Sulfur Dioxide
The effects of SO2 have been extensively reviewed. Total emergency room visits for respiratory problems and increased hospital admission rates have been linked with increased ambient exposure to SO2. In children, decreased lung function has been linked to increases in ambient sulfur dioxide levels and the likelihood of chronic asthma or obstructive lung disease likewise is associated with lifetime exposure to SO2. However, in many of these studies, it is difficult to separate effects of sulfur dioxide from that of particulate air pollutants. Additionally, ambient SO2 may contribute to acid aerosol (H2SO4) formation and may exert effects either as a gas or by contributing to H2SO4 particle formation.
Challenge studies with sulfur dioxide do not demonstrate substantial inflammatory effects at concentrations encountered in ambient air. However, this gas has potent bronchospastic effects, with most asthmatics reacting at 0.50 ppm. In contrast, normal volunteers are unaffected, with concentrations as high as 0.6 ppm while sensitive asthmatics FEV1 can drop by as much as 60% at concentrations as low as 0.25 ppm. SO2-related symptoms in asthmatics include wheezing, chest discomfort, and dyspnea. SO2 has a rapid onset of action, with responses observed within 2 min into exposure, becoming maximal within 5–10 min. Spontaneous recovery occurs within 30 min and exposed asthmatics are refractory to the effects of SO2 for up to 4 h after initial exposure. Repeated exposures to SO2 induce tachyphylaxis as well.
Nasal breathing has been shown to largely mitigate the effect of SO2 in asthmatics, likely due to absorption of this water-soluble gas by the nasal mucosa. Exercise results in a shift from strictly nasal breathing to combined oral and nasal respiration, thus increasing the amount of SO2 that will reach the lower airway, and possibly accounting for the effect of exercise on sensitivity to SO2. Additionally, asthmatics have a high occurrence of nasal co-morbidities (such as allergic rhinitis or sinusitis), which may further decrease nasal airflow, possibly contributing to sensitivity to the effect of SO2 by increasing effect dose to the lower airway.
Nitrogen Dioxide
Epidemiological studies have shown a strong association between ambient air NO2 and both chronic and acute changes in lung function. In human challenge studies, NO2 has been shown to enhance airway inflammation, a prominent feature of asthma. In non-asthmatics, NO2 exposure is associated with an influx of airway PMNs. NO2 has been shown to induce pro-inflammatory cytokine production in epithelial cells following in vitro pollutant exposure. Overall, these data suggest that NO2 could influence airway function of asthmatics by increasing airway inflammation. However, most studies fail to show an effect of low levels of NO2 on non-specific airway reactivity. Higher levels of NO2 (4.0 ppm) may impact airway function of asthmatics.
However, a number of studies have demonstrated that NO2 has a more impressive effect on response to airway allergen challenge in allergic asthmatics. Exposure to 0.4 ppm NO2 for 4 h has been reported to enhance response to airborne allergen. Additionally, a combination of 0.2 ppm SO2 and 0.4ppm NO2 for 6 h enhances immediate bronchial responses of mild asthmatics to inhaled allergen. Exposure to NO2 also enhances late-phase responses of asthmatics to airborne allergen. Likewise, exposure to 0.4 ppm NO2 for 6 h increases allergen-induced ECP in the nasal airways of allergic asthmatics. Taken together, these studies demonstrate that NO2 can augment acute response to allergen in atopic subjects.
Ozone
An overwhelming number of studies demonstrate that there is an association between increased levels of ambient air ozone and exacerbations of asthma, as measured by hospitalizations, rescue medication use, and symptoms. Of note is a 24–48 h time lag between the ozone exposure and occurrence of hospital admission. Gent et al reported that even ozone levels significantly less that the current NAASQ for ozone are also associated with increased exacerbations of asthma. Overall, ozone exposure is strongly associated with increased asthma morbidity, and is a major trigger for asthma exacerbation in summer months.
While ozone is thought of as a major cause of asthma exacerbation, there is mounting evidence that chronic exposure to ozone is linked to increased occurrence of lung disease. A cohort of 3535 children with no history of asthma from 12 schools in southern California was studied for up to 5 years, with 265 children developing a new diagnosis of asthma during this observation period. It was observed that participation in outdoor sports (presumably associated with increased minute ventilation) in areas of increased ozone concentration was a risk factor for asthma development relative to similar exercise in areas where ozone exposures were low. McDonnell and colleagues prospectively studied a cohort of 3091 adult non-smokers. Over a 15-year interval, new diagnoses of asthma by a physician occurred in 3.2% of men and 4.3% of women. In the men (but not the women) with newly diagnosed asthma, the 20-year mean 8-h average for ambient ozone levels was a significant risk factor associated with new asthma (relative risk (RR) of 2.09 for a 27 ppb increase in ambient air ozone. As with NO2, chronic exposure to O3 is also associated with decreased lung function, as noted in a study of 255 college students from regions with high and low pollution levels. In this study, chronic ambient O3 levels were linked to decreased measures of small airways function (as assessed by FEF75 and FEF25–75), which is not altered after accounting for a history of chronic respiratory disease, allergy, second-hand exposure to environmental tobacco smoke, exposure to PM10, and NO2. Taken together, these and other reports indicate that chronic ozone exposure contributes to disease causation.
