AIRWAY HYPERRESPONSIVENESS AND COPD MORTALITY.

Background: Smoking and airway lability which is expressed by histamine airway hyperresponsiveness, are known risk factors for development of respiratory symptoms. Smoking is also associated with increased mortality risks. We studied whether airway hyperresponsiveness 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)). Findings: Mortality from COPD increased with more severe hyper-responsiveness relative risks of 3.83 (95% Cl 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/I, and 1 g/l, respectively compared with no hyperresponsiveness. These risks were adjusted for sex, age, smoking, lung function, body mass index, positive skin tests, eosinophilia, asthma, and city of residence. Interpretation: Increased histamine airway hyper-responsiveness predicts modality 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. [ABSTRACT FROM AUTHOR]