We found that in-home particle concentrations were associated with asthma morbidity, including symptoms and rescue medication use, among not only atopic but also non-atopic children. Although there were fewer non-atopic (n=41) than atopic children (n=92) in this inner-city, predominantly African American cohort, we found substantial, statistically significant relationships between in-home PM concentrations and asthma outcomes in this group. The magnitude of the response to PM was similar in non-atopic and atopic children. To our knowledge, this is the first study to focus on the relationship between atopic status and the health effects of indoor PM.
There has been relatively little attention paid to environmental triggers of non-atopic asthma. Of the few studies that have examined the effect of indoor PM on children with asthma, most have not evaluated susceptibility among non-atopic asthmatics. Studies of children in Seattle found that higher indoor and outdoor PM concentrations were associated with lower maximal midexpiratory flows among a subgroup of 11 children who were not taking anti-inflammatory medications but the atopic status of participants was not assessed.15, 16
In a study based in Southern California, FEV1
was inversely associated with personal and indoor PM concentrations among 19 children with asthma11
In a subset of 12 male children in this study, an analysis of the influence of atopic status on the susceptibility to PM exposure revealed mixed results. Atopic boys showed stronger inverse associations between personal PM and FEV1
, but weaker associations between stationary-site PM and FEV1
, compared to non-atopic boys, (though this latter difference was not significant). In our larger present study, we found evidence that both atopic and non-atopic children were similarly adversely impacted by indoor airborne PM exposure.
In addition to PM, several other indoor pollutants have been shown to impact those with non-atopic asthma and may even disproportionately affect non-atopic as compared to atopic asthma. For example, some studies of secondhand smoke exposure have shown a stronger effect in terms of the incidence and disease severity among non-atopic children with asthma compared to those with atopy.27–30
Based on previous work, we have determined that penetration of outdoor air into indoor space and indoor smoking, cooking, and cleaning activities contributed to elevated in-home PM concentrations.8
Secondhand smoke is likely to contribute to the asthmatic response that is associated with indoor PM exposure in our study. Increased levels of NO2
were associated with increased asthma symptoms and decreased peak flows only among non-atopic asthmatic children in one study,6
and in our inner city Baltimore cohort, indoor NO2
levels were associated with increased asthma morbidity, independent of atopic status.31
These findings suggest that environmental controls aimed at pollutants may be especially important to the non-atopic asthmatic.
Studies have not only suggested that pollutant exposure exacerbates existing non-atopic asthma but also that pollutant exposure may increase susceptibility to the development of non-atopic asthma, though these results have been inconsistent. In a study that investigated susceptibility to the risk of childhood asthma and wheeze with exposure to traffic, living within 75 meters of a major road was associated with a more than 2-fold increased risk of lifetime asthma, prevalent asthma, or current wheeze among children without allergic symptoms but not among those with allergic symptoms.32
Another recent study suggested that traffic-related pollution exposure increased the risk of incident asthma and of asthma-related symptoms and that this effect may be limited to non-atopic asthma but, according the study authors, the small sample size limited their ability to interpret this finding.33
However, other studies have yielded different conclusions, supporting stronger responses to traffic-related pollutant exposure among atopic children.34, 35
Evidence suggests that the cellular response is similar between non-atopic and atopic asthma36–38
but that the allergens and antigens that “trigger” asthmatic responses may differ. Exposure to allergen and a subsequent allergic inflammatory response with associated bronchial hyperreactivity is associated with exacerbation of allergic asthma. For allergic asthma, pollutants may provoke asthma through various mechanisms and hypotheses propose that particulate pollution can directly stimulate an inflammatory response or it can serve as a vehicle for carrying allergen and therefore provoke asthma through atopic pathways. Laboratory evidence supports this concept and suggests that air pollution exposure enhances the effect of allergens on asthma.39–41
Interestingly, exposure to PM collected outdoors in Baltimore has also been shown to directly induce airway hyperresponsiveness and airway inflammation in mice in the absence of exogenous exposure to allergens in a T cell dependent manner.42
Although no known protein allergens have been found in these samples of outdoor Baltimore PM, it is possible previously unrecognized allergens are present or that PM induces cellular damage and leads to modification of self-proteins leading to T cell activation in the absence of atopy. In support of the former hypothesis, Burney and colleagues reported that in human studies exacerbations of asthma were associated with increases in the patient's IgE binding to outdoor airborne particles collected during the weekend preceding the exacerbation as compared to control weekends in both non-atopic and atopic asthmatics.43
Taken together studies suggest that non-atopic patients can respond to previously unrecognized airborne antigens in a manner similar to atopic asthmatics, but in the absence of atopy.
There are limitations to our study, including that we do not have biologic measures to investigate mechanistic differences between atopic and non-atopic responses to indoor pollutant exposure. A study currently underway44, 45
is examining potential differences in the inflammatory and oxidative stress responses between non-atopic and atopic asthmatics. While it is challenging to assess exposure in all microenvironments, our measurement of indoor PM was performed in the home where children spent about half of their time (average of 12 hours) and most of this time was spent in the bedroom where the environmental equipment was placed. We were also able to adjust for ambient PM concentrations in our models. While we were not able to account for additional potential co-pollutants, we were able to adjust for ambient PM concentrations in our models. The classification of atopic status represents a single point in time during pre-school age and we acknowledge that atopic status may change in these children over time. However, we were able to perform skin testing using a comprehensive panel of allergens that represent common environmental exposures in this community. The size of the present study is a strength, providing an evaluation of atopic status in a large, well characterized cohort of patients with extensive environmental monitoring, overcoming some limitations of previous studies of indoor PM that included sample sizes of less than 20 subjects.11, 12, 15, 16
Guideline recommendations for the management of asthma include environmental control practices that focus largely on allergen avoidance for those with atopic asthma.46, 47
There are very few environmental control practice recommendations that address airborne pollutants, mainly due to the lack of strong evidence supporting a beneficial health effect of pollutant reduction. The present study demonstrates that exposure to indoor PM is associated with increased asthma morbidity among both atopic and non-atopic children. As there are relatively fewer competing causes for exacerbations of non-atopic asthma, environmental control practices that decrease exposure to pollutants may confer an even greater health benefit for this group. In the few major asthma intervention trials48, 49
, non-atopic children have sometimes been excluded from participation.49
The inclusion of non-atopic children should be emphasized in future studies and comparison of responses to environmental control practices between non-atopic and atopic should be reported.