Dermatophagoides pteronyssinus proteins and their role in the diagnostics and management of house dust mite allergy: exploring allergenic components.

Component-resolved diagnostics enables the detection of allergen-specific immunoglobulins E (asIgE) to house dust mite (HDM) proteins, which may help clinicians to face the difficulties in diagnostics of HDM allergy. Currently, almost 40 proteins of Dermatophagoides species, that are able to bind asIgE, have been identified, and this number will certainly increase. The association between sensitisation to particular molecules and allergy symptoms is extensively studied. This investigation enables us to identify HDM molecules that promote respiratory, skin, or food allergies, and it could help us predict the possible course of allergic diseases. The individual repertoire of asIgE improves our understanding of immunological response, which underlies allergy symptoms, and helps to form individual therapeutic regimens. This review provides clinicians with information on Dermatophagoides pteronyssinus proteins available in commercial arrays, and their role in the diagnostics and management of HDM allergy.

[LONGITUDINAL EVALUATION OF EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN PEDIATRIC PERENNIAL ALLERGIC RHINITIS USING LABORATORY EXAMINATIONS AND IN VIVO BIOMARKERS].

OBJECTIVE: The purpose of this study was to evaluate the efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) on pediatric perennial allergic rhinitis (AR) based on longitudinal assessment of nasal symptoms, laboratory examination, and in vivo biomarkers. METHOD: The subjects included 40 children with perennial AR who had SLIT with HDM for 2 years. Nasal symptoms, medications, skin prick tests, nasal provocation tests, and peripheral blood tests were evaluated before, 6 months, one year and two years after the onset of SLIT. RESULTS: Total nasal symptom scores, prick test wheal diameter, and peripheral blood eosinophil count decreased in 6 months. Total nasal symptom scores continued to decrease from 6 months to 2 years. Symptom-medication scores and nasal provocation test responses decreased in 1 year. Symptom-medication scores continued to decline from 1 to 2 years. Medication scores and nasal eosinophilia decreased in 2 years. Serum specific IgE to HDM slightly increased transiently and decreased in 2 years. The severity of symptoms and specific IgE to HDM at the baseline, and changes of symptoms and specific IgE to HDM during the first six months and first one year of SLIT were correlated with improvement in symptom scores over two years of SLUT. TNSS at baseline was correlated with that at second year. CONCLUSION: Longitudinal assessment of symptoms, allergen specific IgE, and in vivo biomarkers showed the effectiveness of SLIT. Symptom scores and allergen specific IgE may also be early predictive factors of SLIT efficacy in children with AR.

The impact of adverse reactions on adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy in Japan.

BACKGROUND: Allergen immunotherapy is the only treatment that can achieve remission for allergic diseases. AIMS/OBJECTIVES: To investigate the three-year adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy at a clinic in Japan and identify factors that influence adherence and severe adverse reactions. MATERIAL AND METHODS: In total, 174 patients aged 12 years or older who started sublingual immunotherapy for Japanese cedar pollinosis (n = 72), house dust mite allergy (n = 55), or both (n = 47) between May 2017 and June 2018. Patient age, sex, type of pharmacotherapy used, adverse reactions, blood test results, and duration of continuous treatment were investigated. RESULTS: The three-year treatment continuation rate was 40.8%. Adverse reaction rates were 12.6% for cedar pollinosis and 40.2% for house dust mite allergy. Patients with dose reductions due to severe reactions had lower first-year continuation rates. In the MITICURE® group, patients with severe reactions had significantly higher serum total IgE levels. Severe reactions were more common in MITICURE® patients with seven or more positive antigen types. CONCLUSIONS AND SIGNIFICANCE: Severe adverse reactions reduced early adherence.

Polybrominated diphenyl ethers in paired dust-breast milk samples: Levels, predictors of contamination, and health risk assessment for infants and mothers.

An integrated study on the levels of 7 polybrominated diphenyl ethers (PBDEs) in house dust and breast milk samples from women (N = 30) living in these households was conducted. ∑PBDEs ranged from

Rapid induction of allergen-blocking IgG in dogs vaccinated with plant-based, Der f 2-expressing bioparticles.

