Asthma, Allergy, and the Environment

Prevalence and characteristics of indoor allergen and endotoxin exposures

The NSLAH was the first population-based study to investigate how levels of indoor allergens and endotoxin vary in U.S. households (Vojta et al., Env Health Perspect 2002). The NHANES 2005-2006 assessed indoor allergen and endotoxin levels in bedroom dust collected from nearly 7000 homes, providing the largest nationally representative data resource to date (Salo et al., J Allergy Clin Immunol 2018). Both surveys demonstrated that allergens are found in almost all homes (>99%), cat and dog allergens being the most frequently detected allergens (Salo et al. J Allergy Clin Immunol 2008; Salo et al., J Allergy Clin Immunol 2018). Exposure to multiple allergens was common. More than 90% of NHANES participants had three or more detectable allergens in their homes, and 73% had at least one allergen at elevated levels. Allergen levels were influenced by sociodemographic, regional, climatic and housing factors, but each allergen appeared to have a distinct set of predictors (Arbes et al., J Allergy Clin Immunol 2003; Arbes et al., J Allergy Clin Immunol 2004; Cohn et al., J Allergy Clin Immunol 2004; Salo et al., J Allergy Clin Immunol 2005; Cohn et al., Env Health Perspect 2006; Salo et al., J Allergy Clin Immunol 2018). Allergen and endotoxin levels in the home also varied by room and location. Both surveys showed that lower family income, as well as presence of children, pets, cockroaches, and smokers in the home were consistently associated with higher endotoxin levels, although predictors of elevated endotoxin levels showed variation across climate regions (Thorne et al., Environ Health Perspect 2009; Thorne et al., Am J Respir Crit Care Med 2015; Mendy et al., Environ Int 2018). Presence of pets and pests had a major influence on household allergen burden. Housing characteristics also mattered - elevated exposure to multiple allergens was more likely in mobile homes, older homes, rental homes, and homes in rural areas.

Allergic disease and exposure to indoor allergens and endotoxin

The NSLAH findings highlighted the importance of indoor allergen exposures in asthma exacerbations (Salo et al. J Allergy Clin Immunol 2008). However, the relationship between allergen exposure and asthma is complex and varies by allergen type (Salo et al., Curr Allergy Asthma Rep 2018). For example, exposure to elevated mouse allergen levels significantly increased the likelihood of asthma symptoms only in allergic individuals (Salo et al., Environ Health Perspect 2009), whereas elevated Alternaria levels in the home increased the likelihood of having asthma symptoms in all participants (Salo et al., J Allergy Clin Immunol 2006). Exposure to cat and dog allergens, which is widespread and common in U.S. homes, was associated with increased asthma morbidity in pet-sensitive individuals. Our NHANES finding suggested that 44% of asthma attacks were attributable to exposure to high levels of dog allergen among dog-sensitive asthmatics and 30% were attributable to elevated cat allergen exposure among cat-sensitive asthmatics (Gergen et al., J Allergy Clin Immunol Pract 2018). Although allergic sensitization in adults tends to decrease with increasing age, sensitization to indoor allergens remains an important asthma risk factor in the elderly (Busse et al., Ann Allergy Asthma Immunol 2013). Our studies suggest that asthma-related symptoms are also influenced by endotoxin levels and total dust exposure in the home (Thorne et al., Am J Respir Crit Care Med 2005; Elliott et al., Environ Health Perspect 2007; Thorne et al., Am J Respir Crit Care Med 2015; Mendy et al., J Allergy Clin Immunol 2018).

While asthma in the U.S. is largely allergic in nature (Arbes et al., J Allergy Clin Immunol 2007), the group showed that a significant portion of asthma is independent of IgE levels, either total or specific (Gergen et al., J Allergy Clin Immunol 2009). The data from NHANES 2005-2006 demonstrated that total IgE predicted asthma only in allergic individuals, but not among non-allergic subjects.

Our studies have provided quantitative and qualitative information on sensitization patterns in the general U.S. population and highlighted the importance of different allergens in commonly reported allergic conditions (Arbes et al., J Allergy Clin Immunol 2005; Arbes et al., J Allergy Clin Immunol 2007; Salo et al., J Allergy Clin Immunol 2011; Salo et al., J Allergy Clin Immunol 2014). Although food allergy is a growing public health concern, the national prevalence and patterns of food allergy are not well characterized. In collaboration with investigators at the National Jewish Medical and Research Center, the group developed estimates of the prevalence of and demographic factors for food allergy, identified high-risk populations, and explored associations with other immune-mediated conditions, including asthma, using data from the NHANES 2005-2006 (Liu et al., J Allergy Clin Immunol 2010). In collaboration with researchers at Johns Hopkins, we also examined changes in food sensitization over time in U.S. children (McGowan et al., J Allergy Clin Immunol Pract 2016; McGowan et al., Ann Allergy Asthma Immunol 2016; McGowan et al., Ann Allergy Asthma Immunol 2019).

