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]). FINDINGS: 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. INTERPRETATION: 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.
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]). FINDINGS: 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. INTERPRETATION: 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: Melanie C Matheson; Justine A Ellis; Joan Raven; David P Johns; E Haydn Walters; Michael J Abramson Journal: J Hum Genet Date: 2006-09-01 Impact factor: 3.172
Authors: Margaret W Gerbase; Christian Schindler; Jean-Pierre Zellweger; Nino Künzli; Sara H Downs; Otto Brändli; Joel Schwartz; Martin Frey; Luc Burdet; Thierry Rochat; Ursula Ackermann-Liebrich; Philippe Leuenberger Journal: Am J Respir Crit Care Med Date: 2006-08-24 Impact factor: 21.405
Authors: M J McGeachie; K P Yates; S T Weiss; R C Strunk; X Zhou; F Guo; A L Sternberg; M L Van Natta; R A Wise; S J Szefler; S Sharma; A T Kho; M H Cho; D C Croteau-Chonka; P J Castaldi; G Jain; A Sanyal; Y Zhan; B R Lajoie; J Dekker; J Stamatoyannopoulos; R A Covar; R S Zeiger; N F Adkinson; P V Williams; H W Kelly; H Grasemann; J M Vonk; G H Koppelman; D S Postma; B A Raby; I Houston; Q Lu; A L Fuhlbrigge; K G Tantisira; E K Silverman; J Tonascia Journal: N Engl J Med Date: 2016-05-12 Impact factor: 91.245