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Pharmacology Research & Perspectives Aug 2021Asthma is a heterologous disease that is influenced by complex interactions between multiple environmental exposures, metabolism, and host immunoregulatory processes....
Asthma is a heterologous disease that is influenced by complex interactions between multiple environmental exposures, metabolism, and host immunoregulatory processes. Specific metabolites are increasingly recognized to influence respiratory inflammation. However, the role of protein-derived metabolites in regulating inflammatory responses in the lung are poorly described. The aims of the present study were to quantify polyamine levels in bronchoalveolar lavages (BALs) from healthy volunteers and asthma patients, and to evaluate the impact of each polyamine on inflammatory responses using in vitro models and in a house dust mite (HDM)-induced respiratory allergy model. Spermidine levels were decreased, while cadaverine levels were increased in BALs from asthma patients compared to healthy controls, using Ultra Performance Liquid Chromatography (UPLC). Both spermine and spermidine inhibit lipopolysaccharide (LPS)-induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) in vitro. In addition, oral gavage with spermine or spermidine modulate HDM-induced cell infiltration, cytokine secretion, and epithelial cell tight junction expression in murine models. Spermidine also reduces airway hyper-responsiveness. These results suggest that modulation of polyamine metabolism, in particular spermidine, is associated with respiratory inflammation and these molecules and pathways should be further explored as biomarkers of disease and potential targets for novel therapies.
Topics: Allergens; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cells, Cultured; Cytokines; Disease Models, Animal; Female; Humans; Leukocytes, Mononuclear; Lipopolysaccharides; Lung; Mice, Inbred C57BL; Polyamines; Pyroglyphidae; Mice
PubMed: 34289267
DOI: 10.1002/prp2.837 -
Experimental Gerontology May 2023Elderly asthmatics have higher morbidity and mortality compared with those of youngers. It has been shown that there are also some differences in clinic phenomena...
Similarities and differences in kinetic characteristics of airways inflammation, formation of inducible bronchial-associated lymphoid tissue and remodeling between young and old murine asthma surrogates induced with house dust mite.
Elderly asthmatics have higher morbidity and mortality compared with those of youngers. It has been shown that there are also some differences in clinic phenomena between young and elderly asthmatics, however, there is lack of the kinetic comparisons of the changes in the development of asthma between two populations. To better understand the specific pathophysiological manifestations in older patients with asthma, we dynamically and parallelly compared pathophysiological changes in the airways and lung tissues between young and old murine asthma surrogates based on sensitization and challenge with house dust mite (HDM). Murine models were established in young (6-8-week-old) and old (16-17-month-old) female wild-type C57BL/6 mice. Our data showed that repetitive HDM exposure induced relatively low type 2 immune responses (airway hyperresponsiveness, eosinophils recruitment, expression of type 2 cytokines, mucus secretion, serum HDM specific immunoglobulin E (IgE) and IgG) in old mice. However, the type 3 immune responses (neutrophils infiltration and IL-17A expression) were enhanced in old HDM exposed mice, which sustained longer and higher than that of young mice. Notably, the relatively weakened allergic inflammation characteristics might be associated with lower numbers of CD20 B cells and IgE cells in the iBALTs in old mice compared with those in young mice. Our data suggest that aging might compromise the ability to induce type 2 immune responses, but enhance type 3 immune responses upon repetitive HDM challenge, which might cause relevant phenomena in old experimental mice and might even be applicable to elderly patients with asthma in the clinic.
Topics: Female; Animals; Mice; Pyroglyphidae; Mice, Inbred C57BL; Asthma; Lung; Inflammation; Cytokines; Immunoglobulin E; Lymphoid Tissue; Disease Models, Animal
PubMed: 37019047
DOI: 10.1016/j.exger.2023.112160 -
Scientific Reports Jun 2019Asthma is a chronic inflammatory disorder of the airways. Disease presentation varies greatly in terms of cause, development, severity, and response to medication, and...
