House Dust Mite Allergen Exposure Research Articles

Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma

BackgroundAirway tissue eosinophilia can be an observed feature of obesity associated T2 asthma, but the processes mediating this inflammation are unknown. ObjectiveWe investigated a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma. MethodsWe assessed associations between body mass index and airway eosinophilia, leptin and eotaxin production in 78 asthma participants, 36 of which exhibited obesity. Cultured human airway fibroblasts and mouse models of chronic allergic airway disease were used to evaluate leptin’s effect on eotaxin production and lung eosinophilia. The role of interleukin-13 receptor alpha 2 (IL-13Rα2) in mediating these processes was examined using specific neutralizing antibodies in vitro. ResultsIn T2 asthma participants with obesity, we observed that airway tissue eosinophilia did not associate with traditional T2 inflammation metrics such as peripheral and/or bronchoalveolar lavage fluid (BALF) eosinophil counts or with fractional concentration of exhaled nitric oxide (FeNO). Alternatively, we observed elevated BALF leptin and eotaxin-1 levels. In airway fibroblasts from asthma participants, leptin augmented IL-13-induced eotaxin-1 and -3 production and IL13RA2 expression. In mice, elevated leptin promoted airway IL-13Rα2 and eotaxin production by lung fibroblasts and lung tissue eosinophilia following chronic house dust mite allergen exposure. Inhibition of IL-13Rα2 reduced combined leptin and IL-13-stimulated eotaxin secretion by human airway fibroblasts. ConclusionWe identified a potential association explaining airway tissue eosinophil retention in obesity-associated T2 asthma through leptin-mediated enhancement of IL-13-induced eosinophil chemokine production by airway fibroblasts, a process requiring IL-13Rα2.

Lung pathogenic, P2RX7-dependent CD4 +T cell immune responses to influenza are exacerbated by co-exposure with lung allergens

Abstract Extracellular ATP (eATP) is a danger signal released by inflamed tissues, and can be sensed by immune cells via P2RX7. P2RX7 promotes lung pathology induced by influenza infection, by inducing exacerbated numbers of lung CD4 +T cells. In response to influenza, lung CD4 +T cells are comprised of a type 1 (Th1)-like population, and a subset resembling follicular helper (Tfh) CD4 +T cells; this subset is called tissue-resident helper (Trh). Trh cells amplify lung effector immune responses. Trh cells express high P2RX7 levels, and current research in our laboratory shows that P2RX7 is crucial for Trh cell establishment and subsequent lung damage. We have also found that the intensity of lung damage caused by influenza is positively correlated with P2RX7 +lung Trh cells. It is not clear, however, how concomitant exposure to influenza and type 2 immunity-inducing lung allergens (a common clinical occurrence in the United States) affect P2RX7 +lung Trh cells and their resultant tissue damage. We investigated this, using House Dust Mite (HDM) allergen exposure together with Influenza (PR8) infection. HDM/PR8 co-exposure induced worsening of lung inflammation, compared to single exposure to PR8. This inflammation had type 1 characteristics (i.e. parenchymal immune cell accumulation and absence of mucus). The increased lung damage generated by HDM/PR8 exacerbated the generation of influenza-specific P2RX7 +lung Trh cells. The accumulation of lung Trh cells (and subsequent tissue damage) caused by HDM/PR8 was abolished in T cell-specific P2RX7-knockout mice. Our results suggest that local inflammation, eATP release and sensing, and lung Trh cells together dictate the intensity of lung damage, regardless of the nature of the lung disease agent. R01AI170649

Role of ventilation and cleaning for controlling house dust mite allergen infestation: A study on associations of house dust mite allergen concentrations with home environment and life styles in Tianjin area, China.

