allergic diseases and the indoor environment acknowledgments

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Thanks to Dr A Custovic MSc DM MD PhD, National Asthma Campaign Senior Research Fellow and Honorary Consultant Allergist, working at the North West Lung Centre, Wythenshaw Hospital, Manchester; Euan Tovey, PhD, IRM Allergen Diagnostic Project,University of Sydney, Australia; Michelle Allsopp, and members of the Healthy Flooring Network. The article by the International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee is reproduced with kind permission from the Lancet. This report was commissioned by the Healthy Flooring Network, to specifically look at the connection between indoor allergens, fitted carpets and allergic diseases. Report compiled by Dr. Jill Warner, Senior Lecturer in Allergy and Immunology, University of Southampton, UK for the Healthy Flooring Network I Allergic Diseases and The Indoor Environment Acknowledgments

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Page 1: Allergic Diseases and The Indoor Environment Acknowledgments

Thanks to Dr A Custovic MSc DM MD PhD, NationalAsthma Campaign Senior Research Fellow andHonorary Consultant Allergist, working at the NorthWest Lung Centre, Wythenshaw Hospital, Manchester;Euan Tovey, PhD, IRM Allergen DiagnosticProject,University of Sydney, Australia; MichelleAllsopp, and members of the Healthy Flooring Network.

The article by the International Study of Asthma andAllergies in Childhood (ISAAC) Steering Committee isreproduced with kind permission from the Lancet.

This report was commissioned by the Healthy Flooring Network, to specifically look at the connection between indoor allergens, fitted carpetsand allergic diseases.

Report compiled by Dr. Jill Warner, Senior Lecturer inAllergy and Immunology, University of Southampton,UK for the Healthy Flooring Network

I Allergic Diseases and The Indoor Environment

Acknowledgments

Page 2: Allergic Diseases and The Indoor Environment Acknowledgments

Indoor Allergens 02

Ecology and biology of mites 02

Life cycle and physiology 02

House Dust Mites 02

Introduction 01

Executive Summary III

Fitted Carpets and Allergies VI

II Allergic Diseases and The Indoor Environment

Contents

Distribution of mite allergen in homes 03

Mite Allergens 03

Allergen nomenclature 03

Prevalence of Allergic Diseases across the World 06

Cat and Dog Allergen 05

Distribution of cat and dog allergens 05

Mite allergens and allergic sensitisation 08

Mite allergens and asthma 09

Risk Factors for Allergic Sensitisation 08

Risk Factors – Mite Allergens 08

Clinical intervention studies 14

The Importance of Carpet Removal 14

Carpet Usage 15

Is Fel d 1 more susceptible to vacuuming than Der p 1? 15

Control of Allergens in the Domestic Environment 12

Reduction of Allergens in Carpets 12

Prevalence of Specific Sensitivities In Different Allergic Conditions 11

Conclusions 16

References 17

Tables 21

Article by the International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee 26

Page 3: Allergic Diseases and The Indoor Environment Acknowledgments

Everyone knows at least one person who suffers fromsome form of allergy. Up to a third of the population indeveloped countries is affected by allergic diseasessuch as asthma, eczema and hayfever. Today theprevalence of allergic diseases is extremely high, particularly in the English speaking westernised societies, and it has been clearly shown to haveincreased over the past few decades. The UK has the highest prevalence of asthma symptoms in 13-14year olds in the world, at 19.8%; the second highest prevalence of eczema; and the twelfth highest ofrhinoconjunctivitis. The indoor environment has beencited as one of the possible reasons for this increase.

Indoor AllergensThe factors that are likely to have the most effect on disease management in the short term are those that, while suggested to be potentially useful in primary prevention, also address the problems ofreducing symptoms in already sensitised individuals.Indoor allergens are one such area that might provide possible intervention strategies and it is this theorythat is addressed in this report.

It is thought that the trend for tightly sealed, energyconscious homes, with fitted carpets and upholsteredfurniture creates traps for allergen that previouslywould have been removed by ventilation through ill-fitting doors and windows. This report assessesavailable research from around the world on indoorallergens and finds for the first time that fitted carpetsare significant reservoirs of mite and pet allergens,whose importance has been underestimated in thepast. These allergens play a major role, not just in triggering symptoms but in allergic sensitisation, especially during infancy - a sensitisation which is the very foundation of susceptibility to asthma and allergies in later life.

Prevalence of Allergic Diseases Across the WorldStudies in different populations have shown that up to 85% of people with allergic asthma, but only 5-30%of the non-asthmatic population are allergy skin pricktest positive to mites. Up to 100,000 mites may livein one square metre of carpet. People are allergic toenzymes found in mite faecal pellets.

Mites and their allergens are found in many countriesaround the world. The variation in their numbersdepends mostly on humidity levels. For example, thelevel of mite allergens in very cold or dry climates isgenerally low, whereas higher levels are found in thecoastal areas of Europe and the USA, where the

climate is more suited to mite reproduction.The highest levels are found in regions where the climate is suited to mite growth throughout the year,such as the eastern coasts of Australia, Singaporeand South America.

Distribution of mite allergensMite allergens are often ubiquitously distributedthroughout houses and are found at many sites thatare free of live mites, although sites that mitescolonise (beds, carpets, and soft furnishings) generallyhave the higher allergen levels. Mite populations andtheir allergens are usually found at their highest levelper unit weight of dust in beds, but carpets can contain the largest reservoir in total amount of miteallergens in the house.

The presence of carpets in a home can dramaticallyincrease the total mite allergen load compared to having smooth floors. One study showed that the mite allergen concentration in dust from carpets couldbe 6-14 times higher than that from smooth floors and in some homes could be as high as that found in mattresses. The concentration of mite allergenincreases with increasing age of the carpet and thepresence of a dog is associated with higher mite allergen concentrations than found in petless households. Long pile carpets contain significantlymore mites than short pile carpets.

Distribution of pet allergensPets are the second most important cause of domestic allergy and over 50% of asthmatic childrenare sensitised to allergens of cats and/or dogs.Despite this, these pets are very common in our society and one or other is found in over 50% ofhomes in many countries. It has been suggested that up to one third of cat sensitised individuals live in a home with a cat.

The presence of fitted carpets is particularly stronglyassociated with high pet allergen levels. Even when apet is removed from a home the allergen levels canremain significantly higher than a home which hasnever housed a pet. Carpet levels become extremelyimportant in this situation, as should a cat sensitiveperson move into a home that has previously contained a cat or dog, the allergens will remain in any carpets left in the house and may cause allergicreactions. Cat allergen is also easily spread fromhome to home on the clothes of cat owners, thusaccumulating in the carpets of even non-cat-owners. In one study, dust from schools with carpeted areas

III Allergic Diseases and The Indoor Environment

Executive Summary

Page 4: Allergic Diseases and The Indoor Environment Acknowledgments

contained more cat allergen than the non-carpetedareas. This problem gives a great deal of support tothe idea that carpets should not be present in schoolsas they will increase the chances that pet sensitivechildren will be exposed to allergen concentrationswhich can trigger their allergic reactions.

Risk Factors - Mite AllergensThere is no doubt that exposure to allergens can bring about a sensitisation which could lead to allergies in later life. Once sensitised to mites, forexample, the likelihood of an individual developingasthma is greatly increased. After adjusting for sensitisation to other allergens, the risk of house dust mite sensitised children having asthma approximately doubles for every doubling of the level of exposure to mite allergens.

Sensitisation is more severe in people who live inregions with high exposure levels, and, in turn, asthmais more severe in people who have become sensitisedand are subsequently exposed to high allergen levels.

It is more difficult to demonstrate a direct relationshipbetween mite allergen exposure and prevalence ofasthma symptoms. Many other factors can influencethe symptoms of asthma such as, other sensitivities,cigarette smoke, pollution and infections.

Other allergic diseases have also been strongly linkedto mite allergens. One study demonstrates a cleardose response relationship between exposure tohouse mites and risk of atopic dermatitis. Anothershows that house dust mite allergen can aggravatethe symptoms of seasonal conjunctivitis. Several morestudies link perennial rhinitis with exposure to housedust mite allergens in mite sensitive patients.

Infant Vulnerability It is widely accepted that infants are most at risk ofbecoming sensitised. Studies have shown a significantassociation between increasing degree of sensitisationand increasing exposure during infancy. Thus the most important time for allergen levels to be low is in infancy.

There are now studies which indicate that maternalallergen exposure during pregnancy can influence the development of fetal immune responses, and also new, sensitive techniques have been able tomeasure mite allergen in amniotic fluid, suggestingthat maternal allergen exposure during pregnancy mayplay a role in primary sensitisation.

Reducing Allergen ExposureIn all, exposure to domestic allergens is strongly associated with increased risk of allergic disease, andin some cases increased symptoms. This must givestrong support to the need to find effective methodsof allergen reduction in homes, both for primary prevention of disease and alleviation of symptoms.

If we are to reduce the extremely high prevalence ofallergic disease seen in many countries, and improvethe quality of life of sufferers, we need to employeffective allergen reduction programmes.

Techniques to reduce allergen concentrations duringinfancy have the best chance of reducing the risk ofasthma. Measures to reduce sensitisation can also beemployed to manage established disease.

Epidemiological studies suggest that a 2-fold reductionof allergen exposure at a community level would significantly reduce rates of sensitisation in early childhood, halve the risk of asthma development in sensitised children and similarly reduce asthma severity in clinical terms.

The best results for reducing exposure to house dustmite allergens have been achieved with a combinationof encasing bedding and removing carpets and softfurnishings. Obviously allergen control measures needto be directed primarily towards sites in the home thatcontain most respirable allergen and where peoplespend most of their time. In most homes this meansthe living room and bedroom.

Control of Allergens in the Domestic EnvironmentThis report reviews the effectiveness of a number of treatments for fitted carpets. These include acaricidaltreatment, disinfectants and detergents such as benzyl benzoate, and tannic acid. The results were notdramatic and were not maintained for long periods oftime. The overall conclusion was that if carpets cannotbe removed alternative treatments to these will needto be found.

IV Allergic Diseases and The Indoor Environment

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Steam cleaning was found to be very effective atreducing both mite numbers and allergen in the laboratory, but was less effective in real homes.Intensive vacuuming, shampooing and autoclaving of carpet pieces in the laboratory was also very effective in reducing mite allergen, but only autoclaving reduced live mites. Unfortunately, the most effective methods are not practical techniques for fitted carpets in the home, and the vacuuming and the shampooing were less effectiveand very intensive.

Large reductions in mite densities in beds and carpetswere achieved in a controlled clinical trial with adultasthmatics using liquid nitrogen and vacuum cleaning.Unfortunately, the process can only be carried out by an operator who is fully trained in safety aspects of the use of liquid gases.

Overall, studies of mite allergen reduction in fittedcarpets are very disappointing. The best results wereobtained in the laboratory with little translation intoeffectiveness in the domestic environment. The mostpromising results are seen with intensive vacuumcleaning, but this is probably not practical outside a research setting, on fitted carpets in a real home.Several of the authors commented on these disappointing results in carpets.

The Importance of Carpet RemovalIt was notable that no study was able to reproducethe 10 fold difference between mite allergen concentrations seen between carpeted floors anduncarpeted floors reported from a study in Melbourne.

Surprisingly, very few studies have incorporated carpet removal into their interventions. The majority of successful clinical trials have either removed thecarpets or treated them exhaustively with other cleaning methods. Of the 20 trials reported here, 7 showed significant clinical improvements (and twomore showed a decrease in bronchial hyperreactivity.Of the 7 with notable improvements in symptomscores and medication usage, 4 removed the carpets,1 treated them rigorously with liquid nitrogen, 1 withbenzyl benzoate + encasing the mattress and the final one employed a punishing allergen avoidance regimen in the children’s bedrooms. This study mayalso have removed carpets, but it is not made clear in the methods.

