Indoor allergen exposure and asthma outcomes

Abstract

Purpose of review

The aim of the present review is to discuss updates on research regarding the relationship between indoor allergen exposure and childhood asthma with a focus on clinical effects, locations of exposure, and novel treatments.

Recent findings

Recent data continue to demonstrate that early life sensitization to indoor allergens is a predictor of asthma development later in life. Furthermore, avoidance of exposure to these allergens continues to be important especially given that the vast majority of children with asthma are sensitized to at least one indoor allergen. New research suggests that mouse allergen, more so than cockroach allergen, may be the most relevant urban allergen. Recent evidence reminds us that children are exposed to clinically important levels of indoor allergens in locations away from their home, such as schools and daycare centers. Exposure to increased levels of indoor mold in childhood has been associated with asthma development and exacerbation of current asthma; however, emerging evidence suggests that early exposure to higher fungal diversity may actually be protective for asthma development. Novel treatments have been developed that target TH2 pathways thus decreasing asthmatic responses to allergens. These therapies show promise for the treatment of severe allergic asthma refractory to avoidance strategies and standard therapies.

Summary

Understanding the relationship between indoor allergens and asthma outcomes is a constantly evolving study of timing, location, and amount of exposure.

INTRODUCTION

Exposure to aeroallergens is an important factor in the pathogenesis and control of allergic diseases, including asthma. Indoor allergens are of particular importance and principally include house dust mites, pets such as dogs and cats, pests such as cockroach and rodents, and molds. The relative importance of these different allergens varies based on different environmental factors depending on geographic, climatic, socioeconomic, and housing conditions. The measurement of indoor allergen levels in dust and air samples has allowed for the determination of risk levels associated with the development of sensitization and symptomology. In the present review, we summarize recent data regarding indoor allergen exposures and the associations with asthma morbidity. This review will focus on the most common indoor allergens including allergens from dust mite, cat, dog, mouse, cockroach, and molds. A specific focus has been placed on intriguing recent findings including new methods to measure indoor allergens, inner-city exposures, and allergen exposures in schools or daycare centers. In addition, new treatments that effectively disrupt the association between indoor allergen exposure and asthma symptoms will be presented. This review will not discuss exposures to indoor air pollutants or microbial products that are important, but beyond the scope of this topic.

OVERVIEW AND EPIDEMIOLOGY

Studies indicate that more than 80% of school age children with asthma are sensitized to at least one indoor allergen and that allergic sensitization is a strong predictor of disease persistence in later life [1–3]. In fact, in a cohort of children hospitalized for asthma, 91% were found to be sensitized to at least one indoor allergen [4]. Bjerg et al. [5] have shown that while pollen sensitization is strongly associated with the development of rhinitis, indoor allergen sensitization was more associated with asthma. The timing of sensitization is also an important factor as a recent study demonstrated that aeroallergen sensitization at younger ages was associated with an increased risk of asthma in later childhood [6^▪].

NEW WAYS TO MEASURE INDOOR ALLERGEN EXPOSURE AND TO IDENTIFY ALLERGEN SENSITIZATION

Indoor allergens are typically measured in dust samples that are collected by either vacuuming settled dust or gathering airborne dust from filtered air within a room. Samples may be collected from multiple sites within a home. After collection, fine dust can then be extracted and tested for quantification of individual allergens. Typical dust sampling has relied on spot checks at a certain time point of vacuuming, which measures exposure levels in that exact location. Tovey et al. [7] recently developed a novel method to measure dust mite exposures in individuals over 24-h periods and found that exposures fluctuate over time and beds may not always be the main site of exposure as general considered.

Although home sampling is feasible in the clinical research community, there have not been easy-to-use methods for patients or parents to measure the allergen levels in their homes by themselves. Winn et al. [8] evaluated the use of an in-home test kit that allowed parents of dust mite allergic children the ability to easily and quickly quantify the level of dust mites within the home. This study demonstrated that dust mite levels in the ‘testing’ homes were significantly reduced over time compared with control homes that only received education [8]. The authors speculate that immediate knowledge of dust mite levels motivated the parents to more thoroughly perform dust mite avoidance strategies. Future studies are needed to further evaluate the utility and role of patient-directed or parent-directed home allergen measurements in the care of asthma and allergies.

As healthcare trends toward precision medicine where therapies are tailored toward an individual’s exact need, allergic sensitization testing is also heading in this direction. In keeping with this idea of more focused treatments, Chen et al. [9] demonstrated the clinical utility of latent class analysis to identify patterns of allergic sensitization among children. Analyzing these patterns of allergic sensitization revealed additional associations with asthma than the evaluation of a single allergen or total IgE [9]. Identifying patterns of polysensitization may be useful in treatment decisions and prognosis discussion. For example, it was shown that sensitization to cockroach actually reduced the symptom scores in participants with concomitant dust mite and pollen sensitization [10]. Future studies may continue this trend by viewing the whole sensitization profile in a subject instead of focusing on single allergen results.

