Clinical and Translational Allergy最新文献

Background

Chronic urticaria (CU) is a heterogeneous skin disorder whose genetic drivers are incompletely defined.

Objective

To systematically review and meta-analyse genetic and epigenetic factors that influence susceptibility and treatment response in acute and CU.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, Scopus and Web of Science were searched from inception to 31 July 2024. Original human studies reporting genetic or epigenetic associations with any urticaria subtype were eligible. Random-effects meta-analyses were undertaken when at least three comparable datasets were available.

Results

Sixty-one studies met the inclusion criteria. Associations were confirmed for HLA-B44 (pooled Odds Ratio 8.15, 95% Confidence Interval 1.61–41.29; I² = 86%) and vitamin-D-receptor polymorphisms FokI, TaqI and BsmI, each conferring a 1.5- to 2.1-fold increased risk. Variants in CRTH2, FcεR1α and C-reactive protein predicted antihistamine response, while FCER1G, IL-6, prostaglandin-endoperoxide synthase 2, CCL2 and TNF-pathway genes were over-expressed in lesional tissue, supporting an immune-mediated pathogenesis. Evidence for non-CSU subtypes, acute urticaria, epigenetic modifications and gene–environment interactions was limited.

Conclusions

CU displays an autoimmune-like genetic signature. HLA-B44 and vitamin D receptor variants are susceptibility markers, and pharmacogenetic signals enable personalised therapy. Longitudinal studies integrating environmental exposures and functional genomics are needed to translate these insights into precision care.

Introduction

The relationship between chronic urticaria (CU) and alexithymia, a cognitive-affective impairment characterized by difficulty in identifying and expressing emotions, is complex and underexplored. This study aimed to identify predictors of alexithymia in CU patients by focusing on the impact of coexisting mental illnesses and antihistamine use.

Methods

An online survey was distributed to specialized allergy and dermatology centers from 2021 to 2022. The survey included the TAS-20, UAS-7, UCT, CU-Q2oL, and demographic information. Participants were 18–80 years old, diagnosed with CU, and had no prior diagnosis of alexithymia. The final analysis included a total of 332 respondents from various countries. Regression models were used to investigate the relationship between clinical and demographic factors of patients with CU as key predictors of alexithymia.

Results

Among CU patients, the main predictors of having alexithymia were: presenting mental (OR = 2.406, p < 0.05) and cardiovascular comorbidities (OR = 2.085, p < 0.05), active urticaria (as opposed to being urticaria-free), OR = 1.989, p < 0.05, severe impact on quality of life (OR = 1.973, p < 0.01), and the use of oral first-generation antihistamines (OR = 2.340, p < 0.05). The duration of chronic urticaria diagnosis and other types of treatments (sg-AH use, omalizumab use, and corticosteroid use) do not appear to be significantly associated with alexithymia.

Conclusions

Alexithymia is closely linked to clinical and demographic variables among patients with CU. These findings suggest that comprehensive management of CU should include psychological assessment and support, especially for patients with alexithymia and those using fg-AH. Reducing the reliance on fg-AH and addressing mental health issues may improve outcomes for these patients.

Background

Hereditary angioedema (HAE) is a rare, autosomal dominantly inherited disease characterised by mucocutaneous oedema attacks. Vasoactive mediators and the endothelium play an important role in the pathogenesis of HAE. We aimed to evaluate the endothelial dysfunction in HAE.

Methods

The study included 35 C1 inhibitor deficient (C1-INH) HAE patients aged 18–50 years old without any risk factor that could cause endothelial dysfunction, and 25 sex- and age-matched healthy controls (HCs). Bilateral carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) measurements, and transthoracic echocardiography (ECHO) imaging were performed. Demographic and clinical features of the patients were evaluated.

Results

The percentage of FMD (FMD [%]) in C1-INH HAE patients was significantly lower than in the HCs (p < 0.001). There was no significant difference in the CIMT between C1-INH HAE patients and HCs. In addition, the findings of the ECHO were similar between the groups. C4 and C1 INH levels at diagnosis, gender, age, disease severity, presence of long-term prophylaxis treatment and attack frequency were not associated with FMD (%), whereas disease duration was correlated with lower FMD (%) (r = −0.480, p = 0.003).

