Combining genomewide association study and lung eQTL analysis provides evidence for novel genes associated with asthma.

BACKGROUND: Genomewide association studies (GWASs) of asthma have identified single-nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR. METHODS: A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. RESULTS: A total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. CONCLUSIONS: Combining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.

Allergology in Europe, the blueprint.

The number of patients with allergic diseases in Europe, and thus relevant demand for health care, is continuously increasing. In this EAACI-UEMS position paper, a rationale is given for the medical specialty of allergology. General practitioners and general paediatricians usually cannot elucidate and address all causative factors. Throughout Europe, therefore, the expertise of allergologists (allergists) is required. In collaboration with other medical professionals, they take care of allergic patients, in private practices or in specialized public centres. A well-structured collaboration between allergists and allergy centres offers the possibility of rapid signalling of new trends developing in the population of allergic patients (e.g., in food and drug allergy). Allergy centres also can perform clinical (and basic) research, teach medical students, future allergists and provide postgraduate training. To prevent that the quality of care in one or several countries within Europe lags behind developments in other countries, the UEMS Section and Board on Allergology together with the European Academy of Allergy and Clinical Immunology advocates the status of a full specialty of allergology in each European country, with a further intention to align their activities (blueprint, curriculum and centre visitation) with the UEMS Section of Paediatrics.

Tryptase and histamine metabolites as diagnostic indicators of indolent systemic mastocytosis without skin lesions.

BACKGROUND: Risk indicators of indolent systemic mastocytosis (ISM) in adults with clinical suspicion of ISM without accompanying skin lesions [urticaria pigmentosa (UP)] are lacking. This study aimed at creating a decision tree using clinical characteristics, serum tryptase, and the urinary histamine metabolites methylimidazole acetic acid (MIMA) and methylhistamine (MH) to select patients for bone marrow investigations to diagnose ISM. METHODS: Retrospective data analysis of all adults, in whom bone marrow investigations were performed to diagnose ISM, was carried out. RESULTS: In total, 142 patients were included. SM was absent in all 44 patients with tryptase <10 µg/l, in 45 of 98 (46%) patients with tryptase ≥10 µg/l and in 18 of 52 patients (35%) with tryptase >20 µg/l. Above 43 µg/l, all patients had ISM (n = 11). Male gender, insect venom anaphylaxis as presenting symptom, tryptase, MIMA, and MH were independent ISM predictors. If tryptase was ≥10 µg/l, the diagnostic accuracy of MIMA and MH was high (areas under the ROC curve 0.92). CONCLUSIONS: In suspected patients without UP, the ISM risk is very low (if present at all) if tryptase is <10 µg/l. If tryptase is ≥10 µg/l, this risk depends on MIMA and MH, being low if these are normal, but high if these are elevated. Male gender and insect venom anaphylaxis are additional risk indicators. We recommend refraining from bone marrow examinations in suspected patients without UP if tryptase is <10 µg/l. Our results question the reliability of the minor diagnostic World Health Organization criterion of tryptase >20 µg/l.

High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis.

BACKGROUND: Indolent systemic mastocytosis (ISM) is a rare disease characterized by accumulation of abnormal mast cells in various tissues, including bone marrow. Symptoms are usually related to release of mast cell mediators. The aims are to establish the prevalence of osteoporotic fractures in ISM and to investigate the association with serum tryptase and the urinary histamine metabolites, methylhistamine (MH), and methylimidazole acetic acid. METHODS: The fracture prevalence in 157 patients (65 men; 92 women), mean age 54 ± 12 years, was assessed by vertebral morphometry and data from patient records, supplemented by a questionnaire. Bone mineral density (BMD) of lumbar spine and femoral neck was measured, and tryptase and histamine metabolites were analysed. RESULTS: We registered 235 lifetime fractures in 154 patients, including 140 osteoporotic (low-energy trauma) fractures, of which 62% were vertebral, 1% hip and 36% other nonvertebral fractures. Osteoporotic fractures and osteoporosis were found in 37% and 28% of the patients, respectively. In men, the prevalence of these osteoporotic manifestations (46% <50 years; 73% ≥50 years) was much higher compared with women (18% <50 years; 58% ≥50 years). Older age, male gender, and higher urinary MH were independently related to the osteoporotic manifestations. CONCLUSIONS: This first publication about prevalence of fractures and osteoporosis in patients with ISM shows that the risk of osteoporotic fractures is high, especially in men. Higher urinary MH levels are associated with a higher risk of osteoporotic manifestations. Routine measurements of BMD and vertebral morphometry are warranted in these patients for early detection of osteoporosis.

