Allergy, Asthma & Immunology Research最新文献

The pathogenesis of atopic dermatitis (AD) is multifactorial, involving a dynamic interplay between genetic susceptibility, skin-barrier dysfunction, microbiome alterations, and immune dysregulation, whereas food allergy (FA) arises from the interplay of transcutaneous sensitization to food allergens and failure in the induction of oral tolerance. Skin epicutaneous sensitization is commonly involved in the development of AD and FA. Although clinical trials have been conducted to prevent AD or FA by applications of emollients on the skin after birth, the results are not consistent. For more effective preventive strategies, reliable biomarkers are required to identify high-risk individuals. Skin tape stripping (STS) is a non-invasive technique for identifying these biomarkers in the skin. By analyzing the stratum corneum collected via STS, researchers can gain molecular or cellular insights into the early pathogenesis and potential progression of AD and FA. This review aims to elucidate the critical aspects of AD and FA, underlying their pathogenesis, early manifestations, and STS's potential as a tool for identifying predictive non-invasive biomarkers in infants prior to onset of clinical disease.

Purpose: Limited knowledge exists regarding the psychosocial characteristics of young Asian children affected by food allergies (FAs) and their caregivers. This study aims to assess the usefulness of the Food Allergy Severity Score (FASS) system in evaluating the risk of emotional impacts on young children and caregivers who are dealing with severe FA.

Methods: Children between 2 and 10 years of age who were diagnosed with FA and following an elimination diet were enrolled in the study. The FASS, Korean Parenting Stress Index, and Korean Behavior Assessment System for Children-2 were used for evaluating the above mentioned risk.

Results: Among the 75 participants, 64.0% had a history of anaphylaxis, and 56.0% reported multiple FAs. A total of 160 cases of FASS was documented across 21 types of food and classified as mild (n = 5, 1.07), moderate (n = 100, 2.01-4.01), or severe (n = 55, 4.24-6.84). The concordance of calculated- and stakeholder interpreted-FASS was moderate (kappa 0.587). Children with severe FASS (sFASS) showed increased risk for functional communication (relative risk [RR], 1.57; 95% confidence interval [CI], 0.99-2.48) and increased parental reinforcement (RR, 1.40; 95% CI, 0.91-2.14). Their caregivers exhibited reduced levels of demandingness (RR, 0.59; 95% CI, 0.37-0.94) and role restriction (RR, 0.62; 95% CI, 0.39-0.98). Receiver operating characteristic curves suggested that functional communication (numeric FASS cutoff, 3.47; area under the curve [AUC], 0.695), withdrawal (cutoff, 3.40; AUC, 0.657), developmental social disorders (cutoff, 3.96; AUC, 0.648), and reinforces parent (cutoff, 3.15; AUC, 0.646) were possibly be affected.

Conclusions: The FASS provides an objective tool to assess pediatric FA severity. Early psychosocial intervention for young children with severe FASS and their caregivers may improve prognosis by identifying possible adaptive skill deficiencies and excessive parenting stresses.

Pregnancy is a risk factor for asthma exacerbation and may trigger new-onset asthma in nonasthmatics. This study evaluated the epidemiology of newly diagnosed asthma during pregnancy and the associated risk factors among previously nonasthmatic women. Twelve-year medical data from the Korean National Health Insurance claims database (from January 2007 to December 2018) of Korean women who gave birth between January 2012 and December 2015 were collected. Previously nonasthmatic women were defined as those who had not been diagnosed with asthma for at least 4 years before pregnancy. Asthma flare-up was defined as asthma diagnosed three times or more and treated at least once with an oral corticosteroid. A nested case-control study was performed, and then the derived risk factors were applied to whole study population. Among the nonasthmatic women, 7.5% experienced asthma during pregnancy including episodes requiring hospitalization and 18.6% of them visited emergency room. Older age, primiparity, multi-fetal pregnancy, and rhinitis were identified as the risk factors. Among the entire study population, moderate to severe rhinitis was a significant risk factor across all age groups, while primiparity with multi-fetal pregnancy was one for older pregnant women; 22.7% in those ≥ 34 years old experienced asthma flare-ups compared to only 3.5% in the < 34 age group. A substantial portion of pregnant women with no history of asthma experienced an asthma flare-up during pregnancy. Multi-fetal pregnancy as primiparity at a later age and moderate to severe rhinitis are risk factors for the new development of asthma.

Purpose: Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively.

Methods: The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma.

Results: The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts.

Conclusions: The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.

Purpose: Long-term data are limited on the safety and efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma from Korea. The current subgroup analysis was designed to evaluate the long-term safety and efficacy of dupilumab in patients enrolled from Korean centers in the parent studies (phase 2b and QUEST) and who participated in the TRAVERSE open-label extension (OLE) study.

