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Nitrogen Dioxide Exposure and Airway Responsiveness in Individuals with Asthma
Citation:
Brown, James. Nitrogen Dioxide Exposure and Airway Responsiveness in Individuals with Asthma. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 27(1):1-14, (2014).
Impact/Purpose:
Following review of the first external review draft of the Integrated Science Assessment for Oxides of Nitrogen (NOx ISA), the Clean Air Scientific Advisory Committee suggested that draft materials describing airway responsiveness data be revised in response to their comments and submitted for peer-reviewed publication. The resulting paper provides new analyses of airway responsiveness data and discusses factors that may have affected the experimental determination of airway responsiveness in NO2 studies. The analyses show the log-normal distribution of data and quantify the fraction of individuals with asthma experiencing a clinical relevant increase in airway responsiveness following NO2 exposure. This paper will support the NOx ISA and quantifies the effect of brief NO2 exposures on the respiratory health of individuals with asthma.
Description:
Controlled human exposure studies evaluating the effect of inhaled NO2 on the inherent responsiveness of the airways to challenge by bronchoconstricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway responsiveness of individuals with asthma. However, no meta-analysis has provided a comprehensive assessment of clinical relevance of changes in airway responsiveness, the potential for methodological biases in the original papers, and the distribution of responses. This paper provides analyses showing that a statistically significant fraction, 70% of individuals with asthma exposed to NO2 at rest, experience increases in airway responsiveness following 30-minute exposures to NO2 in the range of 200 to 300 ppb and following 60-minute exposures to 100 ppb. The distribution of changes in airway responsiveness is log-normally distributed with a median change of 0.75 (provocative dose following NO2 divided by provocative dose following filtered air exposure) and geometric standard deviation of 1.88. About a quarter of the exposed individuals experience a clinically relevant reduction in their provocative dose due to NO2 relative to air exposure. The fraction experiencing an increase in responsiveness was statistically significant and robust to exclusion of individual studies. Results showed minimal change in airway responsiveness for individuals exposed to NO2 during exercise. A variety of factors that may affect the assessment of airway responsiveness and how those factors may directionally bias the results of individual studies and the analyses in this current assessment are considered.
URLs/Downloads:
http://www.tandfonline.com/doi/abs/10.3109/08958378.2014.979960
BROWN.PDF (PDF, NA pp, 5694 KB, about PDF)