BACKGROUND: Allergen-carrying virus-like particles are effective and safe means of allergen immunotherapy (AIT) in rodent models. OBJECTIVE: To study the development of allergen-blocking immunoglobulin (Ig)G in dogs injected with Der f 2-carrying enveloped plant-based bioparticles (eBPs). MATERIALS AND METHODS: Laboratory beagle dogs were injected intradermally (ID) or subcutaneously (SC) with Der f 2-eBP three times at 2-week intervals. A basophil mediator release assay was used to compare the reactivity of Der f 2-eBPs to that of recombinant Der f 2. Allergen-specific IgG serum levels were determined by immunoblotting and ELISA. The allergen-blocking potential of postvaccination IgG was assessed by Pet Allergy Xplorer (PAX) macroarray and basophil mediator release inhibition assays. RESULTS: The amount of Der f 2 eBPs needed to induce basophil activation was 1000-fold higher than that of the soluble natural allergen. In both immunisation groups, eBP injections caused no adverse events and induced Der f 2-specific IgG, first detected on Day (D)14 and peaking on D41. The co-incubation of sera with a Der f 2-IgE-rich canine serum pool resulted in a mean PAX inhibition of 70% (ID) to 80% (SC) on D41. For both groups, the inhibition of basophil mediator release reached 75% on D28 and D41. The percentage inhibition of PAX and mediator release correlated significantly with Der f 2 IgG levels. CONCLUSION AND CLINICAL RELEVANCE: Intradermal and subcutaneous injections of Der f 2-eBPs were safe and increased Der f 2-specific IgG. The clinical benefit of immunotherapy will be evaluated in future trials enrolling atopic dogs allergic to house dust mites.

The storage mite Tyrophagus putrescentiae induces greater lung inflammation than house dust mites in mice.

Exposure to storage mite (SM) and house dust mite (HDM) allergens is a risk factor for sensitization and asthma development; however, the related immune responses and their pathology have not been fully investigated. The HDMs Dermatophagoides farinae and Dermatophagoides pteronyssinus and SM Tyrophagus putrescentiae are potent allergens that induce asthma. Most SM-related studies have focused on the allergic reactions of individuals by measuring their immunoglobulin (Ig)E expression. Considering the limited research on this topic, the present study aims to investigate the differences in the immune responses induced by HDMs and SMs and histologically analyze lung tissues in a mouse asthma model to understand the differential effects of HDM and SM. The results revealed that all mite species induced airway inflammation. Mice challenged with T. putrescentiae had the highest airway resistance and total cell, eosinophil, and neutrophil counts in the bronchoalveolar lavage fluid (BALF). The SM-sensitized groups showed more severe lesions and mucus hypersecretions than the HDM-sensitized groups. Although the degree of HDM and SM exposure was the same, the damage to the respiratory lung tissue was more severe in SM-exposed mice, which resulted in excessive mucin secretion and increased fibrosis. Furthermore, these findings suggest that SM sensitization induces a more significant hypersensitivity response in mucosal immunity than HDM sensitization in asthma models.

Trichohyalin gene expression is negatively correlated with the severity of dermatitis in a canine atopic dermatitis model.

Introduction: Canine atopic dermatitis (AD) closely mimics human AD and is recognized as a beneficial animal model. House dust mites (HDM) are a common allergen for both species. The effects of chronic exposure to HDM on the skin have not been studied in this animal model, and it is not known how changes in gene expression correlate to the severity of dermatitis. Methods: We used an established canine model of AD and took biopsies before HDM exposure (D0) and five times during repeated allergen challenges (on Days 1, 2, 8, 15, and 29, hereafter referred to as D1, D2, D8, D15, and D29). The severity of dermatitis was scored on the same days. Results: Trichohyalin (TCHH) gene expression decreased the most (15-fold decrease on D29 vs. D0) and negatively correlated with the severity of dermatitis. Gap-junction protein gene expression increased over 3-fold on D1, D8, and D29 and positively correlated with the severity of dermatitis. Compared to D0, IL-31 gene expression significantly increased on D8 (p = 0.0098), D15 (p = 0.0068), and D29 (p = 0.0187), but the correlation with the severity of dermatitis did not reach significance. Discussion: This is the first report on trichohyalin, a protein belonging to the S100 family, and gap-junction protein gene expression in the context of the clinical severity of AD. We propose that these proteins should be further investigated to better understand their role in this complex disease.

