HDM-sensitized Children Research Articles

Concordance of skin test reactivity between indoor inhalant allergens among children with allergic respiratory disease

BackgroundIn vitro studies have demonstrated cross-reactivity among indoor allergen proteins in children with allergic respiratory diseases. However, there are only few studies evaluating in vivo response. A skin prick test (SPT) with commercial indoor solutions is widely used in clinical practice. We aimed to evaluate SPT agreement in children with allergic respiratory disease between pairs of common indoor allergens.MethodsWe reviewed SPT results of children 2 to 18 years old, diagnosed with respiratory allergic disease. Results from house dust mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), cockroach (Periplaneta americana, Blatella germanica), cat and dog were collected. Sensitization was defined as ≥ 3 mm in wheal diameter. Kappa coefficient (κ) was used to analyze sensitization concordance for each allergen pair.ResultsThe charts of 300 children, 187 (62.33%) males, were reviewed. Mean age was 7.43 ± 3.29 years with 183 (61%), 140 (46.67%), 45 (15%), 30 (10%) sensitizations to house dust mite (HDM), cockroach, cat and dog, respectively. Sensitization concordance between HDM and cockroach was moderate: κ = 0.53 (95% CI: 0.42–0.64). Moderate agreement occurred between dog and cat: κ = 0.41 (95%CI: 0.30–0.52). HDM-sensitized children showed poor concordance with both cat κ = 0.17 (95%CI: 0.09–0.24) and dog κ = 0.09 (95%CI: 0.03–0.14). There was also poor concordance between cockroach-sensitized children to cat κ = 0.19 (95%CI; 0.11–0.28) and dog κ = 0.11 (95%CI; 0.04–0.18).ConclusionWe demonstrated moderate agreement of SPT response between HDM and cockroach as well as dog and cat. This may be due to cross-reactivity. Component-resolved diagnosis should be considered in children with co-sensitization of these allergen pairs.

Altered Serum IgE and IgG4 Response to Dermatophagoides Pteronyssinus Allergens during Specific Immunotherapy

A T U R D A Y Baoqing Sun, MHA, Zheng Peiyan; The First Affiliated Hospital of Guangzhou, Guangzhou, China, State Key Laboratory of Respiratory Disease, National Clinical Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. RATIONALE: We investigated the changes in serum-specific IgE (sIgE) and IgG4 (sIgG4) against house dustmite (HDM) and its components Der p 1 and Der p 2 during specific immunotherapy (SIT), and evaluated the clinical efficacy thereof. METHODS: We retrospectively analyzed 51 HDM-sensitized children aged 5 to 16 years diagnosed with allergic rhinitis and/or asthma, following 36 monthsofSIT.Wealsocollecteddata fromacontemporarycontrol cohort of 50 patients administered routine medications for HDM allergy. . In the test cases, we recorded the sIgE and sIgG4 levels against thewhole allergen ofHDM(Der p), Der p 1 and Der p 2 at baseline and at 6, 12, 24 and 36 months of SIT. RESULTS: The serum sIgE response increased up to 6 months of SIT, but subsequently declined. At 36 months, the anti-Der p 1 and anti-Der p 2 sIgEs plummeted below the baseline. During SIT, the increased serum sIgG4 responsewas the greatest against Der p, followed byDer p 1 and Der p 2. The decline in sIgE/sIgG4 ratio for Der 1 was higher than for the other allergensmaximumdecline. Comparedwith older children, children aged 5 to 8 manifested a clearer sIgG4 response, especially against Der p 1 and Der p 2 versus Der p. CONCLUSIONS: SIT for HDM stimulated an early sIgE and sIgG4 response against HDM allergens. with a progressive decline in the ratio of sIgE/sIgG4, especially against Der p 1. Younger children may manifest a more rapid response to SIT than older ones. S 197 Conjunctival Provocation Test in Daily Practice: Four Ocular Symptoms Vs Ocular Pruritus Score System

Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts.

