Abstract
Objective:
In recent decades, many indoor allergens have been identified, including dust mite, cat, dog, mouse, cockroach and indoor molds, which have important health effects particularly in sensitized asthmatics. This review aims to update our understanding regarding the extent of these exposures in the indoor environment, review strategies for reducing their levels in the environment, and highlight innovative recent trials targeting these exposures and their impact on pediatric asthma morbidity.
Data Sources:
Recent practice parameter updates on indoor allergen exposures, seminal studies, and recent peer-reviewed journal articles are referenced.
Study Selections:
This review cites recent cohort studies of well-characterized pediatric asthmatic patients as well as innovative randomized controlled trials evaluating exposure to environmental allergens, interventions to limit these exposures, and their outcomes.
Results:
Links between indoor aeroallergen exposures and health outcomes have been well established. However, only some allergen reduction interventions have been successful in improving health outcomes.
Conclusion:
There are many complicating factors involved in allergic exposures and health outcomes. The interplay between patient genetic factors, indoor allergic triggers, airborne irritants/pollutants and microbial exposures complicate the study of indoor allergen exposures and their impact on asthma morbidity.
Keywords: Indoor allergens, childhood asthma, home environment, school environment, dust mite, mold, mouse allergen, cockroach allergen, cat allergen, dog allergen
INTRODUCTION
More than 80% of children with asthma are sensitized to at least one indoor allergen.1 This is especially relevant during the COVID-19 pandemic, when most are spending more time at home. There may be sensitive periods during a child’s life when aeroallergen sensitization may have a higher impact on health: a recent study demonstrated that sensitization at a younger age was associated with higher asthma risk later in life.1 Unfortunately, health disparities also increase asthma risk. Children residing in lower-income urban areas have increased asthma severity, decreased asthma control, and thus higher implementation of urgent care or emergency visits.2 This makes understanding indoor allergen exposure, especially in the inner-city, particularly important and an urgent public health matter.
In recent decades, salient indoor allergens have been identified, including dust mite (DM), cat, dog, mouse, cockroach and indoor molds. This review aims to summarize what is known about these allergens, and their effects on asthma control. Possible mitigation strategies and the evidence supporting them are also discussed (Figure 1). Furthermore, we review seminal studies as well as novel randomized controlled trials (RCTs) targeting allergen reduction strategies and their outcomes. To date, many intervention trials with expected positive outcomes have demonstrated mixed results (Table 1). PubMed was used to identify updated practice parameter guidelines on indoor allergen exposures, as well as seminal studies, and recent innovative peer-reviewed intervention trials. Search terms included “indoor allergen” “dust mite” “mouse allergen” “cat allergen” “dog allergen” “mold allergen” “allergen reduction intervention.” Further studies were selected based on relevant citations.
Figure 1:

Common indoor allergens and interventions for reduction of indoor allergen exposure.
Evidence level for effectiveness in reducing allergen noted in parenthesis following recommended intervention. Evidence level graded when available for the intervention according to the Scottish Intercollegiate Guidelines Network recommendations: Ia, evidence from meta-analysis of RCTs; Ib, evidence from at least one RCT; IIa, evidence from well-designed controlled study without randomization; IIb, evidence from at least one other type of well-designed quasi-experimental study; III Evidence from well-designed descriptive studies; IV, Evidence obtained from expert committee reports and/or clinical experience of respected authorities.60
Table 1:
Select Randomized Controlled Trials Evaluating Reduction in Aeroallergen Exposures and Health Outcomes (2001–2021)
| Reference (year) | Allergens Targeted | Population | Intervention | Trial Results: Allergen Outcomes | Trial Results: Health Outcomes |
|---|---|---|---|---|---|
| Carter (2001) 57 | DM, cockroach | 104 inner-city asthmatics aged 6–16 yo |
Intervention group received allergen-impermeable covers, cockroach bait, education regarding dust mite (DM) and roach limitation. Placebo group received (sham) allergen permeable covers, instructions to wash in cold water. Control group received routine medical care |
Significant reduction defined as 70% decrease, no difference found between intervention and placebo groups | Reduction in acute visits for asthma in intervention group Decreased acute visits in those with DM allergy who had decreased DM exposure |
| Morgan (2004) 10 | Indoor allergens and tobacco smoke | 937 inner-city asthmatics with aeroallergen sensitization aged 5–11 yo |
Intervention group received 1 year of education, allergen-impermeable covers, HEPA vacuum and bedroom filter, personalized education and Integrated Pest Management (IPM) based on sensitization and exposure Control group evaluation every 6 months |
Reduced DM, cockroach allergen levels | Reduction in urgent visits Decreased asthma symptom days during the intervention year, as well as the following year |
| Eggleston (2005) 58 | Indoor allergens (cockroach, mouse) PM10 and PM2.5 | 100 low-income 6–12 yo asthmatics |
Intervention group 1 year of education, allergen-impermeable covers, bedroom HEPA filter, IPM based on sensitization and exposure Control group treatment at end of 1 year |
Approx. 50% reduction in cockroach allergen level, approx. 39% reduction in PM10 and PM2.5 | Reduction in daytime asthma symptoms |
|
Bryant-Stephens
(2009) 59 |
DM, pests, pets, tobacco smoke | 264 asthmatics 2–16 yo | Two intervention groups, one immediate and one delayed: education, allergen-impermeable covers, cockroach bait, mice traps, replacement carpet, curtains | Reductions were seen in pests, presence of carpets in bedrooms, and dust. | Nighttime wheezing significantly reduced after the intervention in both groups (P < .001). Mean number of emergency visits decreased by 30% after the intervention. Inpatient visits decreased by 53% (P < .001) after the intervention. |
|
DiMango
(2016) 46 |
DM, cockroach, mouse, cat, dog | 110 asthmatic adults and 137 asthmatic children, all with aeroallergen sensitization | Asthma control optimized prior to randomization. Intervention group 40-wk education, allergen-impermeable covers, bedroom HEPA filter and HEPA vacuum, Control group education not including allergen avoidance |
Intervention group displayed reduced DM, cockroach, mouse, cat, dog Control group: reduced cockroach, DM and mouse | Asthma control improved in both groups |
| Matsui (2017) 37 | Mouse allergen | 350 asthmatic children who were sensitized and exposed to mouse allergen |
