Asthma is the most prevalent chronic respiratory disease worldwide and is the leading chronic disease in children. In the United States (US), an estimated 6.2 million children have asthma.(1) Given that asthma typically starts in early childhood and is chronic in nature, poor asthma control has implications for pulmonary health throughout the life course.
Exposure to environmental allergens is a leading cause of asthma exacerbation, estimated to trigger asthma attacks in 60–90% of children (2) through promotion of airway inflammation and bronchial hyperresponsiveness.(3) Allergens commonly found indoors are particularly important due to increased exposure potential from time spent in the home. Many environmental allergens (e.g., house dust mites, cockroach, mold, pet dander, mice) are associated with asthma exacerbation, however studies around the world have found that exposure to cockroach antigen (e.g., Bla g 1, Per a 2) has the greatest effect, particularly on severe outcomes.(4–7) Among a cohort of moderate to severe asthmatics in New Orleans, Louisiana, children exposed to Bla g 1 > 2U/g were four times as likely to be hospitalized compared to their unexposed peers despite sensitization and exposure to multiple indoor allergens.(5) Similarly, in the National Cooperative Inner-City Asthma Study children in the US sensitized and exposed to cockroach were 3.4 times as likely to be hospitalized.(6) In Poland, 61% of children with cockroach sensitivity had severe asthma, compared to 36% of sensitized children exposed to other indoor allergens.(8) Among patients with persistent asthma in Taiwan, IgE-binding to American cockroach allergen (Per a 2) was associated with severe airway allergy and elevated proinflammatory chemokines.(9)
Most studies of cockroach allergen and asthma outcomes have reported cockroach exposure based on measurement of allergens (e.g. Bla g 1) in dust samples from participants’ homes. However, visual inspection of homes, specifically looking for evidence of cockroaches has been shown to be predictive of allergen exposure. Cohn et al. reported that homes where field staff observed living or dead cockroaches or cockroach stains or occupants reported seeing cockroaches in the previous month were significantly more likely to have Bla g 1 allergen levels above 8 U/g.(10)
Cockroach exposure is common, particularly in urban areas and in the home of those with low income status. Low-income households in the US have been found to be 12 times as likely to have high cockroach allergen (> 8 U/g) compared to households with high income.(11–13) Due to the high prevalence in inner city homes, research has primarily been conducted in urban cohorts. However, in addition to increased exposure to cockroach, inner city residence is also associated with high levels of stress, which is itself associated with negative asthma outcomes. Pertinent to childhood asthma, caregiver stress negatively impacts disease management(14) and can cause stress in the child leading to alterations in immune response (e.g., IgE, Bla g 2 proliferative response) and cytokine expression (e.g., IFN-γ, TNF-α, IL-10, IL-13).(15–17) Exposure to stress has also been shown to increase susceptibility to environmental triggers by modulating the response to oxidative stress.(18, 19) Finally, poor housing condition, which is not uncommon in inner city environments, is associated with cockroach infestation(20, 21) and has been shown in numerous studies to be linked to increased psychological stress.(21, 22)
Despite the high prevalence of both cockroach exposure and stress in inner-city homes, to our knowledge there are no studies evaluating the impact of their joint exposure on childhood asthma morbidity. Therefore, it is possible that the strong association between cockroach and negative asthma outcomes may, in part, be the result of uncontrolled confounding by stress rather than the result of increased potency of cockroach antigen. Given that stress makes children more susceptible to asthma triggers, another possibility is that the strong role of cockroach may be the result of effect modification resulting from joint exposure.(18, 23–25)
The objective of this analysis is to examine the relationship between cockroach exposure, stress, and asthma morbidity by evaluating various pathways by which they may be interrelated. The hypothesized relationships are rooted in the biopsychosocial framework (Fig. 1.) adapted from Wright et. al.(26) Based on this framework three hypotheses were tested. First, that previous findings on the unique association between cockroach exposure and asthma are biased by the lack of control for stress. Second, that joint exposure to cockroaches and stress results in effect measure modification. Finally, that cockroach impacts asthma through its association with stress.(21, 26, 27) To examine this, a mediation analysis examined the mechanistic process that underlies the relationship between cockroach, stress, and asthma.