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Control of house dust mite in managing asthma

BMJ 1999; 318 doi: https://doi.org/10.1136/bmj.318.7187.870 (Published 27 March 1999) Cite this as: BMJ 1999;318:870

Effectiveness of measures depends on stage of asthma

  1. Sonja G M Cloosterman, Epidemiologist (S.Cloosterman{at}hsv.kun.nl),
  2. Onno C P van Schayck, Professor of preventive medicine
  1. Department of General Practice and Social Medicine, 229 University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands Competing interests: None declared
  2. Greater Glasgow Health Board, Dalian House, PO Box 15327, Glasgow G3 8YU
  3. Asthma and Allergic Diseases Center, University of Virginia, Box 225 Health Sciences Center, Charlottesville, VA 22908, USA
  4. School of Health, University of Teesside, Middlesbrough TS1 3BA
  5. Nordic Cochrane Centre, Rigshospitalet, Department 7112, DK-2200 Copenhagen N, Denmark
  6. Executive Office, Unit of Public Health, Municipality of Gotland, S-62181, Visby, Sweden
  7. Centre for Applied Public Health Medicine, University of Wales College of Medicine, Cardiff CF1 3NW

    EDITOR—In their meta-analysis G⊘tzsche et al concluded that measures to control house dust mites are not clinically effective in patients with asthma who are sensitive to mites.1 In the accompanying editorial Strachan commented that this was probably because several control measures used in the included studies did not result in a (relevant) reduction in concentrations of house dust mite allergens. Improvements in clinical condition are consequently not to be expected. Some studies in the meta-analysis found clinical effects while others did not.1 This may not be a result of effectively reducing allergen concentrations but of measuring different groups of asthmatic patients in different stages of disease. We believe that early treatment of mild asthma might have more impact than treating mild to moderate asthma.

    Figure1

    Morning peak flow rates in subjects with allergy to house dust mites and early signs of asthma or confirmed mild asthma during placebo and active strategies to avoid allergens*P<0.05

    We investigated the (clinical) effects of a combined allergen avoidance strategy (use of covers on mattresses and bedding that are impenetrable to house dust mites and use of benzyl benzoate (Acarosan) on living room and bedroom floors) in two groups of subjects allergic to house dust mites. One group had some early signs of asthma2 but no diagnosis and the other had a confirmed diagnosis of mild asthma.3 In the subjects without diagnosed asthma, peak flow rates and symptom scores stabilised during follow up (figure (top)), suggesting that the onset of asthma may have been delayed. The subjects with mild asthma showed no clinical effects during the same follow up (figure (bottom)), although allergen concentrations were reduced, especially on mattresses (10-fold, P=0.0001).3

    We hypothesise that allergen avoidance has more impact as an early preventive measure than as treatment of mild asthma. In established asthma small amounts of allergen may be sufficient to trigger a deterioration in the condition. Furthermore, allergen concentrations will need to be reduced for some time to reverse the already developed process of inflammation. In allergic patients who have not yet develped asthma a reduction in allergen load might prevent further development of the disease as the process of inflammation can probably be slowed down at this early stage. The fact that avoidance measures are more effective in children than in adults supports this idea.4 Thus allergen avoidance measures need to be applied in an early stage of the disease (secondary or even primary prevention5) to be clinically effective.

    In summary, we believe that the conclusion of G⊘tzsche et al covers only one aspect. Measures to control house dust mite might be effective in patients in the early stages of asthma and might therefore be recommended as an early intervention.

    References

    1. 1.
    2. 2.
    3. 3.
    4. 4.
    5. 5.

    Peak expiratory flow rates in populations are not valid measure of asthma

    1. David S Morrison, Specialist registrar in public health medicine
    1. Department of General Practice and Social Medicine, 229 University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands Competing interests: None declared
    2. Greater Glasgow Health Board, Dalian House, PO Box 15327, Glasgow G3 8YU
    3. Asthma and Allergic Diseases Center, University of Virginia, Box 225 Health Sciences Center, Charlottesville, VA 22908, USA
    4. School of Health, University of Teesside, Middlesbrough TS1 3BA
    5. Nordic Cochrane Centre, Rigshospitalet, Department 7112, DK-2200 Copenhagen N, Denmark
    6. Executive Office, Unit of Public Health, Municipality of Gotland, S-62181, Visby, Sweden
    7. Centre for Applied Public Health Medicine, University of Wales College of Medicine, Cardiff CF1 3NW

      EDITOR—The fact that G⊘tzsche et al found that measures to eradicate house dust mite had no significant effect on the severity of asthma is not surprising as they used peak expiratory flow rate as one of their principal measures of severity.1 The enormous heterogeneity of peak expiratory flow rates makes them poor measures of asthma severity when studying populations. Gregg and Nunn's results from mini-Wright peak flow meters show wide variation between people, age and height explaining only 30% of the variation in peak flow rates. 2 3Peak expiratory flow rate nevertheless remains a useful measure for self monitoring of asthma.

