Allergy, Asthma & Immunology Research最新文献

Although postinfectious etiology is the most common cause of subacute cough, there are insufficient data on the epidemiology of associated bacterial infections. We aimed to identify the etiology of bacterial detection in subjects with subacute cough. A multicenter prospective observational study of 142 patients with postinfectious subacute cough was performed between August 2016 and December 2017 in Korea. We obtained 2 nasal swabs from each patient and used a multiplex bacterial polymerase chain reaction (PCR) kit that simultaneously detects Bordetella pertussis, Chlamydophila pneumoniae, Haemophilus influenzae, Legionella pneumophilia, Mycoplasma pneumoniae, and Streptococcus pneumoniae. About 29% (n = 41) of patients with subacute cough were positive for bacterial PCR in nasal swabs. The most common bacteria detected by bacterial PCR was H. influenzae (n = 19, 13.4%), followed by S. pneumoniae (n = 18, 12.7%), B. pertussis (n = 7, 4.9%), M. pneumoniae (n = 3, 2.1%), L. pneumophilia (n = 2, 1.4%), and C. pneumoniae (n = 1, 0.7%). Nine patients had dual positivity for the PCR. In conclusion, bacterial PCR was positive in the nasal swabs of about 29% of subjects with subacute cough, including 5% of positive PCR results for B. pertussis.

Allergic diseases are increasing both in morbidity and mortality. Genetic, environmental, and dietary factors may all be involved in this increase. Nutrition during pregnancy, breastfeeding, and early life may play a particularly important role in preventing allergic diseases. Based on current systematic reviews, the intake of specific nutrients has failed to prevent allergic disease. Prevention strategies have shifted their focus to the overall diet which can be described using diet diversity. Infant and maternal diet diversity in pregnancy has been associated with reduced allergy outcomes in childhood. Overall, diet also seems to have a marked effect on the microbiome compared to single foods. Factors that may negate the allergy-preventative effect of overall diet diversity include the addition of emulsifiers, advanced glycation end-product content, and overuse of commercial baby foods. There is a need to perform randomized controlled trials using overall dietary intake to support international food allergy guidelines. These studies should ideally be conducted by multi-professional teams.

Purpose: Allergic rhinitis (AR) is a T helper type 2 (Th2)-mediated inflammatory disease. The E3 ligase tripartite motif-containing 24 (TRIM24) regulates the recruitment of acetyltransferase CREB-binding protein (CBP) to signal transducer and activator of transcription 6 (STAT6). CBP mediates the acetylation of STAT6 and decreases its activity. To date, the precise role of TRIM24 in AR has not been fully interpreted. Herein, our study aimed to explore the functions of TRIM24 in AR.

Methods: The expression of TRIM24 in peripheral blood mononuclear cells (PBMCs) and CD4⁺ T cells from patients with AR was measured. TRIM24-conditional knockout mice with TRIM24 deficiency in CD4⁺ T cells were generated. Wide-type (WT) AR mice and TRIM24-conditional knockout AR mice were established. Then, AR symptoms and interleukin (IL)-4 levels were compared. Further, the proliferation, activation and polarization of CD4⁺ T cells from WT mice and TRIM24 knockout mice after stimulation were determined. The effects of TRIM24 deficiency on STAT6 activities were also evaluated.

Results: Downregulated TRIM24 expression was detected in PBMCs and CD4⁺ T cells from patients with AR. TRIM24 conditional knockout mice had more sever AR symptoms with elevated IL-4 production. TRIM24-knockout CD4⁺ T cells had similar proliferation and activation when compared to WT CD4⁺ T cells, while they had enhanced Th2 polarization. TRIM24-knockout CD4⁺ T cells had decreased acetylation of STAT6 and enhanced STAT6 activities after IL-4 stimulation. The regulation of STAT6 activities by TRIM24 depended on TRIM24 N terminal RIGN domain and Lys383 acetylation site of STAT6.

Conclusions: TRIM24 suppresses Th2-mediated AR by regulating the acetylation of STAT6.

Purpose: The abnormal expression of tight junction (TJ) plays a vital role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, there is no appropriate tool to distinguish and diagnose epithelial barrier defects in clinical practice. This study aimed to evaluate the predictive value of claudin-3 for epithelial barrier dysfunction in CRSwNP.

Methods: In this study, TJ protein levels were evaluated by real-time quantitative polymerase chain reaction, immunofluorescent, and immunohistochemistry staining in control subjects and CRSwNP patients. The receiver operating characteristic (ROC) curve was created to assess the predictive value of TJ breakdown in clinical outcomes. In vitro, human nasal epithelial cells were cultured at the air-liquid interface to analyze the transepithelial electrical resistance (TER) level.

