Allergy, Asthma & Immunology Research最新文献

Allergic diseases are a major public health problem with increasing prevalence. These immune-mediated diseases are characterized by defective epithelial barriers, which are explained by the epithelial barrier theory and continuously emerging evidence. Environmental exposures (exposome) including global warming, changes and loss of biodiversity, pollution, pathogens, allergens and mites, laundry and dishwasher detergents, surfactants, shampoos, body cleaners and household cleaners, microplastics, nanoparticles, toothpaste, enzymes and emulsifiers in processed foods, and dietary habits are responsible for the mucosal and skin barrier disruption. Exposure to barrier-damaging agents causes epithelial cell injury and barrier damage, colonization of opportunistic pathogens, loss of commensal bacteria, decreased microbiota diversity, bacterial translocation, allergic sensitization, and inflammation in the periepithelial area. Here, we review scientific evidence on the environmental components that impact epithelial barriers and microbiome composition and their influence on asthma and allergic diseases. We also discuss the historical overview of allergic diseases and the evolution of the hygiene hypothesis with theoretical evidence.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

Purpose: Atmospheric fungi are associated with respiratory allergies in humans, and some fungal spores can cause allergic diseases. Environmental and biological factors influence the concentrations of atmospheric spores. In this study, we evaluated the climate change-induced annual variations in fungal spore concentrations and allergic sensitization rates in the Seoul Metropolitan Area over a period of 25 years.

Methods: Fungal spores and pollen were obtained from Hanyang University Seoul and Guri Hospitals; they were identified and counted for 25 years (1998-2022). The study participants included patients who underwent tests for allergic diseases in both hospitals. Their allergenic sensitization rates were determined via allergic skin prick and serum tests, after which their sensitization rates to allergenic fungi and pollens were calculated. The daily climatic variables were obtained from the Korea Meteorological Administration.

Results: The total annual atmospheric fungal concentrations decreased in both areas during the period. Simultaneously, we recruited 21,394 patients with allergies (asthma, 1,550; allergic rhinitis, 5,983; and atopic dermatitis, 5,422) from Seoul and Guri Hospitals for allergenic fungal sensitization evaluations over the period. The allergenic fungal sensitization rates decreased annually in both areas over that time `+(Alternaria [3.5%] and Cladosporium [4.4%] in 1998; Alternaria [0.2%] and Cladosporium [0.2%] in 2022). In contrast, the annual pollen concentrations increased with the sensitization rates to pollen in children.

Conclusions: The atmospheric fungal concentrations decreased annually, with allergic sensitization rate decreasing over the period of 25 years. Allergenic fungal sporulation could decrease with climate changes, such as desertification and drought. Extended monitoring periods and further large-scale studies are required to confirm the causality and to evaluate the impact of climate change.

Purpose: Our study aimed to explore potential prognostic factors in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) patients from easily accessible laboratory data and to investigate whether the combination of these indicators with a score for toxic epidermal necrolysis (SCORTEN) can improve the predictive value.

Methods: Data from 85 SJS/TEN patients hospitalized from 2010 to 2021 were retrospectively analyzed. The primary outcome was in-hospital mortality. Univariate analysis was used to screen for laboratory indexes associated with death. Logistic regression was used to analyze significant risk factors for death. The differentiation and calibration of SCORTEN and modified score were assessed using receiver operating characteristic (ROC) curves and Hosmer-Lemeshow goodness-of-fit test. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate the incremental prognostic value.

Results: Among the 85 patients (37 males, 48 females) aged 14-88 years, the mortality rate was 11.8% (n = 10). SCORTEN had good discrimination and calibration to predict mortality in this cohort of patients (area under the ROC curve [AUC] of 0.874, 95% confidence interval [CI], 0.758-0.990; Hosmer-Lemeshow goodness-of-fit test P = 0.994). Red cell distribution width-standard deviation index (RDW-SD) > 47.9 fL and procalcitonin (PCT) > 0.67 ng/mL were significant risk factors for death. When adding the 2 factors to SCORTEN, AUC was 0.915 (95% CI, 0.833-0.997), but not statistically different compared to SCORTEN alone (P = 0.091). The NRI was 1.2 (95% CI, 0.672-1.728; P < 0.001) and the IDI was 0.09 (95% CI, 0.011-0.173; P = 0.026), still suggesting that the modified score had better discriminatory and predictive power than SCORTEN alone. The modified score also showed good calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.915).

Conclusions: SCORTEN is a good predictor of mortality in SJS/TEN patients in southwest China. Combining RDW-SD > 47.9 fL and PCT > 0.67 ng/mL with SCORTEN may enhance the ability to predict prognosis.

Purpose: Numerous genes have been associated with allergic diseases (asthma, allergic rhinitis, and eczema), but they explain only part of their heritability. This is partly because most previous studies ignored complex mechanisms such as gene-environment (G-E) interactions and complex phenotypes such as co-morbidity. However, it was recently evidenced that the co-morbidity of asthma-plus-eczema appears as a sub-entity depending on specific genetic factors. Besides, evidence also suggest that gene-by-early life environmental tobacco smoke (ETS) exposure interactions play a role in asthma, but were never investigated for asthma-plus-eczema. To identify genetic variants interacting with ETS exposure that influence asthma-plus-eczema susceptibility.

