Meta-analysis of nitrogen dioxide exposure and airway hyper-responsiveness in asthmatics

The effects of 0.1 to 0.6 ppm nitrogen dioxide (NO2) on airway hyper-responsiveness (AHR) to airway challenges in asthmatics have been evaluated in several controlled exposure studies. The authors conducted meta-analyses and meta-regressions of these studies using several effect measures for AHR: a change (in NO2 versus air) in (1) the provocative dose of a challenge agent necessary to cause a specified change in lung function (PD), (2) the change in FEV1 after an airway challenge, and (3) the fraction of subjects with increased AHR. Although several effect estimates from the meta-analyses are statistically significant, they are all so small that they are not likely to be clinically relevant. More importantly, there are no exposure-response associations for any effect estimates based on linear meta-regressions or analyses of effect estimates for exposure groups (0.1 to <0.2 ppm, 0.2 to <0.3 ppm, etc.). This is also generally the case for analyses stratified by airway challenge (specific/nonspecific), exposure method (mouthpiece/whole chamber), and activity during exposure (rest/exercise). The results of these analyses indicate that, to the extent the effects observed are associated with NO2 exposure, they are sufficiently small such that they do not provide evidence that NO2 has a significant adverse effect on AHR at concentrations up to 0.6 ppm.