Treatment of hereditary angioedema with nanofiltered C1-esterase inhibitor concentrate (Cetor®): multi-center phase II and III studies to assess pharmacokinetics, clinical efficacy and safety.

From 1997, plasma-derived C1-inhibitor concentrate (Cetor®) has been available to HAE and AAE patients. Recently, a virus reducing 15 nm nanofiltration step has been introduced in the production process. A randomized, double-blind controlled cross-over study was performed to compare the pharmacokinetics (PK) of nanofiltered (C1-INH-NF) with conventional C1-inhibitor (C1-INH). Efficacy and safety were investigated in an open-label, on-demand and a prophylactic study. No differences in pharmacokinetic parameters between C1-INH and C1-INH-NF were found (13 non-symptomatic HAE patients). Both C1-inhibitor products equally increased plasma C4 levels. In the on-demand study, 14 acute angioedema attacks in 8 patients were analyzed. In the prophylactic study, 1 AAE and 5 HAE patients experienced in total 31 attacks during 748 observation days. In total 180,000 units of C1-INH-NF were administered. No product-related adverse events occurred, and no anti-C1-antibodies were induced. Nanofiltration in the production process of C1-inhibitor did not affect the pharmacokinetics, efficacy, and safety.

Gene expression profile, pathways, and transcriptional system regulation in indolent systemic mastocytosis.

BACKGROUND: Mastocytosis is an uncommon disease resulting from proliferation of abnormal mast cells infiltrating skin, bone marrow, liver, and other tissues. The aim of this study was to find differences in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis compared to healthy controls. The second aim was to define a specific gene expression profile in patients with mastocytosis. METHODS: Twenty-two patients with indolent systemic mastocytosis and 43 healthy controls were studied. Whole genome gene expression analysis was performed on RNA samples isolated from the peripheral blood. For amplification and labelling of the RNA, the Illumina TotalPrep 96 RNA Amplification Kit was used. Human HT-12_V3_expression arrays were processed. Data analysis was performed using GeneSpring, Genecodis, and Transcriptional System Regulators. RESULTS: Comparison of gene expression between patients and controls revealed a significant difference (P < 0.05 corrected for multiple testing) and the fold change difference >2 in gene expression in 2303 of the 48.794 analysed transcripts. Functional annotation indicated that the main pathways in which the differently expressed genes were involved are ubiquitin-mediated proteolysis, MAPK signalling pathway, pathways in cancer, and Jak-STAT signalling. The expression distributions for both groups did not overlap at all, indicating that many genes are highly differentially expressed in both groups. CONCLUSION: We were able to find abnormalities in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis and to construct a gene expression profile which may be useful in clinical practice to predict the presence of mastocytosis and in further research of novel drugs.

Gene expression analysis predicts insect venom anaphylaxis in indolent systemic mastocytosis.

