Allergy, Asthma & Immunology Research最新文献

Purpose: In chronic spontaneous urticaria (CSU), autoimmune thyroid disease is the most common autoimmune comorbidity, and many CSU patients have immunoglobulin (Ig)E or IgG autoantibodies to thyroid peroxidase (TPO). It remains unclear how anti-TPO IgE and IgG autoantibodies are linked to each other and are associated with CSU features, activity, and therapeutic responses.

Methods: CSU patients (n = 146, 92 females, mean age 42.9 years) and healthy normal controls (NCs, n = 30) were assessed for anti-TPO IgE and IgG by enzyme-linked immunosorbent assay, and the clinical and laboratory profiles, disease activity (UAS7), and response to 3 months of H1-antihistamine treatment were evaluated for anti-TPO IgE-positive and/or IgG-positive patients.

Results: Among 146 CSU patients, 67 (46%, NCs: 6.6%) had elevated anti-TPO IgE and/or IgG, and 32 (22%), 35 (24%), and 5 (3%) had elevated anti-TPO IgE, anti-TPO IgG, and both, respectively. Of the patients with anti-TPO IgE and/or IgG, 44% (n = 27) had anti-TPO IgE but not IgG, 48% (n = 30) had anti-TPO IgG but not IgE, and only 8% (n = 5) had anti-TPO IgE and IgG. Compared to anti-TPO IgE-negative patients, anti-TPO IgE-positive ones had greater rates of atopy and antihistamine responses and lower disease activity (UAS7). Anti-TPO IgG-positive patients had greater rates of angioedema and elevated levels of anti-thyroglobulin IgG than anti-TPO IgG-negative patients.

Conclusions: Forty-six percentages of CSU patients have autoantibodies to TPO; most have either IgE or IgG autoantibodies but not both. Anti-TPO IgE and anti-TPO IgG come with distinct CSU profiles, including treatment responses.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin condition influenced by various factors, such as the skin microbiome and metabolome. However, specific contributions of these factors to scalp involvement in AD still need to be explored. In this study, we aimed to assess the associations between the skin microbiome and metabolome in AD patients with scalp dermatitis and healthy controls (HCs).

Methods: A total of 20 AD patients with scalp involvement and 16 HCs were recruited, and their skin samples were collected for analysis. Bioinformatic analysis and 16S rRNA metagenomic sequencing were performed, with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) conducted for AD-associated skin metabolites. Spearman correlation analysis was used to identify the correlations between AD-associated skin bacteria and metabolites.

Results: The results revealed significant differences in bacterial taxa and metabolites between the lesional and non-lesional scalp skin samples of AD patients (groups LS and NL, respectively) and those of HCs (group HC). Notably, group LS showed a significantly increased relative abundance of the genus Staphylococcus and a decreased abundance of Cutibacterium compared to group HC. The reduced abundance of Cutibacterium was also observed when comparing LS to NL. The GC-TOF-MS analysis identified 33 significantly decreased metabolites and 17 significantly increased metabolites in groups LS and NL compared with group HC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that amino acid-related metabolism was significantly altered in the metabolic pathway between groups LS, NL, and HC. Furthermore, Spearman correlation analysis showed significant correlations of the altered bacteria genera and skin metabolites between the 3 groups.

Conclusions: The results of this research provide valuable insights into the associations the skin microbiome and metabolome between groups LS, NL, and HC. Identifying these specific contributions may offer new avenues for understanding the pathogenesis of scalp involvement in AD patients and potentially lead to improving management strategies.

Although combining allergen immunotherapy with biologics has shown promise in treating atopic diseases such as asthma and allergic rhinitis, atopic dermatitis (AD) remains notably underexplored in this context. This study aimed to investigate the efficacy and safety of combining dupilumab with subcutaneous immunotherapy (SCIT) for severe AD refractory to standard treatments. This was a single-center retrospective analysis assessing patients with severe AD treated with combined dupilumab and SCIT, dupilumab, or SCIT alone at the Severance Hospital, Seoul, Korea. The inclusion criteria encompassed severe AD diagnosis, specific immunoglobulin (Ig) E levels to house dust mite allergens, and treatment follow-up for at least 18 months. Eczema Area and Severity Index (EASI) scores, serum biomarker levels, and adverse event records were regularly collected. Forty-eight patients with AD were analyzed, showing significant improvement in EASI scores and favorable changes in serum biomarkers over 144 weeks. The combination therapy led to a sustained reduction in AD severity, a significant reduction in total IgE and specific IgE levels, and an increment in allergen-specific IgG4. All patients experienced only mild and temporary side effects, not requiring treatment discontinuation. Combining dupilumab with SCIT offers a promising therapeutic option for patients with severe, treatment-refractory AD, reducing disease severity and inducing favorable immunological changes without increasing adverse effects.

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.