Nitrogen dioxide exposure and airway responsiveness in individuals with asthma

Abstract

Controlled human exposure studies evaluating the effect of inhaled nitrogen dioxide (NO₂) on the inherent responsiveness of the airways to challenge by broncho-constricting 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 the 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 (i.e. 70% of individuals with asthma exposed to NO₂ at rest) experience increases in airway responsiveness following 30-min exposures to NO₂ in the range of 200 to 300 ppb and following 60-min 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.

• Air pollution
• airway responsiveness
• asthma
• nitrogen dioxide

Declaration of interest

This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. The views expressed in this article are those of the author and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.

Notes

¹Commonly, the provocative dose (PD) is the dose of a challenge agent required to produce a 20% reduction in forced expiratory volume in 1 s (PD20) or a 100% increase in specific airway resistance (PD100).