BACKGROUND: Anaphylaxis to insect venom (Hymenoptera) is most severe in patients with mastocytosis and may even lead to death. However, not all patients with mastocytosis suffer from anaphylaxis. The aim of the study was to analyze differences in gene expression between patients with indolent systemic mastocytosis (ISM) and a history of insect venom anaphylaxis (IVA) compared to those patients without a history of anaphylaxis, and to determine the predictive use of gene expression profiling. METHODS: Whole-genome gene expression analysis was performed in peripheral blood cells. RESULTS: Twenty-two adults with ISM were included: 12 with a history of IVA and 10 without a history of anaphylaxis of any kind. Significant differences in single gene expression corrected for multiple testing were found for 104 transcripts (P < 0.05). Gene ontology analysis revealed that the differentially expressed genes were involved in pathways responsible for the development of cancer and focal and cell adhesion suggesting that the expression of genes related to the differentiation state of cells is higher in patients with a history of anaphylaxis. Based on the gene expression profiles, a naïve Bayes prediction model was built identifying patients with IVA. CONCLUSIONS: In ISM, gene expression profiles are different between patients with a history of IVA and those without. These findings might reflect a more pronounced mast cells dysfunction in patients without a history of anaphylaxis. Gene expression profiling might be a useful tool to predict the risk of anaphylaxis on insect venom in patients with ISM. Prospective studies are needed to substantiate any conclusions.

Intravenous voriconazole after toxic oral administration.

In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate liver enzyme abnormalities, and therefore, oral administration of voriconazole may have a hepatotoxicity profile different from that of intravenous (i.v.) administration. Intravenously administered voriconazole might still be an option after oral-voriconazole-induced toxicity has resolved.

Application of a prediction model for work-related sensitisation in bakery workers.

Identification of work-related allergy, particularly work-related asthma, in a (nationwide) medical surveillance programme among bakery workers requires an effective and efficient strategy. Bakers at high risk of having work-related allergy were indentified by use of a questionnaire-based prediction model for work-related sensitisation. The questionnaire was applied among 5,325 participating bakers. Sequential diagnostic investigations were performed only in those with an elevated risk. Performance of the model was evaluated in 674 randomly selected bakers who participated in the medical surveillance programme and the validation study. Clinical investigations were evaluated in the first 73 bakers referred at high risk. Overall 90% of bakers at risk of having asthma could be identified. Individuals at low risk showed 0.3-3.8% work-related respiratory symptoms, medication use or absenteeism. Predicting flour sensitisation by a simple questionnaire and score chart seems more effective at detecting work-related allergy than serology testing followed by clinical investigation in all immunoglobulin E class II-positive individuals. This prediction based stratification procedure appeared effective in detecting work-related allergy among bakers and can accurately be used for periodic examination, especially in small enterprises where delivery of adequate care is difficult. This approach may contribute to cost reduction.

The effect of encasings on quality of life in adult house dust mite allergic patients with rhinitis, asthma and/or atopic dermatitis.

BACKGROUND: Environmental control has been put forward as an integral part of the management of house dust mite (HDM) allergy in sensitized patients. To validate this statement allergic disorders involved in HDM allergy--allergic asthma, rhinitis and atopic eczema/dermatitis syndrome (AEDS)--should be taken together and studied in terms of the efficacy of environmental control. Because a generic quality of life questionnaire exceeds the border of disease, this may be used as major outcome parameter. RESEARCH OBJECTIVE: To study the effects of bedding encasings in HDM allergic patients with asthma, rhinitis and AEDS. MATERIAL AND METHODS: A total of 224 adult HDM allergic patients with rhinitis and/or asthma and/or dermatitis were randomly allocated impermeable or nonimpermeable encasings for mattress, pillow and duvet. Short form 36 (SF-36) was filled in at baseline and after 12 months. RESULTS: Lower physical (P = 0.01) and emotional (P < 0.001) sumscores were seen in females. Also, the presence of asthma resulted in lower physical sumscore (P = 0.01). However, no effect was seen of encasings on either sumscore. CONCLUSION: Bedding encasings do not improve quality of life in a mixed population of subjects with combinations with rhinitis, asthma and atopic dermatitis and sensitized to HDMs.

Comparison of a generic and a rhinitis-specific quality-of-life (QOL) instrument in patients with house dust mite allergy: relationship between the SF-36 and Rhinitis QOL Questionnaire.

