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Inflammation Feb 2024Cigarette smoke (CS) facilitates adverse effects on the airway inflammation and treatment of asthma. Here, we investigated the mechanisms by which CS exacerbates asthma....
Cigarette smoke (CS) facilitates adverse effects on the airway inflammation and treatment of asthma. Here, we investigated the mechanisms by which CS exacerbates asthma. The roles of IL-33 and IL-35 in asthma development were examined by treatment with IL-33 knockout (IL-33 KO) or transfection of adenovirus encoding IL-35 (Ad-IL-35) in a murine model of cigarette smoke-exposure asthma. Furthermore, the involvement of IL-33 and IL-35 in regulating DCs and Th2/Th17 cells was examined in a coculture system of DCs with CD4 T cells. Additionally, we observed the effect of CpG-ODNs on the balance of IL-33 and IL-35. We show that CS and house dust mite (HDM) exposure induced IL-33 and suppressed IL-35 levels in cigarette smoke-exposure asthma in vivo and in vitro. Treatment with IL-33 KO or Ad-IL-35 significantly attenuated airway hyperreactivity, goblet hyperplasia, airway remodelling, and eosinophil and neutrophil infiltration in the lung tissues from asthmatic mice. Furthermore, we demonstrated reciprocal regulation between CS and HDM-modulated IL-33 and IL-35. Mechanistically, IL-33 KO (or anti-ST2) and Ad-IL-35 attenuated Th2- and Th17-associated inflammation by downregulating TSLP-DC signalling. Finally, administration of CpG-ODNs suppressed the expression of IL-33/ST2 and elevated the levels of IL-35, which is mainly derived from CD4Foxp Tregs, to alleviate Th2- and Th17-associated inflammation by inhibiting the activation of BMDCs. Taken together, the IL-33/ST2 pathway drives the DC-Th2 and Th17 responses of cigarette smoke-exposure asthma, while IL-35 has the opposite effect. CpG-ODNs represent a potential therapeutic strategy for modulating the balance of IL-33 and IL-35 to suppress allergic airway inflammation.
Topics: Animals; Mice; Pyroglyphidae; Interleukin-1 Receptor-Like 1 Protein; Th17 Cells; Interleukin-33; Cigarette Smoking; Cytokines; Asthma; Th2 Cells; Inflammation; Disease Models, Animal; Mice, Inbred BALB C
PubMed: 37737467
DOI: 10.1007/s10753-023-01902-6 -
The Journal of Allergy and Clinical... Jan 2024There is no consensus method to identify anaphylaxis in sublingual immunotherapy (SLIT) trials. Standardized Medical Dictionary for Regulatory Activities (MedDRA)...
BACKGROUND
There is no consensus method to identify anaphylaxis in sublingual immunotherapy (SLIT) trials. Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (SMQs) are standardized groupings of MedDRA terms used in drug safety monitoring.
OBJECTIVE
To develop a method to identify potential anaphylaxis in SLIT-tablet trials using SMQ searches and case definitions of anaphylaxis adopted from the National Institute of Allergy and Infectious Disease.
METHODS
The SMQ search tool contained 2 criteria including treatment-emergent adverse events (AEs): (1) narrow MedDRA terms related to anaphylaxis and (2) all AEs with broad MedDRA terms from at least 2 of 3 categories (respiratory/skin/cardiovascular) occurring on the same day. Criteria were applied to a pooled data set of all subjects from 48 timothy grass, ragweed, house dust mite, and tree SLIT-tablet trials (SLIT-tablet, N = 8200; placebo, N = 7033). Additional search strategies were any treatment-emergent AE with MedDRA preferred term "hypersensitivity" and epinephrine administrations. Identified potential cases underwent blinded independent medical expert review. Nonanaphylaxis cases were designated local AEs or mild to moderate systemic reactions.
RESULTS
Using the SMQ search tool and after subsequent medical review, 8 anaphylaxis cases were identified; 3 were considered treatment-related, resulting in a proportion of anaphylaxis cases/subject of 0.02% (2 of 8200) with SLIT-tablet and 0.01% (1 of 7033) with placebo. One additional anaphylaxis case related to SLIT-tablet was identified by the preferred term "hypersensitivity." The 3 anaphylaxis cases associated with SLIT-tablet treatment were not life-threatening. The epinephrine administration rate was 17 of 8200 (0.2%) with SLIT-tablet treatment and 2 of 7033 (0.03%) with placebo.
CONCLUSIONS
SMQ search criteria for identifying potential anaphylaxis related to SLIT were developed. Anaphylaxis was rare for SLIT-tablets.
