Effect Of House Dust Mite Research Articles

Impact of Aeroallergen Sensitization on Chronic Rhinosinusitis.

This study investigated the impact of aeroallergens on the development and progression of chronic rhinosinusitis (CRS), with a focus on the specific associations between aeroallergens and CRS according to allergen type, number, and extent of sensitization. The medical records of 256 CRS patients were retrospectively analyzed. All were divided into nonallergic, house dust mite (HDM)-allergic, pollen-allergic, and double allergic groups via specific immunoglobulin E (IgE) testing. Clinical characteristics, computed tomography (CT) scores, olfactory functions, and demographic data were compared. Correlation analysis was performed to explore the relationships between the extent of allergen sensitization and CRS severity. Binary logistic regression analysis was used to identify risk factors for hyposmia and anosmia. The allergic group exhibited higher total CT scores than the nonallergic group (P = 0.001). Sensitivity to HDM or pollen allergens alone was not significantly associated with increased CRS severity. No significant differences were observed between the effects of HDM and pollen allergens on CRS severity. However, the double allergic group exhibited significantly higher CT scores (P < 0.001, < 0.001, and 0.003) than the other groups. Although the prevalence rates of anosmia and hyposmia were notably higher in the double allergic group, the difference was not statistically significant. The maximum specific IgE levels to HDM and pollen allergens positively correlated with the CT scores (P = 0.001 and 0.001, respectively). Allergen sensitization, particularly to multiple common allergens, contributed to CRS severity. CRS patients sensitized to both HDM and pollen allergens tended to experience the diminished olfactory function. These findings underscore the importance of considering the allergen sensitization pattern when assessing CRS severity and its potential progression.

Effect of house dust mite allergen on sleep parameters and sleep quality.

The role of nasal problems such as allergic rhinitis in the development of obstructive sleep apnea (OSA) is controversial. The purpose of this study was to analyze the effects of house dust mite (HDM) allergen on sleep-related problems. In a retrospective study patients were classified according to the house dust mite (HDM)-related specific immunoglobulin E (IgE) level into a low HDM-IgE group (group A) and a high HDM-IgE group (group B). Polysomnographic indices, OSA severity, and self-administered questionnaire results were compared between groups. Correlational analysis was used to identify associations between specific IgE values and sleep parameters related to respiratory events. A total of 327 patients were enrolled.N1 stage ratio, apnea index, and apnea-hypopnea index were significantly higher in group B (P = 0.010, 0.003, and 0.002 respectively) than in group A. N2 stage ratio, and lowest and mean oxygen saturation were significantly lower in group B (P = 0.001, 0.001, and < 0.001 respectively). After propensity score matching, the apnea index and lowest and mean oxygen saturation remained significantly different (P = 0.005, 0.005, and 0.001 respectively). Patients in group B were more likely to have severe OSA and worse subjective sleep quality. In correlational analysis, lowest and mean oxygen saturation were significantly negatively correlated with specific IgE values. A high HDM-specific IgE level was associated with the occurrence of respiratory events and oxygen desaturation during sleep, and with the presence of severe OSA, as well as poorer subjective sleep quality.

House dust mite-derived allergens effect on matrix metalloproteases in airway epithelial cells

