House dust mites (HDMs) are associated with an increased prevalence of perennial allergic rhinitis at lower concentrations and asthma at higher concentrations (94). The main HDM species include Dermatophagoides farinae, Dermatophagoides pteronyssinus, Euroglyphus maynei, and Blomia tropicalis. The most significant concentration of HDMs is detected in bedding, especially with increasing temperature and humidity during sleep, in fabric-covered furniture, carpets, and soft toys, as these areas provide an ideal food source in the form of exfoliated human skin (95). There have been numerous proposed measures to avoid dust mites, such as using mattress and pillow encasings, employing high-efficiency particulate air filtration (HEPA) vacuum cleaners, utilizing air purification systems, employing acaricides, controlling humidity, and physically removing mite reservoirs: -

Usage of suitable materials for covering pillows and mattresses: Fine woven fabrics with a pore size of less than 6–10 mm are recommended for pillow and mattress covers. Front-loading washing machines, which do not completely submerge goods in water, are less successful than toploading washing machines at removing mites from blankets when using cold water (96). To eradicate dust mites from blankets, use hot water in a front-loading, high-efficiency washing machine (96). All other materials in the bed should be regularly washed and dried to kill mites. The use of detergent, bleach, and repeated washing can also be important (97, 98).

The two most frequently encountered cockroach species in domestic homes and public buildings are Blatella germanica (German cockroach) and Periplaneta americana (American cockroach). When disrupted, cockroach protein, similar to dust mite allergen, becomes airborne and settles down rapidly (104). Although most studies on cockroaches and asthma have focused on urban areas, cockroaches can also infest buildings in suburban and rural locations, regardless of the socioeconomic status of their occupants (105). The main allergens associated with cockroaches, namely Per a1, Bla g1, and Bla g2, have been found commonly in floor dust, as well as in kitchen cabinets, bathrooms, and basements (106). To reduce cockroach allergens, measures such as blocking entry points, eliminating sources of food, water, and shelter, and using traps and insecticides can be taken (43). HEPA vacuuming and covering mattresses can also help eliminate reservoirs of allergens (43). Gel bait insecticides, particularly those containing fipronil or indoxacarb, and hiring a professional pest control service have been proven effective interventions, while sprays should be avoided (107).

Grass pollens have been classified into 8 classes based on their immunologic properties and contain 20–40 distinct antigens (108). Recent studies suggest that grass pollens are the primary cause of allergic reactions, as they can trigger the rupture of pollen grains, releasing hundreds of toxic starch granules that are small enough (<3 µm) to penetrate and disturb small airways (109). Group I allergens are particularly relevant, as they provoke a reaction in 90%–95% of grass pollen-allergic patients during skin testing (110). Exposure to outdoor tree and grass pollens and fungal spores has been linked to increased allergic illnesses, including asthma (111). Although controlling outdoor pollen levels is challenging, reducing exposure can be achieved by spending less time outdoors, mainly when counts are high and in the morning (112). Besides that, indoor incursion of outdoor allergens can be reduced by closing windows, using air conditioning and high-efficiency particulate arrestor filters, and frequently washing surfaces (112). Additionally, those who are allergic to grass should avoid mowing pollinating grass. Reductions in allergy symptoms have been noticed by employing respirators, goggles, or face masks outdoors (113, 114).

Molds can grow and spread in both indoor and outdoor environments. There are several common types of molds, including Cladosporium species, basidiospores, spores of the Penicillium/Aspergillus type, and Alternaria spp (25). Most mold allergens are encountered by inhaling mold spores of varying sizes and shapes, ranging from 2 to 250 mm, with many being respirable (115). Floods, leaks, condensation, and household molds are primary indoor sources of mold growth (116). Additionally, molds can grow in aeration/conditioning ducts and water pipes (116). Reducing indoor mold exposure is essential to asthma management in sensitized patients. These interventions may include removing mold from hard surfaces, preventing rainwater intrusion, installing ventilation systems in areas such as attics, kitchens, laundry rooms, and basements, repairing plumbing leaks and water seepage by filling gaps and cracks around the foundation, cleaning exterior guttering, and so on (80). Control of indoor relative humidity under 50% by increasing ventilation and covering cold surfaces, washing with detergent, contaminated carpets and removing wallpaper can be taken to discourage mold growth and mold remediation (117). In addition, the US National Institute of Occupational Safety and Health (NIOSH) recommends using an N-95 mask or higher when removing visible mold, while the US Environmental Protection Agency (EPA) advises seeking assistance from an experienced contractor for mold removal (118). Furthermore, building materials that are extensively contaminated with mold should be replaced. While frequent vacuuming may help lower mold spores in dust, replacing rugs with alternative flooring options appears to be more effective (119).

