Allergology International最新文献

Background

Asthma has been identified as different phenotypes due to various risk factors. Age differences may have potential effects on asthma phenotypes. Our study aimed to identify potential asthma phenotypes among adults divided by age as either younger or older than 65 years. We also compared differences in blood granulocyte patterns, occupational asthmagens, and asthma control-related outcomes among patient phenotype clusters.

Methods

We recruited nonelderly (<65 years old) (n = 726) and elderly adults (≥65 years old) (n = 201) with mild-to-severe asthma. We conducted a factor analysis to select 17 variables. A two-step cluster analysis was used to classify subjects with asthma phenotypes, and a discriminant analysis was used to verify the classification of cluster results.

Results

There were three clusters with different characteristics identified in both the nonelderly and elderly asthmatic adults. In the nonelderly patient group, cluster 2 (obese, neutrophilic phenotypes) had a 1.85-fold significantly increased risk of asthma exacerbations. Cluster 3 (early-onset, atopy, and smoker with an eosinophil-predominant pattern) had a 2.37-fold risk of asthma exacerbations and higher oral corticosteroid (OCS) use than cluster 1 (late-onset and LMW exposure with paucigranulocytic blood pattern). Among elderly patients, cluster 2 had poor lung function and more ex-smokers. Cluster 3 (early-onset, long asthma duration) had the lowest paucigranulocytic blood pattern percentages in the elderly group.

Conclusions

The novelty of the clusters was found in age-dependent clusters. We identified three distinct phenotypes with heterogeneous characteristics, asthma exacerbations and medicine use in nonelderly and elderly asthmatic patients, respectively. Classification of age-stratified asthma phenotypes may lead to precise identification of patients, which provides personalized disease management.

Background

Nasal congestion in allergic rhinitis (AR) is caused by vascular hyperpermeability and vascular relaxation of the nasal mucosa. We previously detected high levels of a lipoxygenation metabolite of dihomogammalinolenic acid, 15-hydroxy-8Z,11Z,13E-eicosatrienoic acid (15-HETrE) in the nasal lavage fluid of AR model mice. Here, we investigated the effects of 15-HETrE on vascular functions associated with nasal congestion.

Methods

We measured 15-HETrE levels in the nasal lavage fluid of ovalbumin-induced AR model mice and nasal discharge of patients with AR. We also assessed nasal congestion and vascular relaxation in mice. Vascular contractility was investigated using isolated mouse aortas.

Results

Five ovalbumin challenges increased 15-HETrE levels in AR model mice. 15-HETrE was also detected in patients who exhibiting AR-related symptoms. Intranasal administration of 15-HETrE elicited dyspnea-related behavior and decreased the nasal cavity volume in mice. Miles assay and whole-mount immunostaining revealed that 15-HETrE administration caused vascular hyperpermeability and relaxation of the nasal mucosa. Intravital imaging demonstrated that 15-HETrE relaxed the ear vessels that were precontracted via thromboxane receptor stimulation. Moreover, 15-HETrE dilated the isolated mouse aortas, and this effect was attenuated by K⁺ channel inhibitors and prostaglandin D₂ (DP) and prostacyclin (IP) receptor antagonists. Additionally, vasodilatory effects of 15-HETrE were accompanied by an increase in intracellular cAMP levels.

Conclusions

Our results indicate that 15-HETrE, whose levels are elevated in the nasal cavity upon AR, can be a novel lipid mediator that exacerbates nasal congestion. Moreover, it can stimulate DP and IP receptors and downstream K⁺ channels to dilate the nasal mucosal vasculature.

Background

Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age.

Methods

The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes.

Results

Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23–1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways.

Conclusions

Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

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.