Correspondence
Bed Covers and Dust Mites
N Engl J Med 2003; 349:1668-1671October 23, 2003
- Article
To the Editor:
Woodcock et al.1 and Terreehorst et al.2 (July 17 issue) hoped to show the value of reducing the concentrations of house-dust-mite allergen in the homes of people with allergic asthma and rhinitis. However, they simply affirmed that partially controlling one variable of uncertain leverage within a highly complex, highly interactive adaptive system (such as allergic asthma or rhinitis) is unlikely to have a significant effect on the behavior of the system (clinical outcomes). These two articles are likely to be misinterpreted by the casual reader and the lay press as “proving” that traditional measures for the reduction of exposure to house-dust-mite allergen are not helpful in the care of patients who are allergic to house dust mites, which neither study established. Avoidance remains the cornerstone of good care for patients with allergies. Our challenge remains to discover the means by which this goal may be optimally accomplished.
2 ReferencesPeter B. Boggs, M.D.
Asthma–Allergy Clinic and Research Center, Shreveport, LA 711041
Woodcock 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;349:225-236
Full Text | Web of Science | Medline2
Terreehorst I ,Hak E ,Oosting AJ , et al. Evaluation of impermeable covers for bedding in patients with allergic rhinitis. N Engl J Med 2003;349:237-246
Full Text | Web of Science | Medline
To the Editor:
The studies by Woodcock et al. and Terreehorst et al. both have the same major design flaw. They did not exclude subjects who were allergic to other allergens. Most patients with respiratory allergies are sensitized to more than one allergen.1,2 Eliminating exposure to only one of several clinically significant allergens, in itself, would not be expected to produce a significant effect in a population-based study. For their conclusion that the dust-proof enclosure of bedding is ineffective to have been meaningful, these studies would have had to include only subjects who were sensitized only to dust mites.
2 ReferencesMichael R. Simon, M.D.
Henry Ford Health System, Detroit, MI 482021
Barbee RA ,Lebowitz MD ,Thompson HC ,Burrows B . Immediate skin-test reactivity in a general population sample. Ann Intern Med 1976;84:129-133
Web of Science | Medline2
Gergen PJ ,Turkeltaub PC . The association of individual allergen reactivity with respiratory disease in a national sample: data from the second National Health and Nutrition Examination Survey, 1976-80 (NHANES II). J Allergy Clin Immunol 1992;90:579-588
CrossRef | Web of Science | Medline
To the Editor:
Woodcock et al. and Terreehorst et al. conclude that the control of exposure to house-dust-mite allergen is ineffective in the control of asthma and allergic rhinitis. I would like to highlight some issues that I believe limit the conclusions that these authors draw. First, both studies allowed patients to receive other active treatments, so that the interventions were required to show effectiveness beyond that of the other active treatments. It remains possible that the intervention would have been effective if patients had been otherwise treated. Second, all treatment groups had improvement, which suggests that there may have been a ceiling effect limiting the possibility of showing further improvement. Third, the projection of an effect size of 25 percent in the allergic-rhinitis study was optimistic, since even some drugs approved for the treatment of allergic rhinitis result in improvement of only 7 to 10 percent as compared with placebo1 (Table 1Table 1
Size of the Effect of Montelukast and Loratadine on the Daytime-Nasal-Symptom Score in a Placebo-Controlled Trial in Patients with Allergic Rhinitis.). Fourth, there were no control groups to demonstrate that the studies had sufficient sensitivity to show the effectiveness of any intervention being tested. Although the studies were not tightly controlled and attempted to mimic the real-life effectiveness of the intervention, this approach also results in less certainty regarding any conclusion that a given intervention is ineffective.1 ReferencesBadrul A. Chowdhury, M.D., Ph.D.
Food and Drug Administration, Rockville, MD 20857
chowdhuryb@cder.fda. gov To the Editor:
Both Woodcock et al. and Terreehorst et al. demonstrate that the use of occlusive bedding covers alone may not achieve a clinical benefit. However, in both studies the resultant changes in total personal exposure to aeroallergens are likely to be even smaller than the reported small and nonsustained reductions in reservoir allergen concentrations in beds. By measuring the personal inhalational exposure to mite aeroallergen throughout the day, we found that the period spent in bed accounts for approximately 60 percent of the daily total.1 In addition, our studies2 and those of others3,4 show that although the use of occlusive covers leads to a substantial reduction in reservoir allergen concentrations, this reduction is associated with only a relatively small reduction in the level of exposure to aeroallergens (by a factor of 1.5 to 4).
