Avoidance measures for mite allergy—an update

House dust mites are a major source of allergens in house dust and, thus, the main trigger of perennial allergic respiratory diseases [1–5]. Scientific research on the life cycle, diet, and reproductive behavior of dust mites and on the biology of mite allergens has uncovered mechanisms leading to the development of respiratory allergies and suggests measures that can minimize exposure to dust mite allergens. Here, we discuss the evidence linking house dust mite exposure and respiratory allergies and present the efficacy of avoidance measures and their scientific evidence.


Historical development of mite avoidance measures
Although the importance of house dust as a source of allergens was recognized as early as the 1920s, mites were not identified as the major source of house dust allergens until 1967 [6,7]. Microscopic detection of house dust mites rapidly led to the development of techniques for culturing them, allowing the preparation of house dust mite extracts for skin testing and for the detection of specific IgE antibodies [8][9][10]. This has demonstrated that sensitization to house dust mites is strongly associated with asthma development in many temperate zones worldwide [11]. The impact of these findings was dramatic, as this was the first well-defined year-round allergen [12]. Anti-dust mite measures have played and continue to play an important role in scientific discussions [13].
The first purification of a house dust mite allergen was achieved from a house dust mite culture medium and was initially designated F4Pl and later Der p1. This was used to develop a radioimmunoassay to measure the presence of Der p1 in dust samples [14]. Detailed studies on the source of the allergen initially focused on mite feces [15]. Evidence that particles from this become airborne provided important information about the form of exposure and the size of the particles [15][16][17]. This also showed that the percentage of particles entering the peripheral lung during resting breathing decreases with increasing size [18,19]. Conversely, house dust mite allergens in larger particles (median 9.7 µm) elicit bronchial hyperreactivity at a lower concentration than smaller particles (median 1.1 µm) [20]. The allergens in these particles contribute to progressive inflammation of the airway mucosa in sensitized individuals [21]. The notion that allergen size and sensitization pattern may lead to differences in upper and lower airway 18 Avoidance measures for mite allergy-an update K review involvement is an interesting but insufficiently studied hypothesis [22]. Very little mite allergen remains airborne for more than 10-20 min when stirred up indoors [17]. Thus, probably only a small number of mite fecal particles enter the respiratory tract, usually causing no noticeable symptoms or changes in lung function at the time of exposure [15,21]. Thus, airway inflammation and symptoms in mite allergic individuals are essentially due to chronic exposure to a small number of relatively large particles, in contrast to pollen inhalation, where sufficient allergens can be inhaled to cause massive immediate phase reactions [15,21]. Thus, nasal or bronchial provocation testing also represents an artificial special situation [13,15].
Thus, in inhalation allergies to house dust mites, late-phase allergic responses by effector cells such as eosinophils, T cells, and other inflammatory mechanisms apparently play a greater role than immediate IgE-and mast cell-mediated immediate-phase responses [23][24][25] and rarely lead to immediate respiratory symptoms at the time of exposure [26]. This could also explain the marked allergen-induced nasal and bronchial hyperreactivity [27] which is often more pronounced in mite-allergic patients than in pollenallergic patients, but which can also be reversed, but only with sufficiently long mite abstinence after several months [28][29][30]. Therefore, mite abstinence must always be a long-term therapeutic measure.

Avoiding allergen contact
An intervention to prevent allergen exposure in an already allergic and symptomatic patient is called tertiary prevention, and some intervention studies have been successful in reducing clinical symptoms [31,32]. However, tertiary prevention for mite allergic patients is also quite critically viewed [33,34].
Overall, however, the general principle of "no allergen exposure, no allergic reaction" also seems to make a reduction in mite exposure reasonable [35,36]. In principle, this also applies to primary care-i.e., avoiding the development of sensitization [37,38].
However, since exposure periods of only one week and even with relatively low allergen concentrations are sufficient to trigger primary sensitization, measures with this goal seem almost hopeless in regions where house dust mites are generally present [39,40] especially since exposure can occur anywhere, including the home, school, public buildings, transportation, or the workplace [41]. Consequently, inhalant mite allergy reduction measures serve to control or minimize symptoms of allergic diseases, but they cannot prevent the initiation of sensitization.