Asthma is a chronic inflammatory disorder of the airways. Disease presentation varies greatly in terms of cause, development, severity, and response to medication, and thus the condition has been subdivided into a number of asthma phenotypes. There is still an unmet need for the identification of phenotype-specific markers and accompanying molecular tools that facilitate the classification of asthma phenotype. To this end, we utilised a range of molecular tools to characterise a well-defined group of female adults with poorly controlled atopic asthma associated with house dust mite (HDM) allergy, relative to non-asthmatic control subjects. Circulating messenger RNA (mRNA) and microRNA (miRNA) were sequenced and quantified, and a differential expression analysis of the two RNA populations performed to determine how gene expression and regulation varied in the disease state. Further, a number of circulating proteins (IL-4, 5, 10, 13, 17 A, Eotaxin, GM-CSF, IFNy, MCP-1, TARC, TNFα, Total IgE, and Endotoxin) were quantified to determine whether the protein profiles differed significantly dependent on disease state. Finally, we utilised a previously published assessment of the circulating "blood microbiome" performed using 16S rRNA amplification and sequencing. Asthmatic subjects displayed a range of significant alterations to circulating gene expression and regulation, relative to healthy control subjects, that may influence systemic immune activity. Notably, several circulating mRNAs were detected in just the asthma group or just in the control group, and many more were observed to be expressed at significantly different levels in the asthma group compared to the control group. Proteomic analysis revealed increased levels of inflammatory proteins within the serum, and decreased levels of the bacterial endotoxin protein in the asthmatic state. Comparison of blood microbiome composition revealed a significant increase in the Firmicutes phylum with asthma that was associated with a concomitant reduction in the Proteobacteria phylum. This study provides a valuable insight into the systemic changes evident in the HDM-associated asthma, identifies a range of molecules that are present in the circulation in a condition-specific manner (with clear biomarker potential), and highlights a range of hypotheses for further study.
Topics: Adult; Allergens; Animals; Asthma; Case-Control Studies; Female; Humans; Hypersensitivity; Immunoglobulin E; Male; Middle Aged; Pyroglyphidae; RNA, Messenger
PubMed: 31221987
DOI: 10.1038/s41598-019-45257-1 -
Yonsei Medical Journal Sep 2017Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy. The aim of this study was to evaluate the prevalence and clinical...
Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy. The aim of this study was to evaluate the prevalence and clinical characteristics of LAR in Korean rhinitis patients compared to allergic rhinitis (AR) and non-allergic rhinitis (NAR). A total of 304 rhinitis patients were enrolled from November 2014 to March 2016. A skin prick test, serum total and specific immunoglobulin E, and a nasal provocation test (NPT) with house dust mite (HDM) were performed on all patients. Subjects also documented changes in rhinitis symptoms before and after NPT. Seventy-four patients with nasal hyper-reactivity and 80 patients with subclinical allergy were excluded. AR was diagnosed in 69 (46.0%) patients, NAR in 75 (50.0%) patients, and LAR to HDM in 6 (4.0%) patients. The average medication score and disease duration of each group were 14.5 points and 77.6 months in AR, 12.1 point and 51.1 months in NAR, and 17.7 point and 106.0 months in LAR, respectively. There were no significant differences in the baseline nasal symptom score of the three groups. However, after NPT with HDM, the score of rhinitis, itching, and obstructive were 4.83±1.47 vs. 1.95±2.53, 3.00±2.10 vs. 1.45±2.06, and 5.50±1.38 vs. 2.57±2.84 in LAR and NAR, respectively (p<0.05). LAR patients had longer duration of disease and tended to be older and have higher medication score than other rhinitis patients.
Topics: Adult; Animals; Female; Humans; Male; Nasal Provocation Tests; Prevalence; Pyroglyphidae; Rhinitis, Allergic; Skin Tests; Visual Analog Scale
PubMed: 28792152
DOI: 10.3349/ymj.2017.58.5.1047 -
International Archives of Allergy and... 2013
Topics: Animals; Antigens, Dermatophagoides; Complex Mixtures; Dermatophagoides farinae; Dermatophagoides pteronyssinus; Humans
PubMed: 22947696
DOI: 10.1159/000341271 -
International Archives of Allergy and... 2021Environmental exposure to mites and fungi has been proposed to critically contribute to the development of IgE-mediated asthma. A common denominator of such organisms is...
INTRODUCTION
Environmental exposure to mites and fungi has been proposed to critically contribute to the development of IgE-mediated asthma. A common denominator of such organisms is chitin. Human chitinases have been reported to be upregulated by interleukin-13 secreted in the context of Th2-type immune responses and to induce asthma. We assessed whether chitin-containing components induced chitinases in an innate immune-dependent way and whether this results in bronchial hyperresponsiveness.
