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Scientific Reports Feb 2024Allergens from domestic cats (Felis catus) cause allergy-related health problems worldwide. Fel d 1 is a major allergen that causes severe allergic reactions in humans,...
Allergens from domestic cats (Felis catus) cause allergy-related health problems worldwide. Fel d 1 is a major allergen that causes severe allergic reactions in humans, including rhinitis, conjunctivitis, and life-threatening asthma. Therefore, patients with cat allergies anticipate hypoallergenic cats. We successfully generated Fel d 1 chain 2 (CH2) genome-edited cats using the CRISPR-Cas9 system in this study. T7 endonuclease 1 assay and Sanger sequencing were used to confirm the mutation in CH2 genome-edited cats. Fel d 1 level in CH2 genome-edited cats were assessed by enzyme-linked immunosorbent assay (ELISA). Remarkably, ELISA showed that the level of Fel d 1 in the CH2 homozygous genome-edited cat (Name: Alsik) was extremely low compared with that in wild type domestic cats and could be hypoallergenic cats. Additionally, we successfully cloned the CH2 homozygous genome-edited cat using cytoplasm injection clone technology. The cloned CH2 homozygous genome-edited cat was verified using microsatellite analysis. Creating hypoallergenic cats using the CRISPR-Cas9 system is a significant step forward because these cats can safely approach allergic patients.
Topics: Cats; Animals; Humans; CRISPR-Cas Systems; Hypersensitivity; Allergens; Asthma; Enzyme-Linked Immunosorbent Assay
PubMed: 38424152
DOI: 10.1038/s41598-024-55464-0 -
The Journal of Allergy and Clinical... Jun 2024The most common symptoms of pollen allergy are rhinitis and conjunctivitis. However, in real-world clinical practice, we sometimes encounter patients with pollen allergy...
BACKGROUND
The most common symptoms of pollen allergy are rhinitis and conjunctivitis. However, in real-world clinical practice, we sometimes encounter patients with pollen allergy suffering from severe extrarespiratory symptoms including skin, gastrointestinal, or flu-like symptoms in relation to exposure to sensitized pollen.
OBJECTIVE
To elucidate the extrarespiratory symptoms in patients with pollen allergy.
METHODS
We performed a non-drug-focused prospective study of patients with pollen allergy (n = 384). During the 1-year observational period, they were asked to complete a weekly electronic diary consisting of visual analog scale (VAS) scores to assess all symptoms experienced in various organs over the past week. An association between seasonal pollen levels and seasonal increase in VAS scores was evaluated using a mixed-effects model for repeated measures. A k-means cluster analysis was performed to identify a group of patients experiencing stronger extrarespiratory symptoms.
RESULTS
In patients sensitized to grass or birch pollen, higher seasonal levels of these pollen grains were associated with higher VAS scores for headache, gastrointestinal symptoms, skin symptoms, and fatigue. A cluster analysis identified a group of severe pollen-allergic patients with higher extrarespiratory symptoms (n = 42). This group was characterized by a higher frequency of comorbid food allergy/atopic dermatitis, higher rate of IgE sensitization to pollens, and higher impaired activity and work productivity.
CONCLUSIONS
This 1-year survey identified a small but nonnegligible group of patients with pollen-related extrarespiratory symptoms. More attention should be paid to this patient group considering their impaired activity and work productivity.
Topics: Humans; Rhinitis, Allergic, Seasonal; Japan; Male; Female; Adult; Pollen; Middle Aged; Prospective Studies; Allergens; Surveys and Questionnaires; Seasons; Young Adult; Dermatitis, Atopic; Food Hypersensitivity
PubMed: 38382879
DOI: 10.1016/j.jaip.2024.02.011 -
Clinical Ophthalmology (Auckland, N.Z.) 2024To compare clinical outcomes and patient preference for the dexamethasone intracanalicular insert (DEX) versus topical loteprednol (LOT) or olopatadine (OLO) for the... (Clinical Trial)
Clinical Trial
PURPOSE
To compare clinical outcomes and patient preference for the dexamethasone intracanalicular insert (DEX) versus topical loteprednol (LOT) or olopatadine (OLO) for the treatment of allergic conjunctivitis in a real-world model of allergen exposure.
METHODS
This was a prospective comparative trial. Adults with testing-confirmed bilateral allergic conjunctivitis received DEX in the more symptomatic eye and either LOT 2 times daily or OLO once daily for 30 days in the fellow eye. The primary outcome was patient preference for treatment. Clinical outcomes included ocular itching and hyperemia, lid swelling, and watering/tearing. Safety outcomes included intraocular pressure (IOP).