General information about mite allergy control measures
The aim of the measures is to avoid contact with the allergens to a large extent, to minimize the number of mites to a large extent, and to create unfavorable living conditions for the remaining mite population [42].
For this purpose, allergy-proof bed and mattress covers (encasing), regular washing of the comforters and bed linen at 60°C, can be a useful measure for tertiary prevention, if according to international recommendations a mite allergen concentration < 10 micrograms per gram of dust is achieved.
The following procedure is recommended: Prevention of contact with mite allergen ("encasing"), Killing existing mites, Creation of unfavorable living conditions for the remaining mites, and Removal of mite allergen.
Several Cochrane meta-analyses have highlighted some clinical efficacy of individual of the above-mentioned reduction measures [43,44]. Mite allergenproof covers (so-called "encasings") lead to a reduced exposure of the sensitized patient to mite allergens during sleep. The clinical efficacy of this measure has been extensively demonstrated for patients with mite allergic asthma. Embedded in an overall concept to reduce house dust mite allergens, these individual measures, such as the use of encasing, have a significantly better effect. Measures to reduce mite exposure in the context of secondary and tertiary prevention are also recommended in the 2022 revised guideline on allergy prevention by the German allergological societies [42].

Detection of mite load
In addition to elaborate laboratory chemical detection methods, the detection of significant mite allergen exposure by the guanine method is possible for home use [45,46]. Here, the guanine, which is present in the mites' feces, is detected. However, the tests for home use have been withdrawn from the German market in recent years. If required, test kits from foreign companies can be purchased (e.g., Ventia™ Rapid Allergen Test [RT-DM-1] [Ventia, New South Wales, Australia]).

Prevention of contact with mite allergen
Mite allergen-proof covers are semi-permeable membranes made of polyester, polyamide or natural fibers (cotton), more rarely polyurethane, polytetrafluoroethylene or polyethylene, which completely enclose the mattress, blanket and pillow and can thus significantly reduce allergen exposure in the "bed ecosystem". These membranes are usually made of nonwoven or woven textile and provide a physical barrier to mite allergen-containing particles. They are offered by various companies. An excerpt is shown in Table 1. review Table 1 Extract from supplier overview-encasings (protective covers for mattress, blanket, and pillow), name and manufacturer are listed, internet presence and whether a TÜV Nord test mark is available; For house dust mite allergic children with asthma, clinical studies have demonstrated that such "encasings" can highly significantly reduce allergen exposure and thus reduce asthmatic symptoms [47]. In a recent study, 46 mite-allergic children with asthma were included and the efficacy of impermeable covers for mattresses and pillows versus mite-permeable placebo covers was investigated over the period of one year [48]. Use of the mite-impermeable covers resulted in significant mite allergen reduction in the mattresses as well as significantly reduced need for inhaled steroids compared to children in the placebo group. Also in a study of 52 adolescent and adult patients with allergic asthma, van den Bemt and coworkers demonstrated that "encasing" resulted in a significant reduction of Der p1 on the mattresses as well as a significant improvement in the morning peak flow of the patients [49].
In the case of allergic rhinitis, inconsistent study results were found [44], which may be due to the different quality of the encasings used. For example, in a study of 279 dust mite allergic patients with allergic rhinitis, there was a significant reduction in mite allergen concentration in the mattresses of the patients who received an encasement, but no improvement in the clinical parameters studied compared to the patients who received a mite-permeable placebo cover [50].

Properties, processing and quality criteria of encasings
Mite allergen impermeable covers should meet the following quality criteria: Allergen tightness-pore size The encasing must be able to retain live mites, parts of dead mites, mite excrement and smaller particles to which mite allergens adhere. The pore size should be smaller than 0.5 µm.
Quality criterion: TÜV Nord tested (validated and certified test method with real dust mite allergens).
Allergen tightness-complete equipment All bed components (mattress, blanket, pillow) must be completely enclosed by encasings. A fitted cover for mattresses or toppers is not sufficient. Partner or sibling beds in the same room must also be completely enclosed with encasings.