SummaryBackgroundModels that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma.ObjectiveTo characterize the patterns of peripheral blood mononuclear cells’ (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population‐based birth cohorts using machine learning techniques.Methods PBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 μg/ml). Cytokine expression (IL‐13, IL‐5, IFN‐γ, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping.ResultsA six‐class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: ‘Nonresponders’ (n = 905, 55%); ‘IL‐10 responders’ (n = 49, 3%); ‘IFN‐γ and IL‐13 medium responders’ (n = 56, 3.4%); ‘IL‐13 medium responders’ (n = 351, 21.4%); ‘IL‐5 and IL‐13 medium responders’ (n = 77, 4.7%); and ‘IL‐13 and IL‐5 high responders’ (n = 204, 12.4%). ‘IL‐13 and IL‐5 high responders’ were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma.ConclusionUsing model‐based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL‐13 and IL‐5), and clinical outcomes. ‘IL‐13 and IL‐5 high responders’ class was strongly associated with HDM sensitization. However, among HDM‐sensitized children, one‐third showed no PBMC response to HDM, and the majority of HDM‐sensitized children did not have asthma or wheeze. Our findings suggest that positive HDM ‘allergy tests’ and asthma are associated with a broad range of immunophenotypes, which may have important implications for the use of cytokine‐targeted treatment approaches.

Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy.

PurposeMicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT).MethodsTwenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA.ResultsAfter 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10+CD4+ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups.ConclusionsOur findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.

Suppression of TIM-1 predicates clinical efficacy of sublingual immunotherapy for allergic rhinitis in children

ObjectiveTo evaluate the clinical efficacy of sublingual immunotherapy (SLIT) with house-dust mite (HDM) extract and to examine the change of biomarkers (TIM-1, IL-5 and IL-10) after 6-month SLIT in children with allergic rhinitis (AR). MethodsOne hundred and sixteen HDM-sensitized children with persistent AR were enrolled to assess the clinical efficacy of SLIT by determining the individual nasal symptom score (INSS) and total nasal symptom scores (TNSS) after 6-month SLIT. Moreover, the mRNA expression of TIM-1, IL-5 and IL-10 in peripheral blood mononuclear cells (PBMCs) was examined in 16 well-controlled and 12 uncontrolled AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). ResultsAfter 6-month SLIT, both TNSS and INSS scores were significantly decreased compared with the baseline value (p<0.01). The rates for well-controlled, partly controlled and uncontrolled children were 43.1%, 32.8% and 24.1%, respectively. Accordingly, the mRNA levels of TIM-1 and IL-5 decreased significantly and IL-10 mRNA level increased significantly compared with the baseline value in well-controlled children (p<0.05). ConclusionOur findings suggest SLIT with HDM extract is effective and safe for AR children and TIM-1 may be considered as an indicator for evaluating the clinical efficacy of SLIT.

Feather bedding and house dust mite sensitization and airway disease in childhood

Feather bedding has been inversely associated with child wheeze and also with house dust mite (HDM) allergen levels. We conducted a cross-sectional analysis of the childhood component of a birth cohort study. Our aim was to examine the relation between feather bedding and HDM sensitization and airway disease. A total of 498 children (84% of eligible) residing in Northern Tasmania in 1997 who were eligible for the Tasmanian Infant Health Survey at birth in 1988 or 1989 participated. Outcome measures included atopic sensitization to Dermatophagoides farinae or Dermatophagoides pteronyssinus allergens, spirometric lung function, and child respiratory symptoms using questions from the ISAAC study. HDM sensitization was strongly associated with frequent wheeze (more than 12 episodes of wheeze compared with no wheeze in the past year) (rate ratio [RR], 19.61; confidence interval [CI], 6.94–55.56) but only weakly associated with asthma ever (RR, 1.65; CI, 1.30–2.09). Feather quilt use was associated with reduced HDM sensitization (adjusted RR [ARR], 0.60; CI, 0.45–0.80) and also reduced frequent wheeze episodes over the past year (ARR, 0.24; CI, 0.07–0.86). The reduction in wheeze was more evident among HDM-sensitized children. These findings are consistent with the possible mechanisms for feather bedding of a reduction in initial HDM sensitization and an improvement in respiratory symptoms among HDM-sensitized children. However, prospective studies are required to fully exclude selection bias.