Conclusion

The present study indicated the presence of structural endothelial dysfunction in C1-INH HAE in the absence of atherosclerosis. Moreover, the study revealed that endothelial dysfunction was associated with disease duration, irrespective of disease severity. Further studies are required in order to assess mortality and morbidity due to endothelial dysfunction in C1-INH HAE and to determine the molecular mechanisms underlying endothelial dysfunction in C1-INH HAE.

Background

Anti-IgE therapy can serve as an option for inadequately controlled seasonal allergic rhinitis (SAR) patients. LP-003, a novel anti-IgE antibody, is being tested as an add-on treatment for SAR. This trial aimed to evaluate whether LP-003 is effective and safe for SAR.

Methods

This placebo-controlled double-blind phase 2 randomized clinical trial was conducted in 17 hospitals in China. SAR patients whose symptoms were inadequately controlled despite first-line treatment (nasal corticosteroids with or without oral antihistamine) in the previous two seasons were enrolled between July 6, 2023 and August 7, 2023. Participants were randomized in a ratio of 2:4:3 to receive subcutaneous injections of 100 mg LP-003, 200 mg LP-003 or placebo every 4 weeks for 2 doses. All patients received fluticasone propionate as standard-of-care (SoC). The main outcome was the mean total nasal symptom score (TNSS) during the peak pollen period (PPP). Secondary endpoints included a series of symptom and medication scores, quality of life assessments during PPP and pollen period (PP), immunogenicity and safety.

Results

A total of 180 participants were randomly assigned. The LP-003 + SoC treatment achieved a significantly lower TNSS compared with placebo + SoC (3.31 vs. 4.06, intergroup difference = −0.74, p = 0.0464). For key secondary outcomes, the LP-003 group also achieved significantly lower daily nasal symptom and rescue medication use scores (3.54 vs. 4.42, intergroup difference = −0.88, p = 0.0352), and daily ocular symptom and rescue medication use scores (1.66 vs. 2.19, intergroup difference = −0.54, p = 0.0245) compared to the placebo group. The suppression of free IgE was prevalent and persistent. There was no statistically significant difference in adverse events and severe adverse events between LP-003 and placebo groups.

Conclusions

These findings support LP-003 as a promising add-on option to the SoC for patients with moderate to severe SAR. Fixed dosage regimen and extensive suppression of free-IgE render it a cutting-edge advantage.

Background

Food allergy affects up to 6% of the population and emergency department visits due to accidental food-allergic reactions are increasing. This study evaluated accidental allergic reactions outside the hospital and the number of hospitalizations in food allergic patients as well as the pattern before and after the diagnosis of food allergy by oral food challenge (OFC).

Methods

An electronic questionnaire concerning accidental allergic reactions was sent to 785 patients with challenge verified peanuts, hazelnuts, cow's milk and/or hen's egg allergies at the Allergy Centre, Odense University Hospital, Denmark.

Results

In total, 51% (402/785) responded. Among the 357 who reported at least one accidental allergic reaction, 51.5% (184/357) reported a total of six or less reactions, whereas 22.4% (80/357) had experienced a total of ≥21 reactions. Skin symptoms were commonly reported by children/adolescents (n = 277), whereas symptoms from all other organ systems were more frequently reported by adults (n = 80). In total, 61.6% (220/357) experienced at least one accidental allergic reaction, requiring immediate medical attention, which decreased from 77.3% (170/220) before to 55% (121/220) after establishment of the food allergy diagnosis by OFC. A concomitant proportional increase in the number of hospitalizations was identified (63.5% (108/170) to 72.7% (88/121)). Limitations: We had no exact data on the timing of the accidental allergic reactions for the individual allergens.

Conclusion

Accidental food-allergic reactions are common and often severe. After the diagnostic OFC, the number of patients with reactions decreased, and the proportion of hospitalizations increased, indicating improved disease and healthcare management.