RESULTS
Thirty patients participated and completed the study. All received DEX in the eye with worse symptoms and 15 received LOT and the other 15 received OLO in the other eye. Patients preferred DEX (10/15; 66.7%) over LOT (4/15; 26.7%), with one patient having no preference (p = 0.0103). Patients had no preference between DEX (8/15; 53.3%) and OLO (6/15; 40%), with one patient having no preference (p = 0.1044). In the DEX/LOT cohort, ocular itching and hyperemia improved more with DEX than LOT (p ≤ 0.009), while in the DEX/OLO cohort, the DEX eyes showed greater improvement in conjunctival hyperemia (p < 0.0001) but not itching (p = 0.074). No between-group differences were seen in eyelid swelling or tearing/watering in either cohort. Mean change in IOP was similar between the DEX and LOT eyes (p = 0.4921), and mean IOP rose more in the DEX eyes than the OLO eyes (by <1 mmHg; p = 0.0403).
CONCLUSION
Overall, this real-world study demonstrated that the dexamethasone intracanalicular insert was as effective as a topical antihistamine/mast cell stabilizer and more effective than topical steroids in relieving the signs and symptoms of allergic conjunctivitis. This insert should be considered as an alternative to topical therapy for the treatment of allergic conjunctivitis.
PubMed: 38375441
DOI: 10.2147/OPTH.S440840 -
The World Allergy Organization Journal Feb 2024The influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis...
OBJECTIVE
The influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis (AC), and atopic dermatitis (AD) remains incompletely understood. We performed a rigorous mendelian randomization (MR) study to obtain the unconfounded association between MSAB and allergic diseases in offspring with and without adjustment for the effect of breastfeeding.
METHODS
Utilizing publicly available information of MSAB, breastfeeding, CA, AR, AC, and AD from large-scale genome-wide association studies (GWAS), we performed a two-sample mendelian randomization (TSMR) analysis to assess the respective causal relationship of MSAB and breastfeeding to allergic diseases in offspring. To get a reliable conclusion, MR Egger regression, weighted median, and inverse variance weighted (IVW) were employed to estimate the causality, with IVW as the primary analysis. Multivariate MR (MVMR) analysis was used to assess the effect of MSAB on allergic diseases after adjusting for breastfeeding's impact. Sensitivity analysis was conducted using the Cochran Q test, MR-Egger, and leave-one-out approaches to ensure the reliability and stability of results.
RESULTS
The TSMR analysis demonstrated MSAB increased the risks of CA (P = 0.013, OR: 1.018, 95%CI: 1.004 to 1.033) and AD (P = 0.006, OR: 8.293, 95%CI: 1.815 to 37.884) in offspring. Conversely, breastfeeding decreased the risk of CA (P <0.001, OR: 0.946, 95%CI: 0.918 to 0.974). MSAB still increased the risks of CA (P = 0.0497, OR: 1.013, 95%CI: 1.000017 to 1.026) and AD (P = 0.003, OR: 13.800, 95%CI: 2.490 to 269.246) after adjusting for breastfeeding. We observed no strong indication of a negative causality between MSAB and AC and AR.
CONCLUSION
Our findings provided robust evidence of the adverse effects of MSAB on offspring. We emphasized the urgency of smoking cessation around birth and the importance of breastfeeding even in smoking mothers.
PubMed: 38351904
DOI: 10.1016/j.waojou.2024.100875 -
Clinical Ophthalmology (Auckland, N.Z.) 2024A fixed-combination eye drop has several advantages over combination therapy, however, the intraocular pressure (IOP)-lowering efficacy and safety of the newly available...
PURPOSE
A fixed-combination eye drop has several advantages over combination therapy, however, the intraocular pressure (IOP)-lowering efficacy and safety of the newly available brimonidine + ripasudil fixed-combination (BRFC) eye drops after switching from brimonidine + ripasudil is yet to be established. Therefore, this study aimed to retrospectively investigate the 6-month safety, usability, and IOP-lowering efficacy of BRFC switched from brimonidine and ripasudil.
PATIENTS AND METHODS
Overall, 69 patients with primary open-angle glaucoma (69 eyes) receiving brimonidine + ripasudil were enrolled in this study. Brimonidine + ripasudil was discontinued, and treatment was switched to BRFC without a washout period. The IOP was compared before and at 3 and 6 months after switching to BRFC. The side effects, discontinued cases, and usability (a questionnaire survey) were also investigated.