Intervention group Rodenticide, sealing portals of rodent entry, traps, allergen-impermeable covers, HEPA filter. If mice remained, further treatment to eliminate infestation Control group education regarding mechanisms to reduce mouse in the home |
~70% reduction in mouse allergen in both groups, no difference in allergen levels between them | Reduction in mouse allergen associated with improvements in asthma symptoms, rescue inhaler use, urgent visits. No difference in symptoms between groups. |
|
Rabito
(2017) 45 |
Cockroach allergen | 102 moderate-severe asthmatics aged 5–7 yo, homes cockroach-infested |
Intervention group cockroach trapping and baiting at 0, 1, 3, 6, 9, and 12 mo. Control group cockroach trapping, but no baiting, at 0, 1, 3, 6, 9, and 12 mo. |
Reduction in cockroaches in homes with trapping and baiting. | Reduced asthma symptoms and urgent health visits Less participants with FEV1 <80% predicted |
|
Murray
(2017) 11 |
DM allergen | 286 DM sensitized asthmatics, 3–17 yo, with prior emergency hospital visits |
Intervention group 12 mo. with allergen-impermeable covers for bed Control group 12 mo. with no allergen-impermeable covers |
Mattress DM level reduced by 84% in the intervention group, no change in the placebo group (P< 0.001). Floor DM levels unchanged in both groups (P = 0.48). |
Reduction in hospital visits for asthma exacerbation. No reduction in need for oral corticosteroids. |
|
Phipatanakul
(2021) 33 |
Mouse, rat, cat, dog, DM, mold allergens | 236 asthmatic elementary students |
Intervention group Schoolwide IPM (rodenticide, sealing entry, traps, cleaning, education). Additional treatments for infestation. Classroom HEPA filters. Control group No IPM, sham classroom HEPA filters |
At baseline, 98% classrooms had detectable mouse allergen. More than 90% of baseline levels for cockroach, rat, Alternaria, Aspergillus, DM were undetectable. IPM did not significantly reduce any measured allergens. HEPA filters significantly reduced airborne mouse and dog allergen | Asthma symptom days decreased 0.4 days in the schools with IPM. After use of HEPA filters in classrooms, asthma symptom days were reduced 0.2 days. Neither produced a significant reduction in asthma symptom days overall. Post-hoc, IPM reduced asthma symptoms significantly by 63% early in the school year during fall/winter exacerbation season, but the benefit was not sustained |
DM: dust mite, IPM: Integrated Pest Management, HEPA: High-efficiency particulate air filter
In this review, we also discuss the many complicating factors involved in studying the reduction of allergic exposures and measuring their impacts on health outcomes. Our intent is that this review serves to guide the clinician in advising his or her patients regarding evidence-based allergen reduction strategies, as well as guides the researcher in formulating future successful intervention trials that produce meaningful impacts on child health.
DUST MITES
It has been over half a century since DM was recognized as an important indoor allergen. Two varieties of DM are commonly discussed as relevant allergens, Dermatophagoides pteronyssinus and Dermatophagoides farinae. Eighty-four percent of US homes have detectable DM. Homes that are older, single family, carpeted and without air conditioning generally have higher levels of DM. Demographic factors also play a role; higher population density, lower household income, and co-existence of detectable cockroach and mold allergens are also factors associated with increased DM exposure.3 DM exposure is an unequivocal trigger in many atopic diseases, and for children sensitized to DM, exposure has been casually linked to asthma exacerbations.4
Given the detrimental effects on those sensitized, several evidence-based strategies are recommended to limit exposure to DM. Strategies aimed at reducing humidity to 35–50% are recommended. It is ideal to remove unnecessary carpeting, however, if carpeting cannot be removed, steam vapor treatment demonstrated the greatest DM population reduction (p < 0.05) when compared to vacuuming, or chemical methods of DM mitigation. Overall, the two physical methods, steam vapor and vacuuming, had higher efficacy when compared to chemical methods on reduction of DM (p = 0.002). Further, in a laboratory setting, the steam-vapor treatment effectively killed DM and denatured DM allergen.5
The bedroom is a primary focus of DM avoidance strategies.6 Removing extraneous fabrics and upholstery may eliminate sources of DM.3 Fine woven fabrics with a pore size <6–10 microns in diameter are reasonable as DM encasements for home furnishings such as mattresses and pillows that cannot be removed.7 Washing bedding regularly on a hot cycle and then drying in a dryer can kill DM, but this is best done every week.8, 9 HEPA room filters can trap particles as small as 0.1 mm, but also may disturb DM from the floor.6
Well-designed RCTs in children have demonstrated the efficacy of avoidance measures to reduce DM levels and some have successfully reduced complications of asthma.10 In an RCT published in 2017, Murray and colleagues studied the impact of allergen-impermeable covers on a cohort of DM-sensitized asthmatic children who had been previously hospitalized for asthma. In the intervention group, DM levels in dust from the children’s mattresses were reduced by 84%, with no change in the placebo group (P<0.001). DM levels from the floor were unchanged in both groups (P = 0.48). At 12 months, significantly fewer children in the group using allergen-impermeable covers presented to the hospital with an exacerbation. The risk of emergency department evaluation was 45% lower in the intervention group compared with the control group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36–0.85; P = 0.006). However, there was no significant difference between the groups in the risk of prednisolone use for exacerbation (hazard ratio, 0.82; 95% CI, 0.58–1.17; P = 0.28).11
Unfortunately, not all DM reduction trials have consistently improved health effects.12 Difficulty arises as managing DM is not a “once and done” task, but an ongoing effort, and continuing mitigation measures are paramount to continued success.10
CAT
A National Health and Nutrition Examination Survey revealed that 50% of those questioned had a pet dog or cat, and 14% had both.13 Cat allergens are ubiquitous in society and are easily transferred. In fact, when homes with and without cats were studied, 95% of homes without cats had detectable Fel d 1, and airborne Fel d 1 was present in 25% of these homes.13 Although some families may intentionally avoid having certain pets at home due to a child’s allergies, it is important to understand that pet allergens are often carried into schools on the clothing, shoes, or belongings of other students. Higher environmental levels of cat allergen are associated with higher rates of sensitization and asthma symptoms among sensitized students.14, 15 Cat allergen challenges produced both clinical and biomarker responses in those sensitized, suggesting the detrimental impact of cat exposure on asthma morbidity.13, 16 As children spend a large proportion of their days outside their homes at school and daycare centers, aeroallergen exposures in these environments are critical to understand.
