Asthma is a heterogeneous disease. The subject of mite allergen control has evolved into a debate dominated by a Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187). A not well-discussed aspect of that study is the selection by those authors of a univariate meta-analysis including various interventions. This study extends the meta-analysis by Gøtzsche and Johansen and aims to generate hypotheses on the effectiveness of various bedding interventions, including the coverage of all bedding elements. Trials were selected based on environmental criteria. The interventions were classified according to the number of barriers used. Standardized mean differences yielded the mite load, three physiological outcomes and asthma symptom scores. The influence of covariates was examined with a mixed-effect model using the metafor package for meta-analysis in R. Twelve trials included 1187 observations. The interventions included one barrier or product (six trials), two barriers or partial control (four trials) and three barriers or integral control (two trials). The exposure data showed considerable heterogeneity (I(2) = 93%). The risk of bias significantly (P = 0.04) influenced the final load, the square root of the interaction between the baseline load and the type of intervention as well (95% CI: -0.66 to -0.07 μg/g; P = 0.02). Changes in load showed similar tendencies. Health outcomes showed moderate to considerable heterogeneity (physiological outcomes I(2) = 44-94%; symptom score I(2) = 93%). A meta-regression of bedding interventions indicates that integral control most significantly reduced mite load when the load was high at baseline. The number of trials was too small to allow an appropriate examination of health outcomes. Future studies are suggested to test the hypothesis that allergic patients benefit from integral control when the baseline mite load is high.

The introduction of baked milk products in cow’s milk (CM) allergic children has previously been shown to accelerate induction tolerance in a selected group of children. However, there is no standardized baked milk product on the market. Recently, a new standardized, heated and glycated cow’s milk protein (HP) product was developed. The aim of this study was to measure safety and tolerability of a new, well characterized heated CM protein (HP) product in cow’s milk allergic (CMA) children between the age of 3 and 36 months. The children were recruited from seven clinics throughout the Netherlands. The HP product was introduced in six incremental doses under clinical supervision. Symptoms were registered after introduction of the HP product. Several questionnaires were filled out by parents of the children. Skin prick tests were performed with CM and HP product, sIgE to CM and α-lactalbumin (Bos d4), β-lactoglobulin (Bos d5), serum albumin (Bos d 6), lactoferrin (Bos d7) and casein (Bos d8). Whereas 72% percent (18 out of 25) of the children tolerated the HP product, seven children experienced adverse events. Risk factors for intolerance to the HP product were higher skin prick test (SPT) histamine equivalent index (HEP) results with CM and the HP product, higher specific IgE levels against Bos d4 and Bos d8 levels and Bos d5 levels. In conclusion, the HP product was tolerated by 72% of the CM allergic children. Outcomes of SPT with CM and the HP product, as well as values of sIgE against caseins, α-lactalbumin, and β-lactoglobulin may predict the tolerability of the HP product. Larger studies are needed to confirm these conclusions.

Background: Evidence regarding the clinical effectiveness of mite allergen avoidance for the treatment of asthma is lacking. In previous meta-analyses on mite allergen control, the baseline data were not discussed in detail. This study updates and extends the existing Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187), with a focus on baseline asthma outcomes and allergen exposures. Methods: We used the existing trials in the original Cochrane review and included newly published studies. The baseline data for the mite allergen load from the mattress, the standardized asthma symptom score (ASS), the forced expiratory volume in 1 s percentage of predicted (FEV 1 %pred.), and the histamine provocative concentration causing a 20% drop in FEV 1 (PC 20) were extracted. First, the mean values of the outcomes were calculated. The influence of the mite allergen load was examined with a random-effect meta-regression using the Metafor package in R. Results: Forty-five trials were included; 39 trials reported strategies for concurrent bedroom interventions, and 6 trails reported strategies for air purification. The mite allergen load ranged from 0.44 to 24.83 μg/g dust, with a mean of 9.86 μg/g dust (95% CI 5.66 to 14.05 μg/g dust, I 2 = 99.8%). All health outcomes showed considerable heterogeneity (standardized ASS mean: 0.13, 95% CI 0.08 to 0.18, I 2 = 99.9%; FEV 1 %pred. mean: 85.3%, 95% CI 80.5 to 90.1%, I 2 = 95.8%; PC 20 mean: 1.69 mg/mL, 95% CI 0.86 to 2.52 mg/mL, I 2 = 95.6%). The covariate mite allergen load did not significantly influence health outcomes. Discussion: This meta-analysis shows that mite avoidance studies are characterized by the inclusion of patients with rather mild to moderate asthma and with varying and sometimes negligible levels of allergen exposure. Future studies should focus on patients with severe asthma and increased levels of allergen exposure.

SummaryAsthma affects three hundred million people worldwide. The effectiveness of house dust mite allergen control for asthma treatment is debatable. One aspect that has been little discussed in existing meta‐analyses is the possible role of environmental strategies. Here, we reintroduce the previously defined strategies for mite allergen control and discuss their importance to the debate on clinical effectiveness. The strategy of concurrent bedroom interventions is related to the combined use of a priori defined interventions, while the strategy of exposure‐based control relates to the treatment of relevant textiles after assessing exposure. The air purification strategy aims to purify the human breathing zone of airborne allergens. In Western European patient practice, the use of these strategies differs. A post hoc study of the dominant Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187) appears to indicate that a majority of the underlying trials reported on the strategy of concurrent bedroom interventions, which were mainly executed in a minimal manner. Some trials have reported on the air purification strategy and may potentially alter the debate on effectiveness. No trial has reported on the strategy of exposure‐based control. We therefore hypothesize that the absence of evidence for the effectiveness of mite allergen control for asthma treatment applies to the strategy of concurrent bedroom interventions. The evidence‐based effectiveness of the exposure‐based control strategy appears to be undetermined. The results of our post hoc reanalysis urge that future meta‐analyses of mite allergen control should a priori define the environmental strategy under study. Future trials of mite allergen control are warranted to test the exposure‐based strategy as well as the sparsely tested strategy of air purification.