The major allergen sources from animals include dander (desquamated epithelium), saliva, urine, hair, and feathers, which produce allergens unique to each species. The main source of cat allergen, especially Fel d1, is cat saliva, also in the sebaceous glands and urine of male cats (117). It can be transported through the air by particles larger than 2.5 µm and can remain airborne for long periods (117). Besides, dog allergen, particularly Can f1 and Can f2, is present in dander, saliva, urine, and serum (117). In addition, sensitivity to rodent dander may develop in laboratory workers due to occupational exposure. Still, but the allergenic protein in rodent urine can also contribute to allergic reactions in homes infested with rodents Once asthma is established and sensitization is confirmed, the current general approach is to avoid exposure by removing pets from the home. However, it may take several months (20–24 weeks) to to significantly reduce allergen levels once the pets are removed (120). When the air cleaner was used with the cat in the room, the quantity of the Inhaled Fel d 1 was reduced by up to one-third (121). Several studies demonstrated that air filtration and mechanical washing with detergents also effectively remove cat and dog allergens and indoor air particles (102, 122). Moreover, positive results were obtained from investigating the effectiveness of using a HEPA air cleaner to reduce airborne cat allergens (121). It can be challenging to avoid exposure to cat allergens as they can be present in public places, around pet owners, and even at school. Thus, it is vital to have comprehensive knowledge of potential exposures to other furry animals. Although avoiding the animal is the best option if there is a proven relationship between exposure and symptoms, it is often not feasible and can have a significant emotional impact (117).

Various methods for HDM avoidance have been introduced; however, the effectiveness of those measures is still controversial.

While allergen immunotherapy to HDM was recommended in managing uncontrolled asthma, most meta-analyses found that HDM control in the living environment did not affect asthmatic management or prevention (123–127). Consequently, HDM avoidance was not broadly recommended in the guidelines for asthma management, including Global Initiative For Asthma (GINA) (128). Nevertheless, several considerations should be taken when analyzing the systematic review and meta-analysis data. The combination of different study populations (e.g., adults and children, HDM avoidance measures (e.g., single and multiple methods), period of intervention (e.g., long and short periods), outcomes (e.g., asthmatic symptoms, hospitalization, lung function, quality of life, etc.) in meta-analyses could affect the final result (129, 130). Notably, clinical trials available in the literature were predominantly conducted in mild-to-moderate asthma and/or well-controlled asthma patients, which could blunt the effectiveness of the allergen avoidance interventions.

In adult asthmatic patients, the use of impermeable bed covers and/or pillow covers as the only intervention was found to be not effective in preventing allergic symptoms, suggesting the need for a multi-faceted approach. In a clinical trial with 1,122 adult asthmatic patients, although the concentration of HDM in mattress dust was lower in the intervention group compared to the control group, morning peak expiratory flow rate, mean reduction in steroid dose, symptom scores and quality of life were not significantly different between the two study groups (131). Similar findings were demonstrated in other clinical trials (132, 133). Another study involving adult patients with allergic rhinitis and HDM sensitization also found that using bed encasing had no effect on improving rhinitis-specific visual analog scale as well as mean daily symptom score (134). Notably, two aspects need to be considered simultaneously when conducting studies to investigate the effects of the allergen avoidance methods: the reduction of allergen concentration and the improvement of respiratory allergy symptoms (135). Avoidance measures that fail to reduce allergen levels obviously cannot be expected to reduce allergy symptoms.

In contrast, studies in children with asthma have showed different findings. A randomized trial in 241 children aged 3–17 with asthma demonstrated that using impermeable bedcover reduced HDM concentration in mattress dust and the prevalence of hospital administration due to severe asthma exacerbation (71). In another study, mattress, and pillow encasings also reduced HDM allergen concentrations and the dose of inhaled steroids used by asthmatic patients (136). A multifaceted home-based intervention, including the use of allergen-proof bedcovers and fragrance-free cleaning products as well as avoidance of indoor smoking, showed a significant reduction in daily asthma symptoms, nighttime awakening, and steroid use in children with asthma (137). Other studies in children also found that control of HDM allergens by using single or multiple methods could provide a beneficial effect on asthma management (138–140).

Interestingly, a recent study found that staying at home during COVID-19 pandemic improved asthma control and reduced inhaled corticosteroid use in children with asthma and HDM sensitization (141). This finding suggests that air pollution could be an important confounding factor to consider when investigating the effectiveness of in-door allergen avoidance.

Interventions in most clinical trials were successful in reducing indoor cockroach allergen; however, the effectiveness in asthma management was controversial. Wood et al. (142) demonstrated that utilization of abamectin and professional house cleaning significantly reduced Bla g1 amount in house dusts; however, the concentration was still above 8 U/g (the level associated with asthma symptoms). Results from the Inner-City Asthma Study (ICAS) demonstrated that interventions to concomitantly eliminate multiple indoor allergens (including HDM, cockroach, pet, mold) and tobacco smoke significantly reduced Der f1, Fel d1, and Bla g1 levels, which was associated with a reduction in asthmatic symptoms and morbidity for 2 years of the study (143). Another study showed that insecticide bait application significantly reduced number of cockroaches, which was associated with a lower asthma morbidity in children living in these houses (144).