When there is a cat residing in the home, the most effective means of reducing exposure is to remove the animal.17 Once a cat is removed from the home, however, families must be cautioned that it may take up to six months to reduce cat allergen levels, so immediate improvement is not expected.18 Many families find removing the cat from the home an impossibility. Strategies to limit cat allergen exposure when the animal cannot be rehomed include keeping the animal out of the bedroom, and washing the animal at least twice weekly, however, effects are short-lived. Immersing the cat for 3 minutes removed Fel d 1 and reduced airborne Fel d 1 temporarily, but the benefits persisted for less than 1 week.19 Consistent vacuuming with HEPA vacuum, and using HEPA air filters have been studied as interventions in reducing detectable cat allergen in living room and bedroom samples. After 12 months of consistent vacuuming with HEPA attachment, participants had improved FEV1 and peak expiratory flow compared with those who used a standard vacuum.20 Similarly, HEPA filters have demonstrated efficacy in removing airborne cat allergen and improving airway hyperresponsiveness in asthmatic children who were sensitized to pets.21
Many cat owners affected by allergy find rehoming their animals, frequently bathing their animals and consistently vacuuming impractical. Other effective and practical interventions aimed at limiting the major cat allergen are needed. More recently, modifying a cat’s diet has shown promising results. A specific neutralizing antibody, anti-Fel d 1 IgY, has been added safely to cat’s food. Ingestion by the animal was associated with a reduction in allergen levels and minimization of the owner’s symptoms of allergic rhinitis.22
DOG
Dog allergens have been associated with allergic rhinoconjunctivitis, asthma, and urticaria. In a recent population based study, 12.2% of the US population was sensitized to dog.13 However, sensitization to dog allergen does not always predict clinical signs of allergy.23 There are several distinct dog allergens (Can f 1–7) detectable now with serum component testing. While many may be sensitized to dog IgE, Can f 1 shows the highest positive predictive value for clinical allergy to dog. Can f 5 is expressed in the prostate and secreted in the urine of male dogs. Component testing for dog allergens may confirm sensitization to related lipocalins or albumins of other animals.24 Data for claims of “hypoallergenic dogs” is unsubstantiated as Can f 1 levels are similar between breeds considered “hypoallergenic” and those that are not.25
As seen with cat exposure, dog allergen is detectable even in pet-free environments. Custovic et al evaluated the distribution of Can f 1 in homes with and without a dog and found levels above 10 micrograms/gram in 98% of homes with a dog and 16% of homes without a dog. Airborne Can f 1 was detectable in 30% of homes without a dog.26 Outside of homes, one study of public buildings detected Can f 1 in 100% of dust samples.27 Living with dogs may also reduce pulmonary function, purely by increasing endotoxin levels in a home.28 Strategies for reducing dog allergen include rehoming the dog if possible, frequent bathing of the animal, vacuuming with HEPA-integral vacuum, and the use of HEPA filters.
