Allergen avoidance

Abstract

With allergic diseases that have a seasonal or episodic nature, the causal role of the allergen is often obvious. Thus ragweed pollen in the fall causes symptoms in allergic individuals and moving to the west coast or preventing entry of pollen into the home can decrease symptoms. Similarly, yellow jacket venom can cause anaphylaxis, and avoiding stings is universally recognized as an effective method of preventing these reactions. By contrast, with most indoor allergens and also those fungi that have a long season, naturally occurring changes in exposure over the year are not sufficient to provide evidence about causality. For these allergens and for dust mites in particular, studies on avoidance have provided important evidence about the role of allergens in disease.1Platts-Mills TAE Vervlot D Thomas WR Aalberse RC Chapman cochairmen, MD Indoor allergens and asthma. Third International Workshop.J Allergy Clin Immunol. 1997; 100: S1-24PubMed Google Scholar, 2Boner AL Peroni D Sette L Valletta EA Piacentini G Effects of allergen exposure-avoidance on inflammation in asthmatic children.Allergy. 1993; 48: 119-123Crossref PubMed Scopus (21) Google Scholar, 3Ehnert B Lau-Schadendorf S Weber A et al.Reducing domestic exposure to dust mite allergen reduces bronchial hyperactivity in sensitive children with asthma.J Allergy Clinical Immunol. 1992; 90: 135-138Abstract Full Text PDF PubMed Scopus (356) Google Scholar, 4Platts-Mills TA Tovey ER Mitchell EB et al.Reduction of bronchial hyperactivity during prolonged allergen avoidance.Lancet. 1982; 2: 675-678Abstract PubMed Scopus (555) Google Scholar There are 2 main forms of avoidance studies, those in which the patient is moved to a different (ie, allergen-free) environment and those in which measures designed to decrease exposure are taken in the patient's home. The studies in sanatoria or hospital rooms have been almost uniformly successful and have provided evidence about the levels of mite exposure (generally <0.5 μg of Der p 1/g of dust) that will result in significant symptom improvement.2Boner AL Peroni D Sette L Valletta EA Piacentini G Effects of allergen exposure-avoidance on inflammation in asthmatic children.Allergy. 1993; 48: 119-123Crossref PubMed Scopus (21) Google Scholar, 4Platts-Mills TA Tovey ER Mitchell EB et al.Reduction of bronchial hyperactivity during prolonged allergen avoidance.Lancet. 1982; 2: 675-678Abstract PubMed Scopus (555) Google Scholar, 5Kerrebijn KF Endogenous factors in childhood CNSLD: methodological aspects in population studies.in: Orie NGM van der Lende R Bronchitis III. Royal Vangorcum Assen, The Netherlands1970: 38-48Google Scholar, 6Vervloet D Penaud A Razzouk H et al.Altitude and house dust mites.J Allergy Clin Immunol. 1982; 69: 290-296Abstract Full Text PDF PubMed Scopus (156) Google Scholar The second type of study must always be judged by 2 criteria: (1) Did the measures taken decrease exposure, and (2) did the change in exposure result in a significant clinical improvement? In evaluating the published clinical studies on mite avoidance as a treatment for asthma, only a minority have achieved a prolonged decrease in allergen levels.3Ehnert B Lau-Schadendorf S Weber A et al.Reducing domestic exposure to dust mite allergen reduces bronchial hyperactivity in sensitive children with asthma.J Allergy Clinical Immunol. 1992; 90: 135-138Abstract Full Text PDF PubMed Scopus (356) Google Scholar, 7Platts-Mills TAE Vaughan JW Carter MC Woodfolk JA The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.J Allergy Clin Immunol. 2000; 106: 787-803Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar However, each of those studies reported improvement in asthma symptoms (Table I).3Ehnert B Lau-Schadendorf S Weber A et al.Reducing domestic exposure to dust mite allergen reduces bronchial hyperactivity in sensitive children with asthma.J Allergy Clinical Immunol. 1992; 90: 135-138Abstract Full Text PDF PubMed Scopus (356) Google Scholar, 8Walshaw MJ Evans CC Allergen avoidance in house dust mite sensitive adult asthma.Q J Med. 1986; 58: 199-215PubMed Google Scholar, 9Murray AB Ferguson AC Dust-free bedrooms in the treatment of asthmatic children with house dust or house mite allergy: a controlled trial.Pediatrics. 