Effects of nitrogen dioxide on human health: systematic review of experimental and epidemiological studies conducted between 2002 and 2006.

In order to assess health effects in humans caused by environmental nitrogen dioxide (NO(2)) a systematic review of studies in humans was conducted. MEDLINE database was searched for epidemiological studies and experiments on adverse effects of NO(2) published between 2002 and 2006. The evidence with regard to NO(2) exposure limits was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) grading system and the modified three star system. Of the 214 articles retrieved 112 fulfilled the inclusion criteria. There was limited evidence that short-term exposure to a 1-h mean value below 200 microg NO(2)/m(3) is associated with adverse health effects provided by only one study on mortality in patients with severe asthma (*2+). The effect remained after adjusting for other air pollutants. There was moderate evidence that short-term exposure below a 24-h mean value of 50 microg NO(2)/m(3) at monitor stations increases hospital admissions and mortality (**2+). Evidence was also moderate when the search was restricted to susceptible populations (children, adolescents, elderly, and asthmatics). There was moderate evidence that long-term exposure to an annual mean below 40 microg NO(2)/m(3) was associated with adverse health effects (respiratory symptoms/diseases, hospital admissions, mortality, and otitis media) provided by generally consistent findings in five well-conducted cohort and case-control studies with some shortcomings in the study quality (**2+). Evidence was also moderate when the search was restricted to studies in susceptible populations (children and adolescents) and for the combination with other air pollutants. The most frequent reasons for decreased study quality were potential misclassification of exposure and selection bias. None of the high-quality observational studies evaluated was informative for the key questions due to the choice of the dose parameter (e.g., 1-week mean) and exposure levels above the limit values. Inclusion of study designs unlisted in the SIGN grading system did not bring additional evidence regarding exposures below the current air quality limit values for NO(2). As several recent studies reported adverse health effects below the current exposure limits for NO(2) particularly among susceptible populations regarding long-term exposure further research is needed. Apart from high-quality epidemiological studies on causality and the interaction of NO(2) with other air pollutants there is a need for double-blinded randomized cross-over studies among susceptible populations for further evaluation of the short-term exposure limits.