MOUSE
Important mouse allergenic proteins include Mus m 1 and Mus m 2 from mouse urine, dander and hair follicles. Mouse allergen is ubiquitous, especially in inner-city homes, where studies have detected mouse allergen in 95%−100% of homes.29, 30 Mouse allergen is not only relevant to urban homes, but is also frequently detected in homes of suburban children with asthma.31 In a nationally-representative US survey, 82% of homes overall had detectable mouse allergen.32
Although mouse allergen is prevalent in US homes, exposure to mouse allergen in schools is also common. In a 2021 study of classrooms in the inner-city northeast, 98% contained detectable mouse allergen.33 In an earlier study, by Sheehan and colleagues, mouse allergen was detected in 99% of school dust samples, and levels of mouse allergen in schools were significantly higher than in students’ homes (median settled dust level, 0.90 vs 0.14 μg/g; P < .001).34
Exposure to high levels of mouse allergen in schools is associated with increased asthma symptoms and reduced pulmonary function in children independent of allergic sensitization. Exposure to higher levels of mouse allergen in school (comparing 75th with 25th percentile) was associated with increased odds of having an asthma symptom day (OR = 1.27; 95% CI, 1.05–1.54; P = .02) and 4.0 percentage points lower predicted forced expiratory volume in 1 second (95% CI, −6.6 to −1.5; P = .002).34 Independent of home exposure, school exposure to mouse allergen was linked in a dose-response manner to worsened asthma symptoms and diminished lung function.35
To minimize mouse allergen exposure, integrated pest management (IPM) strategies should be employed, including removal of food sources for rodents, barring pathways of entry, and eliminating rodents already present through traps and rodenticides.36
A 2017 study by Matsui and colleagues evaluated the effect of an IPM intervention on reduction of mouse allergen levels and also its effect on asthma morbidity among children sensitized to mouse. The Mouse Allergen and Asthma Intervention Trial randomized mouse-sensitized asthmatic children to pest management education with formal home IPM or pest management education alone. The IPM intervention included rodenticide, sealing external portals of entry, trap placement, targeted cleaning, installation of allergen proof covers and portable air purifiers. Mouse allergen levels decreased significantly in both groups, but there was no significant reduction in maximal asthma symptom days between the two groups. However, it was noted that clinical benefit increased with greater reduction in mouse allergen. A child experiencing a 90% reduction in bedroom floor mouse allergen levels was estimated to have 14.1 fewer maximal symptom days (P < .001), 16.4 fewer days of short-acting β-agonist use (P < .001), 16.7 fewer days of exercise-related symptoms (P < .001), and 0.8 less acute visits (P < .001) per year compared with baseline.37 Reduction of mouse allergen may reduce future risk of deterioration in lung function: children who had 75% reduction in mouse allergen exposure had increased projected lung growth.38
Meaningfully reducing mouse allergen levels enough to impact clinical outcomes may be complicated by housing characteristics. A subsequent analysis of the above study, published in 2021, evaluated baseline housing characteristics associated with successful mouse allergen reduction after intervention. In the intervention group, higher baseline bedroom floor mouse allergen levels were significantly associated with successful mouse allergen reduction. In the IPM-randomized group, detached or semidetached home, and absence of cockroach infestation were significantly associated with successful mouse allergen reduction. In the education group, higher percentage of clutter-free floor in the bedroom and absence of a basement were significantly associated with successful mouse allergen reduction.39
COCKROACH
Bla g 1 and Bla g 2 are the primary roach allergens studied. In a sample of inner-city homes, cockroach allergen was detectable in 94% of kitchen floor samples.40 Exposure to Bla g 1 levels greater than 1U/g is associated with increased sensitization to roach.40, 41 It follows then that sensitization to cockroach has been reported in as high as 60–80% of asthmatic children living in urban areas, while only 21% in a suburban population.41, 42 Sensitization and exposure to cockroach has been associated with increased hospitalizations and urgent medical evaluation for asthma,43 as well as reduction in lung function.44
The most effective intervention for cockroaches involves professional IPM, which can reduce exposure by up to 90%. Otherwise, strategies for reducing exposure are similar to reducing mouse, including removal of food sources, blocking mechanisms of entry, and eliminating cockroaches already present through traps and insecticides.45
Studies examining reduction in cockroach allergen and associated asthma morbidity have demonstrated mixed results. On one hand, the Inner-City Asthma Study demonstrated that targeting cockroach and DM exposure reduced asthma symptoms during the 1-year intervention and this reduction persisted a year after the intervention ended.10 Another successful RCT by Rabito and colleagues, published in 2017, used a single intervention, insecticidal bait, to reduce cockroach exposure in the homes of children with asthma. Intervention homes had significantly fewer cockroaches than did control homes. Children in control homes had more asthma symptoms and unscheduled health care utilization in the previous 2 weeks (1.82, 95% CI, 0.14–3.50, P = .03; 1.17, 95% CI, 0.11–2.24, P = .03, respectively) and a higher proportion of children with FEV1 of less than 80% predicted (odds ratio, 5.74; 95% CI, 1.60–20.57; P = .01) compared with children living in intervention homes. The authors stressed that insecticidal bait is a low-cost, and safe intervention that reduced cockroach exposure improved asthma outcomes.45 In contrast, in another RCT of inner city adults and children, environmental control measures significantly decreased cockroach allergen levels, but these interventions did not significantly improve health outcomes.46
INDOOR MOLDS
Fungi are ubiquitous in outdoor and indoor environments. They can enter indoor environments and then accumulate on surfaces, with growth occurring where there are sufficient nutrients and moisture. Fungal particles may be related to adverse health effects in those sensitized to mold, as well as those who are not sensitized but have underlying respiratory disease and are susceptible to irritant effects from mold in their environments. Indoor mold exposure may increase risk of asthma development and morbidity, even after controlling for outdoor fungal exposures.47 A prospective cohort study followed 442 children through the first 6 years of life, and determined that exposure to mold in the bedroom, living room, or kitchen during infancy was associated with asthma development.48 A meta-analysis and systematic review concluded that exposure to Penicillium, Aspergillus, and Cladosporium may increase the risk of developing asthma symptoms, while exposure to Penicillium, Aspergillus, Cladosporium, and Alternaria were associated with increased exacerbation of in those with current asthma symptoms.49
For sensitized youngsters, exposure molds in daycare facilities is associated with wheezing. Chen et al. demonstrated that mold exposure in school classrooms was significantly associated with current asthma symptoms. These asthma symptoms then improved over holidays and weekends when the students were out of school,50 similar to what is seen in adult occupational asthma.