Methods: TRAVERSE was a global, multicenter, OLE study that assessed the safety and efficacy of dupilumab 300 mg every 2 weeks for up to 96 weeks in patients (n = 2,282) with uncontrolled, moderate-to-severe asthma who completed prior dupilumab asthma clinical trials. The primary outcome was the incidence of any treatment-emergent adverse events (TEAEs); the secondary outcomes included annualized severe exacerbation rate, pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), and 5-item Asthma Control Questionnaire (ACQ-5) score.

Results: Safety outcomes were consistent with the parent studies and the overall TRAVERSE population; out of 74 patients, 70 experienced ≥ 1 TEAE, and 6 (8.1%) discontinued because of adverse events. During the treatment period, the unadjusted annualized severe exacerbation rate was low (0.470). Improvement in pre-BD FEV1 was seen as early as Week 2 with a mean change from the parent study baseline (PSBL), standard deviation (SD) of 0.42 L (0.47), which was sustained until Week 96. Mean change from PSBL (SD) in ACQ-5 score was -1.32 (0.76) at Week 48.

Conclusions: This subgroup analysis of TRAVERSE showed the long-term safety and efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma enrolled from Korean centers.

Trial registration: ClinicalTrials.gov Identifier: NCT02134028.

This corrects the article on p. 300 in vol. 16, PMID: 38910287.

Purpose: Asthma, an airway inflammatory disease, involves multiple tumor necrosis factors (TNF). TNF ligand superfamily member 11 (TNFSF11) and its known receptor, TNF receptor superfamily 11A (TNFRSF11A), has been implicated in asthma; however, the related mechanisms remain unknown.

Methods: The serum and bronchial airway of patients with asthma and healthy subjects were examined. The air-liquid interface of primary human bronchial epithelial (HBE) cells, and Tnfsf11^+/- mouse, Tnfrsf11a^+/- mouse, and a humanized HSC-NOG-EXL mouse model were established. This study constructed short hairpin RNA (shRNA) of TNFSF11, TNFRSF11A, transforming growth factor β1 (TGFβ1), and transforming growth factor β receptor type 1 (TGFβR1) using lentivirus to further examine the ability of TNFSF11 protein.

Results: This study was the first to uncover TNFSF11 overexpression in the airway and serum of asthmatic human subjects, and the TNFSF11 in serum was closely correlated with lung function. The TNFSF11/TNFRSF11A axis deficiency in Tnfsf11^+/- or Tnfrsf11a^+/- mice remarkably attenuated the house dust mite (HDM)-induced signal transducer and activator of transcription 3 (STAT3) action and remodeling protein expression. Similarly, the HDM-induced STAT3 action and remodeling protein expression in HBE cells decreased after pretreatment with TNFSF11 or TNFRSF11A shRNA. Meanwhile, the expression of the remodeling proteins induced by TNFSF11 significantly decreased after pretreatment with-stattic (inhibitor of STAT3 phosphorylation) in HBE cells. The STAT3 phosphorylation and remodeling protein expression induced by TNFSF11 obviously decreased after pretreatment with TGFβ1 or TGFβR1 shRNA in HBE cells. The above results also verified that blocking TNFSF11 with denosumab alleviated airway remodeling via the TGFβ1/STAT3 signaling in the humanized HSC-NOG-EXL mice with HDM-induced asthma.

Conclusions: TGFβ1/STAT3 action was closely correlated with TNFSF11/TNFRSF11A axis-mediated airway remodeling. This study presented a novel strategy that blocks the TNFSF11/TNFRSF11A axis to exert a protective effect against asthma.

Purpose: Patients with non-eosinophilic asthma (NEA) are less responsive to anti-inflammatory drugs and suffer from frequent asthma exacerbations. The pathogenic mechanism of NEA is not fully understood; however, the roles of monocytes and autoimmune mechanisms targeting airway epithelial cell (AEC) antigens have been proposed.

Methods: The effects of monocyte extracellular traps (MoETs) on cytokeratin 19 (CK19) production in AECs, as well as the impact of CK19-specific immunoglobulin (Ig) G on neutrophil and monocyte activation, were investigated both in vivo and in vitro. Sixty asthmatic patients and 15 healthy controls (HCs) were enrolled, and the levels of serum immune complexes containing CK19-specific IgG and neutrophil extracellular trap (NET)-specific IgG were measured using enzyme-linked immunoassay.

Results: MoETs induced CK19 and CK19-specific IgG production. Furthermore, the levels of serum CK19-specific IgG were significantly higher in the NEA group than in the eosinophilic asthma group. Among patients with NEA, asthmatics with high levels of CK19-specific IgG had higher levels of myeloperoxidase and NET-specific IgG than those with low levels of CK19-specific IgG (P = 0.020 and P = 0.017; respectively). Moreover, the immune complexes from asthmatics with high CK19-specific IgG enhanced NET formation and reactive oxygen species production (neutrophil activation), which were suppressed by N-acetylcysteine and anti-CD16 antibody treatment.

Conclusions: These findings suggest that circulating CK19 and CK19-specific IgG may contribute to NET formation, leading to airway inflammation and steroid resistance in NEA.