MATERIALS AND METHODS
Monocyte/macrophage cell lines were stimulated with chitin-containing or bacterial components in vitro. Chitinase activity in the supernatant and the expression of the chitotriosidase gene were measured by enzyme assay and quantitative PCR, respectively. Non-sensitized mice were stimulated with chitin-containing components intranasally, and a chitinase inhibitor was administered intraperitoneally. As markers for inflammation leukocytes were counted in the bronchoalveolar lavage (BAL) fluid, and airway hyperresponsiveness was assessed via methacholine challenge.
RESULTS
We found both whole chitin-containing dust mites as well as the fungal cell wall component zymosan A but not endotoxin-induced chitinase activity and chitotriosidase gene expression in vitro. The intranasal application of zymosan A into mice led to the induction of chitinase activity in the BAL fluid and to bronchial hyperresponsiveness, which could be reduced by applying the chitinase inhibitor allosamidin.
DISCUSSION
We propose that environmental exposure to mites and fungi leads to the induction of chitinase, which in turn favors the development of bronchial hyperreactivity in an IgE-independent manner.
Topics: Allergens; Animals; Antigens, Fungal; Asthma; Biomarkers; Cell Line; Chitinases; Disease Models, Animal; Female; Lectins, C-Type; Mice; Pyroglyphidae; Respiratory Hypersensitivity; Toll-Like Receptor 2
PubMed: 33730726
DOI: 10.1159/000513296 -
Frontiers in Immunology 2021Allergen immunotherapy (AIT) can induce immune tolerance to allergens by activating multiple mechanisms, including promoting IgG4 synthesis and blunting IgE production....
BACKGROUND
Allergen immunotherapy (AIT) can induce immune tolerance to allergens by activating multiple mechanisms, including promoting IgG4 synthesis and blunting IgE production. However, the longitudinal data of sIgE and sIgG4 to allergen components during AIT are limited.
OBJECTIVE
We sought to investigate the persistence and evolution of sIgE and sIgG4 against house dust mite (HDM) components during AIT and explore their correlation with clinical responses.
METHODS
Sixty allergic rhinitis (AR) with/without asthma patients receiving AIT for HDM were enrolled in AIT group. Thirty AR patients without receiving AIT served as control group. Blood samples were collected for sIgE, sIgG4 to HDM components ( and ) assay at baseline, Month 6 and Month 18 of AIT. Combined symptom and medication scores (CSMS) were obtained accordingly.
RESULTS
In the AIT group, sIgG4 to the HDM components of and significantly increased at Month 18 compared to the baseline (36.2 U/mL 158.8 U/mL, 46.4 U/mL 94.6 U/mL, 80.5 U/mL 152.3 U/mL, 78.3 U/mL 205.1 U/mL, 42.3 U/mL 59.3 U/mL, all <0.05), sIgE to HDM components didn't see differences at baseline and at Month 18 (all >0.05).The numbers of positive HDM component sIgE and sIgG4 increased from 4.5 to 5 and 0 to 1.5 respectively (both <0.05). However, the changes of sIgE, sIgG4, sIgE/sIgG4 ratio and the numbers of positive HDM components had no correlations with the improvement of CSMS after AIT (all ρ<0.3). For the control group, the sIgE and sIgG4 did not change significantly during the observational period (all >0.05).
CONCLUSION
AIT can induce the production of sIgG4 to HDM components. However, the increased sIgG4 levels of HDM component do not correlate with the corresponding sIgE levels at baseline or with AIT response. sIgG4 to HDM components do not qualify as a biomarker to evaluate the efficacy of AIT.
Topics: Allergens; Animals; Antigens, Dermatophagoides; Dermatophagoides pteronyssinus; Desensitization, Immunologic; Humans; Immunoglobulin E; Immunoglobulin G; Pyroglyphidae; Rhinitis, Allergic
PubMed: 35197963
DOI: 10.3389/fimmu.2021.786738 -
Human Vaccines & Immunotherapeutics Dec 2022Among the potential hazards of HDM immunotherapy (AIT) with HDM allergenic extracts is the possible initiation of de novosensitizations caused by a lack of...
