Allergy, Asthma & Immunology Research最新文献

Purpose: Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) tend to have more severe respiratory symptoms than those with asthma or COPD only. In this study, we sought to identify genetic variants associated with ACO.

Methods: ACO was defined as patients with physician-diagnosed or self-reported asthma and COPD. Meta-analysis of genome-wide association studies (GWASs) of ACO was performed in non-Hispanic White (NHW: 4,292 ACO vs. 114,816 controls) and non-Hispanic Black or African American (NHB-AA: 2,335 ACO vs. 45,949 controls). Candidate genes for asthma or COPD were further pairwise compared among ACO, asthma, COPD, and control groups.

Results: The prevalence rates of ACO/asthma/COPD were 2.46/8.89/3.57 (% of 200,369), 4.06/10.00/3.89 (% of 70,329), 1.40/10.21/1.40 (% of 6,093), and 0.43/4.55/0.58 (% of 12,783) for NHW, NHB-AA, Hispanic or Latino White, and non-Hispanic Asian, respectively. Patients with ACO or COPD and asthma were predominantly smokers and non-smokers, respectively. Patients with ACO showed highest blood eosinophil counts. Meta-analysis of GWASs identified rs1420101 (odds ratio [OR], 1.11; P = 8.29 × 10^-9) in interleukin 1 receptor like 1 (IL1RL1) and rs2428305 (OR, 1.16; P = 4.49 × 10^-8) in KIAA1217 associated with ACO. A group of asthma candidate genes (GSDMB, IL33, IL13, TSLP, HLA-DQB1, and IL1RL1) were associated with ACO and asthma but not associated with COPD. A group of COPD candidate genes (HHIP and CHRNA5) were associated with ACO and COPD (lung function or smoking behavior) but not associated with asthma.

Conclusions: Prevalence of chronic respiratory diseases differs in racial/ethnic groups. On the basis of our phenotypic and genetic findings, we speculate that patients who carry asthma and COPD risk alleles, further influenced by smoking, may develop into ACO. IL1RL1 is a biomarker for ACO, and anti-IL1RL1 biologics may be investigated in patients with ACO stratified by single nucleotide polymorphisms and IL1RL1 expression levels.

The association between atopic dermatitis (AD) and autoimmune thyroid disease (AITD) has received increasing attention. We investigated the association between AD and the risk of AITD in the Korean adult population. The medical data from 5,410 individuals aged ≥ 19 years from the Korea National Health and Nutrition Examination Survey 2013-2015 were categorized into 2 groups: (1) the thyroid dysfunction group (if they met the criteria of overt hyperthyroidism or overt hypothyroidism) and (2) the anti-thyroid peroxidase antibody (anti-TPO Ab)-positive group. Thyroid dysfunction and anti-TPO Ab positivity were each regarded as surrogate markers for the risk of AITD. The association between AD and the risk of AITD was investigated using multivariable logistic regression analysis to obtain the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Age-stratified analyses were performed to assess the AD-conferred risks in each age group. Among 5,410 subjects (mean age: 44 years; 51% male), the prevalence of AD, thyroid dysfunction, and anti-TPO Ab positivity was 3.5%, 1.0%, and 6.4%, respectively. Individuals with AD had a higher tendency of having thyroid dysfunction (aOR,1.65; 95% CI, 0.44-6.23) and anti-TPO Ab positivity (aOR, 1.40; 95% CI, 0.73-2.70); however, none of the associations reached statistical significance in this analysis. Nevertheless, in the young adult group (aged 19-39 years), a statistically significant association between AD and thyroid dysfunction (aOR, 5.86; 95% CI, 1.51-22.67) and a marginally significant association between AD and anti-TPO Ab positivity (aOR, 2.05; 95% CI 0.91-4.65; P = 0.08) were found. Among older adults (aged ≥ 40 years), no statistically significant associations were observed for thyroid dysfunction (aOR, 0.41; 95% CI, 0.05-3.30) or anti-TPO Ab positivity (aOR, 1.00; 95% CI, 0.32-3.12). This suggests a relationship between AD and the risk of AITD, highlighting the need to consider comorbid thyroid disease in young adults with AD.