Results: The expression levels of occludin, tricellulin, claudin-3, and claudin-10 were decreased (all P < 0.05), and those of claudin-1 was increased (P < 0.05) in CRSwNP patients as compared to healthy subjects. Additionally, claudin-3 and occludin levels were negatively correlated with the computed tomography score in CRSwNP (all P < 0.05), and the ROC curve indicated that the claudin-3 level had the most predictive accuracy in evaluating epithelial barrier disruption (area under the curve = 0.791, P < 0.001). Finally, the time-series analysis showed the highest correlation coefficient between TER and claudin-3 (cross-correlation function = 0.75).

Conclusion: In this study, we suggest that claudin-3 could be a valuable biomarker for predicting nasal epithelial barrier defects and disease severity in CRSwNP.

Purpose: The prevalence of chronic urticaria (CU) is increasing worldwide, and it imposes a major burden on patients. Few studies have evaluated the efficacy of second-line treatments of CU, particularly for patients being considered for costly third-line treatments such as omalizumab. We compared the efficacy and safety of second-line treatments of CU refractory to standard doses of nonsedating H₁-antihistamines (nsAHs).

Methods: This 4-week, prospective, randomized, open-label trial divided patients into 4 treatment groups: 4-fold updosing of nsAHs, multiple combination of 4 nsAHs, switching to other nsAHs, and adjunctive H₂-receptor antagonist. The clinical outcomes included urticaria control status, symptoms, and rescue medication use.

Results: This study included 109 patients. After 4 weeks of second-line treatment, urticaria was well-controlled, partly controlled, and uncontrolled in 43.1%, 36.7%, and 20.2% of patients, respectively. Complete control of CU was achieved in 20.4% of patients. Among the patients with high-dose nsAHs, the proportion with well-controlled status was higher compared to the patients who received standard doses (51.9% vs. 34.5%, P = 0.031). No significant difference was observed in the proportion of well-controlled cases between the updosing and combination treatment groups (57.7% vs. 46.4%, P = 0.616). However, increasing the dose of nsAHs 4-fold was associated with a higher rate of complete symptom control compared to multiple combination treatment with 4 nsAHs (40.0% vs. 10.7%, P = 0.030). Logistic regression analysis confirmed the higher efficacy of updosing of nsAHs for complete control of CU compared to the other treatment strategies (odds ratio, 0.180; P = 0.020).

Conclusions: In patients with CU refractory to standard doses of nsAHs, both updosing of nsAHs 4-fold and multiple combination treatment with 4 nsAHs increased the rate of well-controlled cases without causing significant adverse effects. Updosing of nsAHs is more effective for complete CU control than combination treatment.

Purpose: Severe asthma (SA) is characterized by persistent airway inflammation and remodeling, followed by lung function decline. The present study aimed to evaluate the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the pathogenesis of SA.

Methods: We enrolled 250 adult asthmatics (54 with SA and 196 with non-SA) and 140 healthy controls (HCs). Serum TIMP-1 levels were determined by enzyme-linked immunosorbent assay. The release of TIMP-1 from airway epithelial cells (AECs) in response to stimuli as well as the effects of TIMP-1 on the activations of eosinophils and macrophages were evaluated in vitro and in vivo.

Results: Significantly higher levels of serum TIMP-1 were noted in asthmatics than in HCs, in the SA group than in non-SA group, and in the type 2 SA group than in non-type 2 SA group (P < 0.01 for all). A negative correlation between serum TIMP-1 and FEV₁% values (r = -0.400, P = 0.003) was noted in the SA group. In vitro study demonstrated that TIMP-1 was released from AECs in response to poly I:C, IL-13, eosinophil extracellular traps (EETs) and in coculture with eosinophils. TIMP-1-stimulated mice showed eosinophilic airway inflammation, which was not completely suppressed by steroid treatment. In vitro and in vivo functional studies showed that TIMP-1 directly activated eosinophils and macrophages, and induced the release of EETs and macrophages to polarize toward M2 subset, which was suppressed by anti-TIMP-1 antibody.

Conclusions: These findings suggest that TIMP-1 enhances eosinophilic airway inflammation and that serum TIMP-1 may be a potential biomarker and/or therapeutic target for type 2 SA.

Purpose: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters.

Methods: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1β, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-β1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster.

Results: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype.

Conclusions: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.