House dust mites produce well-known allergens for asthma and allergy among children. To study house dust mite allergen exposure level in northeast China and characterize its association with indoor environmental factors and cleaning habits, we inspected 399 homes in Tianjin area and collected dust from mattresses. Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p) were detected by the enzyme-linked immunosorbent assay (ELISA) method. The medians of total allergen concentrations for spring, summer, autumn, and winter were 524 ng/g, 351 ng/g, 1022 ng/g, and 1010 ng/g. High indoor air relative humidity (RH), low air change rate, indoor dampness, and frequent changing of quilt cover/bedsheet/pillow case were significantly associated with high house dust mite allergen concentration (relative risk [RR]: RH, 1.18-1.34; air change rate, 0.97-1.00; dampness, 2.92-3.83; changing quilt cover/bedsheet/pillow case, 0.66-0.75). The decrease in the absolute humidity gradient between indoors and outdoors that occurs with increased air change rate may explain why a high ventilation reduces house dust mite allergen concentration. The findings of this study show the importance of ventilation and cleaning for controlling house dust mite allergens. We found that the decrease in additional absolute humidity (e.g., humidity indoor -humidity outdoor ) with increased air change rate may be the main reason that a high ventilation rate reduces house dust mite allergen concentration. Ventilation and cleaning should be both considered for creating a healthy home environment.

Innate Immune Response to House Dust Mite Allergens in Allergic Asthma

Asthma is a major health problem and one of the leading causes of death in the world. The prevalence of asthma in Indonesia is high, with a recurrence >50%. Allergic sensitization in asthma is mainly caused by house dust mite (HDM) allergens, both from the mite’s body and its contaminants (e.g., lipopolysaccharides). HDM allergens stimulate several pathways in the innate immune response based on the HDM allergen groups that sensitize them. The innate immune response to HDM allergen exposure occurs when pattern recognition receptors (PRRs) recognizes the allergen, thereby stimulating respiratory epithelial cells to release cytokines, namely, thymic stromal lymphopoietin (TSLP), interleukin-25 (IL -25), and IL-33. The release of IL-25 and IL-33 activates group 2 innate lymphoid cells (ILC2) to release Th2-type cytokines (i.e., IL-5 and IL-13), resulting in allergic airway inflammation via IgE secretion by B cells, recruitment of eosinophils, and respiratory tract remodeling. Dendritic cells induce an adaptive immune response through Th2 activation in the sensitization and effector phases. Other mediators that contributed to the innate immune response include C-C motif chemokine ligand 20 (CCL-20) and granulocyte-macrophage colony-stimulating factor (GM-CSF). A deeper understanding of the components and mechanisms involved in innate immunity against HDM allergens creates the potential to develop alternative therapeutic targets for allergic asthma treatment.Keywords: house dust mite allergens, innate immunity, allergic asthma, respiratory epithelium, inflammatory cytokines

Multigenerational Epigenetic Regulation of Allergic Diseases: Utilizing an Experimental Dust Mite-Induced Asthma Model.

Environmental exposures have been linked to increased asthma risk, particularly during pregnancy and in early life. Here we use a mouse model of allergic lung disease to examine the effects of pre- and perinatal house dust mite (HDM) allergen exposure on offspring phenotypic and transcriptional outcomes in three generations. We show that maternal HDM exposure (F0) acts synergistically with adult HDM exposure, leading to enhanced airway hyperresponsiveness (AHR) and lung inflammation when compared to mice exposed solely in adulthood. Additionally, a subset of F1 males were not challenged in adulthood, and used to generate F2 progeny, which was then used to generate F3 progeny. Upon adult challenge to HDM, F2, and F3 males generated from the maternal HDM (F0) exposure lineage displayed increased airway reactivity and inflammation when compared to mice exposed solely in adulthood. These findings indicate that maternal allergen exposure is capable of enhancing either susceptibly to or severity of allergic airway disease. To examine the role of epigenetic inheritance of asthma susceptibility induced by maternal HDM exposure, we utilized a genome-wide MeDIP-seq and hMeDIP-seq analysis to identify genes differentially methylated (DMG) and hydroxymethylated (DHG), and their association with the enhanced AHR. In addition, we validated the relationship between DNA methylation and mRNA expression of the DMGs and DHGs in the male sub-generations (F1-F3). We found the expression of Kchn1, Nron, and Spag17 to be differentially hydroxymethylated and upregulated in the F1 exposed to HDM both in early life and in adulthood when compared to F1 mice exposed solely in adulthood. Kcnh1 remained upregulated in the F2 and F3 from the maternal HDM (F0) exposure lineage, when compared to F1 mice exposed solely in adulthood. In summary, we demonstrated that maternal HDM exposure in early life can alter the gene expression and phenotype of offspring upon adult HDM exposure, resulting in more severe disease. These effects persist at least two generations past the initial insult, transmitted along the paternal line.

Associations between Environmental dust composition and Atopic Dermatitis in urban and rural settings.