      In addition to the important distinction made by Strachan between efficacy and clinical effectiveness in efforts to reduce house dust mite,4 the measure of clinical effectiveness should be valid. I suggest that failure to distinguish between two population distributions of peak expiratory flow rate does not provide a valid measure of asthma.

      Footnotes

      • Competing interest None declared

      References

      1. 1.
      2. 2.
      3. 3.
      4. 4.

      Conclusions of meta-analysis are wrong

      1. Thomas A E Platts-Mills, Head, Asthma and Allergic Diseases.,
      2. Martin D Chapman, Professor of medicine and microbiology,
      3. Lisa M Wheatley, Assistant professor of medicine
      1. Department of General Practice and Social Medicine, 229 University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands Competing interests: None declared
      2. Greater Glasgow Health Board, Dalian House, PO Box 15327, Glasgow G3 8YU
      3. Asthma and Allergic Diseases Center, University of Virginia, Box 225 Health Sciences Center, Charlottesville, VA 22908, USA
      4. School of Health, University of Teesside, Middlesbrough TS1 3BA
      5. Nordic Cochrane Centre, Rigshospitalet, Department 7112, DK-2200 Copenhagen N, Denmark
      6. Executive Office, Unit of Public Health, Municipality of Gotland, S-62181, Visby, Sweden
      7. Centre for Applied Public Health Medicine, University of Wales College of Medicine, Cardiff CF1 3NW

        EDITOR—G⊘tzsche et al performed a meta-analysis of the published controlled trials of avoiding dust mite allergen in the treatment of asthma.1 Several past approaches for decreasing mites in houses are known to be ineffective—for example, vacuuming carpets and using acaricidal foams and HEPA (high efficiency particulate air) air cleaners. 1 2 G⊘tzsche et al concede that in 12 of the 23 studies the avoidance measures did not decrease mite allergen concentrations. In addition, five studies did not measure whether exposure to dust mite changed. To include all these studies in one analysis as if they were comparable to controlled trials in which mite allergen concentrations had been decreased significantly is equivalent to analysing the effectiveness of inhaled steroids in studies in which actuation failed to deliver the drug. Indeed, many of the older “avoidance” studies included have so little insight into the factors that influence mite allergen in a house that it is amusing to reread them today.1

        G⊘tzsche et al state that the results were the same for the studies in which successful reduction in exposure to mite allergen was achieved, which is strikingly different from the conclusion of three groups who analysed the same studies.3 Each of these reports concluded that the evidence strongly favoured using physical avoidance measures in treating children with asthma and mite allergy. Five controlled trials of allergen avoidance have achieved a prolonged (6 months) decrease in allergen concentration (references 11, 19, and 23 in the meta-analysis). 4 5 The active avoidance group in four of the studies showed significant improvement. G⊘tzsche et al restricted their calculations to two outcomes (symptoms and morning peak flow), although these were not the primary outcomes of the successful studies. Thus, they did not include the controlled trial by Ehnert and her colleagues in Berlin, which produced the most convincing decrease in mite allergen concentration and highly significant decrease in bronchial hyperreactivity (see figures 2 and 31).

        Allergic patients who are removed from an environment with high mite concentrations improve clinically and in terms of bronchial reactivity.2 The question has always been whether the same effect can be achieved in homes. G⊘tzsche et al reached a negative conclusion by including studies that had no effect, or unknown effects, on mite allergen concentrations and imposing an analysis that was simplistic and unrelated to the successful results. The correct conclusions are, firstly, that reducing mite allergen concentrations in a humid climate is not easy and requires an understanding of the factors that influence mite growth and, secondly, that four of the five controlled trials with a prolonged decrease in these concentrations have achieved impressive clinical results.

        Footnotes

        • Competing interests TAEP-M and MDC have received support for research on indoor allergens from Allergy Control Products (Ridgefield, CT) and from S C Johnson Wax (Racine, WI). Both companies manufacture products used for allergen avoidance.

        References

        1. 1.
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        3. 3.
        4. 4.
        5. 5.