Background

Asthma is a heterogeneous disease with various inflammatory subtypes, including the type-2 (T2) endotype associated with airway eosinophilia. Severe asthma is linked to reduced ventilatory function due to airway structural changes. This study compared the extent of airway remodeling in different immunological endotypes of asthma.

Methods

Severe asthma patients (n = 30) were stratified based on bronchial expression of T2 (e.g., CST1) and T3 (e.g., IL17A) immunity genes as T2-high, T3-high, or low-inflammatory. We analyzed airway wall thickness using endobronchial ultrasound (EBUS), bronchial biopsy morphometry, and mRNA expression of remodeling genes. Bronchial epithelial cell cultures were used to assess cytokine responses.

Results

T2-high asthma patients showed lower predicted FEV1 (59 vs. 74 % in low-inflammatory variant, p = 0.049) and increased submucosa layer (L2) in EBUS (0.203 vs. 0.189 mm, p = 0.018). T2-high asthma patients also had increased airway smooth muscle (ASM) mass (∼2-fold, p = 0.018) and marginally thicker reticular basement membrane. T3-high asthma showed only a trend toward thicker L2 (p = 0.055). Only patients with an eosinophilic signature in endobronchial biopsy demonstrated increased expression of remodeling genes, including TGFB1. A profibrotic profile was also induced in bronchial epithelium stimulated in vitro with IL-13.

Conclusion

These data suggest that T2-signature in severe asthma is associated with increased ASM mass and more pronounced airway obstruction. Overexpression of remodeling genes primarily occurred in patients with signs of eosinophilic infiltration in the bronchial mucosa, suggesting that remodeling may progress with uncontrolled airway inflammation.

Objectives

The evidence regarding the efficacy of probiotics in improving allergic rhinitis (AR) remains inconsistent. This study aimed to evaluate the potential effects of Bifidobacterium animalis subsp. lactis A6 (A6) on perennial AR.

Methods

A randomized, double-blind, placebo-controlled trial was conducted involving 70 adults with perennial AR receiving either probiotic (A6, 5 × 10¹⁰ CFU/sachet per day) or placebo intervention for 8 weeks. Nasal symptoms and quality of life (QoL) were recorded using total nasal symptom scores (TNSS) and the rhinitis quality of life questionnaire (RQLQ). Blood eosinophil count, total immunoglobulin E (IgE), allergen-specific IgE, and immunological parameters were also assessed.

Results

After 8 weeks of intervention, the probiotic group showed a statistically significant greater reduction in TNSS total score compared with the placebo group [−3.11 (3.53) vs. −1.29 (3.34), p = 0.029, Cohen's d = 0.68]. Similar results were noted for serum total IgE and interleukin-13 (IL-13). Comparable findings were seen for RQLQ score only at week 4 but not at week 8.

Conclusions

In conclusion, A6 could statistically significantly alleviate rhinitis symptoms and improve QoL in adults with perennial AR. The effect size, as measured by Cohen's d, suggests that A6 may provide clinically meaningful benefits for AR patients to a certain degree.

Clinical Trial Registration

Chictr.org.cn Identifier no. ChiCTR2200064158.

Objective

Food allergy (FA) impacts health-related quality of life and mental health. Understanding what variables are associated with psychological distress can help healthcare providers direct patients to appropriate support. As part of the study, Global Access to Psychological Services (GAPS) for FA and associations with FA-related psychological distress were explored in adults with FA and caregivers of children with FA.

Methods

Participants completed online surveys in seven languages. Participants reported the types of FA-related distress they or their child experienced, along with demographic and FA-related information. Associations with distress were analysed using regression models.