Environmental exposures are involved in the pathogenesis of the allergic phenotype and in determining which individual triggers a person becomes sensitized to. Atopic dermatitis (AD) may modulate these effects through increased penetration through the skin modifying the immune system and AD may be triggered or intensified by environmental exposures. These exposures and immune-modulating factors may differ in urban and rural environments. To compare house dust composition in urban and rural settings and correlate them with AD outcomes. Dust samples were collected from the beds of 156 children aged 6months to 3years. 42% of participants had atopic dermatitis. Samples were analyzed for bacterial endotoxin, fungal (β-1,3-glucan) levels, and house dust mite, cockroach, dog, cat, mouse, and peanut allergen. Exposures were compared in urban and rural environments and in participants with and without AD. Endotoxin but not fungal β-glucan exposure is higher in the environment of healthy controls than children with AD in both urban and rural settings. House dust mite allergen exposure is high in urban and rural settings with Dermatophagoides detected in 100% of samples. Cat and dog allergen exposure mirrors pet ownership patterns which differ slightly between groups and environments. Mouse allergen exposure is higher in urban homes. Environmental endotoxin may be protective against AD in both urban and rural settings. There are marked differences in allergen exposure in urban and rural settings, but these are unlikely to be important protective or risk factors.

Clinical Validation of House Dust Mite Allergen Exposure in the Environmental Exposure Unit

Clinical Validation of House Dust Mite Allergen Exposure in the Environmental Exposure Unit

Cerium dioxide nanoparticles exacerbate house dust mite induced type II airway inflammation

BackgroundNanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Cerium dioxide nanoparticles (CeO2NPs) have the ability to modify disease outcome but have not been investigated for their effect on models of asthma and inflammatory lung disease. The aim of this study was to examine the impact of CeO2NPs in a house dust mite (HDM) induced murine model of asthma.ResultsRepeated intranasal instillation of CeO2NPs in the presence of HDM caused the induction of a type II inflammatory response, characterised by increased bronchoalveolar lavage eosinophils, mast cells, total plasma IgE and goblet cell metaplasia. This was accompanied by increases in IL-4, CCL11 and MCPT1 gene expression together with increases in the mucin and inflammatory regulators CLCA1 and SLC26A4. CLCA1 and SLC26A4 were also induced by CeO2NPs + HDM co-exposure in air liquid interface cultures of human primary bronchial epithelial cells. HDM induced airway hyperresponsiveness and airway remodelling in mice were not altered with CeO2NPs co-exposure. Repeated HMD instillations followed by a single exposure to CeO2NPs failed to produce changes in type II inflammatory endpoints but did result in alterations in the neutrophil marker CD177. Treatment of mice with CeO2NPs in the absence of HDM did not have any significant effects. RNA-SEQ was used to explore early effects 24 h after single treatment exposures. Changes in SAA3 expression paralleled increased neutrophil BAL levels, while no changes in eosinophil or lymphocyte levels were observed. HDM resulted in a strong induction of type I interferon and IRF3 dependent gene expression, which was inhibited with CeO2NPs co-exposure. Changes in the expression of genes including CCL20, CXCL10, NLRC5, IRF7 and CLEC10A suggest regulation of dendritic cells, macrophage functionality and IRF3 modulation as key early events in how CeO2NPs may guide pulmonary responses to HDM towards type II inflammation.ConclusionsCeO2NPs were observed to modulate the murine pulmonary response to house dust mite allergen exposure towards a type II inflammatory environment. As this type of response is present within asthmatic endotypes this finding may have implications for how occupational or incidental exposure to CeO2NPs should be considered for those susceptible to disease.

Sublingual house dust mite immunotherapy has no impact on decrease of circulating erythrocytes upon airway allergen challenge in allergic rhinitis