Purpose: Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) are commonly used to assess epidermal barrier hydration. We investigated the associations of TEWL and SCH levels in newborns and the incidence of atopic dermatitis (AD) within the first 3 months of age.

Methods: We measured SCH and TEWL levels on the cheeks of 330 healthy full-term Vietnamese newborns within 48 hours after birth using a GPSkin Barrier Pro^® device (GPOWER Inc., Korea). Subsequently, 233 newborns completed the follow-up via telephone calls over a period of 3 months. Any cases of AD and other skin disorders, including seborrheic dermatitis, diaper dermatitis, perianal dermatitis, or contact dermatitis that developed during the follow-up period, were recorded; AD was diagnosed based on the UK Working Party diagnostic criteria.

Results: A total of 233 newborns were followed up during the first 3 months of age, of whom 29 (12.4%) were diagnosed with AD. An increased risk of AD development was associated with higher TEWL levels within 48 hours after birth (adjusted risk ratio [aRR], 1.31; 95% confidence interval [CI], 1.14-1.51; P < 0.001) and longer gestational age (aRR, 2.71; 95% CI, 1.11-6.65, P = 0.029). A receiver operating characteristic curve analysis indicated that the TEWL levels could serve as a predictive factor for AD development in the first 3 months of life, with an area under the curve of 0.77 (95% CI, 0.67-0.86, P < 0.001).

Conclusions: The TEWL levels and gestational age within 48 hours after birth could serve as predictive factors for the development of AD in the first 3 months of life. This finding establishes a basis for the development of optimal prevention methods for AD.

Purpose: The objective of this trial was to evaluate the efficacy and safety of anti-IgE monoclonal antibody (CMAB007) in Chinese patients with inadequately controlled moderate or severe asthma with increased total IgE level despite medium or high dose inhaled corticosteroids (ICS)/long acting β₂-agonist (LABA) treatment.

Methods: This was a multicenter, randomized, placebo controlled, double blinded, phase 3 trial. Eligible patients with moderate or severe asthma with increased total IgE level (60-1,500 IU/mL) receiving optimal ICS-LABA were randomly assigned to receive CMAB007 or placebo treatment at a 2:1 ratio for 24 weeks. The primary efficacy endpoint was asthma exacerbation (AE) rate, the key second endpoints were asthma control test (ACT) score, pulmonary function and safety.

Results: A total of 392 patients were included in the efficacy analysis. AE rate was 0.45 with CMAB007 and 0.66 with placebo (hazard ratio, 0.68; 95% confidence interval, 0.49, 0.96; P = 0.030). The proportions of patients showing an increase of at least 3 points from baseline in ACT scores were greater in the CMAB007 group than in the placebo group at Week 8 (49.8% vs. 36.9%, P = 0.018), Week 16 (59.4% vs. 42.9%, P = 0.003) and Week 24 (60.2% vs. 47.0%, P = 0.019). Greater improvement of pre-bronchodialteor forced expiratory volume in 1 second was achieved in the CMAB007 group at 4 weeks (11.40% vs. 5.03%, P = 0.006), 8 weeks (16.27% vs. 6.57%, P = 0.003), 12 weeks (16.51% vs. 6.60%, P = 0.002) and 16 weeks (20.18% vs. 7.42%, P = 0.002). The incidence of adverse events was similar between the CMAB007 (77.2%) and placebo groups (75.2%).

Conclusions: CMAB007 reduces AE and improves asthma control, lung function and quality of life without additional safety concern in Chinese patients having moderate to severe asthma with increased total IgE level.

Trial registration: ClinicalTrials.gov Identifier: NCT03468790.

Purpose: The impact of coronavirus disease 2019 (COVID-19) on patients with primary immunodeficiency (PID) remains insufficiently characterized. This study aimed to describe the clinical manifestations, disease course, and outcomes of COVID-19 in patients with PID.

Methods: Adult patients with PID who had COVID-19 infection between March 2020 and August 2022 were screened. Demographic and clinical data were retrospectively collected from institutional databases, and additional information was obtained through a patient questionnaire.

