Allergology International最新文献

Background

N-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results.

Methods

Following exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group.

Results

Levels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-<2 years of age and current eczema at 1-<2 and 0-<3 years of age. However, for food allergies, no significant associations were observed in the incidence in each group compared with the lowest intake group at any age.

Conclusions

The findings suggest that n-3 PUFA intake during pregnancy may reduce the risk of developing allergic diseases and symptoms in children. In addition, consumption of n-3 PUFAs or fish is very unlikely to increase the risk of allergy given that the results are from a country with high fish consumption. Trial registration: UMIN000030786 https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000030786.

The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches—proteomics, transcriptomics, and metabolomics—we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories.

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.

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.

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.

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.