Results

N = 1329 adults with FA and N = 1373 caregivers of children with FA from 27 countries participated. Of the 21 different types of distress selected, anxiety about an allergic reaction was the most common (62.5% adults; 72.6% caregivers). Females reported significantly more types of distress than males (p < 0.001). There were significant differences between countries (all p < 0.05-0.001); participants in Australia, Brazil, Canada, and the United Kingdom consistently reported more types of distress than European countries or the United States. In regression models, country of residence, number of FAs, and symptoms were significantly associated with distress. Additional associations included adrenaline autoinjector (AAI) prescription, being female, anaphylaxis and comorbidities in adults; in caregivers having a younger child, longer time elapsed since FA diagnosis, being female, AAI prescription and anaphylaxis; and in children being older and living longer with FA.

Conclusions

FA-related distress is experienced differently across countries. Understanding associations with types of distress can help direct healthcare services and psychological support to where it is needed most.

Background

A double-blind, randomized Phase 3 study (NCT04426890) confirmed that CT-P39 and European Union-approved reference omalizumab (ref-OMA) were comparable in terms of efficacy, quality of life (QoL), pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity up to week 24. Here, we report results from the 16-week follow-up period.

Methods

The study included two 12-week treatment periods (TPs) and a 16-week off-treatment follow-up period. In TP1, 619 patients with chronic spontaneous urticaria (CSU) were randomized to CT-P39 300 mg, ref-OMA 300 mg, CT-P39 150 mg, or ref-OMA 150 mg. A total of 579 patients continued into TP2, in which patients treated with ref-OMA 300 mg were rerandomized to CT-P39 300 mg or to continue on ref-OMA 300 mg; patients initially randomized to CT-P39 300 mg continued this regimen; and patients initially randomized to CT-P39 or ref-OMA 150 mg increased their dose to 300 mg. Efficacy, PK, PD, QoL, safety, and immunogenicity were assessed during the follow-up period.

Results

Improvements in efficacy outcomes observed in the TPs gradually decreased during the follow-up period, but did not return to baseline values. Omalizumab serum concentrations that had increased during treatment subsequently decreased during the follow-up period. After completing treatment at week 24, total and free immunoglobulin E levels returned toward baseline levels. No clinically meaningful differences in QoL, safety, or immunogenicity outcomes were observed across the treatment groups.

Conclusion

Follow-up results support the biosimilarity of CT-P39 and ref-OMA in terms of efficacy, PK, PD, QoL, safety, and immunogenicity in patients with CSU.

Background

In current clinical practice, primary diffuse chronic rhinosinusitis with nasal polyps (CRSwNP) is classified into two endotypes: type 2 and non-type 2. Previous studies on sinonasal health-related quality of life (HRQoL) in CRS have primarily focused on differences between phenotypes. This study aimed to compare HRQoL between the two endotypes in patients with CRSwNP.

The type 2 endotype had a higher median nasal polyp score (NPS) than non-types (4 and 2, respectively), but this difference did not reach significance. Loss of smell was associated with NPS, and facial pain/pressure was inversely correlated with age. Age was significantly associated with loss of smell, but only in non-type 2 CRSwNP.

Methods

This was a prospective, monocentric study conducted between 2018 and 2023 on CRSwNP patients referred for surgery. Health-related quality of life was assessed using the German standardized SNOT-20 questionnaire. Type 2 was defined according to the updated EPOS/EUFOREA 2023 criteria.

Results

A total of 122 patients with CRSwNP were included, 113 (92.6%) of whom were classified as type 2. Type 2 was associated with a significantly worse SNOT-20 German Adapted Version score. Two of the four cardinal symptoms of CRS—loss of smell and rhinorrhea—were significantly more severe and prevalent in the type 2 endotype, with loss of smell being very specific. The most prevalent symptom in both endotypes was nasal obstruction, with no difference between both endotypes.

The type 2 endotype had a higher median nasal polyp score (NPS) than non-types (4 and 2, respectively), but this difference did not reach significance. Loss of smell was associated with NPS, and facial pain/pressure was inversely correlated with age. Age was significantly associated with loss of smell, but only in non-type 2 CRSwNP.

Conclusion

Type 2 CRSwNP has a more severe impact on HRQoL compared with non-type 2 CRSwNP. Hyposmia, rhinorrhea, and potentially NPS may offer endotypic and pathophysiological insights.