Allergy, Asthma & Immunology Research最新文献

The concept of cough hypersensitivity suggests that central sensitization plays a role in the pathophysiology of chronic cough. However, it remains unclear which traits are associated with central sensitization features in patients with chronic cough. A cohort of 317 Korean patients with newly referred chronic cough underwent clinical evaluations. The Central Sensitization Inventory (CSI), a questionnaire originally developed as a screening tool to identify patients with Central Sensitization Syndrome, was also administered. Other patient-reported outcomes (PROs), such as the cough severity visual analogue scale, Leicester Cough Questionnaire (LCQ), Cough Hypersensitivity Questionnaire (CHQ), and the Center for Epidemiological Studies Depression (CES-D) scale, were also administered. Follow-up assessments were conducted one month later. At baseline, the presence of CSI scores of ≥ 40 was associated with being female (89.6% vs. 63.4%; P < 0.001), older age, concomitant symptoms, and cough-related complications. CSI scores correlated with PRO scores, including LCQ (r = -0.424, P < 0.001), CHQ (r = 0.373, P < 0.001), and CES-D (r = -0.660, P < 0.001). Their patterns of correlations were similar in the 1-month longitudinal follow-up data analysis. In conclusion, CSI scores in patients with chronic cough correlated with cough-specific and depression-related PROs, suggesting the potential relevance of central sensitization in certain phenotypes of chronic cough.

Purpose: Despite the emerging biologics, biomarkers and treatment options for asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) are still limited, requiring further research.

Methods: We enrolled 378 ACO patients from a multicenter real-world asthma cohort in Korea and compared the clinical characteristics, lung function, and exacerbation between type 2 (T2)-high and T2-low groups. We used the following comparisons: 1) low vs. high immunoglobulin E (IgE) group (≥ 100 IU/mL), 2) non-atopy vs. atopy group (sensitized to aeroallergen), 3) low vs. high blood eosinophil group (≥ 150/µL), and 4) low vs. high sputum eosinophil group (≥ 2%).

Results: The high sputum eosinophil ACO group (n = 37) showed significantly lower pre- and post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) (45.7% ± 15.8% vs. 55.9% ± 16.2%, P = 0.016; 1.3 ± 0.6 L vs. 1.6 ± 0.5 L, P = 0.013 for pre-BD FEV1; 0.53 ± 0.1 vs. 0.59 ± 0.1, P = 0.018 for post-BD FEV1/FVC) than the low sputum eosinophil ACO group (n = 25). When examining changes in lung function at the 3-month follow-up, there were significant decreases in FEV1 in the high IgE ACO group (n = 104; -11.4% ± 16.7% vs. -4.4% ± 9.2%, P = 0.023) and ΔFEV1/FVC in the high sputum eosinophil ACO group (-0.049 ± 0.063 vs. -0.004 ± 0.064, P = 0.049) than in the low IgE ACO group (n = 44) and in the low sputum eosinophil ACO group, respectively. The risk of asthma exacerbation was significantly higher in the atopic ACO group (odds ratio, 4.2; 95% confidence interval, 1.0-17.4; P = 0.049) in the adjusted model.

Conclusions: Since ACOs with T2-high profiles may have lower lung function and more frequent exacerbations, T2-high specific therapies, such as biologics, should be actively considered in T2-high ACO patients.

Lipids are important skin components that provide, together with proteins, barrier function of the skin. Keratinocyte terminal differentiation launches unique metabolic changes to lipid metabolism that result in the predominance of ceramides within lipids of the stratum corneum (SC)-the very top portion of the skin. Differentiating keratinocytes form unique ceramides that can be found only in the skin, and generate specialized extracellular structures known as lamellae. Lamellae establish tight hydrophobic layers between dying keratinocytes to protect the body from water loss and also from penetration of allergens and bacteria. Genetic and immunological factors may lead to the failure of keratinocyte terminal differentiation and significantly alter the proportion between SC components. The consequence of such changes is loss or deterioration of skin barrier function that can lead to pathological changes in the skin. This review summarizes our current understanding of the role of lipids in skin barrier function. It also draws attention to the utility of testing SC for lipid and protein biomarkers to predict future onset of allergic skin diseases.

Purpose: Chronic rhinosinusitis (CRS) is classified into type 2 (T2) and non-T2 inflammation. T2 CRS presents as a severe form, CRS with nasal polyps (CRSwNP), which often occurs with asthma as a comorbidity worldwide. Some cases of non-T2 CRS show nasal polyposis and refractoriness, mainly in Asian countries. However, its mechanism remains elusive. To investigate a biomarker for the refractoriness of non-T2 CRSwNP via RNA sequencing.

