Allergology International最新文献

Background

The association of allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis with Parkinson's disease (PD) risk is yet unclear. In the few preceding studies, a short follow-up duration was followed for a relatively small study population, and lifestyle behaviors were not adjusted for. Therefore, there is a need for large-scale observation studies on the association of allergic disease with PD risk after considering lifestyle behaviors.

Methods

The study population consisted of 398,936 participants aged 40 years or older who underwent health screening before 1 January 2005 from the Korean National Health Insurance Service database. Starting from 1 January 2005, all participants were followed up until the date of PD event, death, or 31 December 2019. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of PD were calculated using multivariable Cox proportional hazards regression.

Results

Compared to non-allergic disease participants, allergic disease patients had a higher risk for PD (aHR 1.18, 95% CI 1.07–1.30) and especially, allergic rhinitis patients had a higher risk for PD (aHR 1.14, 95% CI 1.00–1.29). Allergic disease was associated with a higher risk for PD (aHR 1.24, 95% CI 1.01–1.52) among participants who were never smokers, did not consume alcohol, and exercised regularly.

Conclusions

Allergic rhinitis was associated with a higher risk for PD compared to participants without allergic rhinitis. This risk-increasing association of allergic rhinitis with PD was preserved even among people with healthy lifestyle behaviors.

Background

Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established.

Methods

This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators’ discretion.

Results

A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were −73.5% at week 4, −81.7% at week 28, and −81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%–95.2%).

Conclusions

Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.

Despite recent advances in asthma treatments, the search for novel therapies remains necessary because there are still patients with recurrent asthma exacerbations and poor responses to the existing treatments. Since group 2 innate lymphoid cells (ILC2) play a pivotal role in asthma by triggering and exacerbating type 2 inflammation, controlling ILC2s function is key to combating severe asthma. Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans and are activated both in a T cell receptor-dependent and -independent manner. MAIT cells are composed of MAIT1 and MAIT17 based on the expression of transcription factors T-bet and RORγt, respectively. MAIT cells play pivotal roles in host defense against pathogens and in tissue repair and are essential for the maintenance of immunity and hemostasis. Our recent studies revealed that MAIT cells inhibit both ILC2 proliferation and functions in a mouse model of airway inflammation. MAIT cells may alleviate airway inflammation in two ways, by promoting airway epithelial cell barrier repair and by repressing ILC2s. Therefore, reagents that promote MAIT cell-mediated suppression of ILC2 proliferation and function, or designer MAIT cells (genetically engineered to suppress ILC2s or promote repair of airway damage), may be effective therapeutic agents for severe asthma.

Semaphorins were originally identified as guidance molecules in neural development. However, accumulating evidence indicates that ‘immune semaphorins’ are critically involved in regulating immune cell activation, differentiation, mobility and migration. Semaphorins are also intimately associated with the pathogenesis of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and eosinophilic chronic rhinosinusitis. Interestingly, reflecting their function in positive or negative regulation of immune cells, levels of some semaphorins are increased while others are decreased in patients with allergic diseases. This review presents the pathogenic functions of immune semaphorins in allergic inflammation and discusses the potential use of these molecules as therapeutic targets for allergic diseases.

Obesity is one of the factors associated with the severity of asthma. Obesity is associated with aggravation of the pathophysiology of asthma, including exacerbations, airway inflammation, decreased pulmonary function, and airway hyperresponsiveness. The present review addresses the characteristics of asthma with obesity, focusing especially on the heterogeneity caused by the degree of type 2 inflammation, sex differences, the onset of asthma, and race differences. To understand the severity mechanisms in asthma and obesity, such as corticosteroid resistance, fatty acids, gut microbiome, and cytokines, several basic research studies are evaluated. Finally, possible future therapies, including weight reduction, microbiome-targeted therapies, and other molecular targeted therapies are addressed. We believe that the present review will contribute to better understanding of the severity mechanisms and the establishment of novel treatments for severe asthma patients with obesity.

Background

Most hospitals use electronic health records (EHR) to warn health care professionals of drug hypersensitivity (DH) and other allergies. Indiscriminate recording of patient self-reported allergies may bloat the alert system, leading to unjustified avoidances and increases in health costs. The aim of our study was to analyze hypersensitivities documented in EHR of patients at Lausanne University Hospital (CHUV).

Methods

We conducted a retrospective study on patients admitted at least 24 h to CHUV between 2011 and 2021. After ethical clearance, we obtained anonymized data. Because culprit allergen could be either manually recorded or selected through a list, data was harmonized using a reference allergy database before undergoing statistical analysis.

Results

Of 192,444 patients, 16% had at least one allergy referenced. DH constituted 60% of all allergy alerts, mainly beta-lactam antibiotics (BLA) (30%), NSAID (11%) and iodinated contrast media (ICM) (7%). Median age at first hospitalization and hospitalization length were higher in the allergy group. Female to male ratio was 2:1 in the allergic group. Reactions were limited to the skin in half of patients, and consistent with anaphylaxis in 6%. In those deemed allergic to BLA, culprit drug was specified in 19%, ‘allergy to penicillin’ otherwise. It was impossible to distinguish DH based on history alone or resulting from specialized work-up.

Conclusions

Older age, longer hospital stays, and female sex increase the odds of in-patient allergy documentation. Regarding DH, BLA were referenced in 4% of inpatient records. Specific delabeling programs should be implemented to increase data reliability and patient safety.

The escalating global allergy epidemic has emerged as a pressing and persistent challenge, exerting a profound impact on human health systems across centuries. This burgeoning predicament can be attributed to contemporary lifestyles, environmental influences, and genetic predispositions. The manifestation of allergy-related factors exhibits dynamic fluctuations contingent on temporal shifts, geographical distinctions, cultural variances, and diverse demographic strata. In this review, we present recent epidemiological insights derived from two distinct birth cohorts: the Japan Environment and Children's Study (JECS), encompassing the entirety of Japan, and the Tokyo Children's Health, Illness, and Development Study (T-Child Study) within Tokyo. Through this comprehensive review, we offer a comprehensive overview of the latest epidemiological discoveries stemming from these pivotal Japanese birth cohorts, thereby affording a unique opportunity to deliberate on imperative strategies for the optimal management of the allergy epidemic.

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP).

Methods

Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments.

Results

LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs.

Conclusions

LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.