All the above studies concentrated on house dust miteallergen, but it cannot be ignored that cat allergen is

the second most common trigger of asthma symptomsin the UK. A recent study showed that intensive cleaning with a high efficiency vacuum cleaner can significantly reduce cat allergen, which would still leadto an improvement in clinical symptoms even if sufferers are sensitive to both cat and mite allergen.

Carpet UsageThe UK has the highest consumption of carpets inWestern Europe and North America, at 3.9 m2 per person, nearly twice as much as the next highest carpet consumers, The Netherlands and Germany, at2.6 m2 per person. In contrast, Finland, Norway andSweden consume only 0.4 m2 per person betweenthem; in these countries the major trigger of asthma is cat and not mite allergen. It has also been reportedthat 98% of British homes have fitted carpets, compared with 16% in France and 2% in Italy.

ConclusionThis report has concentrated on the indoor environment and the allergens that accumulate indomestic situations. There is no doubt that there is a dose response relationship between the level ofexposure to house dust mite allergens and the risk of becoming sensitised to mites, and that exposure of sensitised individuals is associated with a risk of developing asthma.

If we are to reduce the extremely high prevalence ofallergic disease seen in many countries, and improvethe quality of life of sufferers, we need to employeffective allergen reduction programmes. The bestresults for reducing exposure to house dust mite allergens have been achieved with a combination of encasing bedding and removing carpets and soft furnishings.

Fitted carpets, once in place, can be treated with rigorous allergen reduction measures, but these are much more difficult and time consuming thaninstalling encasings for the bed. If people are prepared to follow daily cleaning regimens with effective products, then allergen reduction can beachieved, but such rigorous cleaning is unlikely to bepractical for most people. Ultimately, the removal of fitted carpets, which are difficult to treat sources ofallergen, is likely to be most practical and beneficial in the long term. Serious consideration now needs to be given to alternative furniture and flooring in order to persuade people to alter, what is, a deeplyrooted, cultural practice.

V Allergic Diseases and The Indoor Environment

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• Mite populations and their allergens are usuallyfound at their highest level per unit weight of dust inbeds, but carpets can contain the largest reservoir intotal amount of mite allergens in the house.

• The presence of carpets in a home can dramaticallyincrease the total mite allergen load compared to having smooth floors.

• Up to 100,000 mites may live in one square metre of carpet.

• One study showed that the mite allergenconcentration in dust from carpets could be 6-14

times higher than that from smooth floors and in somehomes could be as high as that found in mattresses.

• The presence of fitted carpets is particularly stronglyassociated with high pet allergen levels.

• One study showed that dust from schools with carpeted areas contained more cat allergen than the non-carpeted areas. This problem gives a greatdeal of support to the idea that carpets should not bepresent in schools as they will increase the chancesthat pet sensitive children will be exposed to allergen concentrations which can trigger their allergic reactions.

• In studies where carpets were intensively treated toreduce mite allergen none of the methods used wereable to reduce mite allergen concentrations by 90%, tomatch the low levels found in uncarpeted floors.

• It is striking that in all studies where there was significant benefit to allergy sufferers, carpets were either removed or were subjected to intensive treatment.

• The UK has the highest consumption of carpets inWestern Europe and North America, at 3.9 m2 per person, nearly twice as much as the next highest carpet consumers, The Netherlands and Germany, at2.6 m2 per person. In contrast, Finland, Norway andSweden consume only 0.4 m2 per person betweenthem; in these countries the major trigger of asthma is cat and not mite allergen.

• It has been reported that 98% of British homes have fitted carpets, compared with 16% in France and 2% in Italy.

• The UK has the highest prevalence of asthma symptoms in 13-14 year olds in the world, at 19.8%;the second highest prevalence of eczema and thetwelfth highest for rhinoconjunctivitis.

VI Allergic Diseases and The Indoor Environment

Fitted Carpets and allergens

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Today, everyone knows at least one person who suffers from some form of allergy. While 30-40 years ago allergies were diagnosed in only a small percentage of people, now up to one third of the population in developed countries are affected by allergic diseases such as asthma, eczema andhayfever. This has great implications for costs, both to the sufferers themselves and the health care providers in each country. It has been estimatedthat in Europe alone the combined direct and indirectcosts of allergic disease amount to about 18 billionpounds per year (1). As the demand on healthcarebudgets is so high it is essential that countries with a high prevalence of allergy work towards methods of primary prevention (2). This is not a simple task. Wedo not have any proven evidence for the causes of theincrease and have to rely on reducing known risk factors for the development of disease in individuals,which may not be the same as the factors responsiblefor the increase in disease in populations.

Known risk factors include: allergen exposure, parentalsmoking, diet and exposure to infection. Currentlynone of these, either individually or in combinationwith others, can be directly implicated as the cause of the increase, but all have been shown to be associated with the onset of disease.

The factors that are likely to have the most effect on disease management in the short term are thosethat, while suggested to be potentially useful in primary prevention, also address the problems ofreducing symptoms in already sensitised individuals.Indoor allergens are one such area that might provide possible intervention strategies and it is this theorythat is addressed in this report, with specific attentionto the role of fitted carpets. It draws broad conclusions on the role that carpets play in determining the total allergen load in the home and the importance of this on the severity of allergic disease.

01 Allergic Diseases and The Indoor Environment

Introduction

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The three major sources of indoor allergens associated with sensitisation and subsequent allergicdisease are house dust mites, pets and moulds. Insome inner city areas cockroaches are also important.

House Dust MitesStudies in different populations have shown that up to85% of people with allergic asthma, but only 5-30% ofthe non-asthmatic population are allergy skin prick testpositive to mites (3-6).

Ecology and biology of mitesMites belong to the class Arachnida, as do spidersand scorpions. At least 50 species have been found in domestic house dust, but in temperate climates the most important, both clinically and numerically, are the mites Dermatophagoides pteronyssinus andDermatophagoides farinae (and its related speciesmicroceras) of the family Pyroglyphidae. In the lastdecade it has also been suggested that anotherspecies, Euroglyphus maynei, may be clinically important (7,8). In tropical and subtropical regionsmites from the genus Blomia have been shown to beclinically important (9). A pictorial key to identificationof dust mites has been published (10) and a databaseof the global distribution and abundance of dust mites and their allergens has been established(D.MITEDATA) (11).

Life cycle and physiologyMites are small and invisible to the naked eye.Identifying species and determining viability can be difficult, but the main morphological characteristicsare well-described (12). Mites hatch from eggs and proceed through larval, protonymphal, andtritonymphal stages before reaching adulthood, whenthey are 300-400µm in length. Data on the proportions of eggs, larvae, nymphs and adults in apopulation can also be used to predict whether thatpopulation is increasing or decreasing in size, and howsuccessful different control measures are likely to be(13). The average life cycle is 3 months, during whichthe female may lay up to 300 eggs. Up to 100,000mites may live in one square metre of carpet (14).

Mites feed on desquamated human skin and fungi thatgrow on the skin scales. Some species of mites(Cheylitidae spp) feed on other mite species (15), butthis appears to be of little consequence when itcomes to controlling mite numbers. Mites have a well-developed gastrointestinal tract with digestion and food absorption primarily in the midgut and waterresorption in the hindgut (16,17).

The faecal pellets vary in size from 10-40µm and eachmite will produce about 20 per day. In contrast to thegastrointestinal system, mites have no specialisedrespiratory structure and oxygen is obtained by passive diffusion across their cuticle. As a result ofthis relatively hard, but pervious layer they are verysensitive to water loss and are essentially in equilibrium with the atmosphere, the relative humiditydetermining their water content. Many studies haveshown a significantly positive correlation between theair humidity in the home and the concentration of miteallergens in the house dust (18,19). Mites appear tothrive best at 80% relative humidity (RH) and 25˚C (20),however the minimum RH that is required to allow anet gain of body water is called the Critical EquilibriumHumidity (CEH) which varies with temperature (21,22).Below the CEH, mites slowly lose water. It may takeseveral weeks before a mite dies from desiccation.Conversely, when the RH rises above the CEH, aseverely dehydrated mite can regain a fully hydratedstate within 1 day (23). This has important implicationsfor mite reduction programmes as reducing air humidity to very low levels (even 0%) for a short periodwill not affect mite survival. In order to destroy a dustmite population, it is much more important to ensurethat RH remains continuously below the CEH, even ifonly slightly so (24). The average relative humidity levels in UK homes are 50-68% (145).

As well as being humidity dependent, mites are photophobic, and these two factors influence theirchoice of habitat – namely, at the base of carpets;inside mattresses; and in bedding, soft furnishingsand soft toys.

02 Allergic Diseases and The Indoor Environment

Indoor Allergens

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Allergen nomenclaturePatients who are allergic to house dust mites producespecific IgE (allergic) antibodies against various miteallergens (or cat allergens if they are allergic to catsetc.). Originally it was decided that if more than 90%of a population allergic to a particular allergen sourceproduced IgE antibodies to a specific allergen then itwould be regarded as a major allergen (25). Howevermore recently this has been modified to define majorallergens as those components to which more than10% of the IgE antibodies of more than 50% of thepatients react, or which contribute more than 10% ofthe allergenic activity of the extract (11)! Most miteallergens are proteins that are soluble in water andare found in the faecal pellets. Although as many as30 or more mite allergens have been identified, five or six appear to predominate, with another four beingsuitably well characterised to be included in thenomenclature system (11). Table 1 (p 21) shows thestructural and functional properties of some common indoor allergens.

The allergens derive their nomenclature from the first3 letters of the genus (for example Der) followed bythe first letter of the species (for example p), followedby numbering of the allergens according to their temporal sequence of purification, which is then modified to recognise homology between allergensfrom related sources (for example Group 1). With Dermatophagoides pteronyssinus, for example,the allergens that have been identified and characterised are referred to as Der p 1, Der p 2…….up to Der p 10. There are knownDermatophagoides farinae equivalents such as Der f 1and Der f 2 and the cat and dog allergens are Fel d 1and Can f 1 and Can f 2 respectively.

Most allergens are enzymes which facilitates theirinteraction with the host’s immune system. Housedust mite allergens are able to increase the permeability of respiratory epithelium thereby gainingaccess to antigen presenting cells located below theepithelium and initiating allergic sensitisation (26).

Distribution of mite allergen in homesMites and their allergens are found in many countriesaround the world (27). Despite the dramatic differencesin climate worldwide, we create not dissimilar livingconditions for ourselves wherever we are. This meansthat we create domestic environments that are alsoshared by mites. They vary in their numbers dependent mostly upon humidity levels. For example,the level of mite allergens in very cold or dry climates

is generally <2µg/g of dust (The Italian Alps,Stockholm, Arizona), whereas levels in countries withclimates more suited to mite reproduction (coastalareas of Europe and the USA) generally have mean levels in the range 2- 15µg/g. Regions where the climate is suited to mite growth throughout most of the year (eastern coasts of Australia, Singapore, South America) have mean allergen levels in the range 10-40µg/g (28).

Mite allergens are often ubiquitously distributedthroughout houses and are found at many sites thatare free of live mites, although sites that mitescolonise (beds, carpets, and soft furnishings) generallyhave the higher allergen levels (29). It is difficult tomake detailed comparisons of mite numbers and miteallergen levels between countries due to differentsampling techniques, but results from a selection ofdifferent countries are shown in Table 2 (p 21).