Methods: RNA sequencing by using nasal polyps (NPs) and ethmoidal mucosa (EM) from CRS subjects and uncinate tissues from controls was performed, and differentially expressed genes (DEGs) were analyzed (cutoffs: expression change > 2-fold, P < 0.01). Immunofluorescence staining and enzyme-linked immunosorbent assay were performed.

Results: We identified DEGs among T2-NP, non-T2-NP, T2-EM, non-T2-EM, and controls (NP vs. controls: 1,877 genes, EM vs. controls: 1,124 genes, T2-NP vs. controls: 1,790 genes, non-T2-NP vs. controls: 2,012 genes, T2-EM vs. controls: 740 genes, non-T2-EM vs. controls: 1,553 genes). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that neutrophil extracellular trap (NET) formation, systemic lupus erythematosus, and the phagosome were enriched in non-T2-NP vs. controls and non-T2-EM vs. controls. Immunofluorescence staining confirmed that NETs were elevated in non-T2-NP. Cytokine analysis demonstrated that NETs were significantly related to the refractoriness in non-T2-NPs.

Conclusions: This study demonstrated DEGs between T2 and non-T2 inflammation. These results suggest that NETs may contribute to the refractoriness in non-T2-NPs and have a promise as a therapeutic strategy for patients with refractory non-T2-NP.

Purpose: The constitutive photomorphogenesis 9 signalosome (CSN) is a highly conserved protein complex comprised of eight subunits, each of which play crucial roles in diverse cellular processes, such as signal transduction, gene transcription, angiogenesis, and cell proliferation. In the context of asthma, a potential emerging target is the programmed death-ligand 1 (PD-L1)-mediated pathway, which serves as a significant immune checkpoint inhibitor in this condition. However, the precise involvement of CSN subunit 5 (CSN5) in bronchial asthma and the interplay between CSN5 and PD-L1 in asthma remain poorly understood.

Methods: The potential association between CSN5 and bronchial asthma was explored in a mouse model of ovalbumin (OVA)-induced asthma. Samples were obtained from human lung microvascular endothelial cell (HMVEC-L) treated with Dermatophagoides pteronyssinus (Der p 1) and CSN5 small interfering RNA. The expression of nuclear factor (NF)-κB, IκBα, inhibitor of κB kinase β (IKKβ), PD-L1, and CSN5 was assessed. Additionally, plasma CSN5 levels in asthma patients, both in stable and exacerbated states, were examined.

Results: Plasma levels of CSN5 were elevated in patients with exacerbated asthma (n = 19) compared to both healthy controls (n = 10) and patients with stable asthma (n = 19). The CSN5 level demonstrated a correlation with lung function in individuals with asthma. Silencing CSN5 in HMVEC-L led to a reduction in NF-κB protein levels at 4 hours and PD-L1 levels at 4, 8, and 24 hours after Der p 1 treatment. In OVA-sensitized/challenged mice, goblet cell hyperplasia, lung fibrosis, and the levels of CSN5, PD-L1, interleukin-13, interferon-γ, phospho (p)-NF-κB, p-IκBα, and p-IKKβ proteins increased at 33 and 80 days compared to control mice. However, these changes were mitigated by treatment with a PD-L1 inhibitor.

Conclusions: These findings suggest that CSN5, along with PD-L1, could serve as a promising target for the treatment of asthma.

Purpose: Allergen exposure is the most potent factor in allergen sensitization, which affects the exacerbation and severity of allergic diseases. Due to industrialization and climate change, the pattern of allergen sensitization has changed over time, and the incidence of allergic diseases has also increased. This study investigated the status of allergen sensitization in the Korean population and its effects on allergic diseases.

Methods: A total of 2,386 participants aged ≥ 10 years, who underwent 7 specific immunoglobulin E tests for aeroallergens (Dermatophagoides farinae [Der f], dog dander, cat epithelium, birch, oak, Japanese hop, and ragweed), were selected among the participants of the 2019 Korean National Health and Nutrition Examination Survey. We compared the demographic characteristics, combined allergic diseases, and sinusitis symptoms between the atopic and non-atopic groups.