Topics: Animals; Humans; Anaphylaxis; Sublingual Immunotherapy; Pyroglyphidae; Epinephrine; Tablets; Allergens; Rhinitis, Allergic; Treatment Outcome
PubMed: 37972922
DOI: 10.1016/j.jaip.2023.11.011 -
Otolaryngology--head and Neck Surgery :... Mar 2024To evaluate the efficacy and safety of dust mite subcutaneous immunotherapy (SCIT) in monosensitized and polysensitized children with allergic rhinitis (AR).
OBJECTIVE
To evaluate the efficacy and safety of dust mite subcutaneous immunotherapy (SCIT) in monosensitized and polysensitized children with allergic rhinitis (AR).
STUDY DESIGN
Prospective cohort study.
SETTING
Tertiary referral center.
METHODS
One hundred thirty children were enrolled and categorized into 2 groups: monosensitized to only dust mites and polysensitized to at least 1 additional allergen beyond dust mites. All patients received SCIT targeting dust mites for 3 years, followed by a 5-year monitoring period. The Total Nasal Symptom Score (TNSS), Symptom and Medication Score (SMS), Visual Analogue Scale (VAS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were assessed before SCIT (T0); at 1 (T1) and 2 (T2) years of SCIT; immediately after SCIT (T3); and 2 years post-SCIT (T5). Safety was assessed based on adverse events (AEs).
RESULTS
Fifty-one monosensitized and 50 polysensitized children completed the study. At T3, 47 monosensitized and 46 polysensitized children were effectively treated, with no significant between-group difference in efficacy (P > .05). The TNSS, SMS, VAS scores, and RQLQ score were significantly lower at T1, T2, T3, and T5 than at T0 in both groups (P < .05). The differences in the TNSS, SMS, VAS score, and RQLQ score between the 2 groups were nonsignificant at T0, T1, T2, and T3 (P > .05), but significant at T5 (P < .05). No serious AEs were reported.
CONCLUSION
Monosensitized and polysensitized children exhibited similar beneficial efficacy and safety after 3 years of dust mite SCIT. Monosensitized children derived more benefits 2 years after discontinuation.
Topics: Child; Animals; Humans; Prospective Studies; Quality of Life; Sublingual Immunotherapy; Treatment Outcome; Antigens, Dermatophagoides; Rhinitis, Allergic; Allergens; Pyroglyphidae; Immunotherapy; Dust
PubMed: 38104318
DOI: 10.1002/ohn.614 -
Allergy and Asthma Proceedings Jan 2024Most patients with allergic rhinitis/conjunctivitis (AR/C) are sensitized to more than one allergen. An ongoing question is the efficacy of single-allergen... (Randomized Controlled Trial)
Randomized Controlled Trial
Most patients with allergic rhinitis/conjunctivitis (AR/C) are sensitized to more than one allergen. An ongoing question is the efficacy of single-allergen immunotherapy in patients who are polysensitized. To evaluate the efficacy and safety of grass, ragweed, tree, and house-dust mite (HDM) sublingual immunotherapy (SLIT) tablets in adults with AR/C who are mono- or polysensitized. Data from adults (ages ≥ 18 years) with AR/C who participated in phase III double-blind, placebo controlled field trials (four grass, two ragweed, two HDM, one tree) were included in the analyses. Efficacy was assessed by the total combined score (TCS) (sum of AR/C daily symptom and medication scores) during the entire pollen season for grass and tree trials, and peak pollen season for ragweed trials versus placebo. Efficacy for the HDM SLIT-tablet was assessed by the total combined rhinitis score (TCRS) (sum of rhinitis daily symptom and medication scores) during the last 8 weeks of treatment versus placebo. For the grass SLIT-tablet, TCS improved by 20% (mean difference 1.33 [95% confidence interval {CI}, 0.44-2.22]) in the subjects who were monosensitized (n = 442) and 20% (mean difference 1.28 [95% CI, 0.90-1.67]) in the subjects who were polysensitized (n = 1857). For the ragweed SLIT-tablet, TCS improved by 19% (mean difference 1.72 [95% CI, -0.20 to 3.63]) in the subjects who were monosensitized (n = 115) and 27% (mean difference 2.27 [95% CI, 1.28-3.27]) in the subjects who were polysensitized (n = 528). For the tree SLIT-tablet, TCS improved by 54% (mean difference 4.65 [95% CI, 2.48-6.82]) in the subjects who were monosensitized (n = 138) and 34% (mean difference 2.51 [95% CI, 1.34-3.69]) in the subjects who were polysensitized (n = 437). For the HDM SLIT-tablet, TCRS improved by 20% (mean difference 1.24 [95% CI, 0.48-1.99]) in the subjects who were monosensitized (n = 468) and 17% (mean difference 0.85 [95% CI, 0.43-1.28]) in the subjects who were polysensitized (n = 1294). The overall safety profile was not qualitatively different between the subjects who were monosensitized and the subjects who were polysensitized. Grass, ragweed, tree, or HDM SLIT-tablet treatment is effective for the specific allergen in question in adults with AR/C and who are monosensitized or polysensitized. Targeting one relevant allergen with SLIT-tablets induces a clinical effect for that allergen in patients who were polysensitized.