Augmented type 2 inflammatory response in allergic rhinitis patients experiencing systemic reactions to house dust mite subcutaneous immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. METHODS: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. RESULTS: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 µg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). CONCLUSION: The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.

The evidence for commercial house dust mite immunotherapy products: A pragmatic systematic review with narrative synthesis.

House dust mite (HDM) allergen immunotherapy (AIT) has an established role in the treatment of perennial allergic rhinitis (AR) and allergic asthma (AA) triggered by HDM sensitization. We aimed to identify all double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AR and AA in humans and to summarize the evidence for AIT products that are currently manufactured and available for clinical use. A total of 56 eligible double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AA and/or AR in humans fit the inclusion criteria and investigated a total of 14 commercial AIT products; together, the 56 studies enrolled a total of 14,619 patients. Of the 56 studies, 39 studies investigated the current manufacturer-recommended maintenance dose (MRMD) of the product, and 17 investigated other doses. We identified 39 studies (12,539 patients randomized) for 8 sublingual immunotherapy (SLIT) products and 17 studies (2,080 patients randomized) for subcutaneous immunotherapy products. For AR, 3 products, the ALK 12 standardized-quality (SQ-HDM) SLIT tablet, the ALK 6 SQ-HDM tablet, and the SG 300 index of reactivity SLIT tablet, had both dose-finding studies (DFSs) and phase III definitive studies (DSs) to demonstrate efficacy of the MRMD of the product. For AA, 2 products, the ALK 12 SQ-HDM SLIT tablet and the ALK 6 SQ-HDM tablet, had both DFSs and DSs for the MRMD. No subcutaneous immunotherapy product had a paired DFS and DS supporting the MRMD. A total of 30 studies of products no longer commercially manufactured were excluded. This study will help to inform clinical care and product selection for the treatment of HDM-induced AR and AA.

Recent prevalence of allergic rhinitis caused by house dust mites among the pediatric population in Fukui, Japan.

Background: Allergic rhinitis (AR) is an IgE-mediated type I allergic chronic nasal disease common among all age groups, including the pediatric population. House dust mites (HDMs) are globally ubiquitous and the most important indoor aeroallergen. However, the recent prevalence of HDM-caused AR (AR-HDM) in Japan remains unknown, especially after the COVID-19 pandemic. Objective: The objective of this study was to investigate the current prevalence of AR-HDM, its clinical features, and the current status of medical examinations in elementary school students. Methods: A survey of 41,000 elementary school students was conducted during July 2021 in Fukui Prefecture, Japan. Parents were asked to complete a questionnaire that examined allergic disease history and clinical background. Results: A total of 17,974 subjects were analyzed in the study. The results showed that the current prevalence of AR-HDM in elementary school children is 18.8%. We found that AR-HDM had already developed before entrance into elementary school in 68.3% of affected subjects. Among these subjects, 82.3% had received some form of treatment, such as prescription medications, whereas 4.2% were treated by allergen immunotherapy. Multiple logistic regression analysis of the onset of AR-HDM revealed that male sex, being the first-born child, comorbidity of bronchial asthma, atopic dermatitis, food allergy, and allergic conjunctivitis are associated with development of AR-HDM. Conclusions: The present study revealed the prevalence of AR-HDM in elementary school children. The results emphasize the importance of appropriate diagnosis and treatment from infancy through early childhood.

Assessment of air quality in the Philadelphia, Pennsylvania subway.