Methods: To conduct a genome-wide interaction study (GWIS) of asthma-plus-eczema according to ETS exposure, we applied a 2-stage strategy with a first selection of single nucleotide polymorphisms (SNPs) from genome-wide association meta-analysis to be tested at a second stage by interaction meta-analysis. All meta-analyses were conducted across 4 studies including a total of 5,516 European-ancestry individuals, of whom 1,164 had both asthma and eczema.

Results: Two SNPs showed significant interactions with ETS exposure. They were located in 2 genes, NRXN1 (2p16) and TNS1 (2q35), never reported associated and/or interacting with ETS exposure for asthma, eczema or more generally for allergic diseases. TNS1 is a promising candidate gene because of its link to lung and skin diseases with possible interactive effect with tobacco smoke exposure.

Conclusions: This first GWIS of asthma-plus-eczema with ETS exposure underlines the importance of studying sub-phenotypes such as co-morbidities as well as G-E interactions to detect new susceptibility genes.

Purpose: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder that leads to secondary ciliary dysfunction. PCD is a rare disease, and data on it are limited in Korea. This study systematically evaluated the clinical symptoms, diagnostic characteristics, and treatment modalities of pediatric PCD in Korea.

Methods: This Korean nationwide, multicenter study, conducted between January 2000 and August 2022, reviewed the medical records of pediatric patients diagnosed with PCD. Prospective studies have been added to determine whether additional genetic testing is warranted in some patients.

Results: Overall, 41 patients were diagnosed with PCD in 15 medical institutions. The mean age at diagnosis was 11.8 ± 5.4 years (range: 0.5 months-18.9 years). Most patients (40/41) were born full term, 15 (36.6%) had neonatal respiratory symptoms, and 12 (29.3%) had a history of admission to the neonatal intensive care unit. The most common complaint (58.5%) was chronic nasal symptoms. Thirty-three patients were diagnosed with transmission electron microscopy (TEM) and 12 patients by genetic studies. TEM mostly identified outer dynein arm defects (alone or combined with inner dynein arm defects, n = 17). The genes with the highest mutation rates were DNAH5 (3 cases) and DNAAF1 (3 cases). Rare genotypes (RPGR, HYDIN, NME5) were found as well. Chest computed tomography revealed bronchiectasis in 33 out of 41 patients. Among them, 15 patients had a PrImary CiliAry DyskinesiA Rule score of over 5 points.

Conclusions: To our knowledge, this is the first multicenter study to report the clinical characteristics, diagnostic methods, and genotypes of PCD in Korea. These results can be used as basic data for further PCD research.

Chronic urticaria (CU) is a common problem with a high disease burden that has a significant negative impact on quality of life. Many patients are undertreated, and awareness of management strategies is low among clinicians. The present study aimed to improve understanding of CU from the patients' perspective, including the disease burden and current healthcare system use. Adult patients who presented to our referral hospital for CU treatment completed self-report questionnaires about demographics, clinical characteristics of CU, the impact of CU on daily life, unmet needs, and the history of medical service usage. This self-report survey included 127 participants (females, 57.0%; mean age, 42.0 ± 13.6 years; mean CU duration, 1.8 ± 3.4 years); 51.6% reported frequent discomfort with CU in daily life, including 44.1% of those who reported a good response to medication. More than half of the respondents reported a depressed mood and anxiety. Although 46.4% of the respondents reported that urticaria completely disappeared while on medication, only 10% were satisfied with the CU management provided by primary care hospitals. The principal cause of dissatisfaction was that they did not know the cause of CU (68.4% of patients). In total, 55% of the patients visited 2 or more hospitals before presenting to our referral hospital and 6.3% had tried folk remedies. In conclusion, most patients report that CU is not adequately controlled. Therefore, in addition to appropriate medication, information on the cause of CU, long-term treatment plan, medication safety, and expected prognosis is required to meet patients' needs.

Purpose: Humulus japonicus (HJ) is one of the most important causes of weed pollinosis in East Asia. The 10 kDa protein with pI 10 in 2-dimensional gel has been recognized as the representative major allergen of HJ, but its major allergens have not been characterized. This study aimed to characterize the major allergen of HJ.

Methods: A major allergen in Japanese hop was detected by proteome analysis; it was purified to homogeneity and its sequence was obtained by transcriptome analysis. The recombinant proteins were produced in Escherichia coli and Pichia expression systems, and their immunoglobulin E (IgE) reactivities were compared to those of the natural counterpart. We also analyzed post-translational modifications such as glycosylation and phosphorylation.

Results: Pectin methylesterase inhibitor, Hum j 6, was found to be the major allergen of HJ, and in silico signal peptide prediction corresponds to a 15.1 kDa protein with a theoretical pI of 8.28. Natural Hum j 6 was recognized by IgE antibodies from 86.4% (19/22) of HJ pollinosis patients, whereas the recombinant proteins did not show strong IgE reactivity. No glycosylation was detected, while at least 15 phosphorylated amino acids, possibly causing the pI and molecular weight shift, were detected by tandem mass spectrometry analysis.

Conclusions: Hum j 6 was identified as the representative major allergen of HJ and seems to be modified significantly after translation. These findings are useful for the development of component-resolved diagnosis and immunotherapy.