Among the potential hazards of HDM immunotherapy (AIT) with HDM allergenic extracts is the possible initiation of de novosensitizations caused by a lack of complementarity between a given HDM vaccine's content and a patient's molecular sensitization profile. To investigate whether immunotherapy with HDM extracts affects changes in the profile of sensitizations to allergens contained in the extract and whether neosensitizations occur. Serum samples from patients with HDM allergies (N=63) who received 1 year of treatment with subcutaneous AIT were tested for allergen-specific IgE (sIgE) reactivity to 7 microarrayed HDM allergen molecules (Der p 1, 2,10,11,23; D far 1 and 2) with ImmunoCAP. The HDM non-AIT patients (N=22) who did not receive immunotherapy constituted the study's control group. The obtained data were analysed at baseline and after 6 and 12 months. In the HDM-AIT group, no neosensitizations after 6 and 12 months of immunotherapy were reported. Conversely, in the HDM non-AIT group, only neosensitizations to Der p 10 were observed. In the study group, sIgE levels against the HDM extract of . . decreased after 12 months of AIT (< .05). SIgE levels against Der f 1, Der p 10, 11 and 23 remained unchanged in the course of 12 months of immunotherapy. In patients with allergic rhinitis with or without concomitant HDM-induced asthma treated with HDM AIT for 12 months, no neosensitizations related to the examined HDM molecules were observed.
Topics: Animals; Humans; Allergens; Antigens, Dermatophagoides; Antibody Formation; Dermatophagoides pteronyssinus; Rhinitis, Allergic; Immunotherapy; Pyroglyphidae
PubMed: 36444880
DOI: 10.1080/21645515.2022.2148815 -
The Cochrane Database of Systematic... Feb 2016Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant allergen. A high quality systematic review has not previously assessed the efficacy and safety of this treatment.
OBJECTIVES
To assess the effects of specific allergen immunotherapy (SIT), including subcutaneous, sublingual, intradermal, and oral routes, compared with placebo or a standard treatment in people with atopic eczema.
SEARCH METHODS
We searched the following databases up to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), Web of Science™ (from 2005), the Global Resource of EczemA Trials (GREAT database), and five trials databases. We searched abstracts from recent European and North American allergy meetings and checked the references of included studies and review articles for further references to relevant trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of specific allergen immunotherapy that used standardised allergen extracts in people with AE.
DATA COLLECTION AND ANALYSIS
Two authors independently undertook study selection, data extraction (including adverse effects), assessment of risk of bias, and analyses. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified 12 RCTs for inclusion in this review; the total number of participants was 733. The interventions included SIT in children and adults allergic to either house dust mite (10 trials), grass pollen, or other inhalant allergens (two trials). They were administered subcutaneously (six trials), sublingually (four trials), orally, or intradermally (two trials). Overall, the risk of bias was moderate, with high loss to follow up and lack of blinding as the main methodological concern.Our primary outcomes were 'Participant- or parent-reported global assessment of disease severity at the end of treatment'; 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'; and 'Adverse events, such as acute episodes of asthma or anaphylaxis'. SCORing Atopic Dermatitis (SCORAD) is a means of measuring the effect of atopic dermatitis by area (A); intensity (B); and subjective measures (C), such as itch and sleeplessness, which we used.For 'Participant- or parent-reported global assessment of disease severity at the end of treatment', one trial (20 participants) found improvement in 7/9 participants (78%) treated with the SIT compared with 3/11 (27%) treated with the placebo (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.02 to 7.96; P = 0.04). Another study (24 participants) found no difference: global disease severity improved in 8/13 participants (62%) treated with the SIT compared with 9/11 (81%) treated with the placebo (RR 0.75, 95% CI 0.45 to 1.26; P = 0.38). We did not perform meta-analysis because of high heterogeneity between these two studies. The quality of the evidence was low.For 'Participant- or parent-reported specific symptoms of eczema, by subjective measures', two trials (184 participants) did not find that the SIT improved SCORAD part C (mean difference (MD) -0.74, 95% CI -1.98 to 0.50) or sleep disturbance (MD -0.49, 95% CI -1.03 to 0.06) more than placebo. For SCORAD part C itch severity, these two trials (184 