In a prospective study, Baxi et. al. followed 280 children with asthma from 37 inner-city schools. Fungal spores were collected twice during the year, and were present in all classroom samples. Exposure to Alternaria was significantly associated with asthma symptom days in students sensitized to Alternaria (OR = 3.61, CI = 1.34–9.76, P = .01), but not in children not sensitized to Alternaria (OR = 1.04, CI = 0.72–1.49, P = .85). Baxi and colleagues also noted a dose-related increase in symptoms in sensitized students. Students sensitized to Alternaria and exposed to high levels of the fungus (≥75th percentile exposure) had 3.2 more symptom days per 2-week period compared with sensitized students exposed to lower levels.51
Interventions to reduce indoor mold exposure include reducing moisture, applying fungicides, and removing contaminated areas. An RCT of 62 asthmatic children living with indoor mold evaluated mold remediation versus information regarding home cleaning. There was a significant decrease in asthma symptom days after remediation compared with baseline, as well as decreased rates of exacerbation compared with the control group.52 However, a Cochrane Review including 12 studies and 8,028 participants, found moderate to very-low quality evidence that repairing mold-damaged homes and offices decreases asthma symptoms and respiratory infections in adults. Furthermore, there was very-low quality evidence that remediating schools for mold reduced student’s visits to physicians due to symptoms of the common cold.53
There are several considerations as to why interventions targeting health outcomes related to reducing mold exposure have not been entirely successful. Many studies have been conducted in homes, when environmental interventions in schools have the potential to impact many students simultaneously, rather on a home by home basis and may improve childhood asthma. Further, in general, the impact of fungal exposure on health is nuanced. Diversity of molds in the environment as well as the timing of the exposure may alter outcomes. A recent study by Tischer et al. reported that exposure to higher fungal diversity in the perinatal period was linked to lower risk of wheezing and aeroallergen sensitization in later childhood.54
CONCLUSION
Associations between indoor aeroallergen exposures and deleterious health outcomes among those sensitized, and in some cases even among those who are not sensitized but have underlying asthma, have been well-established. While we are beginning to understand how to mitigate these exposures, not all allergen reduction interventions have been successful in improving health outcomes.
Evaluating the reduction of indoor aeroallergen exposures and their effects on health outcomes is complex. While some studies did not effectively reduce the target allergen, others offered very aggressive allergen avoidance techniques in both the control as well as intervention arms such that additional interventions did not produce a significant change in the exposure. This complicates the evidence supporting or refuting individual environmental controls for allergen avoidance. Even after successfully reducing levels of the target allergen, studying the impact on health outcomes is complicated as many patients are sensitized to numerous allergens simultaneously. Community-based interventions targeting reduction in levels of multiple aeroallergens simultaneously in public settings may be more effective. Mitigation strategies for one allergen may not adequately address exposure to other relevant allergens. Some studies also may have enrolled patients with relatively controlled disease and low allergen exposure at baseline, thus any intervention was unlikely to effectively reduce exposure enough to meaningfully improve health.6
Asthma is a multifactorial disease, and other triggers besides aeroallergen exposures are known to exacerbate disease. Indoor air pollutants are known to impact asthma control, with exposure linked to increased rates of hospitalization, as well as ICU admissions.55 We are beginning to understand that these pollutant exposures may modify the contribution of indoor aeroallergen exposures on health outcomes. A recently published secondary analysis of an RCT determined that environmental mouse allergen reduction was associated with improvements in asthma, especially among those with high baseline mouse allergen exposure. Lower indoor PM10 was associated with greater improvements in asthma symptoms after mouse allergen reduction.56
The contribution of viral infections on reduced asthma control is especially relevant in the pediatric population. We must appreciate the significance of the combined effects of allergic, irritant and viral triggers on asthma control. A recent blinded factorial RCT randomized 236 asthmatic students from 41 elementary schools and a total of 209 classrooms to a school-wide IPM program, use of HEPA filters in the classroom, or both. Control schools received no IPM, cleaning or education. Asthma symptom days over 2 weeks were studied, with a baseline mean of 2.2 days. After schoolwide IPM, asthma symptom days were reduced to 1.5 versus 1.9 days in the schools with no IPM. After use of HEPA filters in classrooms, asthma symptom days were reduced to 1.6, versus 1.8 in the classrooms with sham HEPA filters. While IPM and HEPA filters did reduce asthma symptom days, neither intervention overall produced significant reduction throughout the school year. However, in post-hoc analysis, students in IPM schools had a significant 63% reduction in asthma symptoms during the fall/winter season (typically a time of peak seasonal exacerbations), but the benefit was not sustained. Importantly, school absences were also significantly decreased in the school-wide IPM intervention. The authors postulate that combined reduction of both allergic and irritant triggers of asthma limited the susceptibility to viral-induced wheeze that is common during the fall/winter season.33 The interplay between indoor allergens, irritants and viral infections complicate the study of the impact on indoor allergens on asthma morbidity. Multifaceted interventions reducing all of these triggers are more likely to be successful.
Designing a successful intervention trial may also involve evaluating predisposing genetic factors. Patient-specific genetics may mediate differences in asthma incidence and severity, even among patients with similar sensitization profiles and comparable aeroallergen exposures. Aside from genetic factors, diversity of microbial exposures in conjunction with environmental aeroallergen exposures may also play a role and complicate our understanding of health outcomes related to indoor aeroallergen exposures. Genetic polymorphisms and microbial exposures likely modify the impact of aeroallergen exposures on asthma control. Further delineating these interactions through carefully conceived, rigorous clinical trials, may be integral to our understanding of the impact of aeroallergen exposures on asthma, and warrant further study.
Key Messages.
In recent decades, many indoor allergens have been identified, including dust mite (DM), cat, dog, mouse, cockroach and indoor molds, which have important health effects particularly in sensitized asthmatics.