Aim of the Study: Many allergens have protease activities. Although the immunomodulatory effects of these antigens are well known, the effects attributed to their protease activities are not thoroughly investigated. We set out to determine the effects of house dust mite (HDM) allergens with varying protease activities on bronchial epithelial cell functions. Materials and methods: BEAS-2B cells were maintained in ALI-culture and stimulated with Der p1 (cysteine protease), Der p6 (serine protease), and Der p2 (non-protease) with and without specific protease inhibitors or heat denaturation. Cell viability and epithelial permeability were measured with MTT and paracellular flux assay, respectively. The effect of heat denaturation on allergen structure was examined using in silico models. Matrix metalloproteinases (MMPs) were investigated at the transcription (qPCR), protein (ELISA), and functional (zymography) levels. Results: Epithelial permeability increased only after Der p6 but not after Der p1 or Der p2 stimulation. Der p2 increased both MMP-2 and MMP-9 expression, while Der p1 increased only MMP-9 expression. The heat-denatured form of Der p1 unexpectedly increased MMP-9 gene expression, which, through the use of in silico models, was attributed to its ability to change receptor connections by the formation of new electrostatic and hydrogen bonds. IL-8 and GM-CSF production were increased after Der p1 and Der p2 but decreased after Der p6 stimulation. IL-6 decreased after Der p1 but increased following stimulation with Der p6 and heat-denatured Der p2. Conclusion: Allergens in house dust mites are capable of inducing various changes in the epithelial cell functions by virtue of their protease activities.

Long-term efficacy of house dust mite subcutaneous immunotherapy in allergic rhinitis patients

Objective:This study was aimed to compare the long-term effects of house dust mite (HDM) subcutaneous immunotherapy (SCIT) in a cohort of Chinese pediatric and adult patients with allergic rhinitis (AR).Method:Total of 48 AR patients received standardized HDM-SCIT for 3 years, and they received 3 years of standardized dust mite-specific subcutaneous immunotherapy, followed by 2 years after treatment. Prior to treatment (baseline) and at the end of the 3-year and 5-year treatment periods, all patients were evaluated for total nasal symptom scores(TNSS),total combined score (TCS;symptoms(nasal+ocular)+daily medication score),and rhinoconjunctivitis quality of life questionnaire(RQLQ).Safety of HDM-SCIT was assessed according to adverse events reported.Result:Fifteen pediatric and 33 adult AR patients completed the study.HDM-SCIT significantly improved symptoms and RQLQ scores at the 3 rd year and 5th year in both children and adults. Superior efficacy was observed at the 3-year and 5-year timepoints in children compared to adults. The safety of HDM-SCIT was comparable in children and adults with AR.Conclusion:A 3-year course of HDM-SCIT is an effective, safe and sustainable long-term treatment in both pediatric patients and adults with AR, although children appear to achieve better long-term efficacy compared to the adults.

IL-1\u03b2 mediates lung neutrophilia and IL-33 expression in a mouse model of viral-induced asthma exacerbation

BackgroundViral-induced asthma exacerbations, which exhibit both Th1-type neutrophilia and Th2-type inflammation, associate with secretion of Interleukin (IL)-1β. IL-1β induces neutrophilic inflammation. It may also increase Th2-type cytokine expression. We hypothesised that IL-1β is causally involved in both Th1 and Th2 features of asthma exacerbations. This hypothesis is tested in our mouse model of viral stimulus-induced asthma exacerbation.MethodWild-type (WT) and IL-1β deficient (IL-1β−/−) mice received house dust mite (HDM) or saline intranasally during three weeks followed by intranasal dsRNA (PolyI:C molecule known for its rhinovirus infection mimic) for three consecutive days to provoke exacerbation. Bronchoalveolar lavage fluid was analysed for inflammatory cells and total protein. Lung tissues were stained for neutrophilic inflammation and IL-33. Tissue homogenates were analysed for mRNA expression of Muc5ac, CXCL1/KC, TNF-α, CCL5, IL-25, TSLP, IL-33, IL-1β, CCL11 and CCL2 using RT-qPCR.ResultsExpression of IL-1β, neutrophil chemoattractants, CXCL1 and CCL5, the Th2-upstream cytokine IL-33, and Muc5ac were induced at exacerbation in WT mice and were significantly inhibited in IL-1β−/− mice at exacerbation. Effects of HDM alone were not reduced in IL-1β-deficient mice.ConclusionWithout being involved in the baseline HDM-induced allergic asthma, IL-1β signalling was required to induce neutrophil chemotactic factors, IL-33, and Muc5ac expression at viral stimulus-induced exacerbation. We suggest that IL-1β has a role both in neutrophilic and Th2 inflammation at viral-induced asthma exacerbations.

