title: Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study.
abstract: BACKGROUND
  Smoking and airway lability, which is expressed by histamine airway hyper-responsiveness, are known risk factors for development of respiratory symptoms. Smoking is also associated with increased mortality risks. We studied whether airway hyper-responsiveness is associated with increased mortality, and whether this risk was independent of smoking and reduced lung function.
  
  
  METHODS
  We followed up 2008 inhabitants of the communities of Vlagtwedde, Vlaardingen, and Meppel (Netherlands), who had histamine challenge test data, from 1964-72 for 30 years. Follow-up was 99% successful (29 patients lost to follow-up) with 1453 participants alive and 526 deaths (246 died from cardiovascular disease, 54 from lung cancer, and 21 from chronic obstructive pulmonary disease [COPD]).
  
  
  RESULTS
  Mortality from COPD increased with more severe hyper-responsiveness; relative risks of 3.83 (95% CI 0.97-15.1), 4.40 (1.16-16.7), 4.78 (1.27-18.0), 6.69 (1.71-26.1), and 15.8 (3.72-67.1) were associated with histamine thresholds of 32 g/L, 16 g/L, 8 g/L, 4 g/L, and 1 g/L, respectively, compared with no hyper-responsiveness. These risks were adjusted for sex, age, smoking, lung function, body-mass index, positive skin tests, eosinophilia, asthma, and city of residence.
  
  
  CONCLUSIONS
  Increased histamine airway hyper-responsiveness predicts mortality from COPD. Although this trend was more pronounced in smokers, an increasing proportion of COPD deaths with increasing hyper-responsiveness was also present among individuals who had never smoked.
authors.affiliation: Department of Epidemiology and Statistics, University of Groningen, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Hospers
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.forename: B
authors.initials: B
authors.lastname: Rijcken
authors.forename: S T
authors.initials: ST
authors.lastname: Weiss
authors.forename: J P
authors.initials: JP
authors.lastname: Schouten
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D015992:Body Mass Index; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000175:diagnosis*; D001985:Bronchial Provocation Tests; D015331:Cohort Studies; D005260:Female; D006632:Histamine; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012306:Risk; D017678:Sex Distribution; D012907:Smoking / Q000009:adverse effects*; D014797:Vital Capacity
chemical_list: D006632:Histamine