Sensitization to dog allergen does not always predict clinical signs of allergy. Serum component testing can identify sensitization to individual dog allergens, and Can f 1 shows the highest positive predictive value for clinical dog allergy.
While pet allergens are likely transferred from homes rather than intrinsic to the schools themselves, other allergens, such as mice, mold and dust mites, are present in high levels in schools themselves and may have critical consequences to asthmatic students.
Trials aiming to reduce allergen exposure and improve asthma control have had mixed results.
Funding:
This research is supported by R01 AI073964, R01 AI073964-02S1, K24 AI106822, U10 HL098102, U01 AI110397, R01 HL137192, U19AR06952 (Phipatanakul). This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health.
Abbreviations:
- DM
dust mite
- HEPA
high-efficiency particulate air filter
- IPM
integrated pest management
- SICAS-II
School Inner-City Asthma Study II
Footnotes
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Conflicts of Interest: W. Phipatanakul is a consultant advisory for Teva, Genentech, Novartis, GSK and Regeneron, for asthma-related therapeutics. M. Maciag declares no relevant conflicts of interest.
REFERENCES:
- 1.Rubner FJ, Jackson DJ, Evans MD, Gangnon RE, Tisler CJ, Pappas TE, et al. Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence. J Allergy Clin Immunol 2017; 139:501–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Szefler SJ, Gergen PJ, Mitchell H, Morgan W. Achieving asthma control in the inner city: do the National Institutes of Health Asthma Guidelines really work? J Allergy Clin Immunol 2010; 125:521–6; quiz 7–8. [DOI] [PubMed] [Google Scholar]
- 3.Portnoy J, Miller JD, Williams PB, Chew GL, Miller JD, Zaitoun F, et al. Environmental assessment and exposure control of dust mites: a practice parameter. Ann Allergy Asthma Immunol 2013; 111:465–507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W. Indoor environmental exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine. Environ Health Perspect 2015; 123:6–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ong KH, Lewis RD, Dixit A, MacDonald M, Yang M, Qian Z. Inactivation of dust mites, dust mite allergen, and mold from carpet. J Occup Environ Hyg 2014; 11:519–27. [DOI] [PubMed] [Google Scholar]
- 6.Wilson JM, Platts-Mills TAE. Home Environmental Interventions for House Dust Mite. J Allergy Clin Immunol Pract 2018; 6:1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Baxi SN, Phipatanakul W. The role of allergen exposure and avoidance in asthma. Adolesc Med State Art Rev 2010; 21:57–71, viii–ix. [PMC free article] [PubMed] [Google Scholar]
- 8.Choi SY, Lee IY, Sohn JH, Lee YW, Shin YS, Yong TS, et al. Optimal conditions for the removal of house dust mite, dog dander, and pollen allergens using mechanical laundry. Ann Allergy Asthma Immunol 2008; 100:583–8. [DOI] [PubMed] [Google Scholar]
- 9.McDonald LG, Tovey E. The role of water temperature and laundry procedures in reducing house dust mite populations and allergen content of bedding. J Allergy Clin Immunol 1992; 90:599–608. [DOI] [PubMed] [Google Scholar]
- 10.Morgan WJ, Crain EF, Gruchalla RS, O’Connor GT, Kattan M, Evans R 3rd, et al. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med 2004; 351:1068–80. [DOI] [PubMed] [Google Scholar]
- 11.Murray CS, Foden P, Sumner H, Shepley E, Custovic A, Simpson A. Preventing Severe Asthma Exacerbations in Children. A Randomized Trial of Mite-Impermeable Bedcovers. Am J Respir Crit Care Med 2017; 196:150–8. [DOI] [PubMed] [Google Scholar]
- 12.Langley SJ, Goldthorpe S, Craven M, Morris J, Woodcock A, Custovic A. Exposure and sensitization to indoor allergens: association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma. J Allergy Clin Immunol 2003; 112:362–8. [DOI] [PubMed] [Google Scholar]
- 13.Gergen PJ, Mitchell HE, Calatroni A, Sever ML, Cohn RD, Salo PM, et al. Sensitization and Exposure to Pets: The Effect on Asthma Morbidity in the US Population. J Allergy Clin Immunol Pract 2018; 6:101–7.e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Esty B, Permaul P, DeLoreto K, Baxi SN, Phipatanakul W. Asthma and Allergies in the School Environment. Clin Rev Allergy Immunol 2019; 57:415–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Almqvist C, Wickman M, Perfetti L, Berglind N, Renström A, Hedrén M, et al. Worsening of asthma in children allergic to cats, after indirect exposure to cat at school. Am J Respir Crit Care Med 2001; 163:694–8. [DOI] [PubMed] [Google Scholar]
- 16.Bacharier LB, Beigelman A, Calatroni A, Jackson DJ, Gergen PJ, O’Connor GT, et al. Longitudinal Phenotypes of Respiratory Health in a High-Risk Urban Birth Cohort. Am J Respir Crit Care Med 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Portnoy J, Kennedy K, Sublett J, Phipatanakul W, Matsui E, Barnes C, et al. Environmental assessment and exposure control: a practice parameter--furry animals. Ann Allergy Asthma Immunol 2012; 108:223.e1–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Wood RA, Chapman MD, Adkinson NF, Jr., Eggleston PA. The effect of cat removal on allergen content in household-dust samples. J Allergy Clin Immunol 1989; 83:730–4. [DOI] [PubMed] [Google Scholar]