1983; 71: 418-422PubMed Google Scholar, 10Van der Heide S Kauffman HF Dubois AEJ de Monchy JGR Allergen reduction measures in houses of allergic asthmatic patients: effects of air-cleaners and allergen-impermeable mattress covers.Eur Respir J. 1997; 10: 1217-1223Crossref PubMed Scopus (111) Google Scholar, 11Htut T Higenbottam TW Gill GW et al.Eradication of house dust mite from homes of atopic asthmatic subjects: a double-blind trial.J Allergy Clin Immunol. 2001; 107: 55-60Abstract Full Text PDF PubMed Scopus (65) Google Scholar From the successful trials, several conclusions about avoidance are possible: first, that effective avoidance is primarily based on physical rather than chemical measures; second, that effective avoidance requires a full regimen in the bedroom; third, that avoidance is only relevant to subjects who are specifically allergic; and finally, that avoidance studies can have a large placebo or Hawthorne effect because patients often change their behavior when they are enrolled in studies of this kind.7Platts-Mills TAE Vaughan JW Carter MC Woodfolk JA The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.J Allergy Clin Immunol. 2000; 106: 787-803Abstract Full Text Full Text PDF PubMed Scopus (118) Google ScholarTABLE IControlled trials of allergen avoidance achieving a prolonged decrease in mite allergen levelsStudyDurationAvoidanceNDecrease in mite allergenPrimary outcome(s)Murray and Ferguson (1983)9Murray AB Ferguson AC Dust-free bedrooms in the treatment of asthmatic children with house dust or house mite allergy: a controlled trial.Pediatrics. 1983; 71: 418-422PubMed Google Scholar1 yPhysical barriers10/10++BHR∗Highly significant improvement.Carswell et al (1996)12Carswell F Birmingham K Oliver J Crewes A Weeks J The respiratory effects of reduction of mite allergen in the bedrooms of asthmatic children—a double-blind controlled trial.Clin Exp Allergy. 1996; 26: 386-396Crossref PubMed Scopus (128) Google Scholar6 moPhysical barriers and Acarosan§Benzyl benzoate powder.24/25+PEFR,†Improvement but not significant. BHREhnert et al (1992)3Ehnert B Lau-Schadendorf S Weber A et al.Reducing domestic exposure to dust mite allergen reduces bronchial hyperactivity in sensitive children with asthma.J Allergy Clinical Immunol. 1992; 90: 135-138Abstract Full Text PDF PubMed Scopus (356) Google Scholar1 yPhysical barriers and tannic acid8/16++BHR∗Highly significant improvement.Van cer Heide et al (1997)10Van der Heide S Kauffman HF Dubois AEJ de Monchy JGR Allergen reduction measures in houses of allergic asthmatic patients: effects of air-cleaners and allergen-impermeable mattress covers.Eur Respir J. 1997; 10: 1217-1223Crossref PubMed Scopus (111) Google Scholar1 yPhysical measures15/15/15++BHR‡Significant improvement.Walshaw and Evans (1986)8Walshaw MJ Evans CC Allergen avoidance in house dust mite sensitive adult asthma.Q J Med. 1986; 58: 199-215PubMed Google Scholar1 yPhysical barriers22/20++PEFRcBHR∗Highly significant improvement.Htut et al (2001)11Htut T Higenbottam TW Gill GW et al.Eradication of house dust mite from homes of atopic asthmatic subjects: a double-blind trial.J Allergy Clin Immunol. 2001; 107: 55-60Abstract Full Text PDF PubMed Scopus (65) Google Scholar12 moHeat treatment10/10/10++BHR‡Significant improvement.BHR, Bronchial hyperreactivity; PEFR, peak expiratory flow rate.∗ Highly significant improvement.† Improvement but not significant.‡ Significant improvement.§ Benzyl benzoate powder. Open table in a new tab BHR, Bronchial hyperreactivity; PEFR, peak expiratory flow rate. Given the importance of controlled trials of mite allergen avoidance both to understanding the role of allergen exposure in disease and in designing treatment, it is very disturbing when the New England Journal of Medicine publishes 2 articles that are interpreted as showing that mattress covers are not an effective measure for treating allergic rhinitis or asthma.13Terreehorst I Hak E Oosting AJ et al.Evaluation of impermeable covers for bedding in patients with allergic rhinitis.N Engl J Med. 2003; 349: 237-246Crossref PubMed Scopus (189) Google Scholar, 14Woodcock A Forster L Matthews E et al.Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.N Engl J Med. 2003; 349: 225-236Crossref PubMed Scopus (279) Google Scholar The studies were striking because they enrolled large numbers of patients, they were continued for a year, and they used mattress covers that were almost certainly effective at preventing live mites or mite allergens from leaving the mattress. Because of their possible impact on treatment, these articles have already received considerable comment.15Chowdhury BA Correspondence: bed covers and dust mites.N Engl J Med. 2003; 349: 1668-1669Crossref PubMed Scopus (4) Google Scholar, 16Tovey ER O'Meata TJO Marks GB Correspondence: bed covers and dust mites.N Engl J Med. 2003; 349: 1669Google Scholar, 17Platts-Mills TAE Allergen avoidance in the treatment of asthma and rhinitis.N Engl J Med. 2003; 349: 207-208Crossref PubMed Scopus (33) Google Scholar Using the criteria proposed above, neither study would be considered successful because there was not a major decrease in allergen compared with that seen in the control population. In addition, there are specific problems with each that make it difficult to reach conclusions in relation to clinical practice. Terreehorst et al,13Terreehorst I Hak E Oosting AJ et al.Evaluation of impermeable covers for bedding in patients with allergic rhinitis.N Engl J Med. 2003; 349: 237-246Crossref PubMed Scopus (189) Google Scholar, 18Terreehorst I Oosting AJ Tempels-Pavlica Z et al.Prevalence and severity of allergic rhinitis in house dust mite allergic patients with bronchial asthma or atopic dermatitis.Clin Exp Allergy. 2002; 32: 1160-1165Crossref PubMed Scopus (60) Google Scholar from the Netherlands, reported a controlled trial of mattress covers in the treatment of allergic rhinitis. There are 2 major problems with this study. First, many of the patients did not present with allergic rhinitis but were initially enrolled in the study as patients with asthma or atopic dermatitis. In keeping with this, the geometric mean total serum IgE level of 230 IU/mL is surprisingly high for an unselected group of patients with allergic rhinitis. Thus the conclusions of the study might only be relevant to highly allergic patients. The other major problem is that the intervention was restricted to covers, and both groups were advised to “wash and clean the bedding weekly at 60°C, to clean the house and to heat and ventilate regularly…” Thus the difference in mattress covers was expected to make a difference against a background of house and bedding cleaning in both the active and placebo groups. Previous authors have always concluded that individual parts of an avoidance protocol cannot be evaluated separately.1Platts-Mills TAE Vervlot D Thomas WR Aalberse RC Chapman cochairmen, MD Indoor allergens and asthma. Third International Workshop.J Allergy Clin Immunol. 1997; 100: S1-24PubMed Google Scholar, 7Platts-Mills TAE Vaughan JW Carter MC Woodfolk JA The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.J Allergy Clin Immunol. 2000; 106: 787-803Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar Tovey et al,16Tovey ER O'Meata TJO Marks GB Correspondence: bed covers and dust mites.N Engl J Med. 2003; 349: 1669Google Scholar in Sydney, have demonstrated that changes measured in dust samples obtained from the mattress surface might not be reflected in directly measured inhaled allergen.19Gore RB Hadi EA Craven M et al.Personal exposure to house dust mite allergen in bed: nasal air sampling and reservoir allergen levels.Clin Exp Allergy. 2002; 32: 856-859Crossref PubMed Scopus (29) Google Scholar Thus although the authors reported a modest but significant decrease in allergens on the mattress, their intervention probably did not have a significant effect on inhaled allergen levels. The problems with testing one intervention (ie, avoidance) while allowing other medications have recently been pointed out by Chowdhury.15Chowdhury BA Correspondence: bed covers and dust mites.N Engl J Med. 2003; 349: 1668-1669Crossref PubMed Scopus (4) Google Scholar However, more serious problems arise from testing one part of an avoidance regimen while carrying out the rest of the protocol. While recognizing that there are major problems with this study on “allergic rhinitis,” it is important to realize that there is very little objective evidence about the effect of allergen avoidance on perennial allergic rhinitis. Indeed, it has always been a mystery how the allergic rhinitis guidelines conclude that the use of mite avoidance measures for perennial rhinitis is “evidence based.”20Allergy report, 2000. Milwaukee: American Academy of Allergy, Asthma, and Immunology; 2001. Available at: http://www.theallergyreport.org/reportindex.htmlGoogle Scholar The report by Woodcock et al14Woodcock A Forster L Matthews E et al.Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.N Engl J Med. 2003; 349: 225-236Crossref PubMed Scopus (279) Google Scholar investigates the use of “allergen impermeable bed covers as a single intervention” in a primary-care setting. Their results add to the already sufficient evidence that single measures, applied without either establishing specific sensitivity or providing education about avoidance, are not effective in the treatment of asthma. However, the most striking feature of the study was how little decrease in allergen was achieved given previous reports from the same group about the efficacy of mattress covers.21Owens S Morganstern M Hepworth J Woodcock A Control of house dust mite antigen in bedding.Lancet. 1990; 335: 396-397Abstract PubMed Scopus (137) Google Scholar They record a modest decrease in allergen levels at 6 months and no significant effect at 12 months. This was in part because they only tested dust from a minority of the homes, and the allergen assays were only carried out on reservoir dust samples from the mattresses. However, the results strongly suggest that the measures taken did not achieve a sustained decrease in inhaled allergen. In a recent review by several members of the group in The Netherlands, they recognize that their studies focus on the effect of covers alone because such studies can be blinded. However, they fail to recognize how much the interpretation is obstructed because of extensive use of avoidance measures, including polished floors and hot washing of bedding by the placebo group.22Sheikh A Hurwitz B Sibbald B Barnes G Howe M Durham S House dust mite barrier bedding for childhood asthma: randomised placebo controlled trial in primary care [ISRCTN63308372].BMC Fam Pract. 2002; 3: 12Crossref PubMed Scopus (21) Google Scholar An excellent example is the study from 2002, in which there was, in addition, a significant dropout of patients in the placebo group because of asthma instability.23Rijssenbeek-Nouwens LH Oosting AJ Bruin-Weller MS Bregman I de Monchy JG Postma DS Clinical evaluation of the effect of anti-allergic mattress covers in patients with moderate to severe asthma and house dust mite allergy: a randomised double blind placebo controlled study.Thorax. 2002; 57: 784-790Crossref PubMed Scopus (57) Google Scholar The studies being discussed here are on secondary avoidance to investigate whether decreasing exposure can reduce symptoms in patients with established disease. It has also been proposed that avoidance can be used to prevent sensitization of individuals with negative skin test results or even from birth (ie, primary avoidance).24Arshad SH Bateman B Matthews SM Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomized controlled study.Thorax. 2003; 58: 489-493Crossref PubMed Scopus (155) Google Scholar, 25Chan-Yeung M Manfreda J Dimich-Ward H Ferguson A Watson W Becker A A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants.Arch Pediatr Adolesc Med. 2000; 154: 657-663Crossref PubMed Scopus (163) Google Scholar, 26Custovic A Simpson BM Simpson A et al.Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomized trial.Lancet. 2001; 358: 188-193Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar, 27Vanlaar CH Peat JK Marks GB et al.Domestic control of house dust mite allergen in children's beds.J Allergy Clin Immunol. 2000; 105: 1130-1133Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Before considering the evidence, it is important to recognize that exposure is necessary for sensitization. Children raised in a community without dust mite allergen (eg, northern Sweden or Los Alamos, NM) do not become allergic to dust mites. Similarly, children raised with minimal or no exposure to cockroach allergens (eg, suburban areas of New Zealand, Delaware, or Sweden) do not become allergic to cockroaches. For many years, primary avoidance studies were designed on the assumption that exposure needed to occur in the subject's home and that not having a cat would protect children from sensitization to cat. For domestic cats, it is now clear that the major allergen, Fel d 1, which is carried on dander particles, spreads throughout the community. Thus significant quantities of Fel d 1 can be found in floor dust from schools, public buildings, and homes without a cat.28Gelber LE Seltzer LH Bouzoukis JK et al.Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital.Am Rev Respir Dis. 1993; 47: 573-578Crossref Scopus (464) Google Scholar, 29Sporik R Ingram JW Price W et al.Association of asthma with serum IgE and skin test reactivity to allergens among children living in high altitude: tickling the dragon's breath.Am J Respir Crit Care Med. 1995; 151: 1388-1392Crossref PubMed Scopus (221) Google Scholar, 30Custovic A Fletcher A Pickering CA et al.Domestic allergens in public places III: house dust mite, cat, dog, and cockroach allergens in British hospitals.Clin Exp Allergy. 1998; 28: 53-59Crossref PubMed Scopus (121) Google Scholar Furthermore, it is now clear that airborne Fel d 1 can be detected in the air of homes without a cat.31Bollinger ME Eggleston PA Flanagan E et al.Cat antigens in homes with and without cats may induce allergic symptoms.J Allergy Clin Immunol. 1996; 97: 907-914Abstract Full Text PDF PubMed Scopus (170) Google Scholar, 32Custis NJ Woodfolk JA Vaughan JW et al.Quantitative measurements of airborne allergens from dust mites, dogs, and cats using an ion charging device.Clin Exp Allergy. 2003; 33: 986-991Crossref PubMed Scopus (74) Google Scholar Thus avoiding having a cat is not an effective measure to prevent sensitization to cats and indeed might have the opposite effect.33Perzanowski MS Ronmark E Platts-Mills TAE et al.Effect of cat and dog ownership on sensitization and development of asthma among preteenage children.Am J Respir Crit Care. 2002; 166: 696-702Crossref PubMed Scopus (250) Google Scholar, 34Hesselmar B Aberg N Eriksson B Bjorksten B Does early exposure to cat or dog protect against later allergen development.Clin Exp Allergy. 1999; 29: 611-617Crossref PubMed Scopus (461) Google Scholar, 35Ronmark E Jonsson E Platts-Mills T Lundbackk B Incidence and remission of asthma in schoolchildren: report from the obstructive lung disease in Northern Sweden studies.Pediatrics. 2001; 107: 37Crossref Scopus (56) Google Scholar In a recent study in New Zealand, those families who chose not to own a cat because of a family history of allergy had a higher prevalence of cat sensitization than comparable families who had a cat (Erwin et al—unpublished data, 2004). For dust mite, there is very little evidence for passive transfer of allergen, and thus the presence of mite allergen in a dust sample is generally taken as evidence that mites are growing locally. On the other hand, children are not raised in a single house, and the question is not only how much allergen it takes but also how long it takes to become sensitized. Clearly some pollens with a relatively short season, such as Chinese elm or maple, can induce sensitization and disease. Are 2 weeks spent with a relative or 3 afternoons a week in daycare sufficient to sensitize to dust mites? This, however, would only be relevant in an area in which granny's house or the daycare center is likely to have high concentrations of dust mite. To return to our previous examples, if you live in Los Alamos and grandma lives in Santa Fe, the child will not be exposed to dust mites in either place. By contrast, attempts to prevent sensitization to dust mites in Sydney, Vancouver, Manchester, or Atlanta might be stymied by the presence of mite allergen in homes other than the child's own home. Obviously, a similar effect could occur with cat, except that exposure to cat allergen is ubiquitous, and therefore it would be impossible to assess the effect of a transient exposure to high levels. Despite these problems, some primary avoidance studies have been effective. For example, Nishioka et al,36Nishioka K Yasueda H Saito H Preventive effect of bedding encasement with microfine fibers on mite sensitization.J Allergy Clin Immunol. 1998; 101: 28-32Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar in Tokyo, showed that aggressive mite avoidance measures in the bedroom can decrease mite sensitization among children with atopic dermatitis. As with many therapeutic strategies, allergen avoidance in the treatment of allergic disease can be seen as a cup that is half full or half empty. The recent epidemiologic evidence argues strongly against cat avoidance as a viable method of decreasing sensitization. Increasingly, the evidence suggests that mite avoidance also fails as a primary measure, perhaps because of short periods of exposure in other homes. On the other hand, decreasing exposure to dust mite allergens is an effective part of the treatment of asthma, rhinitis, and atopic dermatitis.1Platts-Mills TAE Vervlot D Thomas WR Aalberse RC Chapman cochairmen, MD Indoor allergens and asthma. Third International Workshop.J Allergy Clin Immunol. 