Biological effects of inhaled nitrogen dioxide in healthy human subjects

Int Arch Occup Environ Health. 2016 Aug;89(6):1017-24. doi: 10.1007/s00420-016-1139-1. Epub 2016 May 7.


Purpose: Several epidemiological studies indicate that inhaled nitrogen dioxide (NO2) at low concentrations have been statistically associated with adverse health effects. However, these results are not reflected by exposure studies in humans. The aim of the study was to assess the acute functional and cellular responses to different NO2 concentrations in healthy human subjects with various techniques.

Methods: Twenty-five subjects were exposed for 3 h to NO2 concentrations 0, 0.1, 0.5, and 1.5 ppm in a randomized crossover study design during 4 consecutive weeks. In each subject, lung function, diffusion capacity and exhaled nitric oxide were measured and inflammation markers were assessed in blood, nasal secretions, induced sputum and exhaled breath condensate.

Results: From all lung function indices under consideration, only intrathoracic gas volume was borderline significantly increased after 0.5 ppm (p = 0.048) compared to 0.1 ppm NO2. Regarding the cellular effect parameters, the macrophage concentration in induced sputum decreased with increasing NO2 concentration, although these changes were only borderline significant (p = 0.05).

Conclusion: These results do not suggest a considerable acute adverse response in human subjects after 3 h of exposure to NO2 in the NO2 concentration range investigated in this study.

Keywords: Exposure; Human subjects; Nitrogen dioxide; Systemic effects; Topic effects.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Cross-Over Studies
  • Female
  • Healthy Volunteers
  • Humans
  • Inflammation Mediators / analysis
  • Inhalation Exposure / adverse effects*
  • Lung / drug effects*
  • Macrophages / drug effects
  • Male
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism
  • Nitric Oxide / analysis
  • Nitrogen Dioxide / toxicity*
  • Pulmonary Diffusing Capacity / drug effects
  • Pulmonary Elimination / drug effects
  • Respiratory Function Tests
  • Sputum / cytology
  • Sputum / drug effects
  • Young Adult


  • Inflammation Mediators
  • Nitric Oxide
  • Nitrogen Dioxide