Asthma, Allergy, and the Environment
Environmental Cardiopulmonary Disease Group
The Zeldin group is active in research on the role of the environment in the pathogenesis of asthma and allergic diseases. This project has mainly focused on indoor allergen and bacterial lipopolysaccharide (LPS, endotoxin) exposures, which are important asthma risk factors. To achieve better understanding of the role of these exposures in asthma and other allergic diseases, we previously conducted the National Survey of Lead and Allergens in Housing (NSLAH) in collaboration with the Department of Housing and Urban Development (Vojta et al., Env Health Perspect 2002; Jacobs et al., Env Health Perspect 2002). To further these investigations, we developed and implemented an allergy/asthma-focused component for the National Health Nutrition Examination Survey (NHANES) in collaboration with the National Institute of Allergy and Infectious Diseases and the National Center for Health Statistics. This component, included in the NHANES 2005-2006 survey cycle., queried on allergy and asthma prevalence and morbidity, measured levels of common indoor allergens and endotoxin in bedroom reservoir dust, and quantified total and 19 allergen-specific IgEs (sIgE) in serum of participants (Hoppin et al., Am J Epidemiol 2011). In addition to large observational studies, we have conducted environmental interventions to reduce indoor allergen levels in homes.
Prevalence and characteristics of indoor allergen and endotoxin exposures
The NSLAH was the first population-based study to provide information about how levels of indoor allergens and endotoxin vary in U.S. households. The NSLAH surveyed a nationally representative sample of 831 housing units, inhabited by 2,456 individuals, in 75 different locations throughout the U.S. (Vojta et al., Env Health Perspect 2002). Exposure to multiple allergens was common in U.S. homes (Salo et al. J Allergy Clin Immunol 2008). Of the surveyed homes, 52 percent had at least 6 detectable allergens and 46 percent had at least 3 allergens exceeding elevated levels. Alternaria, cat (Fel d 1) and dog (Can f 1) allergens were detected in almost all homes (>99 percent), and these allergens were also most often found at increased levels. Dust mite allergens (Der f 1 and Der p 1) were detected in at least 85 percent of the surveyed homes, and detectable levels of mouse (MUP) and cockroach (Bla g 1) allergens were found in 82 percent and 63 percent of the households, respectively. The NSLAH demonstrated that individual allergen levels are strongly associated with regional, racial/ethnic, and socioeconomic factors, although each allergen appears 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; Arbes et al., J Allergy Clin Immunol 2005; Cohn et al., Env Health Perspect 2006). While residential endotoxin concentrations are variable depending on location sampled within the home and region of the country, increased endotoxin levels in bedrooms are consistently associated with lower family income as well as presence of children, pets and smokers in the home (Thorne et al., Environ Health Perspect 2009; Thorne et al., Am J Respir Crit Care Med 2015).
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. 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, irrespective of participant's allergic status (Salo et al., J Allergy Clin Immunol 2006). 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 (Salo et al., J Allergy Clinical Immunol 2005; Elliott et al., Environ Health Perspect 2007; Thorne et al., Am J Respir Crit Care Med 2015).
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).
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 examined the role of air pollution and phthalate exposures in allergic sensitization and disease (Hoppin et al., Environ Health Perspect 2013; Weir et al., Respir Med 2013).
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).
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 2015).
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). We are currently testing the efficacy of this new method in reducing asthma morbidity in children.
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