Results: A total of 36 patients (19 males, 17 females; median age: 36.5 years) with various PID subtypes were included: 24 with common variable immunodeficiency (CVID), 3 with cytotoxic T-lymphocyte-associated protein-4 haploinsufficiency, 3 with X-linked agammaglobulinemia (XLA), 2 with hypogammaglobulinemia, 1 with lipopolysaccharide-responsive and beige-like anchor protein deficiency, 1 with DiGeorge syndrome, 1 with mitochondrial neurogastrointestinal encephalomyopathy syndrome, and 1 with CVID-like capillary malformation-arteriovenous malformation syndrome 2. Overall, 63.9% (n = 23) were managed as outpatients, while 36.1% (n = 13) required hospitalization. Admission to the intensive care unit was required in 19.4% (n = 7) of the cases. The overall case fatality rate was 8.3% (n = 3), which is higher than the rate observed in the general population. Although the majority experienced a mild clinical course, patients with XLA exhibited prolonged symptoms and persistent seropositivity. Risk factors associated with hospitalization included lymphopenia, elevated C-reactive protein and ferritin levels, dyspnea, COVID-19 Reporting and Data System score ≥ 4 on imaging, need for supplemental oxygen, prolonged symptoms, and extended polymerase chain reaction positivity.

Conclusions: A subset of adult patients with PID may be at increased risk for severe COVID-19.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a multifactorial pathophysiology. Although AD has been characterized by a T helper type 2 cell response, the role of the myeloid populations in the pathogenesis of AD remains unclear.

Methods: Peripheral blood mononuclear cells from 48 AD patients and 48 healthy controls were profiled using mass cytometry, primarily focusing on dendritic cells (DCs) and monocytes. Further analysis of a public single-cell RNA sequencing (scRNA-seq) dataset and immunofluorescence staining of lesional skin in AD were conducted for further validation.

Results: The frequency of circulating cDC1 was significantly decreased in AD compared with healthy controls. The frequency of cDC1 was negatively correlated with disease severity scores and serum immunoglobulin E levels. The expression of FcεRIa was significantly increased in the DC populations, including cDC1, cDC2, plasmacytoid DC, and Axl+ DC. CD163, a marker of the inflammatory DC subset DC3, was increased in AD patients, suggesting an increased DC3 signature in AD patients. Analysis of a public scRNA-seq dataset further corroborated the decreased frequency of cDC1. The expression of cutaneous lymphocyte antigen was increased in cDC1 of AD compared with HC, suggesting increased migration of cDC1 to the skin. Aligned with this hypothesis, the frequency of cDC1 was shown to be increased in AD lesional skin using immunofluorescence staining.

Conclusions: These results provide insight into the potential role of DC and monocyte populations in AD. We report decreased circulating cDC1 frequency and increased DC3 signature. The corresponding increased frequency of cDC1 in AD lesional skin implies their role in modulating AD pathophysiology.

Asthma is a chronic respiratory disease affecting more than 300 million people globally and remains a major cause of morbidity, mortality, and healthcare burden. Traditionally, asthma has been managed using a stepwise treatment algorithm focused on inhaled corticosteroids, bronchodilators, and add-on therapies. While this approach provides a broad framework for care, it does not adequately account for the heterogeneity of the disease, which encompasses diverse clinical phenotypes, underlying endotypes, and variable treatment responses. Many patients with moderate-to-severe asthma continue to experience poor control, frequent exacerbations, and impaired quality of life despite standard therapies. Precision medicine offers an alternative strategy by identifying and targeting specific "treatable traits" across pulmonary, extrapulmonary, and behavioral domains. Advances in biomarker profiling-including blood eosinophils, fractional exhaled nitric oxide, volatile organic compounds, and transcriptomics-have enabled more accurate risk prediction and patient stratification. Imaging techniques, such as high-resolution computed tomography and hyperpolarized magnetic resonance imaging, are improving the ability to detect small airways dysfunction, mucus plugging, and other key disease mechanisms. Biologic therapies directed at type 2 inflammation pathways, including anti-immunoglobulin E, anti-interleukin (IL)5, anti-IL4Rα, and anti-thymic stromal lymphopoietin agents, have significantly reduced exacerbation rates and improved lung function, although biomarker variability, high treatment costs, and limited accessibility remain barriers to widespread use. Emerging oral, inhaled, and long-acting biologics further expand the therapeutic landscape. Looking forward, the integration of multi-omics, deep phenotyping, and artificial intelligence promises to transform asthma management by enabling personalized therapy tailored to individual patient profiles. This narrative review examines the limitations of the conventional stepwise approach, highlights recent advances in phenotyping and targeted treatment, and explores the role of novel technologies in shaping the future of asthma care. By moving beyond the one-size-fits-all model, precision medicine has the potential to improve long-term outcomes, safety, and quality of life for patients with asthma.