Processing-textile
In principle, two types of textile are available as suitable encasing material: woven textile and nonwoven (Fig. 1).
a. Nonwoven fabric is formed from fibers or filaments by mechanical, aero-or hydrodynamic processes. The resulting textile has good filtration properties, but may have varying layer thicknesses and irregularities across the surface. b. Woven textile must be woven particularly tightly, creating a uniformly dense fabric. Postprocessing of the woven textile ("finishing") further reduces the pore size. The polyurethane coating of encasings, which was common in the past, is no longer necessary due to the use of modern fibers and techniques.

Processing-seams and closures
Particularly in the area of seams and zippers, there are small openings which must be covered by special processing (seam/zipper cuffs, Fig. 2) so that no allergens can penetrate. 20 Avoidance measures for mite allergy-an update Water vapor permeability A breathable textile (high air and water vapor permeability) has significant therapeutic benefits, especially for neurodermatitis sufferers and people who perspire heavily, as eczema and itching can be prevented.
Woven, uncoated textile is generally more breathable than fleece.
Quality criterion: TÜV Nord tested (validated and certified test method) Qualitative production All raw materials needed for production must be tested for harmful substances according to OEKO-TEX standards. The manufacturer itself must be ISO certified to ensure the quality standards. There are encasings with OEKO-TEX Standard 100 Class I, which are also suitable for babies.
Quality criterion: Hohenstein Institute, OEKO-TEX Standard 100 Class I Medical device class I according to MDR (Medical device regulation) Encasings are fundamentally different from so-called "allergy bedding". Encaisings have a proven safety and effectiveness. In comparison "allergy bedding" is a commodity of everyday life and therefore does not fall within the scope of the health insurers' obligation to provide benefits (no reimbursement, but personal responsibility of the insured).
Rescribable and reimbursable encasings have: Class I (low risk) registration for non-invasive medical devices, with claims for the treatment and prevention of dust mite allergy, Proven safety: the allergen-tightness within the scope of the perennial application as well as the pollutant-free nature of the raw materials was tested, and Clinically proven efficacy: the recommendation for encasings is found in all dermatological and allergological guidelines (including the current 2022 EDF Guideline, European Dermatology Forum).
Furthermore, a quality management system is required in the manufacturing plants, at least according to ISO 9001, and possibly also ISO 13485. Encasings are eligible for prescription and reimbursement if they have been approved as a medical device (Class I according to MDR). Manufacturers must be able to prove this by means of a declaration of conformity (CE). This is the qualitative prerequisite for reimbursement by statutory health insurers as a medical device.

Other
Synthetic fibers release moisture more quickly, thus drying faster and providing a poorer breeding ground for bacteria than natural fibers such as cotton. Since encasings should be washed as rarely as possible so as not to impair the impermeability of the material, this hygiene aspect plays an important role.
It is important to distinguish between the different types of encasings [51]. All other materials placed on the mattress should be suitable for regular washing [52]. The washing temperature here should be 60°C or higher, and the use of a tumble dryer is helpful for killing live mites [52][53][54]. Furthermore, special mite detergents can be used, with allergen eliminating effect.
The mite-allergen-proof covers ("encasings") awarded the "Material test-suitable for allergy sufferers" test mark by TÜV-Nord is available in German at review Table 2 Extract from the cost coverage for the provision of medical aids by selected statutory health insurers AOK PLUS (differences possible regionally) Patients do not have to make any additional payments and AOK Plus pays 100 euros for the purchase of mite-proof covers for the bed Barmer BARMER pays the aid provider a so-called supply lump sum for the intermediate bed covers. This flat rate includes all products and services as well as comprehensive advice, instruction in use and delivery. Any necessary replacement due to wear and tear or a defect is also free of charge for you for ten years, provided the defect was not caused intentionally or by gross negligence TK If you suffer from a dust mite allergy, TK will pay for the fitting of a mattress, duvet and pillow with special intermediate covers