Modifying factors for allergic disease

The group has also actively investigated the role of modifying factors in the prevalence and exacerbation of allergic diseases. Our collaborative work showed that obesity is associated with asthma and allergic status in children (Visness et al., J Allergy Clin Immunol 2009; Visness et al., J Asthma 2010). More recently, we have examined the role of climatic factors as well as air pollution and phthalate exposures in allergic sensitization and disease (Hoppin et al., Environ Health Perspect 2013; Weir et al., Respir Med 2013; Mendy et al., Environ Int 2018; Mendy et al., Am J Respir Crit Care Med 2019).

Because systemic inflammation might contribute to the development of allergic disease, the group has investigated the role of systemic inflammation in asthma pathogenesis in more detail. Little is known about relationships between cholesterol and inflammatory lung disease, although there is emerging evidence that cholesterol metabolism and inflammation are linked in the lung. In collaboration with Michael Fessler, M.D., the group found novel, inter-racial differences in the relationship between serum cholesterol and allergic disease (Fessler et al., J Allergy Clin Immunol 2009; Fessler et al., Allergy 2010). Our subsequent studies showed associations between atopy and myocardial infarction and characterized the relationship between serum cholesterol and circulating erythrocyte/platelet indices in U.S. adults (Jaramillo et al., J Allergy Clin Immunol 2013; Fessler et al., J Lipid Res 2013). Our recent findings also suggest that residential endotoxin exposure may influence peripheral white blood cell counts and systemic inflammatory state (Fessler et al., Environ Health Perspect 2017).

Environmental Interventions and Allergen Mitigation

The group has conducted studies to test the feasibility and effectiveness of various interventions to reduce indoor allergen levels in homes. Since sensitization to dust mite and cockroach allergens is an important asthma risk factor, the group focused its initial efforts on the development of effective dust mite and cockroach allergen mitigation strategies (Vojta et al., Env Health Perspect 2001). While asthmatics and others with dust mite allergies are encouraged to implement strategies to avoid dust mite exposure, they often lack objective evidence that their efforts are successful in reducing dust mite allergen levels. Commercial in-home test kits have introduced the capability to monitor the effectiveness of allergen reduction strategies by providing an affordable, simple way to measure dust mite allergen levels on a regular basis. Our recent study findings suggest that the use of test kits along with education may beneficially influence behaviors and attitudes toward dust mite reduction strategies and help reduce residential dust mite allergen levels (Winn et al., J Asthma 2016).

The group’s collaborative work with Dr. Coby Schal (North Carolina State University) has resulted in significant reductions in residential cockroach allergen levels through the use of a novel, efficient eradication method (Arbes et al., J Allergy Clin Immunol 2003; Arbes et al., J Allergy Clin Immunol 2004).This method utilizing intensive cockroach extermination was validated in a year-long study where we compared the new method with extermination services provided by commercial pest control companies. Our eradication method proved to be much more effective than pest control services offered by commercial companies. While the homes serviced by commercial pest control companies also experienced reductions in the number of cockroaches in the homes, the magnitude of the reduction was significantly lower than in the homes that received the novel treatment. The cockroach infestation remained relatively high after 12 months, and changes in cockroach allergens in homes serviced by commercial pest control companies were not different from those in untreated control homes (Sever et al., J Allergy Clin Immunol 2007). Although additional research is warranted to test the efficacy of this method in reducing asthma morbidity, a recent study using our cost-effective strategy for cockroach abatement reported improved asthma outcomes in children (Rabito et al., J Allergy Clin Immunol 2017).

Summary

The Zeldin group’s research has:

• Provided nationally representative estimates on indoor allergen and endotoxin exposures in the U.S. population
• Improved understanding of the characteristics and predictors of indoor allergen and endotoxin exposures
• Characterized quantitative and qualitative IgE-mediated sensitization patterns in the U.S. population
• Led to better understanding of the national prevalence patterns of food allergy
• Highlighted the importance of indoor allergens and endotoxin exposures in asthma morbidity
• Increased knowledge on potentially modifiable risk factors for asthma and other allergic diseases
• Led to novel methodologies that are used in epidemiological and interventional studies