THE KEY INNER-CITY ALLERGEN: COCKROACH VERSUS MOUSE

Indoor allergen exposure in inner-city areas has been of particular interest given that children living in urban areas have increased asthma severity, decreased asthma control, and greater healthcare use [11]. In the late 1990s, Rosenstreich et al. [12] found cockroach allergen to be highly detectable in inner-city homes. Furthermore, this study demonstrated that children with asthma who were sensitized and exposed to high levels of cockroach allergen had increased asthma morbidity [12]. This landmark study led to cockroach allergen being deemed the important indoor allergen in urban areas; however, mouse allergen has been gaining recognition in recent years [13]. Mouse allergen has been discovered to be prevalent in inner-city homes [14] with home exposure associated with increased asthma morbidity [15]. Outside the home, a study of urban schools found mouse allergen to be the primary school-based allergen, not cockroach allergen [16]. In support of this, Ahluwalia et al. [17] reported that mouse and not cockroach allergen was the major allergen of relevance in inner-city Baltimore. In a city with high levels of both mouse and cockroach allergens, mouse allergen was more strongly and consistently associated with worse asthma outcomes including acute care visits, decreased spirometry, and bronchodilator reversibility [17]. Supporting these results, a more recent study of urban Baltimore and Boston found that sensitization to mouse allergen, but not cockroach, was an independent risk factor for rhinitis in inner-city children with asthma [18]. Although allergen reduction tactics in the inner city often focus on mouse and cockroach allergen, recent results have led to the suggestion that community-based asthma intervention strategies should prioritize reducing mouse allergen exposure [17]. Admittedly, the predominance and clinical importance of mouse versus cockroach allergen in a particular urban area depends on a variety of factors including weather and building conditions. It is expected that future studies will continue to focus not only on identifying the important inner-city allergen, but also efforts to eliminate exposures and improve asthma outcomes.

AWAY FROM HOME: EXPOSURE TO INDOOR ALLERGENS IN OTHER CHILDHOOD SETTINGS, SUCH AS SCHOOL AND DAYCARE CENTERS

Early studies on indoor allergen exposures and asthma outcomes focused on the home environment. Although parents can do their best to reduce or eliminate allergen exposures in the home, children spend a large portion of the day in schools or daycare centers. In recent years, the exposure to indoor allergens has been studied in these locations outside the home. Cat and dog allergens seem to be particularly ubiquitous in society because of the easy transfer of these pet allergens. This has been confirmed by data demonstrating that clinically relevant levels of pet allergens are found in homes without these animals [19]. Furthermore, a recent study of teenagers found that a large majority of cat-sensitized individuals did not live in a home with a cat [20^▪] suggesting that sensitization occurs because of exposures outside the home or due to allergens tracked into the home. For children, the main location for this possible outside exposure is the school setting. In support of this, Almqvist et al. [21] found that cat allergen was transported into schools and associated with worsening of asthma for students with cat allergy who were subjected to this indirect pet exposure.

Indoor allergen exposures in schools are not limited to allergens being tracked in from home, but are sometimes because of allergens intrinsic to the school settings. Permaul et al. [16] noted mouse allergen to be present in high levels in inner-city schools due to infestation within the schools and not passive transfer from students’ homes [22]. For younger children, exposure to dust mites and molds in day care centers was associated with wheezing [23]. Likewise, researchers in Denmark found that high classroom dampness was associated with increased wheezing and decreased spirometry in exposed students [24]. Finally, mold exposure in school classrooms was shown to be significantly associated with current asthma symptoms and asthma symptoms that improved over holidays and weekends when the students were out of school [25^▪▪]. This pattern of symptomatology is analogous to workplace exposures and health outcomes for adults [26]. These findings have prompted suggestions that governmental health policies should consider environmental interventions in schools to improve childhood asthma. It is expected that future research will focus on intervention tactics in schools to reduce allergen exposures and improve students’ respiratory symptoms. These interventions have been successful in homes [27] and now need to be trialed in the school setting.

MOLD EXPOSURE AND ASTHMA

Molds grow best in warm and moist environments within the home including basements, windows frames, and bathrooms. Aspergillus and Penicillium species are generally regarded as the predominant indoor molds, and Alternaria is important in both indoor and outdoor environments. Recent literature in this field has focused on the association of mold exposure in early childhood with the development of atopic conditions including asthma later in childhood. Sharpe et al. [28^▪] recently discovered that reporting mildew odor in the home was associated with an increased risk of childhood asthma. Supporting this, a birth cohort study demonstrated that exposure to moisture damage and visible mold in early infancy were associated with asthma development [29]. More specific measurement of mold exposure yielded similar findings as Oluwole et al. [30] documented that mold levels in dust samples from both play area floors and bedroom mattresses were significantly associated with current asthma. In a meta-analysis, increased levels of Penicillium, Aspergillus, Cladosporium, and Alternaria species were associated with increased exacerbation of current asthma symptoms in children [31].