- 19.Avner DB, Perzanowski MS, Platts-Mills TA, Woodfolk JA. Evaluation of different techniques for washing cats: quantitation of allergen removed from the cat and the effect on airborne Fel d 1. J Allergy Clin Immunol 1997; 100:307–12. [DOI] [PubMed] [Google Scholar]
- 20.Popplewell EJ, Innes VA, Lloyd-Hughes S, Jenkins EL, Khdir K, Bryant TN, et al. The effect of high-efficiency and standard vacuum-cleaners on mite, cat and dog allergen levels and clinical progress. Pediatr Allergy Immunol 2000; 11:142–8. [DOI] [PubMed] [Google Scholar]
- 21.van der Heide S, van Aalderen WM, Kauffman HF, Dubois AE, de Monchy JG. Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens. J Allergy Clin Immunol 1999; 104:447–51. [DOI] [PubMed] [Google Scholar]
- 22.Satyaraj E, Wedner HJ, Bousquet J. Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen. Allergy 2019; 74 Suppl 107:5–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Gerth van Wijk R Diagnosis of dog allergy: Beware of the dog. J Allergy Clin Immunol 2018; 142:1058–9. [DOI] [PubMed] [Google Scholar]
- 24.Liccardi G, Calzetta L, Milanese M, Passalacqua G, Rogliani P. Can f 5 as a suitable marker of dog allergy: Assess male dog exposure before banning it. J Allergy Clin Immunol 2019; 143:1657–8. [DOI] [PubMed] [Google Scholar]
- 25.Vredegoor DW, Willemse T, Chapman MD, Heederik DJ, Krop EJ. Can f 1 levels in hair and homes of different dog breeds: lack of evidence to describe any dog breed as hypoallergenic. J Allergy Clin Immunol 2012; 130:904–9.e7. [DOI] [PubMed] [Google Scholar]
- 26.Custovic A, Green R, Fletcher A, Smith A, Pickering CA, Chapman MD, et al. Aerodynamic properties of the major dog allergen Can f 1: distribution in homes, concentration, and particle size of allergen in the air. Am J Respir Crit Care Med 1997; 155:94–8. [DOI] [PubMed] [Google Scholar]
- 27.Custovic A, Green R, Taggart SC, Smith A, Pickering CA, Chapman MD, et al. Domestic allergens in public places. II: Dog (Can f1) and cockroach (Bla g 2) allergens in dust and mite, cat, dog and cockroach allergens in the air in public buildings. Clin Exp Allergy 1996; 26:1246–52. [PubMed] [Google Scholar]
- 28.Sicherer SH, Wood RA, Eggleston PA. Determinants of airway responses to cat allergen: comparison of environmental challenge to quantitative nasal and bronchial allergen challenge. J Allergy Clin Immunol 1997; 99:798–805. [DOI] [PubMed] [Google Scholar]
- 29.Phipatanakul W, Eggleston PA, Wright EC, Wood RA. Mouse allergen. I. The prevalence of mouse allergen in inner-city homes. The National Cooperative Inner-City Asthma Study. J Allergy Clin Immunol 2000; 106:1070–4. [DOI] [PubMed] [Google Scholar]
- 30.Matsui EC, Simons E, Rand C, Butz A, Buckley TJ, Breysse P, et al. Airborne mouse allergen in the homes of inner-city children with asthma. J Allergy Clin Immunol 2005; 115:358–63. [DOI] [PubMed] [Google Scholar]
- 31.Matsui EC, Wood RA, Rand C, Kanchanaraksa S, Swartz L, Eggleston PA. Mouse allergen exposure and mouse skin test sensitivity in suburban, middle-class children with asthma. J Allergy Clin Immunol 2004; 113:910–5. [DOI] [PubMed] [Google Scholar]
- 32.Cohn RD, Arbes SJ Jr., Yin M, Jaramillo R, Zeldin DC. National prevalence and exposure risk for mouse allergen in US households. J Allergy Clin Immunol 2004; 113:1167–71. [DOI] [PubMed] [Google Scholar]
- 33.Phipatanakul W, Koutrakis P, Coull BA, Petty CR, Gaffin JM, Sheehan WJ, et al. Effect of School Integrated Pest Management or Classroom Air Filter Purifiers on Asthma Symptoms in Students With Active Asthma: A Randomized Clinical Trial. Jama 2021; 326:839–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Sheehan WJ, Permaul P, Petty CR, Coull BA, Baxi SN, Gaffin JM, et al. Association Between Allergen Exposure in Inner-City Schools and Asthma Morbidity Among Students. JAMA Pediatr 2017; 171:31–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Ownby DR. Will the real inner-city allergen please stand up? J Allergy Clin Immunol 2013; 132:836–7. [DOI] [PubMed] [Google Scholar]
- 36.Phipatanakul W, Matsui E, Portnoy J, Williams PB, Barnes C, Kennedy K, et al. Environmental assessment and exposure reduction of rodents: a practice parameter. Ann Allergy Asthma Immunol 2012; 109:375–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Matsui EC, Perzanowski M, Peng RD, Wise RA, Balcer-Whaley S, Newman M, et al. Effect of an Integrated Pest Management Intervention on Asthma Symptoms Among Mouse-Sensitized Children and Adolescents With Asthma: A Randomized Clinical Trial. Jama 2017; 317:1027–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Grant T, Phipatanakul W, Perzanowski M, Balcer-Whaley S, Peng RD, Curtin-Brosnan J, et al. Reduction in mouse allergen exposure is associated with greater lung function growth. J Allergy Clin Immunol 2020; 145:646–53.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Akar-Ghibril N, Sheehan WJ, Perzanowski M, Balcer-Whaley S, Newman M, Petty CR, et al. Predictors of successful mouse allergen reduction in inner-city homes of children with asthma. J Allergy Clin Immunol Pract 2021; 9:4159–61.e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Eggleston PA, Rosenstreich D, Lynn H, Gergen P, Baker D, Kattan M, et al. Relationship of indoor allergen exposure to skin test sensitivity in inner-city children with asthma. J Allergy Clin Immunol 1998; 102:563–70. [DOI] [PubMed] [Google Scholar]