BACKGROUND: Generic and disease-specific quality-of-life (QOL) questionnaires are commonly used in subjects with allergic rhinitis (AR). AR, however, is closely associated with other disorders such as bronchial asthma and atopic dermatitis (AD). These co-morbid associations may have an effect on the inter-relation of generic and disease-specific QOL outcomes and the behaviour of this inter-relation in time. OBJECTIVE: To unravel the inter-relationships between the outcome of a generic instrument (SF-36) and a disease-specific instrument (Rhinitis QOL Questionnaire (RQLQ)). MATERIALS AND METHODS: In the framework of a randomized clinical trial with respect to the efficacy of impermeable bedding covers in house dust mite (HDM) allergy, SF-36 and RQLQ were administered to 224 adults with AR and/or allergic asthma and/or AD at baseline and after 12 months of intervention. Regression analysis and canonical correlation were used to estimate overlap. RESULTS: Overlap between SF-36 and RQLQ domains in terms of explained variance ranged from 6% to 56%. Canonical correlation yielded low coefficients (0.16-0.27). Moreover, both SF-36 and RQLQ scores did not change significantly during the intervention. CONCLUSION: In patients with HDM allergy characterized by co-morbid associations, SF-36 and RQLQ cover different aspects in QOL. It is advocated to use both simultaneously in performing QOL studies.

Altered beta2-adrenergic regulation of T cell activity after allergen challenge in asthma.

BACKGROUND: Airway inflammation in asthma is orchestrated by recruitment of T helper (Th)2 lymphocytes to the lung and subsequent production of Th2-like cytokines upon allergen challenge. OBJECTIVE: To examine whether allergen-induced dysfunction of the beta2-adrenergic receptor (beta2-AR) contributes to the enhanced T(h2) cell activity in asthma. METHODS: Beta2-adrenergic regulation of cytokine mRNA expression was studied in alpha-CD3/alpha-CD28-activated peripheral blood lymphocytes from seven asthma patients before and 6 h after allergen challenge, in conjunction with the effects of beta2-agonist fenoterol on T cell chemotaxis and signalling pathways. RESULTS: A complete loss of beta2-AR control over expression of the Th2 cytokines IL-4, IL-5 and IL-13, but not of the Th1 cytokine IFN-gamma, was observed after allergen challenge. Furthermore, we found impaired beta2-AR regulation of T cell migration as well as signal transduction pathways, i.e. the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein and the inhibition of the mitogen-activated protein kinase pathway. The loss of beta2-AR control was associated with increased beta-adrenergic receptor kinase expression, which might be involved in beta2-AR desensitization. In addition, we demonstrate for the first time that T cells exposed to the chemokine thymus and activation-regulated chemokine show hyporesponsiveness to fenoterol. CONCLUSION: Our results suggest that allergen-induced loss of beta2-AR control, possibly mediated by chemokine release, plays an important role in enhanced Th2-like activity in asthma.

Differential effect of mattress covers on the level of Der p 1 and Der f 1 in dust.

BACKGROUND: Exposure to house dust mite (HDM) allergens can lead to the development of allergic complaints. Mattress covers seem to be an obvious option for lowering allergen exposure in sensitized individuals. Previous studies have shown that Dermatophagoides pteronissinus was the most prevalent HDM species in the Netherlands. OBJECTIVE: In the present study, we investigated the effect of mattress covers on Der p 1 and Der f 1 concentrations in dust samples in three areas in the Netherlands; Groningen, Utrecht and Rotterdam. METHODS: Dust was obtained from mattresses of 277 patients at the beginning of the study and after 12 months of the placebo-controlled intervention. It was analysed for allergen content by immunoassay. The differential effect of the intervention on Der p 1 vs. Der f 1 was analysed in a subgroup with Der p 1+Der f 1>1 microg/g dust (N=161). It was tested whether the intervention caused a significant change in the Der f 1/Der p 1 ratio. RESULTS: At t=0 we found very similar levels of the group 1 allergens of both species. The relatively high prevalence of D. farinae in our study was geographically restricted: the median Der f 1/Der p 1 ratio was 11.1 in the Rotterdam area compared with 1.32 in the Utrecht area and 0.33 in the Groningen area. Analysis of our data showed that the favourable intervention effect found for the combined allergen data (reduction factor=2.9, P<0.001) is essentially due to a favourable effect of the intervention on the Der f 1 levels only (reduction factor=3.6, P<0.001). The effect on the Der p 1 level was remarkably small (reduction factor: 1.2, P=0.48). In the intervention group, the Der f 1/Der p 1 ratio decreased after 12 months by a factor 2.0, whereas in the placebo group it increased (probability of the intervention effect: P<0.005). CONCLUSION: Mite-impermeable covers are more effective in reducing the level of Der f 1 than that of Der p 1.