In contrast, a clinical trial with multifaceted interventions significantly reduced the levels of indoor allergens; however, the cockroach allergen level (Bla g2) reduction was similar in control and intervention groups (145). In National Cooperative Inner-City Asthma Study (NCICAS), cleaning house and insecticide utilization significantly reduced cockroach allergen Bla g1 level for 2 months, but the allergen levels were increased to the baseline level at the end of the study. The compliance of the study subjects with the cleaning instructions was likely poor (146).

Besides grass pollen immunotherapy, grass pollen avoidance is highlighted for asthma management to prevent exacerbation (112–114). Due to the limited time window of pollen peak occurrences, susceptible individuals should be advised to stay home and avoid outdoor exposure (1, 2). However, there is inconclusive evidence on clinical outcomes. Masks effectively prevent pollen exposure and reduce nasal and conjunctival symptoms (147). The upper respiratory tract is closely related to asthma symptoms (148). In a meta-analysis, the summary effect estimates for a 10 grains/m³ increase in pollen exposure demonstrated a 2% increase in the risk of any allergic or asthmatic symptoms, 1%, 7%, and 11% increase in the risk of lower respiratory symptoms, upper respiratory symptoms, and ocular symptoms, respectively (3). Thus, even short-term pollen exposure increased the risks of asthma symptoms (3). There is a need for studies to personalize the exposure assessment to pollen with asthma control. The AAAAI Aerobiology Committee developed guidelines for hypoallergenic landscape plant selection in pollen-related allergic patients (4). Given that the grass pollen differs from each area depending on the local ecosystem, further studies in various geographical regions are necessary.

Grass avoidance is stressed in specific cases where the seasonal change is closely related to allergic and asthma symptoms. Epidemic thunderstorm asthma is characterized by acute asthma triggered after a thunderstorm (5–7). The incidences of respiratory admissions have been linked to the concentration of airborne allergens in the atmosphere, in association with environmental factors such as rainfall, temperature, and aerosols (5, 8). To prevent epidemic thunderstorm asthma, thunderstorm forecasts, and pollen counts are major factors in issuing public health warnings (7, 8). A case report showed cross-reactivity between Bermuda grass pollen with multiple grains (9). Aside from pharmacological therapy for grass-allergic patients, measures to prevent grass pollen exposure remain mandatory.

Outdoor allergens sensitive patients should limit outdoor activities in high levels seasons (149). In a systematic review including 12 studies with 8,028 participants, the intervention group with repairing houses or mold-damaged offices showed a reduction in asthmatic and respiratory symptoms compared to the control group in adults and children. However, the evidence was moderate to very low-quality (150). In another study, asthmatic children living in a home with indoor mold were distributed into the remediation group and control group. The remediation group received household repairs (e.g., water infiltration reduction, water-damaged building materials removals, and alterations of heating/ventilation/air-conditioning), while the control group was educated about home cleaning. Although there were no changes in total and outdoor mold indices at the end of the study, children in the remediation group significantly reduced symptoms days and decreased exacerbations compared with control asthmatics (151). Similarly, a global allergen avoidance method conducted by an indoor environment counselor enhanced patients’ lung function, and reduced the number of asthma-related hospitalizations, and the use of anti-asthmatic medication (152). Given the close association between fungal exposure and severe asthma, methods to avoid molds should be noted for vulnerable subjects.

Although removing pets from homes is the most advisable, effective long-term strategy to reduce airway responsiveness in asthmatic patients with pet allergy in many studies, it may take at least 20 weeks to decline settled dust as small particles after pet removal (80, 120, 153). There are conflicting results on the effects of pet avoidance in reducing asthma control. HEPA filtration has not been proven to reduce asthma symptoms significantly in people with pet-allergic asthma without pet removals (154). In another study, asthmatic adults, who were sensitized to pets and lived with pets in a shared home, the effect of HEPA was similar (155). Thus, in case of inefficient patient education, allergen interventions, and pharmacotherapy, further studies on allergen immunotherapy should be warranted for pet-allergic patients (156, 157).

The multifaceted integrated pest management intervention (IPM) significantly reduced allergen levels by at least 75% (158). Other approaches (e.g., air purifiers, allergen-proof mattresses, and pillow encasements) may be effectively decrease the concentration of mouse and other animal allergens (159–161). Results from the Inner-City Asthma Study (ICAS) demonstrated that home rodent-specific environmental interventions (e.g., a HEPA air filter placed in the bedroom, filling rodent access points, setting traps, education) reduced mouse allergen levels, asthma-related sleep disorders and limited activities (65). Another randomized trial of the IPM effect in 350 sensitized/exposed asthmatic children showed that prebronchodilator/postbronchodilator forced expiratory flow increased over one year after the mouse allergen concentration was reduced up to 75% (162). In contrast, in The Mouse Allergen and Asthma Intervention Trial (MAAIT) study, 361 mouse-sensitive and exposed children were administered to receive IPM plus pest management education or education alone. There were no significant differences in maximal symptom days between the two groups, although a substantial reduction at 90% of mouse allergen was noted in both groups (163). The lowered level of mouse allergens was associated with fewer hospitalizations and acute care visits (163). Similar findings were demonstrated in other clinical trials (164).