RESULTS
The IOP was not significantly different after switching to BRFC (15.1 ± 3.3 mmHg at baseline, 15.9 ± 3.6 mmHg after 3 months, and 14.6 ± 3.3 mmHg after 6 months). Adverse reactions occurred in four patients (5.8%): allergic conjunctivitis, two patients; irritation, one patient; and blurred vision, one patient. Treatment was discontinued in five (7.2%) patients owing to allergic conjunctivitis, two patients; increased IOP, two patients; and blurred vision, one patient. In the questionnaire survey, 68 patients with eye pain, 67 with itching, 64 with conjunctival hyperemia, 64 with irritation, and 62 with blurred vision reported no change or improved conditions. Additionally, in response to the question regarding preferences for pre-treatment and fixed combinations, 14 participants (20.2%) favored pre-treatment, while 53 (76.8%) preferred fixed combinations.
CONCLUSION
The IOP was maintained for 6 months, with satisfactory safety and comfort of use, with BRFC switched from brimonidine and ripasudil.
PubMed: 38343903
DOI: 10.2147/OPTH.S446962 -
Translational Medicine @ UniSa 2023Recent increases in allergic diseases are thought to be caused by better hygiene, Westernized diets, air pollution, climate change, and other factors that influence host...
Recent increases in allergic diseases are thought to be caused by better hygiene, Westernized diets, air pollution, climate change, and other factors that influence host microbiota, a key player in the induction and maintenance of immunoregulatory circuits and tolerance. The increase of allergic diseases in the elderly is also related to additional factors, such as various comorbidities that may interfere with the development and the type of allergic reactions. Immunosenescence plays a central role in these reactions, altering microbiota responses and triggering inflammageing. In addition, in the elderly, there is a shift from Th1 to Th2 immunity, thus favoring allergic responses. A better understanding of the mechanisms responsible for immunosenescence and its effects on allergic inflammation will most certainly lead to improved therapies.
PubMed: 38343419
DOI: 10.37825/2239-9747.1046 -
Mucosal Immunology Apr 2024Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in...
Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl] (AMG-517)) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, tumor necrosis factor-α production by MCs, eosinophil infiltration and activation, and C-C motif chemokine 11 (CCL11) (eotaxin-1) expression in fibroblasts. Subsequent findings demonstrated that TRPV1 sensory nerves secrete somatostatin (SST), which binds to SST receptor 5 (SSTR5) on MCs and conjunctival fibroblasts. SST effectively inhibited tumor necrosis factor-α production in MCs and CCL11 expression in fibroblasts, thereby reducing eosinophil infiltration and alleviating AC symptoms, including eyelid swelling, lacrimation, conjunctival chemosis, and redness. These findings suggest that targeting TRPV1 sensory nerve-mediated SST-SSTR5 signaling could be a promising therapeutic strategy for AC, offering insights into neuroimmune mechanisms and potential targeted treatments.
Topics: Mice; Animals; Conjunctivitis, Allergic; Tumor Necrosis Factor-alpha; Conjunctiva; Eosinophils; Antineoplastic Agents; Inflammation; TRPV Cation Channels
PubMed: 38331094
DOI: 10.1016/j.mucimm.2024.02.001 -
Allergology International : Official... Jul 2024Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of...
BACKGROUND
Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of atopic conditions on the severity and recurrence of ocular infections including herpes simplex virus (HSV).
METHODS
This study was performed on 474 consecutive patients with infectious keratitis caused by bacteria, fungus, acanthamoeba, HSV, or varicella-zoster virus. The relationships between the atopic condition and specific infectious pathogens and HSV were determined using real-time PCR.
RESULTS
Our findings showed that atopic dermatitis (AD) was significantly associated with the incidence of HSV keratitis (odds ratio (OR), 10.2; P = 0.000). Other associations with AD were observed only with bacteria in an adverse manner. HSV proliferation in the lesions of patients with HSV keratitis whose AD was associated with non-infectious atopic blepharitis were significantly greater by 145-folds (P = 0.000). The presence of asthma or allergic rhinitis also increased the HSV DNA copy numbers. A recurrence of HSV keratitis was observed in 70 patients (43.2 %), and mean time to recurrence was 1647 days. Cox proportional hazard model indicated that the epithelial type of HSV recurrence but not the stromal type was associated with atopic conditions especially with AD. The factors significantly associated with a recurrence was AD associated with non-infectious atopic blepharitis (HR: 6.11, P = 0.000) and asthma (HR: 3.03, P = 0.025).