Allergen content in dust from homes and schools in northern Norway in relation to sensitization and allergy symptoms in schoolchildren

Previous studies have shown a high prevalence of atopic diseases among school children in the community of Sør-Varanger. Moreover, animal dander followed by pollen and house dust mite, were the most common allergens in skin prick tests. To assess the allergen content in homes (living-rooms and mattresses) and classrooms of children living in an arctic area at 70 degrees. The presence of allergens in homes and schools and their relationship to atopy was of particular interest. Dust samples from 38 homes and seven schools in northern Norway were collected by vacuum cleaning. The presence of allergens of dog, birch, timothy, Cladosporium herbarum, codfish and hen egg-white was investigated by radio-allergosorbent test (RAST) inhibition and the presence of major allergens of cat Felis domesticus (Fel d I) and house dust mites (HDM) Dermatophagoides pteronyssinus (Der p I) and Dermatophagoides farinae (Der f I) by enzyme-linked immunosorbent assay (ELISA). Mattresses contained significantly more dust per unit area than living-rooms and classrooms. No statistically significant differences in allergen content for dog, birch, timothy. Cladosporium, codfish and hen egg-white were seen between HDM-sensitized and non-atopic children. Most dust samples contained dog allergens with the highest allergenic activity found in living-rooms of those keeping dogs. An increased level of Fel d I was detected in only one of 38 samples from living-rooms (this family kept a cat) and in 25 of 38 samples from mattresses with ranges from 24 to 84 ng/m2. The highest concentrations were found in mattresses of children keeping cats. Increased levels (> or = 25 ng/m2) of Der p I were found only in homes and virtually only in mattresses of HDM-sensitized children. An increased level of Der f I was found in only one case, i.e. in the mattress of an HDM-sensitized child where additionally Der p I and HDMs were demonstrated microscopically. When relating Der p I to HDM-sensitization an odds ratio of more than 16 (95% CI: 1.6-394.3) was found. All extracts from living-rooms included codfish allergens. Low RAST inhibition values were detected for hen egg-white. Cladosporium, birch and timothy pollen in most samples. Furthermore, the study demonstrated that dust from schools was relatively free of allergens. Previous findings indicating that the main allergen exposure problem in this geographical area is that of pet allergens were confirmed.

Viable fungi in indoor air in homes and schools in the Sør-Varanger community during winter.

The present study investigated the content of fungal aerospores in homes and schools of house-dust-mite (HDM)-sensitized and control children in a subarctic area. During winter, airborne microfungi were collected from the homes and schools of 19 HDM-sensitized children and 19 nonatopic controls, all living in the community of Sør-Varanger, northern Norway. The samples were cultivated and microfungal growth was identified microscopically. Indoor humidity, temperature, and carbon dioxide (CO2) concentrations were measured. Housing conditions and sociodemographic and symptom data were obtained by a questionnaire. Penicillium was the most common microfungus in both homes and schools, followed by various yeasts, Aspergillus, Cladosporium, and Mucor. The number of infected homes was equal in the HDM-sensitized group and the control group, but aerospore counts were higher in the HDM-sensitized group than in the control group. The lowest aerospore counts were found in the schools. High aerospore counts also appeared to be related to high indoor humidity. The keeping of pets and damp indoor conditions were more frequent in homes of HDM-sensitized children than in the control group, whereas parental smoking and carpeting occurred with equal frequency in both groups. This indicates that no allergy sanitation measures had been undertaken, especially in the homes of the HDM-sensitized children.

House-dust mite content in mattresses in relation to residential characteristics and symptoms in atopic and nonatopic children living in northern Norway.