1997; 100: S1-24PubMed Google Scholar, 2Boner AL Peroni D Sette L Valletta EA Piacentini G Effects of allergen exposure-avoidance on inflammation in asthmatic children.Allergy. 1993; 48: 119-123Crossref PubMed Scopus (21) Google Scholar, 3Ehnert B Lau-Schadendorf S Weber A et al.Reducing domestic exposure to dust mite allergen reduces bronchial hyperactivity in sensitive children with asthma.J Allergy Clinical Immunol. 1992; 90: 135-138Abstract Full Text PDF PubMed Scopus (356) Google Scholar, 4Platts-Mills TA Tovey ER Mitchell EB et al.Reduction of bronchial hyperactivity during prolonged allergen avoidance.Lancet. 1982; 2: 675-678Abstract PubMed Scopus (555) Google Scholar, 5Kerrebijn KF Endogenous factors in childhood CNSLD: methodological aspects in population studies.in: Orie NGM van der Lende R Bronchitis III. Royal Vangorcum Assen, The Netherlands1970: 38-48Google Scholar, 6Vervloet D Penaud A Razzouk H et al.Altitude and house dust mites.J Allergy Clin Immunol. 1982; 69: 290-296Abstract Full Text PDF PubMed Scopus (156) Google Scholar, 7Platts-Mills TAE Vaughan JW Carter MC Woodfolk JA The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.J Allergy Clin Immunol. 2000; 106: 787-803Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 8Walshaw MJ Evans CC Allergen avoidance in house dust mite sensitive adult asthma.Q J Med. 1986; 58: 199-215PubMed Google Scholar, 9Murray AB Ferguson AC Dust-free bedrooms in the treatment of asthmatic children with house dust or house mite allergy: a controlled trial.Pediatrics. 1983; 71: 418-422PubMed Google Scholar, 10Van der Heide S Kauffman HF Dubois AEJ de Monchy JGR Allergen reduction measures in houses of allergic asthmatic patients: effects of air-cleaners and allergen-impermeable mattress covers.Eur Respir J. 1997; 10: 1217-1223Crossref PubMed Scopus (111) Google Scholar, 11Htut T Higenbottam TW Gill GW et al.Eradication of house dust mite from homes of atopic asthmatic subjects: a double-blind trial.J Allergy Clin Immunol. 2001; 107: 55-60Abstract Full Text PDF PubMed Scopus (65) Google Scholar, 37Tan BB Weald D Strickland I et al.Double-blind controlled trial of the effect of housedust-mite allergen avoidance on atopic dermatitis.Lancet. 1996; 347: 15-18Abstract Full Text PDF PubMed Scopus (402) Google Scholar The meta-analysis published in 1998 originally tried to interpret the published results on mite avoidance and asthma as negative.38Gotzsche PC Hammarquist C Burr M House dust mite control measures in the management of asthma: meta-analysis.BMJ. 1998; 317: 1105-1110Crossref PubMed Scopus (207) Google Scholar However, that result depended on including a large number of studies that had no effect on allergen exposure. When the analysis was revised, those studies that used physical measures resulted in significant clinical improvement (P < .02).39Gotzsche PC Johansen HK Burr ML Hammarquist C House dust mite control measures for asthma.Cochrane Database Syst Rev. 2001; 3: 001187Google Scholar The 2 recent studies simply reinforce the fact that effective avoidance requires both education and a comprehensive protocol.7Platts-Mills TAE Vaughan JW Carter MC Woodfolk JA The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.J Allergy Clin Immunol. 2000; 106: 787-803Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 13Terreehorst I Hak E Oosting AJ et al.Evaluation of impermeable covers for bedding in patients with allergic rhinitis.N Engl J Med. 2003; 349: 237-246Crossref PubMed Scopus (189) Google Scholar, 14Woodcock A Forster L Matthews E et al.Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.N Engl J Med. 2003; 349: 225-236Crossref PubMed Scopus (279) Google Scholar The implied argument of many commentaries is that allergen avoidance is too expensive or too difficult. These arguments underestimate the intelligence of most patients, who realize that decreasing exposure is the logical treatment for a disease that is caused by exposure and do not like taking medicines on a regular basis. There are very few medicines that are truly without side effects. Recent evidence about adrenal suppression of children receiving high-dose inhaled steroids or the fact that long-acting β2-agonists can increase the incidence of severe attacks of asthma has done nothing to reassure patients about the safety of taking inhaled medicines chronically. Many physicians fail to appreciate the resistance of parents and children