Allergic sensitization to indoor and outdoor allergens and relevance to bronchial hyperresponsiveness in younger and older subjects.

BACKGROUND: Most previous epidemiological studies on the relationship between allergy and bronchial hyperresponsiveness (BHR) have made no distinction between sensitization to indoor and outdoor allergens. We studied the relationship between specific sensitization to allergen and BHR and further assessed whether this was different in young adults and older subjects. METHODS: Specific IgE to indoor allergens (house dust mite and cat) and outdoor allergens (timothy grass and birch) were measured using the CAP System. BHR was defined as PD20 /= 3). Young adults with multiple sensitization had the highest risk of BHR. Subjects who were exclusively sensitized to pollen did not show increased BHR in both age groups. Total IgE had, independently of sensitization, only a significant dose-response relationship with BHR in the oldest age group. CONCLUSIONS: The association between sensitization and BHR is dependent on the nature of the allergen and the level of specific IgE. Furthermore, this study shows for the first time that total IgE is associated with BHR at older ages, independently of sensitization.

Role and interpretation of total serum IgE measurements in the diagnosis of allergic airway disease in adults.

BACKGROUND: While total IgE measurements are often used in clinical practice, it is unclear how they should be interpreted for the diagnosis of allergic disorders. We studied whether total IgE may be used to rule out or predict sensitization and whether there are age or gender differences. METHODS: ROC curves were assessed in subjects with asthma or allergy symptoms from a general population sample. We studied predictive values and likelihood ratios. At least one positive skin test (Phazet) or specific IgE measurement (CAP) served as reference. RESULTS: High negative predictive values, suitable to rule out sensitization, were not found. In younger subjects, high total IgE levels strongly increase the probability of sensitization. The relationship between monosensitization and total IgE was less strong, but meaningful positive likelihood ratios were found at higher levels of total IgE. The discriminating ability of total IgE was better in the age group 20-44 than 45-70 years and comparable in males and females. CONCLUSION: Total IgE is not useful to rule out sensitization to common inhalant allergens. High total IgE may indicate a high probability of sensitization and may be useful to decide whether further investigation is warranted in patients with negative specific allergy tests to a panel of common inhalant allergens.

Occupational asthma due to IgE mediated allergy to the flower Molucella laevis (Bells of Ireland).

BACKGROUND: About 25% of greenhouse flower and/or ornamental plant growers sensitised to workplace flowers or moulds have occupational asthma, a disease that is suffered by 8% of the growers who cultivate these crops. AIM: To document a case of occupational asthma due to IgE mediated allergy to the flower Molucella laevis. METHODS: and RESULTS: There was a history of work related seasonal asthmatic and rhinoconjunctivitis symptoms in a Molucella laevis grower. Bronchial obstruction following exposure to Molucella laevis was documented by a fall in FEV(1) from 89% to 73% of predicted during seasonal exposure to Molucella laevis. Daily PEF measurements showed a fall from 500 to 250 l/min during this period following withdrawal of inhaled steroids. Bronchial reactivity to inhaled methacholine was increased (PC(20) 1.45 mg/ml). Confirmation of sensitisation to Molucella laevis flower pollen extract was done using an SPT and by demonstration of Molucella laevis specific serum IgE (18 IU/ml; class 4). Specific inhalation challenge with Molucella laevis extract provoked an early and late asthmatic reaction (EAR and LAR) with a fall in FEV(1) compared with control day of 40% and 53% respectively, with associated 5.1-fold increase in absolute sputum eosinophil cell counts and 2.9-fold increase in neutrophil cell counts.