Mite populations and their allergens are usually foundat their highest level per unit weight of dust in beds,but carpets can contain the largest reservoir in totalamount of mite allergens in the house (28). Allergen levels in soft furnishings are often similar to thosefound in beds and both clothing and soft toys can contain very high numbers of mites (30).

There are a number of factors that are found most frequently to be associated with high mite numbersand high mite allergen concentrations. Numerous studies confirm the association between indoor humidity and mite allergen levels (31-37). Further indirect associations with humidity include: altitude of building floors (38-40), where higher Der p 1 levelsare found in rooms on the ground floor than rooms on higher storeys; ventilation rates (31,32,39,41), wherelow air exchange is associated with higher Der p 1concentrations; observed dampness (38); use of concrete floors (40); and high occupant densities (32,42).

The presence of carpets in a home can dramaticallyincrease the total mite allergen load from reservoirsites in the home compared to having smooth floors(32,43-46). One study showed that the Der p 1 concentration in dust from carpets could be 6-14times higher than that from smooth floors (32) and in some homes could be as high as that found in mattresses. If the house was also damp this wasassociated with higher carpet dust concentrations ofDer p 1, but not smooth floor dust concentrations ofthe allergen. The concentration of Der p 1 increaseswith increasing age of the carpet (32,40) and the

03 Allergic Diseases and The Indoor Environment

Mite Allergens

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presence of a dog is associated with higher mite allergen concentrations than found in petless households (42). Long pile carpets contain significantly more mites than short pile carpets, butshort pile carpets do not appear to have significantlymore mites than wood or ceramic tiles (43).

Interestingly two studies found no correlation between either mite numbers or mite allergen and thefrequency of vacuuming cleaning (42,43). Mite allergenin dust from carpeted floors is significantly higher inhomes than it is in institutions such as schools andhospitals (35,45,46,47).

The concentration of house dust mite allergen within acarpet in a single room can be highly variable. It ispossible to sample one 1m2 area in a living room andfind undetectable Der p 1 concentrations, whilst sampling another and finding extremely high levels.The distribution is difficult to predict and in generalthere is no clear pattern, except that variation is lessaround furnishings. In one home a difference of149.2µg Der p 1/g dust was found between one sampling area and another (48). This calls into questionthe practice of only sampling a 1m2 area for researchstudies, a frequently employed technique.

The literature search performed for this report onlyfound one study that reported smooth floor dust tocontain significantly higher mite allergen than carpetdust (49). This study was performed in Sweden wherethe mite allergen levels are very low and cat allergenposes more of a problem for sensitisation. Theauthors do not offer any explanation for the unusual finding.

04 Allergic Diseases and The Indoor Environment

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Pets are the second most important cause of domestic allergy and over 50% of asthmatic childrenare sensitised to allergens of cats and/or dogs (50).Despite this, these pets are very common in our society and one or other is found in over 50% ofhomes in many countries (51,52). It has been suggestedthat up to one third of cat sensitised individuals live in a home with a cat (53).

The major cat allergen is Fel d 1 and approximately90% of cat allergic patients make IgE antibodies tothis protein. At least 8 other cat allergens have beenidentified, but they require further characterisation todetermine their relevance to disease. The major dogallergens are Can f 1 and Can f 2.

Fel d 1 is produced primarily in the sebaceous glandsand in the basal squamous epithelial cells of the skin.It is stored mainly on the surface of the epidermis andon the fur (54). Fel d 1 production is under hormonalcontrol (55) and a single cat can produce between 3and 7µg per day (56).Castration of young male cats can result in a 3-5 fold reduction in the level of Fel d 1in skin washings and testosterone treatment of thecastrated cats restores the Fel d 1 level to pre-castration values (57).

The dog allergen Can f 1 is found in the dander, furand saliva (58) and induces a positive skin test reaction in 92% of dog sensitive patients (59).

Distribution of cat and dog allergensThe allergens become widely distributed throughouthomes in which pets are resident and also in environments visited by people who have close contactwith pets. The cat allergen, Fel d 1, has been found in dust from floors and soft furnishings, in the air andeven on walls. It is widely distributed in public places,due to it being carried on clothing (60). This wide distribution is probably because Fel d 1 is present onvery small particles (they can be as small as 0.2µm indiameter) which readily become airborne. The dogallergen Can f 1 is also widely distributed in homesand public places (61). Both cat and dog allergens are found in highest concentrations on upholsteredseats (62), most likely again to the allergens being carried on clothing.

While allergen levels are generally much lower inhomes that do not have a cat or dog compared tothose where the animal is present (53) Fel d 1 isdetectable in most homes and Can f 1 in up to 85% of homes (63). Frequently the levels are higher in the

living room than the bedroom (possibly due to the animals not being allowed in bedrooms, or people not sitting in the bedroom in clothes covered in petallergens). High humidity and poor ventilation give riseto increased pet allergen levels. The presence of fittedcarpets is particularly strongly associated with highallergen levels. One study showed that there is a graded association between dog allergen concentration and the presence of the dog indoors,outdoors, or not there at all (64). This study, which wasin the homes of farmers, also demonstrated that carpet levels of pet allergens were higher than mattress levels. Another study demonstrated thatdamp homes have higher concentrations of cat allergen in the carpets than dry homes, which may be due to a greater settling of the dust in thesehomes (49). However, in general, pet allergens arefound in highest concentrations on upholstered chairs(35,62,65). A study, investigating how the allergen wastransferred from homes to schools in New Zealandfound that the average amount of Fel d 1 carried onthe clothes of a cat owning child was 6.1µg comparedto 0.72µg on the clothes of a non-cat owning child (66).Wool and polyester garments contained more Fel d 1than cotton garments (probably due to washing fre-quency) and girls’ clothes contained more Fel d 1 thanboys’ clothes. It was suggested, by the authors, thatgirls might spend more time indoors than boys, there-fore being exposed to more allergen, or that girls’clothes require less frequent laundering! In theschools where this study was performed dust fromcarpeted areas contained more Fel d 1 than non-carpeted areas and the amount of Fel d 1 correlated with cat ownership rates. This problemgives a great deal of support to the idea that carpetsshould not be present in schools as they will increasethe chances that pet sensitive children will be exposedto allergen concentrations which can trigger their allergic reactions (67).

Even when a pet is removed from a home the allergenlevels can remain significantly higher than a homewhich has never housed a pet (68). It would seem thatthere is an initial reduction in aeroallergen when thepet actually goes, but after this the reduction in reservoirs is slow and variable. Cat allergen levels can remain high for years after the cat is removed.Carpet levels become extremely important in this situation, as should a cat sensitive person move intoa home that has previously contained a cat or dog, the allergens will remain in any carpets left in thehouse and may cause allergic reactions.

05 Allergic Diseases and The Indoor Environment

Cat and Dog Allergens

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Until relatively recently it has been very difficult to provide information on the prevalence of allergic disease across the world as so many different criteriahave been used to define the conditions of asthma,eczema and rhinoconjunctivitis (hayfever). However in 1998 the results of a world-wide study (The International Study of Allergy and Asthma inChildhood – ISAAC) were published which had used astandardised questionnaire to interview 463,801 13-14 year old children in 155 collaborating centres in 56 countries, about their symptoms of these threeatopic disorders (69). It was hoped that this informationwould provide a better understanding of the global epidemiology of allergic disease, to generate newhypotheses and to assess existing hypotheses of possible causes.

There have been few studies of the population prevalence of allergic rhinitis and atopic eczema, andalthough hundreds of asthma prevalence studies havebeen done in various parts of the world, they have seldom used standard approaches. An exception isthe European Community Respiratory Health Survey(ECRHS) (70-72), that involved surveys of asthma and allergic rhinitis prevalence in adults aged 20-44 yearsin 48 centres in 22 countries, although only 9 centresin 6 countries were outside Western Europe. The ECRHS suggested that there were regional riskfactors for asthma and allergic rhinitis in WesternEurope, but it did not comprehensively assess the global patterns. For children, the largest standardised studies of the prevalence of asthma,allergic rhinitis and atopic eczema have involved, at most, four countries (73-75).

The ISAAC study reports the prevalence of asthma in13-14 year olds across the world to vary from 1.6%(Indonesia) to 36.8% (UK) i.e. the highest prevalenceis about 20 times higher than the lowest.

Rhinoconjunctivitis showed a 30 fold variation in prevalence within the population with a range of 1.4%(Albania) to 39.7% (Nigeria). The UK was the twelfthhighest for this disease.

Eczema showed a 60 fold variation with a range of0.3% (Albania) to 20.5% (Nigeria). The UK was the second highest for this disease. The international patterns differed overall for eczema compared tothose for asthma and rhinoconjunctivitis, howeverthere were significant correlations (p<0.001) in prevalence for all disorders across the countries taken as a whole.

The prevalence of having symptoms of at least two outof the three conditions varied from 0.3% to 18.5%.Symptoms, in the last 12 months, of only one of thedisorders were seen in 72.9% of the children.

It must be noted that the ISAAC questionnaire gives a higher prevalence of asthma and probably the otherallergic diseases than more objective clinical basedstudies. Despite best efforts, translations of questions into different languages may not alwaysdiagnose the same clinical condition, particularlywhere there are no near-equivalent terms to describesymptoms and/or where there can be other diseaseswith similar symptoms.

The ISAAC paper showing all the results across theworld is attached to this report (p 26), but to summarise the findings:

For asthma symptoms the highest prevalences werefound in the UK, New Zealand, Australia, and theRepublic of Ireland, followed by most centres in North,Central and South America. The lowest prevalenceswere reported from centres in several EasternEuropean countries, Indonesia, Greece, China, Taiwan,Uzbekistan, India and Ethiopia. There were some verywide variations between different regions in similarparts of the world, which may prove useful informationto investigate causative factors within countries.

By contrast to asthma, rhinoconjunctivitis was reported from areas scattered around the world.Several countries with the highest symptom prevalences were not represented in the highest asthma prevalences; therefore this may indicate that the risk factors differ for the two diseases. For example, the highest prevalence of rhinoconjunctivitis was found in Nigeria, but this country is found only half way up the list for asthma prevalence.

For eczema the highest symptom prevalences includedcentres from many regions of the world, includingsome from Scandinavia (Finland and Sweden) andAfrica (Ethiopia), which were not represented amongthe highest asthma prevalences. However the centreswith low eczema prevalences tended to be the sameas those for asthma and rhinoconjunctivitis.

When self reported symptoms of more than one atopic disorder were taken into account the highestprevalences were observed predominantly in Englishspeaking Western countries. The ECRHS also showed

06 Allergic Diseases and The Indoor Environment

Prevalence of Allergic Diseases across the World

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that the presence of at least one positive allergen specific IgE was strongly associated with Englishspeaking populations (72). The presence of at leastone specific IgE ranged from 16% in Spain to 45% in New Zealand.

Studies from China and Africa showed striking differences in asthma prevalence within populationsdespite a similar prevalence of allergic sensitisation.Therefore risk factors other than allergy may be important in some populations (76,77).

The global pattern of allergic disorders was consistentwith the belief that outdoor air pollution is not a majorrisk factor (78,79). Regions such as China and EasternEurope with the highest air pollutants generally had low asthma prevalence. Those, such as WesternEurope and the USA, with high ozone levels had intermediate prevalences and some with low outdoor pollutants (e.g. New Zealand) had high asthma prevalences.

Therefore, patterns of allergic disease do appear to follow English speaking westernised societies, however there are some areas with a high prevalenceof disease, but low allergic sensitisation, indicatingthat other factors can be important and must not beignored when considering how to reduce the numbersof people with asthma, rhinoconjunctivitis and eczema across the world.

