Indoor Allergen Levels and Household Distributions in Nine Cities Across China

Objective Chinese allergic subjects have high levels of sensitization to house dust mite （HDM） and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samples were collected from nine cities. Major allergens Der p 1 and Der f I from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.Results HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from 〈0.006 to 9.2 μg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.Conclusion HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.

House dust mite allergens and nitrated products: Identification and risk assessment in indoor dust

Air pollutants can potentially lead to nitration of allergic proteins,thus promoting sensitization of these allergens.However,little is currently known about the nitration status of house dust mite(HDM)allergens.We identified the occurrence of nitrated products of two major HDM allergens Der f 1 and Der p 1 in dust samples collected from college dormitories in eastern China and assessed their associated health risk.The results showed that both non-nitrated and nitrated forms of the two allergens were detected in the dust in the range of non-detected(ND)-10.6,1.44-15.4,ND-22.4,ND-7.28μg/g for non-nitrated Der f 1,nitrated Der f 1,non-nitrated Der p 1 and nitrated Der p 1,respectively.The median rates of nitration were determined as 74.0%for Der f 1 and 20.4% for Der p 1 at consideration of one nitration site.Further analysis reveals that the levels of HDM allergens and their nitrated products were found to be generally higher during winter,in dormitories of lower altitude and with female occupants.Furthermore,the calculated risk indexes were at considerably high levels.Our findings suggest that nitrated HDM allergens have already accumulated in the environment at such significant levels and their associated health risk calls for our immediate attention.

Do the microorganisms from laboratory culture spent growth medium affect house dust mite fitness and microbiome composition?

The interaction of house dust mites(HDM)and microorganisms is the key factor in the survival of these mites in human-made environments.Spent growth medium(SPGM)provides the rest of the dict,along with dead mite bodies and microorganisms.SPGM represents a source of microorganisms for the recolonization of mite food and the mite digestive tract.An experiment was performed to observe how adding SPGM to the HDM diet affects HDM population growth,the microbiome composition and the microbial respiration in microcosms.We analyzed American house dust mite(Dermatophagoides farinae)and European house dust mite(Dermatophagoides pleronyssinus)originating from control diets and diets treated with an extract of SPGM from 1-and 3-month-old mite cultures.The microbiome was described using 16S and 18S barcode sequencing.The composition of the bacterial and fiungal microbiomes differed between the HDM species,but the SPGM treatment influenced only the bacterial profile of D.farinae.In the D.farinae microbiome of specimens on SPGM-treated dicts compared to those of the control situation,the Lactobacillus profile decreased,while the Candinium,Staphylococ-cus,Acinetobacter,and Sphingomonas profiles increased.The addition of SPGM extract decreased the microbial respiration in the microcosms with and without mites in almost all cascs.Adding SPGM did not influence the population growth of D.farinae,but it had a variable effect on D.pteronyssimus.The results indicated that the HDM are marginally influenced by the microorganisms in their feces.

Effect of house dust mite immunotherapy on interleukin-10-secreting regulatory T cells in asthmatic children

Background Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response.Interleukin-10 （IL-10） plays a crucial role in inducing allergen-specific tolerance.However the reports of the changes of IL-10 in house dust mite （HDM）-specific immunotherapy were varied.The aim of this study was to evaluate the function of IL-10-secreting regulatory T cells in asthma children successfully treated with HDM immunotherapy.Methods Peripheral blood mononuclear cells （PBMCs） were isolated from 27 patients following 1.5--2 years of HDM-specific immunotherapy （SIT, SIT group） and from 27 matched treated asthmatic children allergic to HDM （asthmagroup）.After 48 hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T cells were measured by four colour flow cytometry.Sera were tested for allergen-specific IgG4 and IgE using the Immuno CAP 100 assay.Results PBMCs from children undergoing immunotherapy following HDM extracts stimuli produced significantly more IL-10 compared with the asthma group.The frequency of iTreg cells and aTreg cells increased in SIT group after HDM stimulation, while it was not affected in the asthma group.Among the iTreg cells and aTreg cells, the frequency of CD4＋CD25-Foxp3-IL-10＋ Treg cells increased the most which was 2 times higher than that in unstimulated cultures in SIT group.The levels of HDM-specific IgG4 of SIT group was significiently higher compared with asthma group, but there was no correlation of the levels of HDM-specific IgG4 and IL-10 secreting Treg cells.Conclusions HDM-specific immunotherapy can successfully upregulate the frequency of IL-10-secreting Treg cells.CD4＋CD25-Foxp3-IL-10＋ Treg cells may play a key role in inducing the immune tolerance in HDM-specific immunotherapy.

Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation

The cysteine protease caspase-1(Casp-1)contributes to innate immunity through the assembly of NLRP3,NLRC4,AIM2,and NLRP6 inflammasomes.Here we ask whether caspase-1 activation plays a regulatory role in house dust mite(HDM)-induced experimental allergic airway inflammation.We report enhanced airway inflammation in caspase-1-deficient mice exposed toHDMwith a marked eosinophil recruitment,increased expression of IL-4,IL-5,IL-13,aswell as full-length and bioactive IL-33.Furthermore,mice deficient for NLRP3 failed to control eosinophil influx in the airways and displayed augmented Th2 cytokine and chemokine levels,suggesting that the NLPR3 inflammasome complex controls HDM-induced inflammation.IL-33 neutralization by administration of soluble ST2 receptor inhibited the enhanced allergic inflammation,while administration of recombinant IL-33 during challenge phase enhanced allergic inflammation in caspase-1-deficient mice.Therefore,we show that caspase-1,NLRP3,and ASC,but not NLRC4,contribute to the upregulation of allergic lung inflammation.Moreover,we cannot exclude an effect of caspase-11,because caspase-1-deficient mice are deficient for both caspases.Mechanistically,absence of caspase-1 is associated with increased expression of IL-33,uric acid,and spleen tyrosine kinase(Syk)production.This study highlights acritical role of caspase-1 activation andNLPR3/ASCinflammasomecomplex in the down-modulation of IL-33 in vivo and in vitro,thereby regulating Th2 response in HDM-induced allergic lung inflammation.