The unfavorable effects of concomitant asthma and sleeplessness due to the atopic eczema/dermatitis syndrome (AEDS) on quality of life in subjects allergic to house-dust mites.

BACKGROUND: Allergic rhinitis, asthma or the atopic eczema/dermatitis syndrome (AEDS) may independently impair quality of life in patients. However, although many allergic patients may suffer from more than one disorder, the effect of concomitant disease -- in particular, the impact of AEDS -- is largely unknown. As part of a large multicenter clinical trial on the efficacy of mattress casings in house-dust mite (HDM) allergy, generic quality of life in a mixed population of 224 subjects with rhinitis (n = 198) and/or asthma (n = 111) and/or AEDS (n = 64) was studied. The study aimed to estimate quality of life impairment in these atopic patients and to address the question/issue of whether one atopic disorder goes beyond other existing allergic diseases, thereby causing further impairment to quality of life. METHODS: Generic quality of life was assessed by SF-36. Quality of life in the atopic group was compared with a Dutch norm population. Multiple linear regression was used to determine the effects of disease (i.e. the presence of allergic rhinitis, asthma or AEDS) or disease severity, as assessed by visual analog scores (VAS) for asthma, rhinitis, VAS sleeplessness and VAS itching being considered as major symptoms in AEDS on SF-36 domains. RESULTS: Compared to the norm group, atopic patients were impaired in: physical functioning; role physical functioning; general health; vitality; and social functioning. The diagnosis of asthma was negatively associated with the SF-36 subscales for physical functioning (P = 0.02), and general health (P < 0.01). In line with these findings, asthma severity (VAS asthma) was negatively associated with physical functioning (P < 0.01), role physical functioning (P < 0.01), general health (P < 0.0.1), social functioning (P = 0.01), emotional functioning (P = 0.01), and vitality (P = 0.01). VAS sleeplessness had significant negative effect on role physical functioning (P < 0.01), bodily pain (P < 0.01), General health (P = 0.01), mental health (P < 0.01), social functioning (P < 0.01), and vitality (P < 0.01). In contrast, neither the diagnosis of allergic rhinitis or AEDS, nor VAS itching as an outcome parameter of AEDS, exerted additional effects on the SF-36 domains. CONCLUSIONS: Patients with atopic disease based on HDM allergy may have impaired quality of life. The majority of these patients have allergic rhinitis. The (co)existence of asthma, expressed in terms of diagnostic criteria or symptom severity, or the presence of sleep disorders as a consequence of AEDS, may further impair quality of life.

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.

BACKGROUND: The use of anti-allergic mattress covers in patients with asthma can result in a large reduction in the level of house dust mite allergen in dust samples. Apart from a reduction in histamine induced bronchial hyperresponsiveness, there are few data on the effect of mattress covers on clinical efficacy and quality of life in patients with moderate to severe asthma. METHODS: Thirty patients with asthma and house dust mite allergy were studied in a randomised, double blind, placebo controlled study. Before and after using anti-allergic covers for 1 year, dust was collected from the mattresses to determine concentrations of Dermatophagoides pteronyssinus (Der p 1), and bronchial hyperresponsiveness and quality of life were measured. The patients scored their symptoms (lungs and nose), morning and evening peak flow values, and rescue medication for 14 days before and after the intervention period. RESULTS: There was a significant reduction in the concentration of Der p 1 in the dust collected from the mattresses in the actively treated group after 1 year compared with before treatment; no change was found in the placebo group. In both the actively treated and placebo groups there was no significant improvement in PC(20) histamine. Quality of life improved similarly in both groups. The symptom score of the lower airways did not significantly change in either group. A significant decrease in nasal symptom score was seen in the actively treated group compared with before treatment, but there was no significant difference between the groups. No changes in morning and evening peak flow values, peak flow variability, nor in the use of rescue medication were found in either group. CONCLUSION: The use of anti-allergic mattress covers results in significant reductions in Der p 1 concentrations in carpet-free bedrooms. However, in patients with moderate to severe asthma, airways hyperresponsiveness and clinical parameters are not affected by this effective allergen avoidance.