BACKGROUND: Subways are popular and efficient modes of transportation in cities. However, people are exposed to high levels of particulate matter (PM) in subways. Subway air quality in the United States has been investigated in a few cities, but data is lacking on simultaneous measurement of several pollutants, especially ultrafine particles (UFP) and black carbon (BC), in combination with different size fractions of PM. OBJECTIVES: The goals of this study are to assess air quality in a belowground subway and compare it with outdoor ambient levels, to examine temporal variability of PM in the subway, and to analyze the correlation between PM and BC. METHODS: Particulate matter of varying sizes (PM1, PM2.5, PM10), UFP, and BC were measured using DustTrak, nanoparticle detector, and micro aethalometer, respectively. Measurements were made at the belowground subway platform and the aboveground street level at 15th Street subway station in Philadelphia during summer 2022. RESULTS: Belowground mean PM1, PM2.5, and PM10 were 112.2 ± 61.3 µg/m3, 120 ± 65.5 µg/m3, and 182.1 ± 132 µg/m3, respectively, which were 5.4, 5.7, and 7.6 times higher than the respective aboveground street levels. The UFP lung deposited surface area (LDSA) (59.4 ± 36.2 µm2/cm3) and BC (9.5 ± 5.4 µg/m3) belowground were 1.7 times and 10.7 times higher than the aboveground. The pollutant concentration varied from day-to-day on both the locations. A higher positive correlation was found between the belowground BC and PM2.5 (r = 0.51, p < 0.05) compared to the aboveground (r = 0.16, p < 0.05). IMPACT: This study showed high levels of particulate matter exposure at a belowground subway station in Philadelphia. Particulate matter levels were about 5 to 8 times higher at belowground subway station than the corresponding aboveground street level. Higher levels were also observed for UFP lung deposited surface area (LDSA), while black carbon levels showed the highest concentration at the belowground level by a factor of ten compared to the aboveground level. The study shows the need for air quality management at belowground subways to reduce particulate matter exposure for the commuters.

Itaconate suppresses house dust mite-induced allergic airways disease and Th2 cell differentiation.

Itaconate was initially identified as an antimicrobial compound produced by myeloid cells. Beyond its antimicrobial role, itaconate may also serve as a crucial metabolic and immune modulator. We therefore examined the roles of aconitate decarboxylase 1 (Acod1) and itaconate in house dust mite (HDM)-sensitized and -challenged mice, a model of T helper 2 (Th2)-driven allergic airways disease. HDM treatment induced lung Acod1 mRNA expression and bronchoalveolar lavage (BAL) itaconate levels in wild-type C57BL/6 mice. Acod1 knockout mice (Acod1-KO) with negligible BAL itaconate showed heightened HDM-induced type 2 cytokine expression, increased serum IgE, and enhanced recruitment of Th2 cells in the lung, indicating a shift towards a more pronounced Th2 immune response. Acod1-KO mice also showed increased eosinophilic airway inflammation and hyperresponsiveness. Experiments in chimeric mice demonstrated that bone marrow from Acod1-KO mice is sufficient to increase type 2 cytokine expression in wild-type mice, and that restitution of bone marrow from wild type mice attenuates mRNA expression of Th2 cytokines in Acod1-KO mice. Specific deletion of Acod1 in lysozyme-secreting macrophages (LysM-cre+Acod1flox/flox) recapitulated the exaggerated phenotype observed in whole-body Acod1-KO mice. Adoptive transfer of Acod1-KO bone marrow-derived macrophages also increased lung mRNA expression of Th2 cytokines. In addition, treatment of Th2-polarized CD4 cells with itaconate impeded Th2 cell differentiation, as shown by reduced expression of Gata3 and decreased release of IL-5 and IL-13. Finally, public datasets of human samples show lower Acod1 expression in subjects with allergic asthma, consistent with a protective role of itaconate in asthma pathogenesis. Together, these data suggest that itaconate plays a protective, immunomodulatory role in limiting airway type 2 inflammation after allergen challenge by attenuating T cell responses.

The Impact of High-Fructose Diet and Co-Sensitization to House Dust Mites and Ragweed Pollen on the Modulation of Airway Reactivity and Serum Biomarkers in Rats.

The topic of ragweed pollen (RW) versus house dust mites (HDMs) has often been deliberated, but the increasing incidence of co-sensitization between them has been scarcely addressed. Utilizing Sprague Dawley rats, we explored the effects of co-sensitization with the combination of HDMs and RW pollen extracts in correlation with high-fructose diet (HFrD) by in vitro tracheal reactivity analysis in isolated organ bath and biological explorations. Our findings unveiled interrelated connections between allergic asthma, dyslipidemia, and HFrD-induced obesity, shedding light on their compounding role through inflammation. The increased CRP values and airway hyperresponsiveness to the methacholine challenge suggest a synergistic effect of obesity on amplifying the existing inflammation induced by asthma. One of the major outcomes is that the co-sensitization to HDMs and RW pollen led to the development of a severe allergic asthma phenotype in rats, especially in those with HFrD. Therefore, the co-sensitization to these allergens as well as the HFrD may play a crucial role in the modulation of systemic inflammation, obesity, and airway reactivity.

Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients.

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA- memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA- T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.

Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma.

BACKGROUND: Calprotectin, a calcium-binding protein, plays a crucial role in inflammation and has been associated with various inflammatory diseases, including asthma. However, its regulation and impact on steroid hyporesponsiveness, especially in severe asthma, remain poorly understood. METHODS: This study investigated the regulation of calprotectin proteins (S100A8 and S100A9) by IL-17 and its role in steroid hyporesponsiveness using in vitro and in vivo models. Calprotectin expression was assessed in primary bronchial fibroblasts from healthy controls and severe asthmatic patients, as well as in mouse models of steroid hyporesponsive lung inflammation induced by house dust mite (HDM) allergen and cyclic-di-GMP (cdiGMP) adjuvant. The effects of IL-17A stimulation on calprotectin expression and steroid response markers in bronchial epithelial and fibroblast cells were examined. Additionally, the therapeutic potential of paquinimod, a calprotectin inhibitor, in mitigating airway inflammation and restoring steroid response signatures in the mouse model was evaluated. RESULTS: The results demonstrated upregulation of calprotectin expression in asthmatic bronchial fibroblasts compared to healthy controls, as well as in refractory asthma samples compared to non-refractory asthma. IL-17 stimulation induced calprotectin expression and dysregulated glucocorticoid response signatures in lung epithelial and fibroblast cells. Treatment with paquinimod reversed IL-17-induced dysregulation of steroid signatures, indicating the involvement of calprotectin in this process. In the HDM/cdiGMP mouse model, paquinimod significantly attenuated airway inflammation and hyperresponsiveness, and restored steroid response signatures, whereas dexamethasone showed limited efficacy. Mechanistically, paquinimod inhibited MAPK/ERK and NF-κB pathways downstream of calprotectin, leading to reduced lung inflammation. CONCLUSION: These findings highlight calprotectin as a potential therapeutic target regulated by IL-17 in steroid hyporesponsive asthma. Targeting calprotectin may offer a promising approach to alleviate airway inflammation and restore steroid responsiveness in severe asthma. Further investigations are warranted to explore its therapeutic potential in clinical settings and elucidate its broader implications in steroid mechanisms of action.

Biological Sex Is an Effect Modifier of Allergen-Mediated Alteration of the Lung Proteome.

Asthma exhibits a distinct sex bias in the disease prevalence, severity, and response to therapy. However, sex-related differences in alterations of the lung proteome mediated by aeroallergens critical in asthma, such as house dust mites (HDM), remain unknown. In this study, we define sex-related differences in the lung proteome using an HDM-challenged mouse model by 1D LC-MS/MS. Sex-disaggregated data analysis showed that 406 proteins were uniquely altered in females, 273 proteins were uniquely altered in males, and 414 proteins were altered in both females and males in response to HDM. In a linear mixed model analysis, sex modified the HDM exposure effect for 163 proteins, i.e., a significant sex:exposure interaction was identified in 84 proteins in females and 35 proteins in males. Of these, 12 proteins showed a significant sex effect in both female and male lungs. We further selected 3 proteins Tjp1, Lamtor1, and G3BP2 for independent confirmation studies. Our findings detail the sex-specific lung proteome in response to an aeroallergen critical in asthma and demonstrate that sex is a significant effect modifier of HDM response. These results will serve as a valuable resource for delineating sex-specific mechanisms in aeroallergen-driven responses in asthma research.

High Serum Allergen-Specific IgE of House Dust Mite in Predicting the Risk of Comorbidity in Children with Allergic Conjunctivitis.