House dust mite (HDM) allergy is a predominant cause for perennial allergic rhinitis (AR) in Europe. We recently reported that circulating erythrocyte numbers decrease after airway allergen challenge in a murine asthma model and in grass-pollen sensitized AR subjects. Consequently, we aimed to evaluate these findings in HDM sensitized AR subjects and the influence of preceding allergen immunotherapy. Seventy-seven (age 26.8 ± 7.3 years; 54.5% female) HDM-allergic rhinitis subjects previously enrolled in a randomized, monocentric sublingual immunotherapy (SLIT) trial at the Vienna Challenge Chamber (VCC) were included. Subjects had either received placebo (n = 22), low-dose HDM (n = 29) or high-dose HDM specific sublingual immunotherapy (n = 26) daily for 24 weeks. Blood sampling was performed before and after 6 hours of HDM allergen exposure. Overall, specific airway allergen challenge resulted in a significant decrease in circulating erythrocytes and hematocrit (p < 0.001), and elevation of leukocytes (p < 0.001), particularly segmented neutrophils (p < 0.001). Gender had no significant effect on the observed changes in circulating blood cells. Erythrocytes decreased and neutrophil counts increased significantly after airway allergen challenge regardless of preceding immunotherapy. These findings imply a rapid systemic mobilization of neutrophils occurring within immediate type hypersensitivity response upon a specific allergen challenge, which is possibly inversely linked with the erythrocyte numbers.

House Dust Mite Allergen Exposure in Adults Is Associated with Strong Specific Sensitization But Not with Clinical and Functional Respiratory Health Outcomes

Background: Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunological response to dust mite allergens in those who are IgE sensitised to house dust mite (HDM). Objectives: The aim of this analysis is to utilise information collected as part of a large international observational multicentre study in order to explore, in adults, associations of respiratory symptoms, including severity of symptoms with mattress house dust mite allergen levels. Methods: Mattress house dust mite concentrations were measured in a population based sample of 2890 adults aged between 27 and 56 years living in 22 centres in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust mite concentrations, adjusting for individual and household confounders. Results: There was no overall association of respiratory outcomes with measured house dust mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician diagnosed asthma. There was an association of high serum specific IgE levels to HDM (&gt; 3.5 kUA/L) with mattress house dust mite concentrations. Conclusions: In conclusion, in a large international cross-sectional survey of adults there was evidence of an association of house dust mite concentrations with high levels of serum specific IgE to HDM, but not with clinical and functional respiratory health outcomes.

House dust-mite allergen exposure is associated with serum specific IgE but not with respiratory outcomes.

Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunologic response to dust-mite allergens in those who are IgE sensitized to house dust-mite. Mattress house dust-mite concentrations were measured in a population-based sample of 2890 adults aged between 27 and 56years living in 22 centers in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust-mite concentrations, adjusting for individual and household confounders. There was no overall association of respiratory outcomes with measured house dust-mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician-diagnosed asthma. However, there was a positive association of high serum specific IgE levels to HDM (>3.5kUA /l) with mattress house dust-mite concentrations and a negative association of sensitization to cat with increasing house dust-mite concentrations. In conclusion, there was no evidence that respiratory symptoms in adults were associated with exposure to house dust-mite allergen in the mattress, but an association of house mite with strong sensitization was observed.

The correlation between the seasonal variation of house dust mite allergens exposure level in household and the level of asthma control in asthmatic children

The prevalence of allergic asthma has been rising continually which is correlated with the increasingly closed living environment. House dust mites are the major sources of indoor aeroallergens which induce asthma in sensitized people. To monitor the seasonal variation of house dust mite (HDM)-allergens exposure level in the asthmatic children, which was evaluated to show its correlation with the level of asthma control, HDM allergic sensitization and fraction of exhaled nitric oxide, and to provide basic data for HDM environmental control. A total of 48 HDM-allergic asthmatic children were enrolled from the asthma clinic in the hospital from March 2011 to January 2012 (boys 34 and girls 14, aging from 3 to 14 years, mean age 8 years and 4 months) in the present study. Dust samples from mattresses, pillows, bedroom floor, living room floor and sofas were collected in each season within one year in the household of all the enrolled patients. The concentrations of Der p 1 and Der f 1 were measured by the enzyme-linked immunosorbent assay (ELISA). To record the Asthma Control Test (ACT) score or Children Asthma Control Test (C-ACT) score for each patient and to collect the data of doctor monitoring asthma control level each time when the patient was clinic visited. The concentration and its classification of the serum specific IgE to HDM was determined by fluoroenzyme-immunometric assay. The average concentration of Der f 1 of all dust samples was significantly higher than that of Der p 1 (0.13 µg/g vs 0.02 µg/g, P < 0.05). The concentrations of Der f 1 from mattresses, pillows and sofas dust samples were significantly higher than those from bedroom floor and living room floor dust samples (0.69 µg/g, 0.42 µg/g and 0.22 µg/g vs 0.07 µg/g and 0.07 µg/g, P < 0.05). The Der f 1 exposure level from mattress dusts in summer but no others was negatively correlated with asthma control level (r = -0.318, P = 0.036). The Der f 1 exposure level from any area dusts in summer and the Der p 1 exposure level from pillows dusts in autumn was negatively correlated with ACT/C-ACT score respectively. The Der f 1 from mattress dusts in winter was positively correlated with classification of sIgE to Der f 1. The Der p 1 exposure level from most areas in each season was positively correlated with classification of sIgE to Der f 1 and Der P 1. Der f 1 was the predominant mite allergen in household dust and mainly came from mattresses, pillows and sofas. The role of the HDM allergen exposure level on the asthma control level and HDM allergic sensitization for the asthmatic children were depended on its area, season and HDM species, which suggested that the future assessment of clinical effect by the HDM environmental control should consider these factors.

