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Abstract: Background: Reducing near‐fatal asthma exacerbations is a critical problem in asthma management. Objectives: To determine patterns of factors preceding asthma exacerbations in a real‐world setting. Methods: In a nationwide prospective study of 190 patients who had experienced near‐fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2‐week period before admission. Results: Three distinct clusters of symptoms were defined employing the self‐reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle‐aged patients with low Body mass index and tendency to depression who had stopped anti‐asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle‐aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long‐acting beta‐agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild‐moderate symptoms. There were no differences in overuse of short‐acting beta‐agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters. Conclusion: To reduce severe or life‐threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti‐type 2 response‐targeted therapies should be considered for cluster C. [ABSTRACT FROM AUTHOR]

Background Booklice, belonging to the order Psocoptera, are small household insect pests that are distributed worldwide. Liposcelis bostrychophila, a common home-inhabiting species of booklouse, infests old books, sheets of paper, and stored food. Recent entomological and serological studies demonstrated that L. bostrychophila accounted for the majority of detectable insects in house dust and could be a potent inducer of respiratory allergy. Our recent proteomic analysis identified a potent allergenic protein from L. bostrychophila, designated Lip b 1, and determined its partial amino acid sequences. Methods Cloning of c DNAs for Lip b 1 was performed by large-scale transcriptome analysis ( RNA-seq) and subsequent reverse transcription polymerase chain reaction. The full-length amino acid sequences deduced from Lip b 1 cDNAs were bioinformatically analyzed. The recombinant proteins of glutathione S-transferase ( GST)-fused Lip b 1 were analyzed by Western blot and enzyme-linked immunosorbent assay. Results Lip b 1 c DNAs encoding two types of 254-amino acid proteins were cloned. The clones shared 87% identity, and the deduced molecular weights and isoelectric points were consistent with those determined in our previous study. The two types of Lip b 1 proteins in the GST-fused form were similarly reactive with sera from allergic patients sensitized with L. bostrychophila. Conclusions Lip b 1 is a novel protein possibly causing booklouse allergy. [ABSTRACT FROM AUTHOR]

RATIONALE: IL-18 is a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses. Recent murine and human genetic studies have shown its role in the pathogenesis of asthma. OBJECTIVES: We conducted an association study in a Japanese population to discover variants of IL-18 that might have an effect on asthma susceptibility and/or progression and conducted functional analyses of the related variants. METHODS: The IL-18 gene locus was resequenced in 48 human chromosomes. Asthma severity was determined according to the 2002 Global Initiative for Asthma Guidelines. Association and haplotype analyses were performed using 1,172 subjects. MEASUREMENTS AND MAIN RESULTS: Although no polymorphisms differed significantly in frequency between the control and adult asthma groups, rs5744247 C>G was significantly associated with the severity of adult asthma (steps 1, 2 vs. steps 3, 4; P = 0.0034). We also found a positive association with a haplotype (P = 0.0026). By in vitro functional analyses, the rs5744247 variant was found to increase enhancer-reporter activity of the IL-18 gene in bronchial epithelial cells. Expression levels of IL-18 in response to LPS stimulation in monocytes were significantly greater in subjects homozygous for the susceptibility G allele at rs5744247 C>G. Furthermore, we found a significant correlation between the serum IL-18 level and the genotype of rs5744247 (P = 0.031). CONCLUSIONS: Although the association results need to be replicated by other studies, IL-18 variants are significantly associated with asthma severity, and the rs5744247 variant reflects higher transcriptional activity and higher expression of IL-18 in LPS-stimulated monocytes and a higher serum IL-18 level. [ABSTRACT FROM AUTHOR]

A correction to the article "Molecular-based allergy diagnosis of allergic bronchopulmonary aspergillosis in Aspergillus fumigatus-sensitized Japanese patients" that was published in 2015 issue is presented.

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., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship　between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples., Methods: We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC)., Results: We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively)., Conclusions: The gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS., Trial Registration: This study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018., (© 2024. The Author(s).)