Quantifying the personal exposure to aeroallergens is technically more difficult because of the inherent variability in the quantity and size of the particles carrying aeroallergens. However, it is a more clinically relevant measure of allergen exposure. This technical challenge needs to be met more adequately in the future in order to permit the design and testing of potentially beneficial allergen-avoidance interventions.
4 ReferencesEuan R. Tovey, Ph.D.
Timothy J. O'Meara, Ph.D.
Guy B. Marks, M.B., B.S., Ph.D.
Woolcock Institute of Medical Research, Sydney 2050, Australia
ert@mail.med. usyd. edu. au 1
O'Rourke SD ,Tovey ER ,O'Meara TJ . Personal exposure to mite and cat allergen. J Allergy Clin Immunol 2002;109:Suppl:S47-S47 abstract.
CrossRef | Web of Science2
O'Meara T ,Vasram R ,Mosses C ,Tovey E . Bed washing and mattress encasing result in only a small reduction in personal allergen exposure. Allergy Clin Immunol Int 2000;12:Suppl 2:54-54 abstract.
CrossRef3
Sakaguchi M ,Inouye S ,Sasaki R ,Hashimoto M ,Kobayashi C ,Yaseuda H . Measurement of airborne mite allergen exposure in individual subjects. J Allergy Clin Immunol 1996;97:1040-1044
CrossRef | Web of Science | Medline4
Carswell 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;26:386-396
CrossRef | Web of Science | Medline
To the Editor:
The studies examining the effect of allergen-impermeable bedding covers are summarized on the Journal's Web site as showing “no effect” and providing “no benefit.” However, other controlled clinical trials have demonstrated benefit in children.1,2 The finding of a decrease in symptoms among patients who used bed encasings was supported by decreased airway responsiveness to histamine in one study,1 and substantial benefit from encasings has been shown when the clinical relevance of sensitivity to dust mites is supported by a positive response to bronchial provocation with dust mites.2
The two reports in the Journal therefore argue against the indiscriminate prescription of bedding covers for patients with asthma or rhinitis, even when the skin test is positive. However, this conclusion does not argue against the value of encasings for patients in whom a positive skin test is supported by a clinical judgment that dust mites contribute to the symptoms. Treatment for suspected aeroallergen sensitivity with the avoidance of dust mites, the removal of cats or dogs from the home, specific immunotherapy, or the new anti-IgE therapy all require careful and thoughtful assessment of the degree to which the allergens in question actually contribute to the disease in the individual patient.
2 ReferencesMiles Weinberger, M.D.
University of Iowa, Iowa City, IA 52242
miles-weinberger@uiowa.edu 1
Murray AB ,Ferguson AC . Dust-free bedrooms in the treatment of asthmatic children with house dust or house dust mite allergy: a controlled trial. Pediatrics 1983;71:418-422
Web of Science | Medline2
Halken S ,Host A ,Niklassen U , et al. Effect of mattress and pillow encasings on children with asthma and house dust mite allergy. J Allergy Clin Immunol 2003;111:169-176
CrossRef | Web of Science | Medline
Author/Editor Response
We agree with Dr. Boggs that the avoidance of offending allergens should remain the cornerstone of good care for patients with allergies. Complete and successful avoidance is clearly beneficial, and the case of hay fever provides a very good example: patients with hay fever and seasonal asthma are asymptomatic during the winter months, when there is no exposure to the sensitizing allergen. However, we would emphasize that our study did not address the question of whether the complete avoidance of house-dust-mite allergen works, but instead was a pragmatic study of effectiveness (rather than efficacy), investigating whether allergen-impermeable bed covers improve asthma control in typical adults with asthma in primary care.
The real challenge from the perspective of practicing physicians is to establish whether effective allergen avoidance can be achieved through measures that are practical, cost effective, and flexible enough to suit individual needs and to determine which patients may benefit from such interventions. This issue is much more complex than the simple question of whether allergen avoidance works. For example, symptoms of hay fever do not occur in the absence of exposure, but although we could advise patients to spend certain seasons in a bubble, we have no practical measures that are acceptable to the majority of patients for effectively reducing their personal exposure.
We agree with Tovey et al. that it is very difficult to quantify personal allergen exposure, and our article emphasizes that we need a better understanding of how to measure the level of personal exposure to mite allergens and how to reduce it effectively. Quantifying personal exposure to aeroallergens may allow effective avoidance strategies to be designed. Our study does not rule out the possibility that the intervention would have been effective for patients who were otherwise untreated (as Dr. Chowdhury suggests) or for the tiny minority of the patients who were sensitized only to dust mites (as Dr. Simon suggests).