FGF2 is overexpressed in asthma and promotes airway in airway epithelial cells

Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.

Prevalence of sensitivity to cockroach allergens and IgE crossreactivity between cockroach and house dust mite allergens in Chinese patients with allergic rhinitis and asthma

Background Cockroaches are an important indoor allergen source causing allergic rhinitis and asthma. The aim of this study was to investigate the cockroach prevalence in mainland of China and the cross-reactivity of IgE between cockroach and house dust mite allergen in Chinese patients.Methods The cockroach sensitization pattern was based on a skin prick test （SPT） obtained from a national multicenter prevalence study, in which 6304 patients from 25 allergy centers across China participated. Factors, including different regions of China, age, gender and the correlations between the American and German cockroaches and house dust mite Der p were investigated. Eighteen out of 1236 clinical sera from south China were selected to perform the cross-inhibition assay between house dust mites and cockroaches.Results Totally 25.7% of patients were SPT positive to the American cockroach （Periplaneta Americana, Per a） and 18.7% SPT positive to the German cockroach （Blattella germanica, Bla g）. The prevalence of positive cockroach SPT was higher in southern than in northern China, higher in adults than in children, and higher in males than in females.Patients had relatively low levels of cockroach SPT reactions, mainly class 1 or 2. Of the SPT positive cockroach patients,88% were also SPT positive to house dust mite （Dermatophagoides pteronyssinus, Der p）. An IgE cross-inhibition study confirmed that Der P sensitization could cause false positive SPT reactions against cockroach.Conclusions A relatively high prevalence of cockroach sensitivity was found in mainland of China. However, a cross-inhibition study showed that only a small number of patients appear to have Bla g and/or Per a as primary sensitizing source. The importance of cockroaches as a risk factor for sensitization and triggers of allergic symptoms in mainland of China needs to be further investigated.

Allergic rhinitis facts from an Irish pediatric population

Objective:Assessing the main allergens in the pediatric population from the largest urban area in the country.Methods:Clinical letters of patients referred with possible allergic rhinitis(AR)were retrospectively reviewed over the past 5 years.Results:Five hundred and fifty‐five patients were included.Males suffer twice as often with AR than females and have high titers of allergens.House dust mites(44.7%)and grass pollen(29%)were the main allergens in our area,with 48%of patients sensitized to both allergens.Half of the patients had the diagnosis of AR confirmed with positive allergen‐specific tests.For the other half,the diagnosis was based on a clinical assessment performed by a pediatric otolaryngologist.Conclusions:Half of suspected AR children have environmental allergen sensitivity confirmed by testing,and a large number had a clinical diagnosis of AR after an otolaryngology consultation.Our findings can help clinicians to initiate AR treatment considering the most problematic allergens in the area.

Suppression of Immunotherapy on Group 2 Innate Lymphoid Cells in Allergic Rhinitis

Background： Group 2 innate lymphoid cells （ILC2s） are regarded as a novel population of lineage-negative cells that induce innate Type 2 responses by producing the critical Th2-type cytokines interleukin （IL）-5 and IL-13. ILC2s as key players in the development of allergic rhinitis （AR） have been proved, however, the effect of subcutaneous immunotherapy （SCIT） with dermatophagoides pteronyssinus extract （Der p-SCIT） on ILC2s in AR patients is not clear. This study aimed to investigate the response of ILC2s of peripheral blood in house dust mites （HDM）-sensitized Chinese patients with AR who received SCIT with Der P extract. Methods： Seven healthy controls without symptoms of AR who had negative reactions to any of the allergens from skin-prick testing, nine patients diagnosed with persistent AR according to the Allergic Rhinitis and its Impact on Asthma （ARIA） guidelines, and 24 AR patients who received Der p-SCIT for 1.0-3.5 years were recruited for the study. ILC2s in the peripheral blood were evaluated using flow cytometry. The severity of their symptoms of all participants was rated based on the Total 5 symptom score. Results： Among 40 participants, 9 AR patients were assigned to the untreated group, 24 AR patients receiving Der p-SCIT were assigned to the immunotherapy group, and 7 healthy controls without symptoms of AR were assigned to healthy control group. The mean Total 5 symptom score of immunotherapy group was significantly lower than that of untreated group （4.3 ± 1.4 vs. 10.1 ± 2.5, P 〈 0.001 ）. Similarly, the levels of ILC2s in the peripheral blood ofimmunotherapy group were significantly reduced compared with that in untreated group （P 〈 0.001 ）, but were not significantly different from healthy controls （P = 0.775）. Further subgroup analysis based on the duration of SCIT therapy （ 1.0-2.0 years [SCIT1-2], 2.0-3.0 years [SCIT2_3], and 3.0-3.5 years [SCIT3_3.5]） showed that the percentage of ILC2s was not significantly different between SCIT1-2, SCIT2-3, and SCIT3-3.5 groups （SCIT1-2 vs. SCIT2-3： P = 0.268; SCIT1-2, vs. SCIT3-3.5： P = 0.635; and SCIT, 3 vs. SCIT3-3.5： P = 0.787）. Conclusions： The present study highlighted the suppression ofDer p-SCIT on ILC2s in HDM-AR patients. ILC2s identified in peripheral blood can be used as an effective biomarker for Der p-SCIT.