Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma.
To examine the prevalence and characteristics of work-related ...asthma (WRA) in adult patients with severe asthma.
We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA.
Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001).
Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA.
Abstract Background Allergic rhinitis affects 10 to 40% of the population. It reduces quality of life, school and work performance, and is a frequent reason for office visits in general practice. ...Medical costs are large but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma – ARIA guidelines in 2010 prompting its update. Objective To provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patient values and preferences, and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides updated and new recommendations about the pharmacological treatment of allergic rhinitis. It specifically addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or their combination. The ARIA guideline panel provides specific recommendations for the choice of treatment, the rationale for the choice, and discusses specific considerations that clinicians and patients may want to review in order to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of allergic rhinitis may improve patients’ quality of life, school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but ...little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity.
Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site.
Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10−8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 95% CI 1.51–14.09, P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 95% CI 1.09–13.67, P < 0.002).
LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.
Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmatic ...patients.
To investigate the clinical implications of serum periostin levels in patients with aspirin-exacerbated respiratory disease (AERD) based on its overlapping TH2-mediated pathogenesis with the eosinophilic asthma.
Serum periostin levels were measured by human periostin enzyme-linked immunosorbent assay (ELISA) in serum samples from 277 adults with asthma. Serum periostin levels were compared between patients with AERD and aspirin tolerant asthma (ATA) with other asthma phenotypes, such as severe or nonsevere asthma and eosinophilic or noneosinophilic asthma. The association of serum periostin levels with clinical parameters (including disease severity and comorbid condition) was analyzed.
Serum periostin levels were significantly higher in patients with AERD vs ATA, patients with severe asthma vs nonsevere asthma, and patients with eosinophilic asthma vs noneosinophilic asthma (P=.005, P=.02, and P=.001, respectively). Multivariate regression analysis revealed serum periostin levels as a significant parameter to predict AERD phenotype (P=.006) together with severe asthma phenotype (P=.04). In addition, serum periostin levels correlated with blood eosinophil counts (Spearman ñ = 0.244, P<.001) and sputum eosinophil counts (Spearman ñ = 0.261, P < 0.001). Higher serum periostin levels were noted in comorbid AERD patients with more severe chronic rhinosinusitis (Lund-Mackay stages 3 and 4) than those with less severe chronic rhinosinusitis (Lund-Mackay stages 1 and 2) (P = .03).
Serum periostin levels are significantly elevated in AERD patients and associated with AERD phenotype and disease severity.
Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear.
Our aim was to evaluate the ...real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors.
Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model.
In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 n = 158), intermediate (cluster 2 n =1 43), and poor responses (cluster 3 n = 85). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (<40 kU/L) predicted nonresponse (odds ratio OR = 3.10 P = .018). Early responders were associated with a higher initial omalizumab dose (≥300 mg) (OR = 2.07 P = .016), higher basophil counts (OR = 2.0 P = .014), total IgE levels exceeding 798 kU/L (OR = 0.37 P = .047), and lower platelet-to-lymphocyte ratio (OR = 0.50 P = .050).
Real-world data reveal 3 distinct clusters for response to omalizumab treatment; confirm low serum total IgE level (<40 kU/L) as a predictor of nonresponse; and identify potential biomarkers, including IgE level, basophil count, and PLR, for early responders.
Background Although the mechanism that underlies aspirin hypersensitivity is not completely understood, an IgE-mediated response was reported for a patient with aspirin-intolerant chronic urticaria ...(AICU). Objective We investigated whether genetic polymorphisms on the α-chain of the high-affinity IgE receptor (FcεRIα) gene were associated with the AICU phenotype. Methods We genotyped 2 promoter polymorphisms (−344C>T and −95T>C) of FcεRIα gene in the Korean population, and the functional effect of the −344C>T polymorphism was analyzed by using a luciferase reporter assay and an electrophoretic mobility shift assay. Results The rare allele frequency of the −344C>T polymorphism was significantly higher in the patients with AICU compared with the other subjects ( P = .008 for AICU vs aspirin-tolerant chronic urticaria; P = .03 for AICU vs controls). This polymorphism was also significantly associated with total serum IgE concentrations and a higher rate of atopy in the patients with AICU ( P = .01 and .05, respectively). The reporter plasmid that carried the −344T allele exhibited significantly higher promoter activity in a rat mast cell line (RBL-2H3) compared with the promoter activity of the −344C allele ( P < .001). We found that transcription factor Myc-associated zinc finger protein preferentially bound the −344C promoter. Moreover, patients with AICU with the heterozygous CT genotype of the −344C>T polymorphism exhibited greater anti-IgE–mediated histamine release compared with those with the homozygous CC genotype. Conclusion These results suggest that the −344C>T polymorphism of the FcεRIα promoter may be associated with increased expression of FcεRIα on mast cells and enhanced release of histamine. Clinical implications The FcεRIα −344C>T polymorphism may contribute to the development of AICU.
Background Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various ...inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. Objective To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. Methods We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. Results In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 ( P = .001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE ( P = .004) and total eosinophil count ( P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study ( P = .01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. Conclusions These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.
Chronic rhinosinusitis (CRS) is a common comorbid condition of asthma that affects the long-term outcome of asthmatic patients. CRS is a heterogeneous disease requiring multiple biomarkers to explain ...its pathogenesis. This study aimed to develop potential biomarkers for predicting CRS in adult asthmatic patients in a real-world clinical setting.
This study enrolled 108 adult asthmatic patients who had maintained anti-asthmatic medications, including medium-to-high doses of inhaled corticosteroid plus long-acting β2-agonists, and compared clinical characteristics between patients with CRS (CRS group) and those without CRS (non-CRS group). CRS was diagnosed based on the results of paranasal sinus X-ray and/or osteomeatal-unit CT as well as clinical symptoms. Type-2 parameters, including blood eosinophil count, serum levels of periostin/dipeptidyl peptidase 10 (DPP10) and clinical parameters, such as FEV1% and fractional exhaled nitric oxide (FeNO), were analyzed. All biomarkers were evaluated by logistic regression and classification/regression tree (CRT) analyses.
The CRS group had higher blood eosinophil counts/FeNO levels and prevalence of aspirin-exacerbated respiratory disease (AERD) than the non-CRS group (n = 57, 52.8% vs. n = 75, 47.2%; P < 0.05), but no differences in sex/smoking status or asthma control status were noted. The CRS group had higher serum periostin/DPP10 levels than the non-CRS group. Moreover, logistic regression demonstrated that serum periostin/DPP10 and the AERD phenotype were significant factors for predicting CRS in asthmatic patients (adjusted odds ratio, 2.14/1.94/12.39). A diagnostic algorithm and the optimal cutoff values determined by CRT analysis were able to predict CRS with 86.27% sensitivity (a 0.17 negative likelihood ratio).
Serum periostin, DPP10 and the phenotype of AERD are valuable biomarkers for predicting CRS in adult asthmatic patients in clinical practice.
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