Multiple House Dust Mite Allergen- Sensitization Profiles in Children with Allergic Asthma

Background: Allergic asthma is a common chronic inflammatory disorder which affects populations, with increasing prevalence among children. The risk of developing asthma is uncertain but depends on the interaction of environmental and genetic factors. The role of house dust mite (HDM) allergen exposure in the development of sensitization and asthma remains unclear. Objective: This study determined the sensitization profiles of common HDM species in a population of asthmatic children, which is essential in the development of highly specific and accurate diagnostic and therapeutic strategies for asthma in children. Methods: The immunoglobulin E-binding activity of allergens from the HDM species Blomia tropicalis (Bt), Dermatophagoides farina (Df), and Dermatopahagoides pteronyssinus (Dp) were determined in 250 age- and sexmatched paediatric allergic asthma and non-atopic Filipino subjects using Enzyme-linked immunosorbent assay and western blot analysis. Results: Majority of the allergic asthma patients tested were sensitized with multiple allergens from different HDM species where 33% exhibited sensitizations to any two HDM species and 26% were sensitized with allergens from three HDMs. HDM allergens of different molecular weights bind to IgE in allergic asthma patients tested. In addition a significant correlation was observed between total IgE and HDM-specific IgE level among allergic asthma patients (Bt p-value=0.038; Df p-value=0.045; Dp p-value=0.003), suggesting a significant contribution of dust mite allergens in the up-regulation of total serum IgE levels of allergic asthma patients. Conclusion: The results obtained in this study suggest that the HDM species Bt, Dp, and Df are important sources of allergens that trigger multiple sensitization in children with allergic asthma in the Filipino population. The incorporation of Bt, Dp, and Df allergens in the panel of diagnostic allergens for HDM allergy and allergic asthma is highly recommended.

Allergen-Specific Immunotherapy for Allergic Rhinitis in the Elderly: Is it Never Too Late?

Evaluation of: Bozek A, Ignasiak B, Filipowska B, Jarzab J. House dust mite sublingual immunotherapy: a double-blind, placebo-controlled study in elderly patients with allergic rhinitis. Clin. Exp. Allergy 43(2), 242-248 (2013). There is a well-accepted tenet in allergen-specific immunotherapy (SIT), especially for respiratory allergies such as rhinitis and asthma: this approach should be, in general, reserved for the pediatric population and young adults. This belief is based on the fact that SIT is considered the only therapy able to modify the course of allergic diseases. In the case of allergic rhinitis, for example, SIT could reduce the risk of asthma developing. Therefore, SIT is evaluated with 'the sooner the better' conviction. In elderly people with respiratory allergies, the 'course' of the disease is considered too advanced and therefore the room and therapeutic value of SIT is considered very limited. Bozek et al. evaluated the clinical efficacy of sublingual SIT (SLIT) with house dust mite (HDM) extracts in elderly (age >60 years) patients with a long history of allergic rhinitis due to HDM allergen exposure. In a 3-year double-blind placebo-controlled study, SLIT was able to significantly reduce the nose-related symptoms and the medication score. The conclusions of the authors were that SLIT with HDM allergens resulted in a significant clinical improvement in the active group compared with the placebo group, particularly during the period of the year in which the heating would be on. This therapy was well tolerated. These observations may lead to the more frequent use of SLIT immunotherapy in the elderly.