07 Allergic Diseases and The Indoor Environment

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As the previous section has demonstrated, the prevalence of allergic diseases is extremely high incertain parts of the world, and has been clearly shownto have increased over the past few decades (80-82).This has lead to much research investigating the possible reasons for this increase that might lead toways in which primary prevention can be implemented.Three major areas have been cited:

1) Indoor environment;2) Changes in diet; 3) Increased hygiene (2).

This report will concentrate on the evidence suggesting a role for the indoor environment and willmostly be focussed on the role of mite allergens withreference to the small number of reports on cat allergen and the mould Alternaria, as being the cause and/or trigger factors for allergic disease.

It is very important to differentiate between factors(and levels of factors) that cause allergic disease andthose that trigger symptoms in already sensitised individuals. These may be very different. Most studieshave concentrated on the role of these factors in asthma, with little information available on other allergic diseases.

Researchers have tried very hard to develop thresholdvalues for allergen exposure which are associated with1) sensitisation and 2) exacerbation of disease symptoms. The most widely quoted are those proposed by The First International Workshop on MiteAllergens and Asthma (27). They suggested that exposure to 2µg or more of Group 1 mite allergens per gram of dust (e.g. Der p 1 or Der f 1) be regardedas a risk for the development of IgE antibody and asthma, and a higher level of 10µg Group 1 mite allergens/g be regarded as a risk for an acute attackof asthma. Similar values have been placed on the catallergen Fel d 1 (83) with 1µg/g representing a risk forbeing sensitised to cats and a higher level of 8µg/gbeing the level at which most cat allergic patients willexperience symptoms. Similarly levels of 2µg/g and10µg/g Can f 1 are the levels significant for sensitisation and symptoms for dogs (84).

While quoting these thresholds one must be awarethat it is difficult to make direct comparisons betweendifferent studies as the method of sampling the dustwill vary from one to another, affected by issues suchas: which vacuum cleaner was used, what filter headwas employed, what filter size was incorporated, how

long the sampling continued and even the enthusiasmof the operator (85)! Nevertheless the collection of dustsamples from domestic environments has remainedbasically little changed for two decades (86)!

There has been much discussion over the years about whether reservoir or airborne levels are moremeaningful in terms of exposure and whether allergenshould be measured in ng/g of dust or ng/m2 of surface sampled. Overall it is generally agreed thatreservoir levels should be reported as both allergenper unit weight and allergen per unit area and thatwhile airborne levels are probably most closely relatedto exposure, they are difficult to measure (unlessnotable disturbance is occurring in the sampling environment) and cannot, as yet, form part of a standardised allergen measurement programme. New techniques are currently under development thatmay make the sampling of airborne allergens moreavailable and thereby provide allergen assessmentsthat are more meaningful in terms of actual exposure(ER Tovey – personal communication).

Risk Factors – Mite Allergens

Mite allergens and allergic sensitisationThe evidence for risk factors with a direct role in asthma causation is most complete for house dustmite allergens. The previously mentioned ability of theenzymes to actively damage airway epithelium (26)

makes their biologic significance highly plausible andthere is a great consistency of evidence for therebeing a dose-response effect in sensitisation (87).

Factors which have been proposed as being importantdeterminants of allergen specific immune responsesare: an individual’s degree of susceptibility to allergens, the immunogenic properties of the allergen,and the degree of exposure (88). In any populationthere is a gradient in the ability to respond to allergens: ranging from individuals who do not becomesensitised regardless of exposure to others who showextensive sensitisation to many different allergens.The ability to respond is genetically determined,although the exact pattern of inheritance is disputed(89). Even among individuals with a tendency torespond the development of sensitisation to an allergen is dependent on exposure. This is best illustrated by patterns of exposure: in NorthernEurope, where ragweed pollen is rare, sensitisation to it is equally rare; similarly the pollen of the olivetree is not recognised as an allergen in NorthAmerica; additionally among groups where it is rare to

08 Allergic Diseases and The Indoor Environment

Risk Factors for Allergic Sensitisation

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find a domestic cat, sensitisation to cat is uncommon.Between the extremes of no allergen exposure andexcess allergen exposure there is a gradation of exposure to a particular allergen. If sufficient exposure occurs the probability of sensitisation for susceptible individuals becomes extremely high.House dust mite allergens are highly immunogenic andin areas where mite exposure is high, such as the UK,parts of mainland Europe, Australia, New Zealand,coastal areas of North America and South America,the level of mite exposure appears to sensitise "most"potentially atopic children (90).

The most vulnerable time appears to be during infancyand both retrospective (91) and prospective (92)

studies have shown a significant association betweenincreasing degree of sensitisation and increasing exposure during infancy. However, it must be emphasised that the role of allergen exposure is atwo-stage process whereby exposure leads to thedevelopment of sensitisation and exposure of sensitised subjects leads to the development of asthma (93). Thus levels of sensitisation become moresevere in people who live in regions with high exposure levels (94), and asthma becomes moresevere in people who have become sensitised andwho are exposed to high allergen levels (95).

Most studies which have investigated the relationship between exposure and sensitisation haveconcentrated on individuals at high risk of developingatopy, but one group looked prospectively at the effectof allergen exposure on an unselected group of schoolchildren, performing skin prick tests to inhalant allergens at 12 month intervals over a period of twoyears, and measuring Der p 1 levels in mattresses (96).The children were divided into those with previous positive skin tests (other than to mites) and thosewithout. In non-atopic children, only extremely highexposure to Der p 1 (>60µg/g) represented a significant risk of sensitisation. Exposure to levels ofDer p 1 of >9µg/g conferred a definite risk of sensitisation in the whole population. For childrenalready sensitised to other inhalant allergens, a significant risk of sensitisation was conferred by>2µg/g of Der p 1, as suggested by The FirstInternational Workshop.

Once an individual is sensitised to mites the likelihoodof their developing asthma is greatly increased. Afteradjusting for sensitisation to other allergens, the risk

of house dust mite sensitised children having asthmaapproximately doubles for every doubling of the levelof exposure to mite allergens (97).

It must not, however, be forgotten that in areas wheremite allergen is very low, or unmeasurable, other allergens will take this role. For example, in LosAlamos, New Mexico, 67% of asthmatic children aresensitised to dog and 62% to cat. In this location thelevels of mite allergens are very low, but more than75% of families keep a cat or dog (84,93). In areas ofAustralia and the USA (Arizona) where the climatedoes not favour mite population growth and reproduction, sensitisation to the mould Alternariarepresents the most important risk factor for asthma(98,99). In some parts of Scandinavia, with low levels of mite allergen, sensitisation to domestic pets hasthe strongest association with asthma (100), but shouldsensitisation to mites occur at these low levels thenthere is still a close association between the mite sensitisation and asthma (19, 101).

Mite allergens and asthmaThe relationship between mite allergen exposure and sensitisation is very clear, but it is more difficultto demonstrate a direct relationship between miteallergen exposure and prevalence of asthma. Manyother factors can influence the symptoms of asthmasuch as, other sensitivities, cigarette smoke, pollutionand infections.

Most difficulty in determining whether mite exposurein its own right is affecting the development of asthmaoccurs in areas where the general level of exposure ishigh. A study performed in the south west of Franceconcluded that the risk of the occurrence of asthma insensitised individuals depends upon the degree ofatopy (number of positive skin tests), but that miteallergen exposure was not predictive of the occurrenceof asthma. The authors’ hypothesis is that house dust mite exposure is so ubiquitous in this area thatvirtually all genetically predisposed individuals becomesensitised to mites, whatever the house dust miteallergen level, which in most cases was above thethreshold for sensitisation (102). Another study, in New Zealand, also showed that current Der p 1 levelsshowed no association with current asthma (103), asdid a study of 8-10 year old children in Sydney,Australia (104). However all these areas have very high mite and mite allergen levels. In all three studies the majority of homes had Group 1 allergenlevels >10µg/g.

09 Allergic Diseases and The Indoor Environment

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Other studies in areas where the allergen levels arelower or more variable have been able to demonstratea relationship between severity of asthma symptoms(as determined by bronchial hyperresponsiveness[BHR] and lung function measurements) and mite allergen exposure in mite sensitive patients (105-109). The majority of these studies reported housedust mite allergen levels up to a maximum of 15µg/gand the only one that was higher (approximately650µg/g) (109) showed a huge variation between the low and high Der p 1 levels, giving room for differences in symptoms.

This ability to demonstrate a difference in symptomsin relation to house dust mite allergen levels, despitethe inability to identify a simple threshold level forprovocation of asthma symptoms, is central to thehypothesis that reducing allergen concentrations in the domestic environment is a viable method for themanagement of allergic disease. If different allergenlevels were not associated with different degrees ofsymptom severity there would be little point in instigating allergen reduction programmes.

Nevertheless, it is fairly uniformly accepted that themost important time for allergen levels to be low is ininfancy and that this is the most vulnerable time forsensitisation to occur. Techniques to reduce allergenconcentrations at this time in life have the bestchance of reducing the risk of asthma (91,92,110,111).There are now studies which indicate that maternalallergen exposure during pregnancy can influence thedevelopment of fetal immune responses (112,113) andalso new, sensitive techniques have been able tomeasure Der p 1 in amniotic fluid (114), suggesting thatmaternal allergen exposure during pregnancy may playa role in primary sensitisation.

One of the most frequently asked questions concerning domestic allergens is "Are we exposed tohigher concentrations of allergens in homes than during the periods when asthma prevalence waslower?" The answer is not simple as, although itseems likely that in certain environments, such as in Australia and New Zealand, the levels of cat andhouse dust allergens have been high for many years,the homes themselves have changed (115). Our energyconscious, tightly sealed homes with fitted carpetsand upholstered furniture may be traps for allergenthat previously would have been removed by ventilation through ill-fitting doors and windows. Theconcentrations measurable in the dust may be thesame, but the amount trapped in the air in the house

may have increased. Until we have more reliable methods of sampling airborne allergen this cannot bemeasured and even then we will not have comparisonsfrom 30 years ago. However, this lack of evidenceshould not deter us from attempting reduce the allergen load in the future.

As mentioned at the start of this section, mostresearch on the role of domestic allergens as risk andtrigger factors for allergic disease has been in asthma,but there are a few studies that have investigated therole of house dust mite allergen exposure in other diseases. One study has demonstrated clear doseresponse relationship between exposure to housemites and risk of atopic dermatitis (116). The studydemonstrated a relative risk of 4.7 with exposure toincreased numbers of house dust mites in the mattresses of atopic dermatitis patients comparedwith a control group of asthma patients not sensitisedto mite. The authors hypothesise that this could bedue to the increased skin scales (mite food) in themattresses of patients with atopic dermatitis leadingto increased mite numbers. This is supported by trials of house dust mite allergen reduction in atopic dermatitis patients, showing an improvement in symptoms (117).

Another interesting study showed that exposure tohouse dust mite allergen plays an important role in the aggravation of the symptoms of vernal keratoconjunctivitis (118). The study was performed in Israel and the severity of the symptoms of the vernal keratoconjunctivitis in house dust mite sensitivepatients peaked at the same time of year (summer) as the numbers of house dust mites.

There are also several studies that show that perennial rhinitis is associated with exposure to house dust mite allergens in mite sensitive patients.

In all, exposure to domestic allergens is strongly associated with increased risk of allergic disease, andin some cases increased symptoms. This must givestrong support to the need to find effective methodsof allergen reduction in homes, both for primary prevention of disease and alleviation of symptoms.