Purpose: To investigate the patterns of allergens in allergic conjunctivitis (AC) and the association with allergic comorbidity. Methods: This retrospective cross-sectional study enrolled 2972 children with AC. Clinical data, including sex, age, allergic comorbidities (allergic asthma, allergic rhinitis, and atopic dermatitis), and serum allergen-specific immunoglobulin E (sIgE), were collected from the electronic medical record (EMR). The categorical variables were compared with the chi-square test. The characteristics of allergens in children of different ages and comorbidities were analyzed by trend chi-square. The sensitivity level of HDM associated with AC and comorbidities was assessed by odds ratios (ORs) with 95% confidence intervals of logistic regression analysis. Results: A total of 2972 children (2015 boys and 957 girls) with AC were included in the study. The mean age was 3.78 (0.5~12) years. The most common allergen was house dust mite(HDM) (43.41%). With age, the positive rate for inhaled allergens gradually increased, and the positive rate for ingested allergens decreased. With the number of comorbidities increasing, the positive rates of sensitization were 38.33%, 74.51%, 80.72%, and 89.05%, and the incidence of polysensitization was 44.66%, 56.48%, 59.54%, and 74.59%, respectively. With the increase of HDM-sIgE level, the number of comorbidities and the risk increased gradually. Conclusion: HDM is the most common allergen in AC children of different ages. High levels of HDM-sIgE may be a predictor for allergic comorbidities. Children with polysensitization and high levels of HDM sIgE will be an important target population for future intervention in other allergy-related disease prevention.

Monensin Suppresses Multiple Features of House Dust Mite-Induced Experimental Asthma in Mice.

Despite intense efforts to develop efficient therapeutic regimes for asthma, there is a large demand for novel treatment strategies in this disease. Here we evaluated the impact of monensin, a drug with potent anti-mast cell effects, in a mouse model of asthma. Allergic airway inflammation was induced by sensitization of mice with house dust mite (HDM) antigen, and effects of monensin on airway hyperreactivity and inflammatory parameters were studied. Following intraperitoneal administration, monensin did not suppress airway hyperreactivity but was shown to have anti-inflammatory properties, as manifested by reduced eosinophil- and lymphocyte infiltration into the airway lumen, and by suppressed inflammation of the lung tissue. After intranasal instillation, monensin exhibited similar anti-inflammatory effects as seen after intraperitoneal administration. Moreover, intranasally administered monensin was demonstrated to suppress goblet cell hyperplasia, and to cause a reduction in the expression of genes coding for key inflammatory markers. Further, monensin blocked mast cell degranulation in the airways of allergen-sensitized mice. Together, this study reveals that monensin has the capacity to suppress key pathological events associated with allergic airway inflammation.

Association between house dust endotoxin and kidney injury: findings from the national health and nutrition examination survey (NHANES) 2005-2006.

BACKGROUND: House dust endotoxin is thought to be associated with systemic inflammatory responses and respiratory diseases. Previous studies have indicated that lung injury and systemic inflammation could lead to kidney damage. However, the potential link between house dust endotoxin and the increased risk of kidney injury remains unexplored. OBJECTIVES: This cross-sectional study and retrospective study aim to investigate the relationship between house dust endotoxin levels and renal markers, specifically the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), utilizing data from the NHANES 2005-2006 survey cycle. RESULTS: Proteinuria was assessed using the UACR, with values categorized into negative (UACR ≤ 30 mg/g) and positive (UACR > 30 mg/g) groups. Significant differences in house dust endotoxin levels were observed between these groups (p value = 0.003). Weighted logistic regression analysis indicated that higher levels of house dust endotoxin were associated with an increased rate of positive UACR (OR [95% CI]: 1.57 [1.20, 2.05]; p value = 0.003). This association remained significant after adjusting for covariates such as age, gender, race, poverty income ratio (PIR), Type 2 Diabetes Mellitus (T2DM), and hypertension (OR [95% CI]: 1.46 [1.08, 1.97]; p-Value = 0.021). However, no significant correlation was found between house dust endotoxin levels and eGFR (Estimate [95% CI]: 1.19 [-1.28, 3.66]; p value = 0.32). CONCLUSIONS: Our findings suggest a significant association between house dust endotoxin levels and proteinuria, based on data from the NHANES 2005-2006 survey cycle. This association indicates that elevated levels of house dust endotoxin may be linked to kidney damage. Further research is necessary to elucidate the specific relationship between exposure to house dust endotoxin and the risk of developing kidney disease.