Mouse Allergen Exposure in Urban Schools and Its Effect On Childhood Asthma Morbidity

S U N D A Y 502 Most House Dust Mite Aeroallergen Exposure Occurs During the Day, Not in Bed Euan Tovey, PhD, Christiana Willenborg, BSc, Daniel Crisafulli, MSc, Janet Rimmer, MD, Jason Sercombe, MSc, Guy Marks, PhD, MD; Woolcock Institute of Medical Research, Sydney, Australia, University of Sydney, Australia, Prince of Wales Hospital, Sydney, Australia. RATIONALE: The bed is frequently regarded as the main site of house dust mite (HDM) exposure, despite a lack of explicit data. We measured people’s patterns of personal airborne HDM exposure and activity over 24 hour periods. METHODS: 12 adult subjects each collected nine (8x2 hrs + 1x8 hrs) samples of inhalable aeroallergen over 24 hours using a shoulder-mounted IOM filter and 2L/minute air pump carried in a back-pack. HDM allergen Der p 1 was measured using amplified ELISA. Location and activity were recorded by diary and automated still and video camera. Particle counts were also made in the breathing zone overnight. Fourteen distinct activities were identified. Differences in exposure between these activities were estimated by mixed model regression in which subjects were assigned random intercepts. RESULTS: Compared to the 24 hour geometricmean, exposurewas lower in bed overnight (relative ratio (RR) 5 0.17, 95% CIs 0.07 to 0.45, p 0.01). Most of the aeroallergen exposure occurred during the day and was associated with being active in domestic and crowded public situations. Overnight exposure to>5mmparticles was only transiently high around the time of bed entry, with additional small peaks associated with sporadic movement during sleep. CONCLUSIONS: Contrary to conventional belief, the bed may not be the main site or source of HDM allergen exposure. Future interventions should address other sources of exposure, and measure exposure in ways other than sampling bed reservoirs.

Airway Vascularity is not Associated with Airway Hyper-responsiveness in a Non-human Primate Model of Asthma

It is now accepted that the asthmatic airway is “remodeled” from its normal state and there is a clinical assumption that features of this remodeling are associated with airway hyper-responsiveness. One feature of airway remodeling is vascular remodeling where the airway has a higher density of vascularity than a normal airway. We used an established primate model of asthma to formally address the relationship between vascular remodeling, airway inflammation and hyper-responsiveness. Twenty-four male rhesus macaques were exposed to combination of filtered air, house dust mite allergen (HDMA) and ozone for six months. Airway hyper-responsiveness was measured at the end of the six-month exposure. Using a defined unbiased stereologic approach the density of airway blood vessels, epithelial expression of vascular endothelial growth factor (VEGF) and airway abundance of eosinophils was quantitated. The results demonstrated that combined ozone and HDMA exposure generated the highest degree of airway hyper-responsiveness. By contrast the HDMA only exposure generated the highest degree of airway VEGF expression, vascular density and number of eosinophils. Taken together these results imply that airway eosinophils, VEGF and increased vascular density are not the primary contributing factor to increased airway hyperresponsiveness in the rhesus macaque model of asthma.

Die Leitlinie Allergieprävention auf dem Prüfstand

The recommendations of the revised guideline Primary Allergy Prevention published in 2009 are summarized and discussed. The updated guidelines do not further recommend reducing house dust mite allergen exposure as a measure of primary prevention. New suggestions include the avoidance of overweight, and reduction of the exposure to indoor and/or outdoor air pollutants. In line with the current guidelines, there is no scientific evidence that prolonged introduction of solid food is an allergy-preventive measure. Consequently, even children with a family history of atopy can introduce solid foods at the beginning of the 5th month. The recommendations on avoiding environmental tobacco smoke, breast feeding over 4 months, avoiding a mold-promoting indoor climate, vaccination according to current recommendations, and avoidance of furry pets (especially cats) in risk babies have remained unchanged.