10 Allergic Diseases and The Indoor Environment

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The allergens that trigger different allergic conditionswill differ from one country to another depending uponexposure. In the UK the triggers for asthma have been studied in most detail and have shown that inasthmatic individuals 50-75% are allergic to housedust mites; 50-70% are allergic to grass pollen; 35-55% to cat; 10-40% to dog; 10-20% to tree pollen; 10-15% to moulds and <10% to foods (119-121).

In rhinitis 20-40% are allergic to house dust mites, butthe greatest trigger is pollen (122-124).

In eczema, particularly in early childhood, the majortriggers are frequently foods. However, one studyshowed that inhalant allergens do play a significantrole with over 60% of a mixed group of children andadults having specific IgE antibody to house dust mite allergen, even when those with concurrent asthma were removed. Similar responses were seen to grass pollen (125).

11 Allergic Diseases and The Indoor Environment

Prevalence of Specific Sensitivities inDifferent Allergic Conditions

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Epidemiological models suggest that a 2-fold reductionof allergen exposure at a community level would significantly reduce rates of sensitisation in early childhood (92,94), halve the risk of asthma developmentin sensitised children (95), and similarly reduce asthmaseverity in clinical terms (126).

The optimal allergen avoidance is found in schoolsand institutions at high altitude, where severe asthma sufferers can spend long periods of time inenvironments that contain very low or undetectableamounts of the common allergens triggering their disease. Beneficial results have been seen when allergic individuals have moved from the humidMediterranean coast of France, where house dust miteallergen levels are high, to a low mite environment inThe French Alps (127), or from the plains of Italy to theAlps (128). Impressive reductions in the severity ofasthma and levels of anti-house dust mite IgE havebeen seen in both locations, but they are reversed onreturning to the high house dust mite environment. Inthe Netherlands, children admitted to a high altitudeasthma centre showed reduction in blood eosinophils,reduced peak flow variability and improved airwayhyperresponsiveness (129).

Unfortunately not all allergic individuals can be sent tosuch institutions (although they would be excellentplaces to spend the vulnerable first year of life in anyprimary prevention study), so attempts have to bemade to recreate these low allergen havens in normaldomestic environments.

Obviously allergen control measures need to be directed towards sites in the home that contain mostrespirable allergen and where people spend most oftheir time. In most homes this means the living roomand bedroom. The sites that contain most allergenare: beds, carpets, soft furnishings, soft toys, and, in some cases, infrequently laundered clothes. Levelsin clothing can be as high as in any other domesticsite. Clothing is constantly disturbed and is a highlyproximal source. Not all allergen reduction techniquesare suitable for all sites of allergen accumulation.Therefore, specific techniques have been developed todeal with specific areas of the homes e.g. anti-allergybedcovers, which are likely to be more effective atreducing exposure to allergens in the mattress, duvetand pillow than vacuuming and safer than spraying thebed with potentially toxic chemicals.

Any successful allergen reduction programme is likelyto consist of more than one intervention in order to

deal appropriately with the different sources of allergens. The most frequently employed techniquesinclude: removal of carpets, high efficiency vacuumcleaning, bedcovers, dehumidification and increasedventilation, acaricides, and heating or freezing. Othertechniques that have been investigated include: ionisers and air filtration devices.

The effectiveness of all of these devices is extremelyvariable in reducing domestic allergens and whilst several have shown significant reductions in housedust mite allergens in specific source materials, fewhave been able to translate these reductions into clinical benefit. Some studies did not assess clinicalbenefit, purely measuring changes in allergen concentrations to assess the effectiveness of theintervention. These studies indicate potentially usefulinterventions, but the components of the allergenreduction regime cannot be specifically recommendedto patients as potential additional management fortheir disease unless clinical benefit has been proven.People who are looking for techniques to reduce allergen concentrations may wish to try them in theirown homes as part of an allergen reduction schedule.In the following sections, studies that have simplymonitored allergen concentrations are reviewed firstfollowed by studies on clinical benefits. The effects on carpets are summarised in Table 3 (p 22).

Reduction of Allergens in CarpetsAs mentioned previously, carpets are some of themajor allergen retaining sources in the domestic environment. Different carpet types may retain greateror lesser amounts of allergen dependent upon theirconstruction and the material of which they are made.One study investigated the retention properties of 26types of custom made carpets by spiking them withreference dust containing Fel d 1 and then measuringthe ability to remove that allergen with a standardisedvacuum technique (130). They found that the carpetproperties that render the carpet most likely torelease allergen to vacuuming are: low pile densityand height, fluorocarbon coating of fibres, high denierper filament, and low surface area fibres (e.g. squarehollow fibre rather than trilobal). Another study showedthat woollen carpets have significantly higher concentrations of Der p 1 in the air above them thando synthetic carpets, possibly due to electrostaticcharge (131). Should allergic individuals decide to keep their carpets a careful decision on carpet typewould need to be made concerning the ability toactively remove allergen from the carpet, whilst notcreating an overall high allergen load in the room air.

12 Allergic Diseases and The Indoor Environment

Control of Allergens in the Domestic Environment

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Acaricidal treatment of carpets is probably the mostfrequently studied technique for removal of mites andtheir allergens. The first studies investigated disinfectants and detergents (132) and found that themost effective chemical was benzyl benzoate, althoughall the agents were more effective on hard floors thancarpeted floors. Another detergent (Metsan) was investigated in The Cape Peninsula (where Der p 1 levels are high) for its properties in reducing Der p 1levels in carpets and mattresses on its own and incombination with an acaricide (Acarosan) (133). Theresults showed that a single application of Metsanalone could significantly reduce the concentration ofDer p 1 in carpets measured 3 months after the singleapplication and that the addition of the acaricideenhanced the effect. No reduction in mattress Der p 1was seen with either treatment. The reduction in carpet Der p 1 was approximately 50%, with allergenconcentrations of >10µg/g still remaining in bothtreatments. Two studies from Charlottesville Virginia,USA (134,135) investigated the effectiveness of tannicacid, benzylbenzoate and two commercial carpet cleaners on Groups 1 and 2 mite allergens and Fel d1 in carpet dust. The results were not dramatic andwere not maintained for long periods of time, howeverbenzyl benzoate and the two commercial carpet cleaners significantly reduced group 1 dust mite allergens. Tannic acid was more effective on Der f 1than Der p 1 and nothing was effective on Fel d 1. The overall conclusion was that if carpets cannot beremoved alternative treatments to these will need tobe found as their effectiveness is extremely limited.There are also concerns about the frequent use ofpotentially toxic chemicals in the home.

Steam cleaning and hot water washing extraction hascaptured the interest of several groups with variedresults. When carpets in homes were exposed to hotwater washing extraction no reduction in mite numberswas seen, although there was a 3.3 fold reduction inDer p 1 (136). The authors concluded that carpet cleaning in this format was unlikely to be effectiveenough to show any clinical benefit. Conversely, whenpieces of carpet were exposed to steam cleaning100% reduction in mite numbers and 86.7% reductionin Der p 1 was achieved, with the conclusion that thetreatment looked highly promising (137).

Several groups have also investigated vacuuming.In Amsterdam comparisons were made between dry vacuuming, wet cleaning, shampooing and autoclavingof carpet pieces. None of the techniques, where thecontent of live mites was checked after treatment,

showed any reduction in mite numbers (it wasassumed that autoclaving killed all the mites), but allshowed some reduction in Der p 1, with autoclavingproving the most effective. Unfortunately neither theautoclaving nor the wet washing would be practicaltechniques to treat fitted carpets in situ and the vacuuming and the shampooing were less effectiveand very intensive (138).

Low temperature washing with detergents and washingwith added benzyl benzoate was moderately effectiveon carpet pieces, showing a 50% and 100% reductionrespectively in mite numbers (139).

A comparison of vacuuming with application of tannicacid on a combined concentration of Der p 1 and Der f1 showed reductions of 50% and 34% respectively inSweden (140), while in New Zealand daily vacuumingof carpets showed reductions in Der p 1/g and Der p1/m2 of 48% and 68.5% (141).

A study of the application of benzyl benzoate in Bristol,UK did not demonstrate any reduction Der p 1 in thebedroom carpet (142), nor did the application of an anti-mite shampoo to bedroom carpets in Melbourne, Australia (143).

Ventilation systems and dehumidifiers, despite showing reduction in mite numbers and Der p 1 inmattresses showed no effect on either in bedroom or living room carpets (144-148).

Therefore, overall, these studies of mite allergenreduction in carpets are very disappointing. The bestresults were obtained in the laboratory with little translation into effectiveness in the domestic environment. The most promising results are seenwith intensive vacuum cleaning, but this is probablynot practical outside a research setting. Several of the authors commented on these disappointing resultsin carpets. It was notable that no study was able toreproduce the enormous difference between mite allergen concentrations seen between carpeted floorsand uncarpeted floors, with dust from uncarpetedfloors containing only 10% of the allergen found indust from carpeted floors, (41.1µg Der p 1/g and4.1µg Der p 1/g respectively) reported from a study in Melbourne (143).

This report aims to focus mostly on the effect of allergen reduction techniques on allergens in carpets,but it is important to mention other techniques thataddress the issues of allergens in other sources in

13 Allergic Diseases and The Indoor Environment

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the home. As mentioned above, whilst mechanical ventilation was not effective on allergens in carpets ithas been shown to be highly effective on mite allergenconcentrations in mattresses (149,150). This is interesting, as the opposite might be expected, dueto the mattress containing a greater reservoir of

water and more frequent replenishment from humanoccupancy. The majority of studies have been done inthe dry, cold climate of northern Scandinavia andthere has been much scepticism about whether theresults can be repeated in warmer, damper climates.Originally it was thought that this was not possible (145-148), but newer, more effective products look more promising (151).

Mite densities have been reduced successfully by theuse of electric blankets to decrease mattress humidity(152)1. In field trials, the inert freezing agent, liquid nitrogen, combined with intensive vacuum cleaning,was found to be very effective at killing and removingmites (153); mean densities of live mites in dust samples from five treated mattresses were reducedfrom 310/g to 3/g in 8 weeks. Large reductions inmite densities in beds and carpets were also achievedin a controlled clinical trial with adult asthmatics (154)

using liquid nitrogen and vacuum cleaning.Unfortunately, the process can only be carried out by an operator who is fully trained in safety aspects of the use of liquid gases.

For beds, barrier methods are most effective and studies in which mites are vacuumed through mattresscovers showed a reduction in the order of 30-100 foldcompared with those in the dust on the mattressesthemselves (155,156). The majority of studies suggestclinical improvement following use of mattress covers,usually combined with cleaning measures (155,157-159).

Another allergen denaturing solution was tested inboth Australia and UK and was shown to produce amoderate reduction in mite allergens in carpets, blankets and soft furnishings (160,161), but, again, not sufficiently effectively to suggest that an improvement in symptoms would be seen.

There are no studies of air filtration devices alone that have shown any clinical improvement and,although HEPA filters have been shown to be effectiveat reducing cat allergen concentrations in rooms, theopinion is that they cannot be recommended in theabsence of other forms of environmental control (162).

There is very little scientific evidence to support theclaims of manufacturers that ionisers are of benefit to patients with allergy to domestic allergens. A double-blind cross-over study using active and placebo ionisers in homes showed no improvement of asthmatic symptoms during the period of active ionisation, even though a significant reduction wasseen in airborne Der p 1. In fact an increase in nocturnal cough was recorded during the active period (163). Ionisers, therefore are not presently recommended for use in the home for symptomaticrelief of asthma.