participants) did not find that the SIT improved itch (MD -0.24, 95% CI -1.00 to 0.52). One other non-blinded study (60 participants) found that the SIT reduced itch compared with no treatment (MD -4.20, 95% CI -3.69 to -4.71) and reduced the participants' overall symptoms (P < 0.01), but we could not pool these three studies due to high heterogeneity. The quality of the evidence was very low.Seven trials reported systemic adverse reactions: 18/282 participants (6.4%) treated with the SIT had a systemic reaction compared with 15/210 (7.1%) with no treatment (RR 0.78, 95% CI 0.41 to 1.49; the quality of the evidence was moderate). The same seven trials reported local adverse reactions: 90/280 participants (32.1%) treated with the SIT had a local reaction compared with 44/204 (21.6%) in the no treatment group (RR 1.27, 95% CI 0.89 to 1.81). As these had the same study limitations, we deemed the quality of the evidence to also be moderate.Of our secondary outcomes, there was a significant improvement in 'Investigator- or physician-rated global assessment of disease severity at the end of treatment' (six trials, 262 participants; RR 1.48, 95% CI 1.16 to 1.88). None of the studies reported our secondary outcome 'Parent- or participant-rated eczema severity assessed using a published scale', but two studies (n = 184), which have been mentioned above, used SCORAD part C, which we included as our primary outcome 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'.Our findings were generally inconclusive because of the small number of studies. We were unable to determine by subgroup analyses a particular type of allergen or a particular age or level of disease severity where allergen immunotherapy was more successful. We were also unable to determine whether sublingual immunotherapy was associated with more local adverse reactions compared with subcutaneous immunotherapy.
AUTHORS' CONCLUSIONS
Overall, the quality of the evidence was low. The low quality was mainly due to the differing results between studies, lack of blinding in some studies, and relatively few studies reporting participant-centred outcome measures. We found limited evidence that SIT may be an effective treatment for people with AE. The treatments used in these trials were not associated with an increased risk of local or systemic reactions. Future studies should use high quality allergen formulations with a proven track record in other allergic conditions and should include participant-reported outcome measures.
Topics: Adult; Allergens; Animals; Child; Dermatitis, Atopic; Dermatophagoides farinae; Dermatophagoides pteronyssinus; Desensitization, Immunologic; Humans; Randomized Controlled Trials as Topic
PubMed: 26871981
DOI: 10.1002/14651858.CD008774.pub2 -
Medicine Jan 2022Sublingual immunotherapy (SLIT) has been increasingly used instead of subcutaneous immunotherapy. SLIT was initially approved for use among adults; however, it has...
Sublingual immunotherapy (SLIT) has been increasingly used instead of subcutaneous immunotherapy. SLIT was initially approved for use among adults; however, it has become more widely accepted for children. Few studies have evaluated the effectiveness of SLIT in the treatment of dust mite allergies among children, including adverse effects. This study aimed to investigate the effectiveness of SLIT in children with dust mite allergies, as well as its adverse effects, at a pediatric general outpatient clinic.I analyzed the data of 181 patients aged 4 to 12 years who tested positive for mite antigen-specific immunoglobulin E, exhibited nasal and/or eye symptoms, and received Miticure. Symptoms were evaluated using the Japanese rhino-conjunctivitis quality of life (QOL) questionnaire no. 1. Wilcoxon tests were used to compare the pretreatment and post-treatment symptom scores. Adverse events were tallied, and Kaplan-Meier curves and Wilcoxon tests were used to assess the proportion of dropouts.The mean QOL score at the baseline was 2.17 (standard deviation [SD] 1.45). After 1 week, the mean symptom QOL score was 1.63 (SD 1.32); the lowest mean score was found in week 41 (0.48, SD 0.63). A significant decline in the occurrence of all symptoms, including sneezing, nasal discharge, nasal congestion, itchy eyes, and teary eyes, was observed. Adverse effects were observed in 76 (42.0%) patients; the most common adverse effect was itchy mouth.SLIT improves symptoms with minimal adverse effects in pediatric patients.
Topics: Administration, Sublingual; Animals; Antigens, Dermatophagoides; Child; Child, Preschool; Desensitization, Immunologic; Drug-Related Side Effects and Adverse Reactions; Dust; Female; Humans; Hypersensitivity; Immunoglobulin E; Male; Pruritus; Pyroglyphidae; Rhinitis, Allergic; Sublingual Immunotherapy; Treatment Outcome
PubMed: 35089222
DOI: 10.1097/MD.0000000000028690