Persistent Airway Inflammation but Accommodated Antioxidant and Lung Function Responses after Repeated Daily Exposure to Nitrogen Dioxide

Abstract

Nitrogen dioxide (NO2) is a common indoor and outdoor air pollutant that may induce deterioration of respiratory health. In this study the effects of repeated daily exposure to NO2 on airway antioxidant status, inflammatory cell and mediator responses, and lung function were examined. Healthy nonsmoking subjects were exposed under controlled conditions to air (once) and to 2 ppm of NO2 for 4 h on four consecutive days. Lung function measurements were made before and immediately after the end of each exposure. Bronchoscopy with endobronchial biopsies, bronchial wash (BW), and bronchoalveolar lavage (BAL) was carried out 1.5 h after the air exposure and after the last exposure to NO2. Repeated NO2 exposure resulted in a decrease in neutrophil numbers in the bronchial epithelium. The BW revealed a twofold increase in content of neutrophils (p < 0.05) and a 1.5-fold increase in myeloperoxidase (MPO) (p < 0.01) indicative of both migration and activation of neutrophils in the airways. After the fourth NO2 exposure, antioxidant status of the airway fluid was unchanged. Significant decrements in FEV1 and FVC were found after the first exposure to NO2, but these attenuated with repeated exposures. Together, these data indicate that four sequential exposures to NO2 result in a persistent neutrophilic inflammation in the airways, whereas changes in pulmonary function and airway antioxidants are resolved. We conclude that NO2 is a proinflammatory air pollutant under conditions of repeated exposure.

Indoor NO2 air pollution and lung function of professional cooks

“…In addition, the presence of indoor pollutants, even at low concentrations, may have an important biological impact because of long periods of exposure. This is much more than the four peaks reported in experimental study (36). In this real situation, more than producing a chronic and silent inflammatory process, NO 2 and the other pollutants can really be harmful, producing chronic damage to the respiratory system.…”

“…Frampton et al (35) found an inflammatory response that persisted at least 18 h after exposure, while Blomberg et al (36) demonstrated major decrements in FEV 1 just after exposure and this lung function indicator response was attenuated after repeated exposures, even in the presence of a persistent neutrophilic inflammation in the airways. They concluded that NO 2 is a proinflammatory air pollutant under conditions of repeated exposure.…”

Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use.

“…Four experimental studies of mild atopic asthmatic adults have shown an enhancement of airway responses to allergens after exposure to 260-400 ppb NO 2 (30)(31)(32)(33). There is also some evidence that NO 2 exposure leads to persistent neutrophilic infiltration in human airways (34) and to increased histamine release in histocultured human nasal mucosa (35). The inflammatory mechanisms of pollen and fungal allergens in allergic respiratory disease have also been described (36)(37)(38).…”

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…Healthy subjects have been exposed acutely to NO 2 concentrations that range from 0.3 ppm to 2.0 ppm (1-4 hours); sensitive subgroups, including asthmatics and chronic obstructive pulmonary disease patients have been exposed to 0.26-1.00 ppm. Above 1 ppm, clear evidence of inflammation has been observed in healthy subjects in a number of studies (Helleday et al, 1995;Devlin et al, 1999;Pathmanathan et al, 2003;Blomberg et al, 1999), but the picture is less established at concentrations between 0.2 ppm and 1.0 ppm (Vagaggini et al, 1996;Jörres et al, 1995;Gong et al, 2005;Frampton et al, 2002;Riedl et al, 2012), partially because of inconsistent responses in the varying end-points examined.…”