Clinical intervention studiesOne of the most important aspects of a clinical studyis that it is placebo controlled to account for anyimprovements in symptoms which can be attributedsimply to being part of a trial and therefore receivingextra attention. Unfortunately this is not always easyto achieve with an allergen reduction programme andsome reported studies are uncontrolled before andafter investigations. Table 4 (p 24) (adapted from Marks GB [179]) gives an overview of the effectiveness of a range of placebo controlled intervention studies, both in reducing allergen and in improving symptoms. The most effective studies comprised a combination of encasing the mattressand removing or rigorously treating the carpet.

The Importance of Carpet RemovalSurprisingly, very few studies have incorporated carpetremoval into their interventions. Those that have, haveincluded other measures as well, which makes anyassessment of the individual contribution of removingthe carpet difficult to ascertain. However, it is clearthat the majority of clinical trials that have reportedimprovements in symptoms have either removed thecarpets or treated them exhaustively with other cleaning methods. Of the 20 trials reported here, 7 showed significant clinical improvements(154,155,157,166, 170, 175 and 176) and two more showed a decrease in bronchial hyperreactivity (BHR) (169,177).Of the 7 with notable improvements in symptomscores and medication usage, 4 removed the carpets(155,157,166,170), 1 treated them rigorously with liquidnitrogen (154), 1 with benzyl benzoate + encasing themattress (175) and the final one employed a punishingallergen avoidance regimen in the children’s bedrooms(176). This study may also have removed carpets, but itis not made clear in the methods. The scheduleincluded "changing" bedclothes, mattress, rugs, carpets, upholstered furniture and soft toys due to them being major sources of house dust

14 Allergic Diseases and The Indoor Environment

1. It must be noted that it is not recommended, however, that people sleep withthe electric blankets switched on as electromagnetic fields associated with electric blankets have been implicated as a possible risk factor in breast cancer.

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accumulation. The rest of the schedule consisted of:1) daily washing of floors and damp dusting, shakingof bedclothes outside the bedroom and bedclothes left on the window sill; 2) weekly vacuuming of both sides of the mattress,thorough cleaning of all surfaces with a damp cloth,changing of bedsheets and washing at >60 degrees Celsius; 3) monthly washing of pillows and blankets at 60degrees Celsius. As it emphasises washing of floors in the bedroom it can probably be assumed that thecarpets were removed.

Is Fel d 1 more susceptible to vacuuming than Der p 1?All the above studies concentrated on house dust mite allergen, but it cannot be ignored that cat allergen is the second most common trigger of asthmasymptoms in the UK (and the most common in somecountries where mite allergen is low). A recently conducted study of the use of high efficiency vacuumcleaners in the homes of allergic asthmatic patientsconfirmed the lack of effectiveness of vacuuming inthe reduction of Der p 1 in carpets, soft furnishing andmattresses in homes. However, it demonstrated thatFel d1 concentrations can be significantly reduced witha daily vacuuming regimen (even in homes where a cat is present) with an associated improvement inmedication usage, lung function and BHR in cat sensitive individuals (in non-cat containing homes)(180). It must be stated that cat sensitive patients are frequently also allergic to house dust mite, but itseems that the reduction of the cat allergen alone,can result in improvement in the clinical parameters of asthma in these patients, even when house dustmite allergen is unchanged. This must be taken into account when advocating total removal of allergen sources rather than treating them in-situ.

Carpet UsageIt has proved difficult to obtain accurate figures of the differences in carpet usage across the world, however it seems clear that the UK has the highestconsumption in Europe and North America. In 1999consumption per capita for the countries where information was available was as follows:

Annual Carpet Consumption in Europe and North America

Country Square metres per person

UK -3.9*

Holland -2.6*

Germany -2.6*

USA -2.4

Belgium -2.1

Canada -1.9

Denmark -1.9

Switzerland -1.7

France -1.5*

Austria -1.0

Portugal -0.7

Spain -0.6

Italy -0.4

Norway, Finland and Sweden -0.4

All figures are based on personal communication with Laurance W Bird, DuPont NylonMarketing. * All figures other than those marked * are calculated using population statistics for 1997 from the United Nations Statistics Division and statistics for 1998from the Swiss Federal Statistical Office.

Across Western Europe the carpet consumption follows the climate conditions generally with coldernorthern countries having the higher consumption. The average UK consumer is said to replace carpetingevery 6 years (181). This, of course, must be tempered by the lower use of carpeting in Scandinavia,where housing is generally more energy efficient,despite the cold conditions. It must be noted that the major trigger of asthma in Northern Scandinavia is cat and not mite. It has been reported (Proctor andGamble Concept and Usage Research for Febreze1997) that 98% of British homes have fitted carpets,compared with 16% in France and 2% in Italy.

15 Allergic Diseases and The Indoor Environment

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Allergic diseases have increased in prevalence dramatically over the last 3 decades, particularly inWestern, English speaking, countries. The UK has thehighest prevalence of asthma in the 13 year old population in the world. The theories that have beenput forward to explain this have 3 main focuses:

1) Indoor environment; 2) Diet; 3) Hygiene and infection.

This report has concentrated on the indoor environment and the allergens that accumulate indomestic situations, with particular reference to therole of fitted carpets as reservoirs for these allergens.There is no doubt that there is a dose response relationship between the level of exposure to housedust mite allergens and the risk of becoming sensitised to mites, and that exposure of sensitisedindividuals is associated with a risk of developingasthma. Measures to reduce sensitisation can also beemployed to manage established disease and if weare to reduce the extremely high prevalence of allergicdisease seen in many countries, and improve the quality of life of sufferers, we need to employ effectiveallergen reduction programmes. The best results forreducing exposure to house dust mite allergens havebeen achieved with a combination of encasing beddingand removing carpets and soft furnishings. It is notable that in almost all of the studies wherethere was significant benefit to allergy sufferers, carpets were either removed or subjected to intensivetreatment. Fitted carpets, once in place, can be treated with rigorous allergen reduction measures, but these are much more difficult and time consumingthan installing encasings for the bed.

If people are prepared to follow daily cleaning regimens with effective products, then allergen reduction can be achieved, but such rigorous cleaningis unlikely to be practical for the majority of people.Ultimately the removal of fitted carpets is likely to bemost practical and beneficial in the long term. Seriousconsideration now needs to be given to alternative furniture and flooring in order to persuade families toalter, what is, a deeply rooted cultural practice.

16 Allergic Diseases and The Indoor Environment

Conclusions

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7. Colloff MJ. A review of biologyand allergenicity of the house dust mite Euroglyphus maynei(Acari: Pyroglyphidae). Exp ApplAcarol 1991;11:177-198.

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26. Winton HL, Wan H, CannellMB, Thompson PJ, Garrod DR,Stewart GA, Robinson C. Classspecific inhibition of house dustmite proteinases which cleave celladhesion, induce cell death andwhich increase the permeability oflung epithelium. Brit J Pharmacol1998;124:1048-1059.

27. Platts-Mills TAE, de Weck AL.Dust mite allergens and asthma – a world-wide problem.

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28. Tovey ER. Allergen exposureand control. Exp Appl Acarol1992;16:181-202.

29. Tovey ER, Chapman MD, Platts-Mills TAE. The distribution of house dust mite allergen in thehouses of patients of asthma. AmRev Resp Dis 1981;124:630-635.

30. Bischoff E, Fischer A. Newmethods for the assessment ofmite numbers and results obtainedfor several textile objects.Aerobiologia 1990;6:23-27.

31. Harving H, Korsgaard J, Dahl R. House dust mites andassociated environmental conditions in Danish homes.Allergy 1993;48:106-109.

32. Van Strien RT, Verhoeff AP,Brunekreef B, Van Wijnen JH. Mite antigen in house dust: relationship with different housingcharacteristic in The Netherlands.Clin Exp Allergy 1994;24:843-853.

33. Munir AKM, Bjorksten B,Einarsson R, Ekstrand-Tobin A,Moller C, Warner A, Kjellman NIM.Mite allergens in relation to homeconditions and sensitisation ofasthmatic children from three climatic regions. Allergy1995;50:55-64.

34. Chan-Yeung M, Becker A, LamJ, Dimich-Ward H, Ferguson A,Warren P, Simons E, Broder I,Manfreda J. House dust mite allergen levels in two cities inCanada: effect of season, humidity,city and home characteristics. ClinExp Allergy 1995;25:240-246.

35. Custovic A, Fletcher A,Pickering CAC, Francis HC, GreenR, Smith A, Chapman M, WoodcockA. Domestic allergens in publicplaces III: house dust mite, cat,dog and cockroach allergens inBritish hospitals. Clin Exp Allergy1998;28:53-59.

36. Hirsch TH, Range U, WaltherKU, Hederer B, Lassig S, Frey G,Leupold W. Prevalence and determinants of house dust miteallergen in East German homes.Clin Exp Allergy 1998;28:956-964.

37. Dharmage S, Bailey M, RavenJ, Cheng A, Rolland J, Thiens F,Forbes A, Abramson M, Walters EH.Residential characteristics influence Der p 1 levels in homesin Melbourne, Australia. Clin ExpAllergy1999;29:461-469.

38. Kuehr J, Frischer T, KarmausW. Natural variation in mite antigendensity in house dust and

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39. Sundall J, Wickman M,Pershagen G, Nordvall S.Ventilation in homes infested with house dust mites. Allergy 1995;50:106-112.

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41. Harving H, Korsgaard J, DahlR, Clinical efficacy of reduction in house dust mite exposure inspecially designed, mechanicallyventilated "healthy" homes. Allergy 1994;49:866-870.

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45. De Andrade AD, Charpin D,Birnbaum J, Lanteaume A,Chapman MD, Vervloet D. Clinicalaspects of allergic disease. Indoorallergen levels in day nurseries. JAllergy Clin Immunol1995;95:1158-1163.

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126. Custovic A, Taggart SCO,Francis HC, Chapman MD,Woodcock A. Exposure to housedust mite allergens and the clinicalactivity of asthma. J Allergy ClinImmunol 1995;98:64-72.

127. Vervloet D, Penaud A, RazoukH. Altitude and house dust mites.Am Rev Respir Dis 1982;69:290-296.

128. Peroni DG, Boner AL, ValloneG, Antolini I, Warner JO. Effectiveallergen avoidance at high altitudereduces allergen induced bronchialhyperresponsiveness.

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129. Van Velzen E, van den BosJW, Benckhuijsen JAW, van Essel T,de Bruijn R, Aalberse R. Effect ofallergen avoidance at high altitudeon direct and indirect bronchialhyperresponsiveness and markersof inflammation of children withallergic asthma. Thorax1996;51:582-584.

130. Lewis RD, Breysse PN. Carpetproperties that affect the retentionof cat allergen. Ann Allergy asthmaImmunol 2000;84:31-36.

131. Price JA, Pollock I, Little SA,Longbottom JL, Warner JO.Measurement of airborne mite antigen in homes of asthmatic children. Lancet 1990;336:895-97.

132. Scober G, Wetter G, BischoffE, Van Bronswijk JEMH, Kniest FM.Control of house dust mites(Pyroglyphidae) with HomeDisinfectants. Exp Appl Acarol1987;3:179-189.

133. Manira A, Berman D, ToerienA, Weinberg EG, Potter PC. Theeffects of a single treatment of anacaricide, Acarosan, and a detergent, Metsan, on Der p 1allergen levels in the carpets andmattresses of asthmatic children.S African Med J 1994;84:278-280.

134. Woodfolk JA, Hayden ML,Miller JD, Rose G, Chapman MD,Platts-Mills TAE. Chemical treat-ment of carpets to reduce allergen:A detailed study of the effects of tannic acid on indoor allergens. J Allergy Clin Immunol 1994;94:19-26.