        Power dressing is important in meta-analysis

        1. S J Muncer, Reader
        1. Department of General Practice and Social Medicine, 229 University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands Competing interests: None declared
        2. Greater Glasgow Health Board, Dalian House, PO Box 15327, Glasgow G3 8YU
        3. Asthma and Allergic Diseases Center, University of Virginia, Box 225 Health Sciences Center, Charlottesville, VA 22908, USA
        4. School of Health, University of Teesside, Middlesbrough TS1 3BA
        5. Nordic Cochrane Centre, Rigshospitalet, Department 7112, DK-2200 Copenhagen N, Denmark
        6. Executive Office, Unit of Public Health, Municipality of Gotland, S-62181, Visby, Sweden
        7. Centre for Applied Public Health Medicine, University of Wales College of Medicine, Cardiff CF1 3NW

          EDITOR—The paper by G⊘tzsche et al1 highlights a recurring problem with systematic review and meta-analysis—namely, ignoring or paying lip service to the importance of power. The continued publication of articles with inadequate power in social and health science journals has been noted on many occasions,24 without any apparent effect.3 Articles of inadequate power are, however, often combined into meta-analyses with scant regard to their power. The power of a study is the probability that it will lead to significant results.2 For example, in a recent systematic review of the literature examining the prevention of pregnancy nine of the 15 articles included had low statistical power.5 Given this low statistical power, should these articles have been included?

          In the study by G⊘tzsche et al the main result is that 41 out of 113 patients exposed to treatment interventions improved compared with 38 out of 117 in the control groups. If we imagine this had been run as a single experiment with this number of subjects and perform a χ2 test on the results, the results will indeed be non-significant (χ2=1.27, P=0.161, φ=0.076). Suppose that we had originally believed that the effect size of treatment would be small—that is, about 0.12—then an adequate sample with a power of 0.8 to detect a significant difference would be 785 subjects for the 0.05 level and 1168 for the 0.01 level.

          To put it another way, the power of the study by G⊘tzsche et al to detect a significant difference of a small effect size is inadequate. It is also inadequate to detect a medium effect size. Given that this is the case, would it be published if it were a single study, and should it be published because it is a meta-analysis?

          Footnotes

          • Competing interests None declared.

          References

          1. 1.
          2. 2.
          3. 3.
          4. 4.
          5. 5.

          Authors' reply

          1. Peter C G⊘tzsche, Director (p.c.gotzsche{at}cochrane.dk),
          2. Cecilia Hammarquist, Director,
          3. Michael Burr, Consultant
          1. Department of General Practice and Social Medicine, 229 University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands Competing interests: None declared
          2. Greater Glasgow Health Board, Dalian House, PO Box 15327, Glasgow G3 8YU
          3. Asthma and Allergic Diseases Center, University of Virginia, Box 225 Health Sciences Center, Charlottesville, VA 22908, USA
          4. School of Health, University of Teesside, Middlesbrough TS1 3BA
          5. Nordic Cochrane Centre, Rigshospitalet, Department 7112, DK-2200 Copenhagen N, Denmark
          6. Executive Office, Unit of Public Health, Municipality of Gotland, S-62181, Visby, Sweden
          7. Centre for Applied Public Health Medicine, University of Wales College of Medicine, Cardiff CF1 3NW

            EDITOR—Our conclusion was: “Current chemical and physical methods for eradicating mites or reducing exposure to mites seem to be ineffective and cannot be recommended as prophylactic treatment for asthma patients who are sensitive to mites.” This conclusion is still valid as none of the correspondents have provided data to the contrary.

            The hypothesis by Cloosterman and van Schayck that avoidance measures might be more effective if they are applied early is interesting. However, as they suggest, it needs further testing. Their trial included only 29 patients, and forced expiratory volume in 1 second at baseline was already as high as 99% of the predicted values.

            Morrison's comment that peak flow is highly variable is less relevant. Any variation can be overcome if the sample size is big enough, and the difference in peak flow we found corresponded to only −3 l/min (95% confidence interval −25 to 19 l/min). This does not suggest we missed any worthwhile effect.

            Contrary to the statements of Platts-Mills et al, we quoted odds ratios for five end points (not just two), and we included the paper of Ehnert et al as reference 11. As we stated, there was no overall effect on bronchial hyperreactivity. Platts-Mills et al claim that physical avoidance measures have an effect. They refer to a small study by Murray and Ferguson of 20 patients, which we excluded as it is not a randomised trial. Furthermore, they refer to a conference abstract. We are aware of this trial and of other trials, and these will be included in the updated Cochrane version of our review.1 We agree with Platts-Mills et al that removing patients from an environment with a high mite concentration may be beneficial. We also wish to point out that vote counting (four out of five studies give positive results) is a notoriously unreliable method.2

            Muncer's comment is relevant to those planning trials but not to a meta-analysis, which is a retrospective systematic review of what has been done. A meta-analysis is therefore always informative, whatever the power might be.

            References

            1. 1.
            2. 2.
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