Effect of house dust mite on neutrophil apoptosis by cytokine secretion in lymphocytes

Although extract of Dermatophagoides farinae (DF) alone had no effect on neutrophil apoptosis, it inhibited neutrophil apoptosis in neutrophils cocultured with lymphocytes in both normal and allergic subjects. DF showed a stronger inhibition on the apoptosis of allergic neutrophils cocultured with allergic lymphocytes than that of normal neutrophils cocultured with normal lymphocytes. DF induced the secretion of IL-6, IL-8, MCP-1, and GM-CSF of the normal and allergic lymphocytes. The cytokine secretion due to DF in allergic lymphocytes is higher than in normal lymphocytes. The cytokine secretion of normal and allergic lymphocytes induced by DF was suppressed by PAR2i, a PAR2 inhibitor, LY294002, a PI3K inhibitor, AKTi, an Akt inhibitor, PD98059, an ER K inhibitor, and BAY-11-7085, an NF-κB inhibitor. Phosphorylation of ERK induced by DF was suppressed by PAR2i, LY294002 and AKTi, and NF-κB activity due to DF was inhibited by PAR2i, LY294002, AKTi, and PD98059.

The crucial role of IL-22 and its receptor in thymus and activation regulated chemokine production and T-cell migration by house dust mite extract.

House dust mite (HDM) is known as one of the factors that causes atopic dermatitis (AD). Interleukin (IL)-22 and thymus and activation regulated chemokine (TARC) are related to skin inflammatory disease and highly expressed in AD lesions. However, the effects of HDM on IL-22 production in T cells and on TARC production and IL-22Rα receptor expression in keratinocytes are unknown. To identify the role of HDM in keratinocytes and T cells, we investigated IL-22Rα expression and TARC production in the human keratinocyte cell line HaCaT and IL-22 production in T cells treated with HDM extract as well as their roles in HDM-induced skin inflammation. HDM extract not only increased IL-22Rα expression and TARC production in HaCaT but also enhanced IL-22, tumor necrosis factor (TNF)-α and interferon (IFN)-γ production in T cells. The HDM extract-induced IL-22 from T cells significantly increased the production of IL-1α, IL-6 and TARC in HaCaT cells. In addition, we found that TARC produced in HDM extract-treated HaCaT induced T-cell recruitment. These results suggest that there is a direct involvement of HDM extract-induced IL-22 in TARC production and T-cell migration. Taken together, TARC production in HaCaT through the interaction between IL-22 and IL-22Rα facilitates T-cell migration. These data show one of the reasons for inflammation in the skin lesions of AD patients.

Anti-apoptotic Effects of House Dust Mite, S100A8 and S100A9 on Spontaneous Apoptosis of Neutrophils in Coculture with Immune Cells and in the Presence of T Helper Cytokines

House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-γ), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-β). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

Different anti-apoptotic effects of house dust mite allergen on eosinophil apoptosis between atopic and non-atopic asthmatic subjects

House dust mite is a major allergen in allergic diseases such as asthma. In this study, we investigated the effects of house dust mite on constitutive eosinophil apoptosis in normal and asthmatic subjects. We classified asthmatic subjects into those with atopic and non-atopic asthma depending on the presence of DP-specific IgE or/and DF-specific IgE in serum. Both blood and bronchoalveolar lavage fluid (BALF) eosinophils in atopic asthma were elevated when compared with normal and non-atopic eosinophils. Dermatophagoides pteronissinus extract (DP) inhibited constitutive eosinophil apoptosis of atopic asthmatic subjects, but not that of normal and non-atopic subjects. DF had no effect on eosinophil apoptosis in normal and asthmatic subjects. The anti-apoptotic effects of DP were not altered by E64, a cysteine protease inhibitor, or aprotinin, a serine protease inhibitor, and Der p1 and Der p 2 had no effect on eosinphil apoptosis of normal and asthmatic patients, including atopic and not-atopic patients. Anti-apoptotic signaling mediated by DP in atopic asthma was associated with the TLR4/PI3K/Akt/ERK/NF-κB pathway. Activation of procaspase 3 and procaspase 9 was delayed by DP stimulation. Our results indicate that DP induces eosinophilic inflammation by inhibiting eosinophil apoptosis, and that the inhibitory effect is associated with exposure of asthma subjects to DP. A better understanding of the difference between atopic and non-atopic asthma will help elucidate the pathogenesis and develop methods for treatment of asthma.

Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: A randomized, double-blind, placebo-controlled trial

Investigations meeting current standards are limited for the effect of house dust mite (HDM) allergy immunotherapy in asthmatic patients. This trial investigated the efficacy and safety of a standardized quality (SQ; allergen standardization method proprietary to the trial sponsor) HDM SLIT-tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease. This publication reports the results of the endpoints related to asthma. Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were randomized 1:1:1:1 to double-blind daily treatment with one of 3 active doses (1, 3, or 6 SQ-HDM) or placebo. Their use of inhaled corticosteroid (ICS) was standardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control. The primary end point was a reduction in ICS dose from the individual subject's baseline dose after 1 year of treatment. The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg (P = .004). Relative mean and median reductions were 42% and 50% for 6 SQ-HDM and 15% and 25% for placebo, respectively. No statistically significant differences were observed for the other assessed asthma parameters, reflecting the intended controlled status of the trial subjects. The most common adverse events were local reactions in the mouth. The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo. Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control. All active doses were well tolerated.

Gene‐by‐environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

House dust mite extract downregulates C/EBP in asthmatic bronchial smooth muscle cells

Reduced translation of CEBPA mRNA has been associated with increased proliferation of bronchial smooth muscle (BSM) cells of asthma patients. Here, we assessed the effect of house dust mite (HDM) extracts on the cell proliferation ([(3)H]-thymidine incorporation), inflammation (interleukin (IL)-6 release) and upstream translation regulatory proteins of CCAAT/enhancer-binding protein (C/EBP)α in human BSM cells of healthy controls and asthmatic patients. HDM extract significantly increased IL-6 protein and proliferation of BSM cells of asthma patients only. HDM extract reduced the C/EBPα expression in BSM cells of asthma patients, which coincided with significantly increased levels of calreticulin (CRT) protein, an inhibitor of CEBPA mRNA translation. HDM extract elicited both protease-dependent and -independent responses, which were mediated via protease-activated receptor (PAR)2 and CRT, respectively. In conclusion, HDM extract reduced CEBPA mRNA translation, specifically in asthmatic BSM cells, and 1) upregulated CRT, 2) activated PAR2, and increased 3) IL-6 expression and 4) the proliferation of asthmatic BSM cells. Hence, HDM exposure contributes to inflammation and remodelling by a nonimmune cell-mediated mechanism via a direct interaction with BSM cells. These findings may potentially explain several pathological features of this disease, in particular BSM cell hyperplasia.

The Effect of Dust-Mites on Nitric Oxide Production

Aim: We aimed to investigate the effect of house dust mite on the level of nitric oxide in patients who had dust mite in their houses and suffering from rhinitis and/or asthma and/or eczema-like allergic symptoms and were positive for skin tests (Prick). Materials and Methods: The effect of dust-mites on nitric oxide concentration was investigated using Griess method in patients who had allergic symptoms and were positive for skin tests. Results: The plasma nitric oxide level was found to be statistically higher in patients who had dust mite in their houses and suffering from allergic symptoms and were positive for skin tests than in patients who did not have dust mite in their houses but were positive for skin tests or negative for skin tests. In addition, there was no statistical difference in the level of nitric oxide between the patients who did not have dust mite in their houses but were positive for skin tests and the patients who did not have dust mite in their houses and were negative for skin tests. Conclusions: There seems to be an effect of house dust mite on the level of nitric oxide. However, the molecular mechanism underneath of this effect is not yet clear. A plausible explanation for this might be the intrinsic radical properties of nitric oxide and its protective effect against the parasitic agents.