Topics: Adult; Animals; Humans; Allergens; Ambrosia; Conjunctivitis; Conjunctivitis, Allergic; Dermatophagoides pteronyssinus; Poaceae; Pyroglyphidae; Rhinitis, Allergic; Sublingual Immunotherapy; Tablets; Treatment Outcome; Double-Blind Method
PubMed: 38151733
DOI: 10.2500/aap.2024.45.230068 -
Annals of Allergy, Asthma & Immunology... Mar 2024A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary.
OBJECTIVE
To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR).
METHODS
A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed.
RESULTS
The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed.
CONCLUSION
The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach.
TRIAL REGISTRATION
https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.
Topics: Animals; Humans; Quality of Life; Pyroglyphidae; Sublingual Immunotherapy; Treatment Outcome; Antigens, Dermatophagoides; Rhinitis, Allergic; Allergens; Rhinitis, Allergic, Perennial; Double-Blind Method; Conjunctivitis; Immunoglobulin G
PubMed: 37913839
DOI: 10.1016/j.anai.2023.10.029 -
American Journal of Rhinology & Allergy Jul 2024Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD). (Review)
Review
BACKGROUND
Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD).
OBJECTIVE
To review the relationship between inhalant allergens and AD.
METHODS
A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens.
RESULTS
Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization.
CONCLUSION
There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern.
Topics: Humans; Dermatitis, Atopic; Allergens; Animals; Pyroglyphidae; Bronchial Provocation Tests; Inhalation Exposure
PubMed: 38623643
DOI: 10.1177/19458924241246855 -
Allergology International : Official... Jul 2023The relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider...
BACKGROUND
The relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider vitamin D and allergen exposure. This study aimed to determine the associations between the season of birth, house dust mite (HDM) and Japanese cedar pollen (JCP) sensitization, and allergic rhinitis and pollinosis, while taking vitamin D levels and allergen exposure into account.
METHODS
This study included 4323 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. A logistic regression model was used to analyze the association between the season of birth and sensitization to JCP or HDM (judged by specific immunoglobulin E) at age 2 and allergic rhinitis or pollinosis at age 3, adjusted for HDM or JCP exposure and vitamin D levels with potential confounders.
RESULTS
Participants born in spring or summer were more likely to have pollinosis than were those born in winter (adjusted odds ratio [aOR]: 2.08, 95% confidence interval [CI]: 1.13-3.82 for spring; aOR: 1.89, 95% CI: 1.03-3.47 for summer). Participants born in summer were more likely to have HDM sensitization than were those born in winter (Der p 1, aOR: 1.53, 95% CI: 1.10-2.15; Der f 1, aOR: 1.44, 95% CI: 1.03-2.01). Exposure to JCP and HDM were associated with pollinosis and HDM sensitization, respectively.
CONCLUSIONS
Spring and summer births were associated with the development of pollinosis, and summer birth was associated with HDM sensitization, even when vitamin D and allergen exposure were considered. Further studies on mechanisms other than vitamin D and allergen exposure are required.
Topics: Female; Animals; Humans; Child; Child, Preschool; Rhinitis, Allergic, Seasonal; Pollen; Vitamin D; Cohort Studies; Japan; Seasons; Cryptomeria; Allergens; Pyroglyphidae; Dermatophagoides pteronyssinus; Vitamins; Rhinitis, Allergic
PubMed: 36725444
DOI: 10.1016/j.alit.2023.01.003 -
Veterinary Dermatology Feb 2024Canine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic... (Review)
Review
BACKGROUND
Canine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic sensitisation.
OBJECTIVE
This review summarises the current evidence on the role of genetic and environmental factors and allergic sensitisation in the pathogenesis of cAD since the last review by ICADA in 2015.
MATERIALS AND METHODS
Online citation databases and proceedings from international meetings on genetic factors, environmental factors and allergens relevant to cAD that had been published between 2015 and 2022 were reviewed.
