Association of indoor nitrogen dioxide with respiratory symptoms in children: application of measurement error correction techniques to utilize data from multiple surrogates.

In 1991, Neas et al. reported that indoor nitrogen dioxide (NO(2)), a byproduct of high-temperature combustion, was significantly associated with lower respiratory symptoms among a cohort of 1,159 white children aged 7-11 years in six US cities studied from 1983 to 1988. For each 15 p.p.b. increment of NO(2), the multivariate adjusted odds ratio (OR) was 1.4 (95% confidence interval (CI)=[1.1, 1.7]). Although indoor NO(2) concentration in the ambient air was assessed only in a subset of the children, the prevalence of lower respiratory symptoms and surrogate exposure variables were available in all of the children at the time of the indoor monitoring program. This paper evaluates the effect of indoor NO(2) exposure on the annual risk of lower respiratory symptoms by applying a regression calibration method to the 2,891 children in the overall study with complete covariate and outcome data, 1,137 of whom had NO(2) directly measured and 1,754 of whom only surrogate exposure data were available. An estimate of the indoor annual NO(2) exposure effect (p.p.b.) is obtained, which is adjusted for measurement error induced by the use of surrogate NO(2) sources among the 1,754. These sources include the presence of a gas stove with or without a pilot light, the presence of a kerosene space heater, the presence of a wood stove, and the usage of a stove for heating, and residential characteristics, including fan usage for kitchen ventilation and the total number of rooms in the home. After adjusting for age, gender, city, parental history of respiratory diseases, and smoking inside the children's home (packs/day), a 15-p.p.b. increment in NO(2) exposure was found to be associated with a significant 50% increased annual risk of lower respiratory symptoms (OR=1.5, 95% CI=[1.2, 1.8]). Simulation results indicated that, under conditions similar to those observed in these data, the estimator is unbiased and has a coverage probability close to the nominal value. Using the methodology illustrated in this paper, it became possible to utilize all data available and obtain a 34% more precise estimate of the NO(2) exposure effect on lower respiratory symptoms, which was adjusted for measurement error due to using NO(2) surrogates instead of directly measured NO(2).