CONCLUSIONS
Atopic conditions, especially AD with atopic blepharitis, are significantly associated with the development, increased proliferation, and shorter time to a recurrence on HSV keratitis.
Topics: Humans; Female; Male; Recurrence; Adult; Middle Aged; Adolescent; Aged; Dermatitis, Atopic; Keratitis; Young Adult; Keratitis, Herpetic; Child; Simplexvirus; Incidence; Child, Preschool; Aged, 80 and over
PubMed: 38310042
DOI: 10.1016/j.alit.2024.01.008 -
The Journal of Allergy and Clinical... Jun 2024Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ) sublingual immunotherapy (SLIT) tablets have been confirmed across large clinical trials in adults with grass, tree, ragweed, and house dust mite (HDM) allergic rhinitis with or without conjunctivitis.
OBJECTIVE
This pooled analysis investigates whether the reduction in symptom burden found across the clinical trials is supported by improvements in QoL.
METHODS
A total of 11 phase II/III randomized placebo-controlled trials across the SQ grass, tree, ragweed, and HDM SLIT tablets (grass: N = 3179; ragweed: N = 767; tree: N = 634; HDM: N = 2221) were included. QoL was assessed using the standardized Rhinitis Quality of Life Questionnaire (RQLQ), with the exception of 3 grass trials, which used the nonstandardized version. The overall RQLQ scores were expressed as a mean of 7 domains. In the pooled analysis, treatment was used as fixed effect; and the trial, and the interaction between region/country and trial as random effects.
RESULTS
The pooled analysis showed consistent and statistically significant improvements in overall RQLQ scores across all 4 SQ SLIT tablets versus placebo (pooled estimate [95% CI], P value-grass: -0.20 [-0.28 to -0.12], P < .001; tree: -0.42 [-0.58 to -0.26], P < .001; ragweed: -0.36 [-0.55 to -0.17], P < .001; HDM: -0.28 [-0.39 to -0.17], P < .001). Furthermore, significant improvements versus placebo for all 4 SQ SLIT tablets were seen across the 7 individual domains.
CONCLUSIONS
The proven efficacy of SQ SLIT tablets to reduce symptoms across 4 of the most common respiratory allergens is supported by concurrent significant improvements in RQLQ scores overall and for all 7 domains.
Topics: Humans; Quality of Life; Sublingual Immunotherapy; Adult; Conjunctivitis, Allergic; Allergens; Pyroglyphidae; Rhinitis, Allergic; Animals; Ambrosia; Tablets; Male; Female; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic; Poaceae; Trees; Clinical Trials, Phase II as Topic; Treatment Outcome
PubMed: 38307205
DOI: 10.1016/j.jaip.2024.01.038 -
Cureus Dec 2023Allergic rhinitis (AR) is a chronic ailment triggered by immunoglobulin E (IgE)-mediated reactions to allergens. Generally, AR is accompanied by asthma and... (Review)
Review
Allergic rhinitis (AR) is a chronic ailment triggered by immunoglobulin E (IgE)-mediated reactions to allergens. Generally, AR is accompanied by asthma and conjunctivitis. The risk factors of AR include both inhalant and occupational allergens and genetic factors. Although AR is not a life-threatening condition, it poses a significant risk of morbidity and hampers work-related performance. Currently, the diagnosis of AR is based on clinical history and physical examination of the patients. Furthermore, several laboratory tests such as skin pricking test (SPT), nasal allergen challenge (NAC), and computed tomography (CT) are also recommended in some cases. Nasal cytology can aid in the differentiation of rhinitis because of allergy or infection. Apart from this, molecular diagnostic modalities such as basophil activation test (BAT) and Immune Solid-Phase Allergy Chip (ISAC) can also be employed for the confirmatory diagnosis of AR. Immunotherapy has demonstrated efficacy in the management of AR, with only mild side effects. With the advancement in the diagnostic realm of AR, personalized treatment approach has also gained significant popularity. Immunotherapy is gaining evidence on becoming a personalized treatment approach for the management of AR. This article provides a comprehensive overview, aiming to bridge the gap between evolving diagnostics and personalized therapeutic strategies for allergic rhinitis.
PubMed: 38292952
DOI: 10.7759/cureus.51370