RESULTS
Despite intensive research efforts, the detailed genetic background predisposing to cAD and the effect of a wide range of environmental factors still need more clarification. Genome-wide association studies and investigations on genetic biomarkers, such as microRNAs, have provided some new information. Environmental factors appear to play a major role. Lifestyle, especially during puppyhood, appears to have an important impact on the developing immune system. Factors such as growing up in a rural environment, large size of family, contact with other animals, and a nonprocessed meat-based diet may reduce the risk for subsequent development of cAD. It appears that Toxocara canis infection may have a protective effect against Dermatophagoides farinae-induced cAD. House dust mites (D. farinae and D. pteronyssinus) remain the most common allergen group to which atopic dogs react. Currently, the major allergens related to D. farinae in dogs include Der f 2, Der f 15, Der f 18 and Zen 1.
CONCLUSIONS AND CLINICAL RELEVANCE
Canine atopic dermatitis remains a complex, genetically heterogeneous disease that is influenced by multiple environmental factors. Further, well-designed studies are necessary to shed more light on the role of genetics, environmental factors and major allergens in the pathogenesis of cAD.
Topics: Dogs; Animals; Allergens; Dermatitis, Atopic; Genome-Wide Association Study; Dog Diseases; Pyroglyphidae; Dermatophagoides pteronyssinus; Antigens, Dermatophagoides
PubMed: 37840229
DOI: 10.1111/vde.13210 -
ACS Nano Aug 2023It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP...
It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP inhalation exposure have been less explored. We tested the effect of CuO NP aerosols on immune responses in healthy, house dust mite (HDM) asthmatic, or allergen immunotherapy (AIT)-treated asthmatic mice (BALB/c, females). The AIT consisted of a vaccine comprising HDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatment involved mice being immunized (via subcutaneous (sc) injection; 2 doses) while concomitantly being exposed to CuO NP aerosols (over a 2 week period), starting on the day of the first vaccination. Mice were then sensitized twice by sc injection and subsequently challenged with HDM extract 10 times by intranasal instillation. The asthmatic model followed the same timeline except that no immunizations were administered. All mice were necropsied 24 h after the end of the HDM challenge. CuO NP-exposed healthy mice showed a significant decrease in T1 and T2 cells, and an elevation in T-bet Treg cells, even 40 days after the last exposure to CuO NPs. Similarly, the CuO NP-exposed HDM asthma model demonstrated decreased T2 responses and increased T-bet Treg cells. Conversely, CuO NP inhalation exposure to AIT-treated asthmatic mice resulted in an increase in T2 cells. In conclusion, immunomodulatory effects of inhalation exposure to CuO NPs are dependent on immune conditions prior to exposure.
Topics: Female; Mice; Animals; Copper; Inhalation Exposure; Asthma; Pyroglyphidae; Immunity; Nanoparticles; Oxides
PubMed: 37463491
DOI: 10.1021/acsnano.3c01668 -
Respiratory Research Jul 2023Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested...
INTRODUCTION
Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested effects of Chronic Intermittent Hypoxia (CIH) - a hallmark of OSA - on airway hyperresponsiveness (AHR), in a rat model of chronic allergen-induced inflammation.
METHODS
Brown Norway rats were exposed to six weeks of CIH or normoxia (NORM) concurrent with weekly house dust mites (HDM) or saline (SAL) challenges. At endpoint, we assessed responses to seven Methacholine (Mch) doses (0, 4, 8, 16, 32, 64, 128 mg/mL) on a FlexiVent system (Scireq). Maximal (or plateau) responses (reactivity) for total respiratory system Resistance (R) and Elastance (E), Newtonian airway resistance (R a measure of central airways function) and tissue damping (G, a measure of distal airways function) were plotted.
RESULTS
HDM/CIH-treated animals demonstrated the highest reactivity to Mch in R and E compared to all other groups (HDM/NORM, SAL/CIH and SAL/NORM p < 0.05 for all comparisons, for doses 5-7 for R, and for doses 4-7 for E). The enhanced R response was due to an increase in G (doses 4-7, p < 0.05 for comparisons to all other groups), whereas R was not affected by CIH.
CONCLUSIONS
In rats chronically challenged with HDM, concurrent CIH exposure induces AHR primarily in the distal airways, which affects the respiratory system frequency-dependent elastic properties.
Topics: Rats; Animals; Pyroglyphidae; Allergens; Respiratory Hypersensitivity; Lung; Hypoxia; Methacholine Chloride; Inflammation; Sleep Apnea, Obstructive; Disease Models, Animal
PubMed: 37468919
DOI: 10.1186/s12931-023-02493-4