- 41.Matsui EC, Wood RA, Rand C, Kanchanaraksa S, Swartz L, Curtin-Brosnan J, et al. Cockroach allergen exposure and sensitization in suburban middle-class children with asthma. J Allergy Clin Immunol 2003; 112:87–92. [DOI] [PubMed] [Google Scholar]
- 42.Gruchalla RS, Pongracic J, Plaut M, Evans R 3rd, Visness CM, Walter M, et al. Inner City Asthma Study: relationships among sensitivity, allergen exposure, and asthma morbidity. J Allergy Clin Immunol 2005; 115:478–85. [DOI] [PubMed] [Google Scholar]
- 43.Rosenstreich DL, Eggleston P, Kattan M, Baker D, Slavin RG, Gergen P, et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med 1997; 336:1356–63. [DOI] [PubMed] [Google Scholar]
- 44.Svendsen ER, Gonzales M, Commodore A. The role of the indoor environment: Residential determinants of allergy, asthma and pulmonary function in children from a US-Mexico border community. Sci Total Environ 2018; 616–617:1513–23. [DOI] [PubMed] [Google Scholar]
- 45.Rabito FA, Carlson JC, He H, Werthmann D, Schal C. A single intervention for cockroach control reduces cockroach exposure and asthma morbidity in children. J Allergy Clin Immunol 2017; 140:565–70. [DOI] [PubMed] [Google Scholar]
- 46.DiMango E, Serebrisky D, Narula S, Shim C, Keating C, Sheares B, et al. Individualized Household Allergen Intervention Lowers Allergen Level But Not Asthma Medication Use: A Randomized Controlled Trial. J Allergy Clin Immunol Pract 2016; 4:671–9.e4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Pongracic JA, O’Connor GT, Muilenberg ML, Vaughn B, Gold DR, Kattan M, et al. Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children. J Allergy Clin Immunol 2010; 125:593–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Karvonen AM, Hyvärinen A, Korppi M, Haverinen-Shaughnessy U, Renz H, Pfefferle PI, et al. Moisture damage and asthma: a birth cohort study. Pediatrics 2015; 135:e598–606. [DOI] [PubMed] [Google Scholar]
- 49.Sharpe RA, Bearman N, Thornton CR, Husk K, Osborne NJ. Indoor fungal diversity and asthma: a meta-analysis and systematic review of risk factors. J Allergy Clin Immunol 2015; 135:110–22. [DOI] [PubMed] [Google Scholar]
- 50.Chen CH, Chao HJ, Chan CC, Chen BY, Guo YL. Current asthma in schoolchildren is related to fungal spores in classrooms. Chest 2014; 146:123–34. [DOI] [PubMed] [Google Scholar]
- 51.Baxi SN, Sheehan WJ, Sordillo JE, Muilenberg ML, Rogers CA, Gaffin JM, et al. Association between fungal spore exposure in inner-city schools and asthma morbidity. Ann Allergy Asthma Immunol 2019; 122:610–5.e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Kercsmar CM, Dearborn DG, Schluchter M, Xue L, Kirchner HL, Sobolewski J, et al. Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources. Environ Health Perspect 2006; 114:1574–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Sauni R, Verbeek JH, Uitti J, Jauhiainen M, Kreiss K, Sigsgaard T. Remediating buildings damaged by dampness and mould for preventing or reducing respiratory tract symptoms, infections and asthma. Cochrane Database Syst Rev 2015; 2015:Cd007897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Tischer C, Weikl F, Probst AJ, Standl M, Heinrich J, Pritsch K. Urban Dust Microbiome: Impact on Later Atopy and Wheezing. Environ Health Perspect 2016; 124:1919–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Silverman RA, Ito K. Age-related association of fine particles and ozone with severe acute asthma in New York City. J Allergy Clin Immunol 2010; 125:367–73.e5. [DOI] [PubMed] [Google Scholar]
- 56.Sadreameli SC, Ahmed A, Curtin-Brosnan J, Perzanowski MS, Phipatanakul W, Balcer-Whaley S, et al. Indoor Environmental Factors May Modify the Response to Mouse Allergen Reduction Among Mouse-Sensitized and Exposed Children with Persistent Asthma. J Allergy Clin Immunol Pract 2021; 9:4402–9.e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Carter MC, Perzanowski MS, Raymond A, Platts-Mills TA. Home intervention in the treatment of asthma among inner-city children. J Allergy Clin Immunol 2001; 108:732–7. [DOI] [PubMed] [Google Scholar]
- 58.Eggleston PA, Butz A, Rand C, Curtin-Brosnan J, Kanchanaraksa S, Swartz L, et al. Home environmental intervention in inner-city asthma: a randomized controlled clinical trial. Ann Allergy Asthma Immunol 2005; 95:518–24. [DOI] [PubMed] [Google Scholar]
- 59.Bryant-Stephens T, Kurian C, Guo R, Zhao H. Impact of a household environmental intervention delivered by lay health workers on asthma symptom control in urban, disadvantaged children with asthma. Am J Public Health 2009; 99 Suppl 3:S657–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60.Custovic A, Murray CS, Gore RB, Woodcock A. Controlling indoor allergens. Ann Allergy Asthma Immunol 2002; 88:432–41; quiz 42–3, 529. [DOI] [PubMed] [Google Scholar]
