, treatment requirements, and evidence of infection were followed up. In the retrospective study, the cases of nine patients who had been evaluated for asthma and who subsequently died during an asthma attack were reviewed; where possible allergen levels in their house dust and specific IgE antibodies to common indoor allergens were measured.
  
  
  RESULTS
  Analysis of the patients in the prospective study revealed two categories of responses to steroid dose reduction: (1) asthmatic persons who either maintained or improved peak flow values on steroid reduction; these patients were predominantly allergic to indoor allergens; (2) asthmatic persons whose condition deteriorated; these patients were unable to tolerate reduction in steroid dose. The second group included persons with sensitization to fungal antigens who had asthmatic exacerbations in association with culture-documented fungal colonization. The retrospective study revealed that in five of the eight fatalities caused by asthma, exposure to a relevant allergen had occurred at home before death.
  
  
  CONCLUSIONS
  Some steroid-dependent persons with severe asthma are allergic to inhalant allergens and may benefit from avoiding allergens. In some cases there is no evidence that antigen exposure from diet, inhalants, fungal infections, or sinusitis is relevant to their disease. However, persons with severe asthma include individuals infected with and sensitized to fungal antigens. The results suggest that cases of severe asthma should be investigated to identify treatable causes.
authors.affiliation: Division of Asthma, Allergic Disease and Clinical Immunology, University of Virginia Health Sciences Center, Charlottesville.
authors.forename: R S
authors.initials: RS
authors.lastname: Call
authors.forename: G
authors.initials: G
authors.lastname: Ward
authors.forename: S
authors.initials: S
authors.lastname: Jackson
authors.forename: T A
authors.initials: TA
authors.lastname: Platts-Mills
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D000935:Antifungal Agents / Q000627:therapeutic use; D000946:Antigens, Fungal / Q000276:immunology; D001249:Asthma / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D000305:Adrenal Cortex Hormones; D000485:Allergens; D000935:Antifungal Agents; D000946:Antigens, Fungal