New research has now focused on the diversity of mold exposures and the associated clinical outcomes because there is growing evidence that exposure to a wide diversity of mold species may actually be protective. For example, Tischer et al. [32^▪▪] found that exposure to higher fungal diversity shortly after birth was associated with a decreased risk of developing wheezing and aeroallergen sensitization in later childhood. Future work should continue to evaluate the role of fungal diversity on the development of atopic conditions.

NEW TREATMENTS TO DISRUPT THE ALLERGEN–ASTHMA ASSOCIATION

Allergen avoidance is considered the first line of treatment for patients with indoor allergen sensitivities and asthma. In general practice, allergen avoidance should be tailored based on an individual’s-specific allergen sensitivities and known environmental exposures. In research, most of the studies in which environmental controls have been effective implemented a multifaceted approach. For example, Morgan et al. [27] demonstrated that a comprehensive environmental intervention in the home was able to reduce levels of indoor allergens and resulted in improved asthma outcomes in children. Certainly, future studies will continue to focus on efficient and cost-effective strategies to reduce allergen exposures in homes and locations outside the home. After allergen avoidance, the mainstays of initial medication therapy include antihistamines, corticosteroids, and leukotriene receptor antagonists.

In recent years, novel therapies targeting TH2 pathways have been successful in decreasing the asthmatic response to allergen triggers. These medications provide hope for the future for patients with allergies and asthma refractory to environmental avoidance strategies and standard medications. Most notably, Krug et al. [33^▪▪] recently reported promising outcomes in individuals taking a DNAzyme that is able to cleave and inactivate GATA3, an important transcription factor of the TH2 pathway. In patients with allergic asthma, treatment with this DNAzyme was able to significantly attenuate both late and early asthmatic responses after allergen challenge [33^▪▪]. Similar disruption of the allergen exposure and asthma pathway was seen after treatment with a monoclonal antibody against thymic stromal lymphopoietin, which is a cytokine thought to be important in initiating allergic inflammation [34]. Other new therapeutic approaches targeting specific cytokines in the TH2 inflammatory pathway have shown promising results for improving asthma outcomes [35–37].

Finally, recent advances in dust mite allergen immunotherapy have shown promising results. Virchow et al. [38] evaluated individuals with dust mite allergy-related asthma and found treatment with novel dust mite sublingual allergen immunotherapy, when compared with placebo, was shown to improve asthma control. A very important secondary finding in this study was that there were no differences in outcomes detected between polysensitized individuals and those monosensitized to dust mite, demonstrating the clinical efficacy of single allergen immunotherapy even in patients with sensitization to multiple allergens [38]. Zolkipli et al. [39^▪] used dust mite allergen oral immunotherapy prophylactically in high-risk, but not yet sensitized, infants less than 12 months of age and found that this early life treatment reduced the development of sensitization to any allergen. The use of single allergen immunotherapy is often the concern regarding oral immunotherapy; however, the targeting of treatment with dust mite allergen makes sense given that this is known to be the most frequent indoor allergen associated with asthma worldwide. In fact, recent laboratory data demonstrated that house dust mite exposure selectively increased the proliferation of bronchial smooth muscle in patients with severe asthma [40]. It is expected that future research will continue to develop oral immunotherapy with a particular focus on dust mites.

CONCLUSION

Exposure to indoor aeroallergens is an important factor in the pathogenesis and control of childhood asthma. Although previous research focused on allergen exposures in homes, emerging research is shifting toward the importance of allergen exposures in schools and daycare centers. Furthermore, new techniques are being developed to more easily and efficiently measure levels of allergen exposure. In urban areas, mouse allergen has become an important exposure and may replace cockroach allergen as the most relevant indoor allergen exposure. Studies continue to demonstrate the association between mold exposure in early childhood and asthma development and symptoms. Although avoidance strategies are always the first line of defense in the treatment of allergies and asthma, novel therapeutics are being developed for patients with severe asthma triggered by allergens.

KEY POINTS.

• Indoor allergen sensitization is common in young children with asthma, and this sensitization is a predictor of asthma persistence later in life.

• Cockroach allergen has traditionally been considered the primary inner-city indoor allergen; however, recent data suggest that mouse allergen may be the most relevant urban allergen exposure.

• In addition to home exposures, children are exposed to a wide variety of clinically relevant allergens in schools and daycare centers.

• In general, exposure to mold in homes and schools has been associated with asthma development and exacerbation of current asthma; however, emerging evidence suggests that early exposure to higher fungal diversity may actually be protective for asthma development.

• In recent years, novel therapies targeting TH2 pathways that have been successful in decreasing asthmatic responses to allergens show promise for the treatment of severe allergic asthma refractory to avoidance strategies and standard therapies.