The 8‐year follow‐up of the PIAMA intervention study assessing the effect of mite‐impermeable mattress covers

Exposure to high levels of house dust mite (HDM) allergens is associated with the development of allergic sensitization to HDM, a risk factor for the development of asthma, rhinitis, and allergic dermatitis. We studied the effect of an early intervention with mite-impermeable mattress covers on HDM allergen levels and the development of asthma and mite allergy throughout the first 8 years of life. High-risk children (allergic mother) were prenatally recruited and randomly allocated to two groups receiving mite allergen-impermeable (n = 416) and placebo mattress covers (n = 394) or no intervention (n = 472). Asthma and allergies were assessed yearly by questionnaire. Specific immunoglobulin E and bronchial hyper-responsiveness were measured at the age of 8 years. Mattress dust samples collected at different time points were analyzed for HDM allergens. At the age of 8 years, levels of HDM allergen Der f1 but not Der p1 were lower in the active than the placebo mattress cover group. In repeated measures analyses, we found a temporary decreased risk of asthma symptoms at the age of 2 years in the intervention group compared to the placebo group and a temporary association between higher HDM allergen exposure at the age of 3 months and more asthma symptoms. Early intervention with mite-impermeable mattress covers is successful in reducing exposure to Der f1; it only temporarily reduces the risk of asthma symptoms and does not reduce the risk of hay fever, eczema, and allergic sensitization.

Associations of allergic sensitization and clinical phenotypes with innate immune response genes polymorphisms are modified by house dust mite allergen exposure

IntroductionPolymorphisms within innate immunity genes are associated with allergic phenotypes but results are variable. These associations were not analyzed with respect to allergen exposure. We investigated associations of TLR and CD14 polymorphisms with allergy phenotypes in the context of house dust mite (HDM) exposure.Material and methodsChildren, aged 12-16 years (n=326), were recruited from downtown and rural locations and assessed by allergist. Skin prick tests, total and HDM-specific sIgE measurements were done. HDM allergen concentrations in dust were measured. Genetic polymorphisms were identified using restriction fragment length polymorphism (RFLP).ResultsAllergic rhinitis, asthma and atopy were more prevalent in urban area. Although HDM allergen concentrations were higher in rural households, sIgE were present more frequently in urban children. In the whole population no association was found between HDM exposure and sensitization. In children with CD14/−159CC, CD14/−159TT and TLR9/2848GA genotypes increased exposure to HDM was associated with reduced incidence of allergic rhinitis. Significant associations of increased HDM exposure with reduced incidence of atopy were found for the whole population and subjects with CD14/−159CC, CD14/−1359GT, TLR4/896AA and TLR9/2848GA genotypes. Among children with CD14/−159CC and CD14/−1359GG significant positive correlation between HDM allergen concentrations in household and sensitization to HDM was observed. In contrast, protective effect of high HDM allergen exposure against specific sensitization was seen in subjects with TLR4/896 AG.ConclusionsDevelopment of specific sensitization and allergy may be associated with innate immune response genes polymorphisms and is modified by allergen exposure.

Allergy prevention

The further increase of allergies in industrialized countries demands evidence-based measures of primary prevention. The recommendations as published in the guideline of 2004 were updated and consented on the basis of a systematic literature search. Evidence from the period February 2003-May 2008 was searched in the electronic databases Cochrane and MEDLINE as well as in reference lists of recent reviews and by contacting experts. The retrieved citations were screened for relevance first by title and abstract and in a second step as full paper. Levels of evidence were assigned to each included study and the methodological quality of the studies was assessed as high or low. Finally the revised recommendations were formally consented (nominal group process) by representatives of relevant societies and organizations including a self-help group. Of originally 4556 hits, 217 studies (4 Cochrane Reviews, 14 meta-analyses, 19 randomized controlled trials, 135 cohort and 45 case-control studies) were included and critically appraised. Grossly unchanged remained the recommendations on avoiding environmental tobacco smoke, breast-feeding over 4 months (alternatively hypoallergenic formulas for children at risk), avoiding a mold-promoting indoor climate, vaccination according to current recommendations, and avoidance of furry pets (especially cats) in children at risk. The recommendation on reducing the house dust mite allergen exposure as a measure of primary prevention was omitted and the impact of a delayed introduction of supplementary food was reduced. New recommendations were adopted concerning fish consumption (during pregnancy / breast-feeding and as supplementary food in the first year), avoidance of overweight, and reducing the exposure to indoor and outdoor air pollutants. The revision of this guideline on a profound evidence basis led to (1) a confirmation of existing recommendations, (2) substantial revisions, and (3) new recommendations. Thereby it is possible to give evidence-based and up-to-date recommendations on primary prevention of allergies.