Purpose: Biallelic repeat expansions in the Replication Factor C Subunit 1 (RFC1) gene are associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Recent studies have shown that chronic cough often precedes neurological symptoms in CANVAS by 10-20 years, suggesting a potential link between RFC1 repeat expansion and chronic cough. However, the prevalence and clinical relevance of RFC1 expansions in chronic cough, particularly in non-Caucasian populations, remain unknown.

Methods: We analyzed 128 consecutive patients with chronic cough who were enrolled in the Korean Chronic Cough Registry at 2 tertiary clinics. All patients underwent a comprehensive clinical evaluation and were followed up for at least 6 months to assess treatment response and to identify the diagnosis of refractory chronic cough (RCC). RFC1 repeat expansions, including both biallelic and monoallelic variants, were assessed using flanking and repeat-primed polymerase chain reactions. Whole genome sequencing (WGS) was performed in selected cases to explore additional genetic variants.

Results: RFC1 repeat expansions were identified in 12 patients with chronic cough, comprising 3 biallelic (2.3%), and 9 monoallelic (7.0%) carriers. RCC was diagnosed in 55 of the 109 subjects who completed follow-up. The percentage of RFC1 expansions was significantly higher in RCC than in non-RCC (18.2% vs. 1.9%, P = 0.005), comprising 5.5% biallelic and 12.7% monoallelic expansions in the RCC group. Carriers had longer cough duration (11.0 vs. 4.0 years, P = 0.048) and poorer cough-specific quality of life (Leicester Cough Questionnaire score: 8.5 ± 2.2 vs. 10.5 ± 3.4; P = 0.027). All of the biallelic carriers were diagnosed with RCC and showed poor response to antitussive therapies. WGS identified no additional pathogenic variants in most cases.

Conclusions: This is the first study to evaluate RFC1 repeat expansions in non-Caucasian patients with chronic cough. The findings suggest that RFC1 expansions may define a distinct, treatment-refractory phenotype of chronic cough.

Purpose: Cow's milk protein allergy (CMPA) is the most common food allergy in childhood. Oral immunotherapy (OIT) has proven effective in achieving tolerance in children with persistent CMPA (pCMPA), although the underlying immunological mechanisms that allow for tolerance remain incompletely understood. We aimed to characterize the immune profile of pCMPA children following successful OIT and compare it to healthy controls (HC).

Methods: Thirty pCMPA children and 33 HC were recruited. T and B cell populations were assessed by flow cytometry, and specific immunoglobulins (sIgs) to milk allergens were measured by fluorometric enzyme-immunoassay.

Results: Compared to HC, pCMPA children showed reduced B cells and activated T cells. Activated CD4⁺ T cells negatively correlated with OIT duration. Although sIgEs to casein remained ≥ class 3 in some patients, overall post-OIT sIgEs were lower compared to pre-OIT levels. Additionally, sIgG4 increased after OIT, particularly in patients with detectable sIgA. After OIT, pCMPA patients with sIgEs ≥ class 3 presented shorter relapse periods and fewer B cells and T cells compared to those with sIgEs < class 3. Interestingly, sIgEs correlated positively with regulatory T cells, though different sIgEs specificities showed distinct relationships with immune parameters. Age-related differences were observed: only children > 10 years showed significant reductions in T and B cells compared to their respective age-matched controls.

Conclusions: OIT modulates immune activation in pCMPA, reducing sIgE and increasing sIgG4 levels. Different relations between distinct sIgs and immune parameters may denote different stimulating and tolerance-inducing capacities for distinct cow's milk components. Age and time since OIT completion influence immune recovery, highlighting the complexity of tolerance mechanisms.