IKK
Our contract partner is obligated to inform you about the range of allergy bedding available without extra payment and to advise you in this regard. They must offer you a selection of allergy bedding that is suitable for your care situation as well as medically necessary and for which you will not be charged any additional costs. Only if you nevertheless decide in favor of allergy bedding that goes beyond what is medically necessary will you have to bear the additional costs incurred as a result DAK If your doctor has diagnosed you with a dust mite allergy, we will cover the cost of anti-allergenic bedding. All you need is a doctor's prescription. You are free to choose from all DAK-Gesundheit contract partners. The amount of cost coverage for a complete set is limited to 40 euros. In principle, no costs are covered for partner equipment. However, it is possible to obtain partner equipment from the contractual partner at your own expense at the favorable DAK conditions www.tuev-nord.de, search term "Raumlufthygiene". There are differences in the reimbursement of miteallergen-proof covers on the part of the cost bearers. Table 2 shows an excerpt regarding the reimbursement by the statutory health insurance.
In private health insurance, there is no general stipulation on the reimbursement of encasings. Here, insured persons can take out individual insurance coverage tailored to their personal needs. The contractually agreed benefits are generally provided if the treatment is medically necessary. Therefore, it is checked whether a mite allergy is present and whether a treatment to reduce the allergen exposure is necessary. The amount of the insurance benefits depends on the selected insurance coverage and will be checked individually.
We consider the use of encasings to be particularly useful in combination with allergen immunotherapy, especially in the initial phase of allergen immunotherapy. A template from the Ärzteverband deutscher Allergologen (AeDA) can be used for the prescription of encasings.

Acaricides
Acaricides are pesticides or biocides used to control mites. Generally, one can distinguish between mite sprays and mite washes. The mite sprays are mostly based on neem oil, eucalyptus, geraniol and many more. The formerly contained benzyl benzoate is now only allowed in washing additives (excerpt of acaricides on the market in Table 3). Use as a mite reduction measure may be considered, although no controlled studies of efficacy and absolute population size reduction of individual acaricides are known.

Humidity control
House dust mites depend on relatively high ambient humidity for growth and reproduction, but can survive for extended periods in low-humidity environments [55]. This helps to explain why both dust mite exposure and mite-related respiratory symptoms can vary seasonally and argues for a possible role for humidity reduction measures in mite scarcity [56,57]. 22 Avoidance measures for mite allergy-an update K review Here, a relative humidity of 45-50% is given as a threshold value to achieve a relevant effect [56,57]. However, the results from controlled studies on the effect of dehumidification measures on mite abundance have been markedly inconsistent [58][59][60]. This is probably related to the fact that even short periods of increased humidity are sufficient for the survival and reproduction of dust mites. In addition, house dust mites can be found in large numbers even in desert areas if they find high humidity locally, e.g., in apartments where evaporative coolers are used [61][62][63].

Air purifier
Technical options for cleaning indoor air of particulate solids include electrostatic cleaners, in which the charged particles adhere to plates in the device [64]. Alternatively, filters are used in which the particles are physically trapped in the filter. HEPA (high efficiency particulate air) filters consist of a large area of folded paper that allows air to pass through and filter out 99.7% of particles down to 0.1 microns in size. The criticism here is that the exhaust air can swirl out dust and thus possibly swirl up more allergens than the filter removes from the air [65]. The complexity of these various issues underscores the importance of patient education and involvement. There is evidence that HEPA filters can reduce respiratory symptoms in mite allergic patients, suggesting that they may be helpful as part of a multifaceted avoidance strategy [66,67].

Carpets, furniture, curtains
Several studies have shown that in addition to mattresses, carpets and upholstery materials are important sources of dust mite allergens [68,69]. Shifting furniture, fluffing or moving pillows, curtains or bedding can release significant amounts of mite allergens into the air [15].
Vacuum cleaners can remove particulate matter such as mite allergens from carpets and upholstered furniture, but cannot reduce live mites to any significant extent because mites can cling to almost any surface with gripping tools on their feet [70,71]. Even with modern vacuum cleaners, it is therefore impossible to remove all dust mite allergens from a carpet or upholstered furniture. Therefore, humidity control should be emphasized at this point as part of the strategy. Placing carpets in the sun to clean and dry, as has traditionally been done, seems to be most effective. It should be remembered that vacuum cleaners can also stir up dust [72] which should be investigated in industry standard tests [73]. Suitable high-quality filters or extractors can filter out most of the allergen containing particles [74]. Steam cleaners provide little additional benefit in reducing mite allergens [75,76].