What our study does show conclusively is that allergen-impermeable bed covers as a single intervention for the avoidance of exposure are clinically ineffective for the routine management of asthma in adults in primary care. We agree with Dr. Weinberger that small studies in children have suggested some benefit, and we discuss this evidence in detail in the article. However, studies of appropriate size involving children urgently need to be completed. We remain unsure how “clinical judgment” helps, unless it is quantifiable and transferable.
Patients spend millions of dollars on allergen-proof bedding worldwide. If physicians are going to recommend this intervention, then it is incumbent on us to know the size of the benefit that can be expected in various circumstances. The complete avoidance of mite allergen may indeed improve asthma control, but we need properly designed and powered multifaceted studies of allergen avoidance involving adults and children in order to test this hypothesis. Misinterpretations “by the casual reader and the lay press” will continue to occur unless we generate objective data on the benefits of allergen avoidance in homes.
Ashley Woodcock, M.D.
Adnan Custovic, M.D., Ph.D.
Wythenshawe Hospital, Manchester M23 9LT, United Kingdom
ashley.a. woodcock@man. ac. uk Author/Editor Response
Both our study and the study by Woodcock et al. provide strong evidence that bedding or mattress covers alone do not benefit allergic patients with rhinitis or asthma. Boggs and Chowdhury emphasize that there is no evidence yet that a complete allergy-control program could be of benefit; however, providing such evidence was not the main goal of our studies. We agree that studies are now warranted to demonstrate the possible clinical effectiveness of such intensive and expensive programs.
To avoid interference by medication, all patients in our study underwent a washout period before the efficacy variables were measured. Since the range of scores on the rhinitis-specific visual-analogue scale as a primary outcome measure was 0 to 100 points and the mean score at 12 months was approximately 40 points in both groups, a ceiling effect cannot be expected to have influenced our results. Furthermore, the power provided with the study population of 232 patients was adequate for the detection of smaller differences than the 25 percent reduction in the mean score on the visual-analogue scale that was postulated in the calculation of the necessary sample size. Moreover, the data did not show a trend in favor of bedding covers.
Simon addresses an important point with regard to the heterogeneity of sensitization. We therefore analyzed a subgroup of 74 patients who were not sensitized to perennial allergens other than house-dust mites, and we did not detect a treatment effect in this subgroup as compared with patients who were sensitized to other perennial allergens as well as to dust mites. Furthermore, interference by sensitization to pollen was irrelevant, because the effects were recorded outside of the pollen season.
Other studies that demonstrated a positive effect, as mentioned by Weinberger, were small trials involving children with allergic asthma, and the data from these studies are therefore not applicable to patients with allergic rhinitis. We tested all the patients in our study for sensitivity to house-dust mites not only with the use of skin tests, but also with nasal provocation. Moreover, the majority had nasal symptoms resulting from exposure to dust in their homes. Therefore, we believe that such exposure was a major component of the sustained nature of the allergic signs and symptoms.
The data provided by Tovey et al. and other groups may further explain the absence of a clinical effect of bedding covers. We agree that quantifying personal allergen exposure is essential when measures other than the use of bedding covers alone are evaluated for their potential clinical benefit for patients who are sensitized to house-dust mites.
Ingrid Terreehorst, M.D.
Erasmus Medical Center, 3015 GD Rotterdam, the NetherlandsEelko Hak, Ph.D.
University Medical Center Utrecht, 3508 AB Utrecht, the NetherlandsRoy Gerth van Wijk, M.D., Ph.D.
Erasmus Medical Center, 3015 GD Rotterdam, the Netherlands
r.gerthvanwijk@erasmusmc. nl - Citing Articles (4)
Citing Articles
1
Tanja Maas, Janneke Kaper, Aziz Sheikh, J. André Knottnerus, Geertjan Wesseling, Edward Dompeling, Jean WM Muris, Constant Paul van Schayck, Tanja Maas. 2009. Mono and multifaceted inhalant and/or food allergen reduction interventions for preventing asthma in children at high risk of developing asthma. .
CrossRef2
Euan R. Tovey, Catarina Almqvist, Qiang Li, Daniele Crisafulli, Guy B. Marks. (2008) Nonlinear relationship of mite allergen exposure to mite sensitization and asthma in a birth cohort. Journal of Allergy and Clinical Immunology 122:1, 114-118.e5
CrossRef3
Thomas A.E Platts-Mills. (2004) Allergen avoidance. Journal of Allergy and Clinical Immunology 113:3, 388-391
CrossRef4
Stephen T. Holgate. (2004) Does encasing bedding to exclude house dust mites benefit patients with rhinitis?. Current Allergy and Asthma Reports 4:2, 100-101
CrossRef