135. Woodfolk JA, Hayden ML,Couture N, Platts-Mills TAE.Chemical treatment of carpets toreduce allergen: Comparison of theeffects of tannic acid and othertreatments on proteins derivedfrom dust mites and cats. J AllergyClin Immunol 1995;96:325-333.

136. Tovey ER, McDonald LG. Carpet cleaning. Med J Australia1993;158:579.

137. Colloff MJ, Taylor C, MerrettTG. The use of domestic steamcleaning for the control of housedust mites. Clin Exp Allergy1995;25:1061-1066.

138. De Boer R. The control ofhouse dust mite allergens in rugs.J Allergy Clin Immunol1990;86:808-814.

139. Bischoff ERC, Fischer A,Liebenberg B, Kniest FM. Mite control with low temperature washing. I Elimination of livingmites on carpet pieces. Clin ExpAllergy 1996;26:945-952.140. Munir AKM, Einarsson R,

19 Allergic Diseases and The Indoor Environment

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141. Adilah N, Fitzharris P, Crane J,Siebers RW. The effect of frequentvacuum cleaning on the house dustmite allergen Der p 1 in carpets: apilot study. NZ Med J1997;110:438-439.

142. Weeks J, Oliver J, BirminghamK, Crewes A, Carswell F. A combined approach to reduce miteallergen in the bedroom. Clin ExpAllergy 1995;25:1179-1183.

143. Sporik R, Hill DJ, ThompsonPJ, Stewart GA, Carlin JB, NolanTM, Kemp AS, Hoskings CS. TheMelbourne House Dust Mite Study:Long term efficacy of house dustmite reduction strategies. J AllergyClin Immunol 1998;101:451-456.

144. Wickman M, Emenius G,Egmar AC, Axelsson G, PershagenG. Reduced mite allergen levels indwellings with mechanical exhaustand supply ventilation. Clin ExpAllergy 1994;24:109-114.

145. Custovic A, Taggart SCO,Kennaugh JH, Woodcock A.Portable dehumidifiers in the control of house dust mites andmite allergens. Clin Exp Allergy1995;25:312-316.

146. Fletcher AM, Pickering CAC,Custovic A, Simpson J, KennaughJ, Woodcock A. Reduction in humidity as a method of controllingmites and mite allergens: the useof mechanical ventilation in Britishdomestic dwellings. Clin Exp Allergy1996;26:1051-1056.

147. Crane J, Ellis I, Siebers R,Grimmet D, Lewis S, Fitzharris P. A pilot study of the effect ofmechanical ventilation and heatexchange on house dust mites and Der p 1 in New Zealandhomes. Allergy 1998;53:755-762.

148. Niven R, Fletcher AM,Pickering AC, Custovic A, Sivour JB,Preece AR, Oldham LA, Francis HC.Attempting to control mite allergens with mechanical ventilation and dehumidification in British houses. J Allergy ClinImmunol 1999;103:756-762.

149. Harving H, Korsgaard J, Dahl R. Mechanical ventilation indwellings as preventive measuresin mite asthma. Allergy Proc1988;9:283.

150. Harving H, Hansen LG,Korsgaard J, Nielsen PA, Olsen OF,Romer J, Svendsen UG, OsterballeO. House dust mite allergy andanti-mite measures in the indoorenvironment. Allergy 1991;46:33-38.

151. Warner J A, Frederick J M,Bryant T N, Weich C, Raw G J,Hunter C, Stephen F R, McIntyre DA, Warner J O. MechanicalVentilation and High EfficiencyVacuum cleaning: a combined strategy of mite and mite allergenreduction in the control of mitesensitive asthma. J Allergy ClinImmunol. 2000;105:75-82.

152. Mosbech H, Korsgaard J, Lind P. Control of house dust mitesby electrical heating blankets. J Allergy Clin Immunol 1988;81:706-710.

153. Colloff MJ. Use of liquid nitrogen in the control of housedust mite populations. Clin Allergy1986;16:411-417.

154. Dorward AJ, Colloff MJ,MacKay NS, McSharry C,Thompson NC. Effect of housedust mite avoidance measures in adult atopic asthma. Thorax1988;43:98-102.

155. Walshaw MJ, Evans CC.Allergen avoidance in house dustmite sensitive adult asthma. QuartJ Med 1986;58:199-215.

156. Sarsfield JK, Gowland G, Toy R, Norman ALE. Mite sensitiveasthma of childhood. Trial of avoidance measures. Arch DisChild 1974;49:716-721.

157. Murray AB, Ferguson AC.Dust free bedrooms in the treatment of asthmatic childrenwith house dust or house dust mite allergy: a controlled trial.Pediatrics 1983;71:418-422.

158. Howarth PH, Lunn A, TomkinsS. Bedding barrier intervention inhouse dust mite respiratory allergy.Clin Exp Allergy1992;22:140(abstr).

159. Hegarty J M, Jessop W J,Warner J O, Warner J A. AControlled Trial of A Bed CoveringSystem in House Dust MiteSensitive Asthmatic Children.European Respiratory Journal1997;10:361-366.

160. Green WF, Nicholas NR,Salome CM, Woolcock AJ.Reduction of house dust mites and mite allergen: effects of spraying carpets and blankets with Allersearch reagent. Clin ExpAllergy 1989;19:203-207.

161. Warner J A, Marchant J L andWarner J O. Allergen avoidance inthe homes of allergic asthmaticchildren: The effect of AllersearchDMS. Clinical and ExperimentalAllergy 1993;23:279-286.

162. Nelson HS, Hirsch R, OhmanJL, Platts-Mills TAE, Reed CE,Solomon WR. Recommendationsfor the use of residential air

cleaning devices in the treatmentof allergic respiratory diseases. JAllergy Clin Immunol 1988;82:661-669.

163. Warner J A, Marchant J L,Warner J O. A double blind trial ofionisers in asthmatic children.Thorax 1993;48:330-333.

164. Burr ML, St. Leger AS, NealeE. Anti-mite measures in mite sensitive adult asthma. A controlled trial. Lancet1976;1:333-335.

165. Burr Ml, Dean BV, Merrett TG, Neale E, St. Leger AS, VerrierJones ER. Effects of anti-mitemeasures on children with mitesensitive asthma: a controlled trial. Thorax 1980;35:506-512.

166. Korsgaard J. Preventativemeasures in mite asthma. A controlled trial. Allergy1983;38:93-102.

167. Gillies DNR, Littlewood JM,Sarsfield JK. Controlled trial ofhouse dust mite avoidance in children with mild to moderateasthma. Clin Allergy 1987;17:105-111.

168. Reiser J, Ingram D, MitchellEB, Warner JO. House dust miteallergen levels and an anti-mitemattress spray (natamycin) in thetreatment of childhood asthma.Clin Exp Allergy 1990;20:561-567.

169. Ehnert B, Lau-Schanendorf S,Weber A, Buettner P, Schou C,Wahn U. Reducing domestic exposure to dust mite allergenreduces bronchial hyperreactivity in sensitive children with asthma. J Allergy Clin Immunol1992;90:135-138.

170. Huss K, Squire EN, CarpenterGB. Effective education of adultswith asthma who are allergic todust mites. J Allergy Clin Immunol1992;89:836-843.

171. Dietemann A, Bessot JC,Hoyet C, Ott M, Verot A, Pauli G. A double blind placebo controlledtrial of solidified benzyl benzoateapplied in dwellings of asthmaticpatients sensitive to mites. Clinicalefficacy and effect on mite aller-gens. J Allergy Clin Immunol1993;91:738-746.

172. Marks GB, Tovey ER, GreenW, Shearer M, Salome CM,Woolcock AJ. House dust miteallergen avoidance; a randomisedcontrolled trial of surface chemicaltreatment and encasement of bedding. Clin Exp Allergy1994;24:1078-1083.

173. Huss RW, Huss K, Squire ENet al. Mite allergen control withacaricide fails. J Allergy ClinImmunol 1994;94:27-32.

174. Sette L, Comis A, Marcucci F,Sensi L, Piacentini GL, Boner AL.Benzyl benzoate foam: effects onmite allergens in mattress, serum,and nasal secretory IgE toDermatophagoides pteronyssinus,and bronchial hyperreactivity in children with allergic asthma.Pediatr Pulmonol 1994;18:218-227.

175. Carswell F, Birmingham K,Oliver J, Crewes A, Weeks J. Therespiratory effects of mite allergenin the bedrooms of asthmatic chil-dren – a double blind controlledtrial. Clin Exp Allergy 1996;26:386-396.

176. Bahir A, Goldberg A, MekoriYA et al. Continuous avoidancemeasures with or without acaricidein dust mite allergic asthmatic children. Ann Allergy AsthmaImmunol 1997;78:506-512.

177. Van der Heide S, KauffmanHF, Dubois AEJ, de Monchy JGR.Allergen reduction measures inhouses of allergic asthmaticpatients: effects of air cleanersand allergen impermeable mattresscovers. Eur Resp J 1997;1217-1223.

178. Closterman SGM, SchermerTRJ, Bijl-Hofland ID et al. Effects of house dust mite avoidance measures on Der p 1 concentrations and clinical condition of mild adult house dustmite allergic asthmatic patients,using no inhaled steroids. Clin ExpAllergy 1999; 29:1336-1346.

179. Marks GB. House dust miteexposure as a risk factor for asthma: benefits of avoidance.Allergy 1998;53(Suppl 48):108-114.

180. Carpet and Floor CoveringReview June 1999 pg 14.

181. Popplewell EJ, Innes VA, LloydHughes S, Jenkins EL, Khdir K,Bryant TN, Warner JO, Warner JA.The effect of high efficiency andstandard vacuum cleaners on mite,cat and dog allergen levels andclinical progress. Pediatr AllergyImmunol 2000; in press.

182. Sporik RS, Squillace SP,Ingram JM, Rakes G, HonsingerRW, Platts-Mills TAE. Mite, cat, and cockroach exposure, allergensensitisation, and asthma in children: a case control study of three schools. Thorax1999;54:675-680.

20 Allergic Diseases and The Indoor Environment

Page 27: Allergic Diseases and The Indoor Environment Acknowledgments

21 Allergic Diseases and The Indoor Environment

Der p 8 26kd Glutathione-S-Transferase

Tables

Source Allergen Molecular wgt Function

House Dust Mite

Dermatophagoides spp Der p 1 25kd Cysteine Protease

Der p 2 14kd Epididymal protein

Der p 3 ~30kd Serine protease

Der p 4 ~60kd Amylase

Der p 5 14kd Unknown

Der p 6 25kd Chymotrypsin

Der p 7 22-28kd Unkown

Can f 2 27kd Calycin

Der p 9 24kd Collagenolytic serine protease

Der p 10 36kd Tropomyosin

Euroglyphus maynei Eur m 1 25kd Cysteine protease

Blomia tropicalis Blo t 5 14kd Unknown

Mammals

Cat - Felis domesticus Fel d 1 36kd Uteroglobulin

Dog - Canis familiaris Can f 1 25kd Calycin

Table 1 Structural and Functional Properties of some common Indoor Allergens

CountryCarpet Level of Der p 1 (mg/g dust)(Ref. No.)