to using medicines to control a disease. Over the last 10 years, there has been a successful movement to establish guidelines for the management of many chronic diseases, including asthma.20Allergy report, 2000. Milwaukee: American Academy of Allergy, Asthma, and Immunology; 2001. Available at: http://www.theallergyreport.org/reportindex.htmlGoogle Scholar, 40Guidelines for diagnosis and management of asthma: Expert Panel Report II. National Institutes of Health, Bethesda (MD)1997Google Scholar, 41National Asthma Education and Prevention Program Expert Panel Report: guidelines for the diagnosis and management of asthma. Update on Selected Topics 2002.J Allergy Clin Immunol. 2002; 110: S141-S219PubMed Google Scholar The guidelines focus on “evidence-based” treatments, and it might be worth considering the meaning of that term. To be considered evidence based requires a large, double-blind, placebo-controlled trial. Inevitably, almost all of these studies are designed and sponsored by a pharmaceutical company. This results in strict rules about the design of the studies, the enrollment criteria, and above all the treatments that are allowed in parallel or in the control group. Clearly, companies are unlikely to invest in testing another company's drug, a drug that is off patent, or a physical procedure, such as allergen avoidance. Sponsored studies generally would not allow patients outside the criteria, for example patients with atopic dermatitis in a rhinitis study. Equally, these studies are very careful to restrict the concomitant use of other treatments that could confuse the result. As has recently been pointed out, the effect size recorded in some studies that are considered to be evidence based is not very large.15Chowdhury BA Correspondence: bed covers and dust mites.N Engl J Med. 2003; 349: 1668-1669Crossref PubMed Scopus (4) Google Scholar Reading through controlled trials of either allergen avoidance or immunotherapy, there are some consistent themes: the studies are difficult to blind, the numbers enrolled are generally modest, and in many cases other treatments have been allowed.42Adkinson Jr, NF Eggleston PA Eney D et al.A controlled trial of immunotherapy for asthma in allergic children.N Engl J Med. 1997; 334: 501-506Google Scholar In some of the successful studies on allergen avoidance, a significant result has been recorded despite small numbers because the effect size was so large (Table I).3Ehnert B Lau-Schadendorf S Weber A et al.Reducing domestic exposure to dust mite allergen reduces bronchial hyperactivity in sensitive children with asthma.J Allergy Clinical Immunol. 1992; 90: 135-138Abstract Full Text PDF PubMed Scopus (356) Google Scholar, 7Platts-Mills TAE Vaughan JW Carter MC Woodfolk JA The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.J Allergy Clin Immunol. 2000; 106: 787-803Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar The 2 recent studies focused on achieving blinding of the investigators and the subjects at the cost of not achieving a real difference in exposure.13Terreehorst I Hak E Oosting AJ et al.Evaluation of impermeable covers for bedding in patients with allergic rhinitis.N Engl J Med. 2003; 349: 237-246Crossref PubMed Scopus (189) Google Scholar, 14Woodcock A Forster L Matthews E et al.Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.N Engl J Med. 2003; 349: 225-236Crossref PubMed Scopus (279) Google Scholar Taken together, it is clear that recent studies should not change our conclusions. Allergen avoidance remains a cornerstone of treatment of allergic patients who present with rhinitis, asthma, or atopic dermatitis. Successful treatment requires defining specific sensitivity (skin tests or serum IgE antibodies), education, and an overall plan to reduce exposure in the home.7Platts-Mills TAE Vaughan JW Carter MC Woodfolk JA The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.J Allergy Clin Immunol. 2000; 106: 787-803Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar Success will always depend on the involvement of the patient, the relevance of other allergens, and exposure outside the patient's home. In a world in which a large proportion of the population is taking tablets or inhalers every day, we should take full advantage of a treatment strategy that can be maintained easily without side effects, improve symptoms consistently, decrease bronchial hyperreactivity, and decrease reliance on drug treatment.