Comparison of expression profiles induced by dust mite in airway epithelia reveals a common pathway

Airway epithelial cells have shown to be active participants in the defense against pathogens by producing signaling and other regulatory molecules in response to the encounter. In previous manuscripts, we have studied the effect of house dust mite (HDM) extract on both an epithelial cell-line (H292) and primary nasal epithelial cell. When we compare these responses we conclude that the H292 cells more closely resemble nasal epithelium of healthy controls (share 107 probe-sets) than of allergic individuals (share 17 probe-sets). Interestingly, probably because of an absent intraindividual variation between samples, more probe-sets (8280) change expression significantly in H292 than in either healthy (555) or allergic (401) epithelium. A direct comparison of all the responses in these epithelial cells reveals a core-response to HDM of just 29 genes. These genes (CCL20, IL-8, CXCL2, CXCL1, IL-1B, AREG, TNFAIP3, HBEGF, PTGS2, BMP2, LDLR, PLAUR, PLAU, NFKB2, NFKB1, JUN, ATF3, EGR1, NPC1, TICAM1, EPHA2, CTGF, DUSP1, SPRY1, TLR-3, complement factor C3, IVNS1ABP, SerpinB3, and PSAT1) have described links with allergy or inflammation and may even describe the well-established relationship between viral infections and allergic exacerbations or allergy development.

Effect of House Dust Mite (HDM) Avoidance Measure on The Clinical Symptoms in Dogs with Atopic Dermatitis (AD)

RATIONALE: Majority of dogs with atopic dermatitis (AD) are known to be spontaneously sensitive to house dust mite (HDM) allergen. Canine AD can be utilized as an animal model for human AD. We examined effect of HDM avoidance measure on the clinical symptoms in 6 dogs with AD. METHODS: Six dogs that suffered from AD and were sensitive to HDM allergen were enrolled. Clinical diagnosis with AD was based on Willemse's criteria. All of the 6 dogs were shown to be sensitive to HDM allergen by measurement of antigen-specific serum IgE or intradermal skin test. HDM avoidance measure was performed by withdrawing conventional bedding and introducing HDM-free bedding in the owner's houses. The clinical symptoms of the dogs were quantitatively evaluated by recording pruritus score, skin lesion index, and medication score before, during, and after the HDM avoidance measure for 6 months. RESULTS: Before the trial, Der 1 levels were 0.55∼35.0 μg/g of fine dust (mean 1.6 μg/g) in the bedding and 0.25∼8.8 μg/g (mean 1.8 μg/g) on the floor. After the trial, they decreased to 0.02∼0.37 μg/g (mean 0.1 μg/g) in the bedding and 0.04∼0.92 μg/g (0.3 μg/g) on the floor. Scores of the clinical symptoms of AD clearly decreased in 4 of the 6 dogs with AD after the trial. Serum HDM-specific IgE levels in 3 dogs examined also markedly decreased after the trial. CONCLUSIONS: Decreasing the amount of Der 1 in the house may have an efficacy to control the clinical symptom in dogs with AD.

Effect of house dust mite on serum complement activation and total haemolytic activity in vitro in normal subjects and in patients with bronchial asthma.

House dust mite (Dermatophagoides farinae) has been shown to activate the complement system in vitro by both the classical and alternative pathways in normal serum and in two groups of (skin test positive and skin test negative) patients with bronchial asthma. The activation was dose dependent in the lower range of allergen concentrations. Skin test positive asthmatic subjects showed the maximum activation. Skin test negative patients had activation between skin test positive patients and normal subjects. However, at the higher allergen concentration normal serum and bronchial asthma patients showed similar results.