The occurrence of house-dust mites (HDMs) was investigated in the mattresses of 19 children previously found to be skin prick test (SPT) positive to HDM and in 19 nonatopic children derived from an extensive survey of 424 schoolchildren, all living in northern Norway. Domestic mites were counted and identified microscopically. Mite counts ranging from 10 to 1800 mites per gram mattress dust were found in 10 of the 19 HDM-sensitized children compared to none in the control group, corresponding to an odds ratio of more than 20. Of the 540 domestic mites found, 70 were identified by species. Dermatophagoides pteronyssinus (Dpt) was the only HDM species identified (64 mites), while five were storage mites and one was a Tarsonemus species. Positive radioallergosorbent tests (RAST) to Dpt were demonstrated in 9/10 children with and in 5/9 without mite infestation compared to none in the control group. Elevated IgE levels were also found more frequently in children with mite-infested mattresses than in those without. IgE levels were within normal levels in all 19 children in the control group. Latent atopy was found in four children, three with and one without mite infestation. There was no correlation between the concentration of mites and the degree of sensitization. Poor ventilation, increased humidity, and water leak(s) were associated with the presence of domestic mites in mattresses. As HDM growth is highly dependent on humidity and microhabitat, it should be possible to avoid HDM exposure and allergy in this region.

Mite allergens during 18 months of intervention

In Stockholm, Sweden, 17 children with newly diagnosed sensitization to house-dust mites (HDM) and 11 children with previously diagnosed HDM-sensitization were included in a study of HDM-allergen avoidance. Mattress dust was collected on repeated occasions during 18 months and assayed for concentration of major HDM allergens. During the first 12 months, the parents of the intervention group were instructed to intensify cleaning and airing of the child's bedroom. During the last 6 months of the study, the mattresses and pillows of seven children in the intervention group and sibling controls were encased in semipermeable polyurethane covers. The homes exhibited a high absolute indoor humidity throughout the year, and even during the winter the mean levels exceeded 7 g/kg. No mite allergen reduction was seen in the intervention group during the first year. However, among the newly diagnosed HDM-sensitized children, there was a mean reduction of the mattress mite allergen concentration of 83% (P = 0.02), and this was most pronounced in the homes with low humidity. At the end of the mattress encasement period, an average difference of 98% (P < 0.001) was found between the vacuumed amount of mite allergen on top of the covers and that underneath.

House dust mite sensitization in children and residential characteristics in a temperate region

House dust mite (Hdm) infestation used to be rare in Stockholm, but Hdm-sensitized children are now frequently observed, which probably indicates an increased infestation rate. This study was performed to elucidate determinants of Hdm sensitization in children living in the area. In a case-control study, 53 Hdm-sensitized children (cases), a group of non-Hdm-sensitized atopic children (N = 54), and a group of nonallergic neighborhood children (N = 53) were included. Mattress dust was analyzed with ELISA for content of Hdm allergens. Indoor humidity and temperature were measured, and questionnaire data were collected. Asthma was significantly more common in the Hdm-sensitized group than in the atopic control group. Hdm allergens were found in 40%, 19%, and 23% of the dust samples of the case group, atopic group, and neighborhood control groups, respectively. Only 15% of the dust samples of the Hdm-sensitized children contained Hdm allergens above the recommended threshold levels of sensitization of 2000 ng/gm of dust. Inadequate ventilation, which partly appeared to be a consequence of energy saving, appeared to be a risk factor for Hdm sensitization. This result may apply also to other temperate regions and suggests that the problem is preventable.

Sensitization of children in the Stockholm area to house dust mites.

Atopic sensitization of children in the Stockholm area to house dust mites (HDM) was investigated in a case-control study. Sixty children with and 60 without positive skin prick tests for HDM were matched for age and sex. HDM-sensitized children had previously more often lived in other areas known to be mite infested than the control children. Sensitization to mites was related to dampness in the homes, but no significant relationship was found to the type of residence, frequent visits to a summer house in the archipelago or parental smoking. Dust samples from mattresses of the children with the strongest positive reactions to mites in skin prick tests and the respective controls were subjected to an enzyme immunoassay, to measure the content of the major allergens of the Dermatophagoides (D.) species D. pterinyssinus, D. farinae and D. microceras. Mattress dust samples from the beds of HDM-sensitized children contained significantly higher HDM antigen concentrations than those from the beds of controls. Private houses contained significantly more HDM antigens than flats and 10 of 11 homes in which a dampness problem was recognized contained mite antigens. It is postulated that mite infestation is increasing in the area, energy-saving measures creating improved conditions for HDM survival.