Northern Sweden 0.03 (33)

0.08 (33)

0.13 (34)

0.25 (33)

0.41 (169)

0.49 (34)

0.50 (182)

1.80 (148)

2.00 (32)

2.50 (47)

2.70 (173)

4.50 (141)

5.90 (182)

22.8 (133)

17.2 (37)

Central Sweden

Canada (Winnipeg)

Southern Sweden

Germany (Berlin)

Canada (Vancouver)

New Mexico (Los Alamos)

UK (Manchester)

The Netherlands (Amsterdam)

Hong Kong

North America (Baltimore)

New Zealand (Wellington)

North America (Charlottesville)

Australia (Melbourne)

South Africa (Cape Peninsula)

Table 2 Levels of Der p 1 in carpet dust in different countries

Page 28: Allergic Diseases and The Indoor Environment Acknowledgments

Dai

ly v

acuu

min

gC

arpe

tD

er p

1/g

Der

p 1

/m2

Yes

Yes

48%

68.5

%1997

141

Wel

lingt

onN

Zea

land

22 Allergic Diseases and The Indoor Environment

140

1993

Link

opin

gS

wed

en50%

34%

Yes

Yes

Der

p 1

+

Der

f 1

Car

pet

+ f

urni

shin

gsC

arpe

t + f

urni

shin

gsVa

cuum

ing

Tann

ic A

cid

Tech

niqu

e

Ben

zyl b

enzo

ate

Car

pet

Mite

nos

.Ye

s

Yes

100%

1987

132

133

134/

135

136

137

138

139

1994

1993

1995

1996

1990

1994/

1995

Utr

echt

,H

olla

nd

Cap

e To

wn

S.

Afric

a

Cha

rlott

s-vi

lle,

US

A

Syd

ney,

Aust

ralia

Gla

sgow

,S

cotla

nd

Amst

erda

mH

olla

nd

Mai

nz,

Ger

man

y

50%

50%

76% - -

3.3

fol

d

100%

86.7

%

-23.5

%-

40% -

24% -

83%

Yes

50%

100%

Yes

Yes

Yes

No

Yes

Yes

No

Yes

No

Yes

No

Yes

No

Yes

Not

don

eYe

s

Der

p 1

Mite

nos

.D

er p

1

Mite

nos

.D

er p

1

Mite

nos

.

Mite

nos

.

Mite

nos

.D

er p

1M

ite n

os.

Der

p 1

Mite

nos

.D

er p

1M

ite n

os.

Der

p 1

Gro

up 1

mite

Gro

up 2

mite

Fel d

1

Car

pet

Car

pet

Car

pet

Car

pet

piec

es

Car

pet

piec

es

Car

pet

piec

es

Car

pet

piec

es

Met

san

and

Acar

osan

Ste

am c

lean

ing

Ste

am c

lean

ing

Vacu

umin

g

Wet

cle

anin

g –c

old

Sha

mpo

o –c

old

Auto

clav

ing

Low

tem

p w

ash

with

det

erge

ntAs

abo

ve w

ith

benz

yl b

enzo

ate

Tann

ic a

cid

Ben

zyl b

enzo

ate

Com

mer

cial

cle

aner

s

Sou

rce

Mat

eria

lTr

eate

dA

llerg

enM

easu

red

Alle

rgen

R

educ

tion

% o

rfo

ld r

educ

tion

Cit

yR

efer

ence

Year

Table 3 Intervention strategies in carpets– non clinical

Page 29: Allergic Diseases and The Indoor Environment Acknowledgments

23 Allergic Diseases and The Indoor Environment

Ben

zyl b

enzo

ate

145

148

1999

Man

ches

ter,

UK

Mec

hani

cal v

entil

atio

n an

d de

hum

idifi

catio

n

Tech

niqu

e

No

142

143

144

146

147

1995

1994

1995

1998

1996

1998

Bris

tol,

UK

Mel

bour

ne,

Aust

ralia

Sto

ckho

lm

Man

ches

ter,

UK

Man

ches

ter,

UK

Wel

lingt

onN

Zea

land

- - - - - - - - - - -

No

No

No

No

No

No

No

No

No

No

No

No

Der

p 1

Der

p 1

Mite

nos

.D

er p

1N

o N

ot b

y in

terv

entio

n

Mite

nos

.D

er p

1

Mite

nos

.D

er p

1

Mite

nos

.D

er p

1

Mite

nos

.D

er p

1

Mite

nos

.D

er p

1

Der

p 1

Der

p 1

No

Not

by

inte

rven

tion

Der

p 1

Bed

room

car

pet

Bed

room

car

pet

Livi

ng r

oom

flo

or d

ust

Livi

ng r

oom

car

pet

Bed

room

car

pet

Livi

ng r

oom

car

pet

Bed

room

car

pet

Livi

ng r

oom

car

pet

Bed

room

car

pet

Livi

ng r

oom

car

pet

Bed

room

car

pet

Mec

hani

cal v

entil

atio

n

Deh

umid

ifica

tion

Mec

hani

cal v

entil

atio

n

Mec

hani

cal v

entil

atio

n

Anti-

mite

sha

mpo

o

Sou

rce

Mat

eria

lTr

eate

dA

llerg

enM

easu

red

Alle

rgen

R

educ

tion

% o

rfo

ld r

educ

tion

Cit

yR

efer

ence

Year

Table 3 (continued) Intervention strategies in carpets– non clinical

Page 30: Allergic Diseases and The Indoor Environment Acknowledgments

24 Allergic Diseases and The Indoor Environment

Age

Gro

up

Adul

t

Adul

t

Chi

ldre

n

Chi

ldre

n

Chi

ldre

n

Chi

ldre

n

Adul

ts

Adul

ts

Car

diff

, U

K

Aarh

us,

DK

Gla

sgow

, U

K

Vanc

ouve

r,C

anad

a

Live

rpoo

l, U

K

Car

diff

, U

K

Har

roga

te,U

K

Lond

on,

UK

Was

hing

and

va

cuum

ing

Enca

sing

, va

cuum

ing

Nat

amyc

in o

n m

attr

esse

s

Was

hing

, va

cuum

ing,

en

casi

ng

mat

tres

s

New

bed

ding

, va

cuum

ing,

w

ashi

ng,

redu

ced

indo

or h

umid

ity,

carp

ets

rem

oved

Enca

sing

, w

ashi

ng,

dust

ing,

rem

oval

of

sof

t fu

rnis

hing

san

d ca

rpet

s

Enca

sing

, sy

nthe

tican

d co

tton

be

ddin

g, w

ashi

ng,

rem

oval

of

carp

ets,

redu

ced

hum

idity

Liqu

id n

itrog

en t

om

attr

esse

s an

dca

rpet

s

32

cros

s-ov

er

26/2

7

13/1

2

23/2

3

9/9

23/2

3

10/1

0

15/2

0

6 w

eeks

8 w

eeks

6 m

onth

s

4 w

eeks

12 m

onth

s

6 w

eeks

6 m

onth

s

8 w

eeks

Non

e

Non

e

Non

e (e

xcep

tIg

E)

Non

e

Whe

ezin

g,

BH

R

Impr

oved

sym

ptom

scor

es

Impr

oved

sym

ptom

scor

es,

med

icat

ion

usag

e, lu

ngfu

nctio

n, B

HR

.

Sym

ptom

scor

es,

lung

func

tion,

m

edic

atio

nus

age,

IgE

,B

HR

164

165

166

167

155

167

168

154

1976

1980

1983

1983

1986

1987

1990

1988

Not

mea

sure

d

No

Floo

r, bu

t no

t m

attr

ess

Not

mea

sure

d

Yes

Yes

No

Yes

Cit

yIn

terv

enti

on(s

)N

Inte

rven

tion

/co

ntro

lLe

ngth

Of

Follo

w-u

pR

educ

tion

in H

ouse

dust

mit

e/al

lerg

enR

efer

ence

Year

Clin

ical

be

nefit

Table 4 Allergen Avoidance Trials - clinical

Page 31: Allergic Diseases and The Indoor Environment Acknowledgments

25 Allergic Diseases and The Indoor Environment

Age

Gro

up

Chi

ldre

n

Adul

ts

Adul

ts

Adul

ts

Chi

ldre

n

Chi

ldre

n

Chi

ldre

n

Chi

ldre

n

Adul

ts

Ber

lin,

Ger

man

y

Bris

tol

Tel A

viv,

Isra

el

Was

hing

ton

DC

, U

SA

Str

asbo

urg,

Fran

ce

Syd

ney,

Aust

ralia

Lond

on,

UK

Italy

Bal

timor

e,U

SA

1)B

enzy

l ben

zoat

eto

mat

tres

s an

dca

rpet

s2)e

ncas

ing,

tan

nic

acid

to

carp

ets

Ben

zyl b

enzo

ate

tobe

ddin

g, f

urni

ture

and

carp

et,

enca

s-in

g, h

ot w

ashi

ng

1)A

caric

ide+

avoi

danc

e 2)

Plac

ebo

+ a

void

-an

ce 3

) Av

oida

nce

alon

e

23/2

6

1)

13

2)

17

3)

16

Enca

sing

, re

mov

alof

car

pets

and

sof

tfu

rnis

hing

s, h

otw

ashi

ng,

redu

ced

indo

or h

umid

ity

Ben

zyl b

enzo

ate

tom

attr

ess,

bed

ding

and

furn

iture

Ben

zyl

benz

oate

/tan

nic

acid

to

bedd

ing

furn

iture

,car

pet,

enca

sing

Ioni

sers

Ben

zyl b

enzo

ate

tom

attr

ess

Ben

zyl b

enzo

ate

to c

arpe

ts

8/8

26/2

6

11/1

2

17/1

8

20

cros

s-ov

er

14/1

0

6/6

12m

onth

s

12 w

eeks

12 m

onth

s

6 m

onth

s

6 w

eeks

Sho

rt t

erm

6 m

onth

s

6 m

onth

s

12 m

onth

s

1)

Non

e2)

BH

R

Sym

ptom

scor

es

Non

e

Non

e

Non

e

Non

e

Sym

ptom

scor

es,

med

icat

ion

usag

e

Sym

ptom

scor

es

Non

e

169

170

171

172

163

174

175

176

173

1992

1992

1993

1994

1994

1994

1996

1997

1994

1)

No

2)

Yes

No

(red

uctio

n in

bot

hac

tive

and

cont

rol)

No

Yes

(tra

nsie

nt)

Yes

No

Yes

Yes,

in a

ll gr

oups

No

Cit

yIn

terv

enti

on(s

)N

Inte

rven

tion

/co

ntro

lLe

ngth

Of

Follo

w-u

pR

educ

tion

in H

ouse

dust

mit

e/al

lerg

enR

efer

ence

Year

Clin

ical

be

nefit

Table 4 (continued) Allergen Avoidance Trials - clinical

Page 32: Allergic Diseases and The Indoor Environment Acknowledgments

26 Allergic Diseases and The Indoor Environment

Age

Gro

up

Chi

ldre

n

Adul

ts

Adul

ts

Sou

tham

pton

,U

K

Gro

ning

en,

Hol

land

Str

asbo

urg,

Fran

ce

Enca

sing

1)

Air

Filte

r2)

Enca

sing

3)

Air

filte

r +

4)

Enca

sing

Acar

osan

to

carp

ets,

enc

asin

g

31

cros

sove

r

15

15

15

76/8

1

3 m

onth

s

6 m

onth

s

20 w

eeks

Non

e

BH

R in

3)

com

pare

d w

ith1)

and

2)

Non

e

159

177

178

1997

1997

1999

Yes

Yes

(in m

attr

ess

in 2

)an

d 3)

Yes

Cit

yIn

terv

enti

on(s

)N

Inte

rven

tion

/co

ntro

lLe

ngth

Of

Follo

w-u

pR

educ

tion

in H

ouse

dust

mit

e/al

lerg

enR

efer

ence

Year

Clin

ical

be

nefit

Table 4 (continued) Allergen Avoidance Trials - clinical

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