Effects of controlled studies on mite allergen avoidance
The design of a controlled study of mite allergen avoidance is complex and captures many parameters of daily life that are difficult to control (including ventilation behavior, length of stay in rooms, cleaning behavior of mattresses, blankets, sheets, etc.) [77]. In addition, behavioral changes may occur simply due to participation in the study and improved access to information in both the control and intervention groups, which may, for example, render the (additional) effect of an encasing undetectable [50].
Also, in polysensitized patients, symptomatology may be maintained by allergens other than house dust mites, so that the effect of the tested exemption measure is not detectable [78], or patients with relatively well-controlled disease or minimal dust exposure are included [79]. Therefore, it is important to know the mite allergen exposure precisely before starting the intervention over a longer period of time and under different living conditions [31,32,35,74,80].
Despite all these difficulties, successful studies have been conducted, with the main intervention usually related to beds.
The studies presented below focused on controlled study designs, in addition to the use of physical barriers (encasings), heat treatment to kill mites, additional use of tannic acid to denature mite allergens, and a complex design with measures to control exposure to animal dander, cockroaches, and dust mites [81,82].
Murray et al. included children with mite asthma and preceding asthma exacerbations with need for hospitalization in a controlled, effectively blinded study of mite abstinence [82]. The result was a significant decrease in exacerbations over the next year.

Discussion
The important role of mite sensitization in the manifestation of perennial allergic rhinoconjunctivitis and/or allergic asthma in industrialized countries is unquestionable [83,84]. Improved drug therapy options [85] and the modern allergen immunotherapy [36,86] contribute significantly to an improved morbidity and mortality of these diseases.
Studies on the correlation of early exposure to house dust mites and later development of asthma and/or allergic sensitization show partly contradictory results. Only actual complete allergen exposure avoidance can prevent sensitization. For the development of tolerance, the exposure of the immune system to allergens is necessary. It can be assumed today that small allergen amounts tend to lead to sensitization, whereas higher allergen concentrations tend to induce tolerance. In the U.S. birth cohort study URECA, exposure to house dust mite allergen in the first year of life was not associated with an review increased risk of recurrent wheeze at 3 years of age [87]. In a subsample, the microbial content of house dust was additionally examined [87]. A combined analysis of this embedded case-control study showed the lowest rate of allergic sensitization and "wheezing" at 3 years of age in the group of children who had high exposure to both indoor allergens and bacterial endotoxins in the first year of life, suggesting a synergistic effect. In a Finnish birth cohort study, a subanalysis captured associations between quantity and diversity of microbial markers in house dust samples collected at 2 months of age and children's later respiratory symptoms and allergies [88,89]. Here, microbial diversity correlated negatively with asthma risk at 6 years of age [88] and at 10.5 years [89]. Other studies found differences in the qualitative and quantitative allergen composition and microbial diversity of house dust from homes where children with and without asthma symptoms grew up [90][91][92]. In particular, the indoor microbiota in urban, poorer neighborhoods appeared to be associated with a risk of developing respiratory symptoms. Further studies are needed to clarify whether the childhood microbiome is altered by this and to better characterize protective and risk factors.
Interventions to reduce the exposure to dust mite allergens in the household are therefore currently not proven useful with the aim of primary prevention, but can be recommended for tertiary prevention of allergic diseases, as evidence of efficacy exists here. We therefore recommend a therapy trial of at least 6 weeks with mite control measures in the case of mild symptoms and additional allergen-specific immunotherapy if there is no improvement. In the case of moderate to severe symptoms, allergen-specific immunotherapy should be administered at the same time as the above-mentioned control measures.
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