Results: The prevalence of allergen sensitization in the general Korean population was 45%, and Der f was the most frequent cause of sensitization (39.9%). The prevalence of sensitization to indoor allergens was highest among teenagers and those belonging to the 20- to 29-year age group (P < 0.001). In contrast, there was a high prevalence of sensitization to outdoor allergens among individuals belonging to the age group of 60-69 years. The prevalence of atopic dermatitis (odds ratio [OR], 2.559; 95% confidence interval [CI], 1.689-3.878), allergic rhinitis (OR, 3.075; 95% CI, 2.426-3.897), and otitis media (OR, 1.481; 95% CI, 1.092-2.007) significantly increased by allergen sensitization. Patients with allergen sensitization were more likely to experience the symptoms of rhinitis and sinusitis.

Conclusions: The study findings confirmed that allergen sensitization occurs in approximately half of the general Korean population and affects the prevalence and symptoms of allergic diseases. This suggests that active allergy tests and diagnosis of allergic diseases are necessary in Koreans.

Asthma is a chronic heterogeneous disease characterized by various symptoms and persistent airway inflammation, resulting in progressive lung function decline. Classifying asthma phenotypes/endotypes is crucial because the underlying mechanisms and long-term outcomes vary from patient to patient. Recent trials have identified several biomarkers for classifying asthma phenotypes/endotypes, and current treatments have been developed on the basis of these biomarkers. Conventional biomarkers, including immunoglobulin E, blood/sputum eosinophil counts, airway obstruction or reversibility, and fractional exhaled nitric oxide, are widely used to diagnose asthma. However, these markers have some limitations, necessitating the discovery of additional biomarkers. Therefore, this review summarizes recently suggested biomarkers for representing type 2-high (eosinophilic) vs. type 2-low (neutrophilic) asthma, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and severe asthma. Additionally, we discuss the potential benefits of these biomarkers in classifying specific phenotypes/endotypes and managing asthmatic patients.

Purpose: Wheezing in early life is most frequently caused by viral lower respiratory tract illnesses, constituting a significant disease burden in children. This study aimed to investigate the association of wheezing in early life with autoimmune diseases throughout childhood.

Methods: A population-matched retrospective cohort study was conducted in Korea between 2002 and 2017. The cohort comprised 34,959 children admitted with viral wheezing before 2 years of age and an equal number of the matched unexposed children born in 2002 and 2003. Exposed infants were defined as those hospitalized for bronchiolitis or bronchial asthma before the age of 2. Unexposed controls were matched by sex and birth year at a 1:1 ratio, using incidence density sampling. A Cox proportional hazard model controlled for multiple risk factors was employed.

Results: The median age at hospitalization for wheeze was 9 months (interquartile range, 5-15 months), and 63% of the exposed infants were male. Over the mean 15-year follow-up period, the incidence rate of autoimmune diseases was 74.0 and 62.2 per 10,000 person-years in the exposed and matched unexposed cohorts, respectively. The adjusted hazard ratio for any autoimmune disease in the exposed cohort was 1.15 (95% confidence interval, 1.09-1.23) in comparison with the unexposed cohort. The exposed cohort revealed an augmented risk for specific autoimmune diseases, including juvenile idiopathic arthritis, Kawasaki disease, Henoch-Schönlein purpura, psoriasis, idiopathic thrombocytopenic purpura, and immunoglobulin A nephropathy. Risks were heightened for children with multiple wheezing episodes or a persistent wheezing episode after the age of 2 years.

Conclusions: This research identifies associations between early-life wheeze and the development of autoimmune diseases in childhood. Understanding these relationships can aid in recognizing the underlying pathophysiology of early-life wheeze and childhood autoimmune diseases, contributing to management strategies for these conditions.

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children.

Prurigo nodularis (PN) is a chronic neuroinflammatory dermatosis with severe pruritus that has limited efficacy in various conventional treatments. This study investigated the outcomes of upadacitinib treatment in patients with refractory PN. A prospective study was conducted to screen for potential chronic infections prior to treatment. Upadacitinib was administered at a daily dose of 15 mg for 24 weeks, and the treatment response was assessed using the itch Numeric Rating Scale (NRS), investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). Adverse events were monitored at each visit. Ten patients, with an average age of 48.8 years, were included in the study. All participants were treated with systemic cyclosporine before receiving upadacitinib, which yielded limited responses. At baseline, the mean prurigo severity scores assessed using the IGA, DLQI, and itch NRS were 3.4, 17.8, and 8.1, respectively; after 24 weeks of treatment, these scores significantly reduced to 1.0, 0.6, and 0.8, respectively. No severe adverse effects were observed. In conclusion, upadacitinib could be considered an alternative therapeutic option with good tolerability for refractory PN.