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SummaryBackground To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). Objective To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. Methods An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/Q-ToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. Results A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE4 and LTE4/PGF2α ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE4 and LTE4/PGF2α ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE4 levels were significantly correlated with the fall in FEV1% after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). Conclusions and Clinical Relevance Serum metabolite level of LTE4 and LTE4/PGF2α ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/Q-ToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

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, P0.001). 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.

Baker's asthma is the most prevalent occupational asthma, and IgE-mediated response is known as a major pathogenesis. However, recent studies have suggested the involvement of innate immune response because wheat flour contains bacterial endotoxins or lipopolysaccharides. To further understand a role of innate immune response in the development of work-related respiratory symptoms (WRS) in bakery workers, we investigated mannose-binding lectin (MBL), one of the initiating components of the complement cascade in a single cohort of bakery workers. A total of 373 bakery workers completed a questionnaire regarding WRS. The bakery workers were divided into 2 groups according to previous history of allergic rhinitis (AR)/bronchial asthma (BA): those with history of AR/BA (group I) and those without (group II). We measured serum MBL levels by using enzyme-linked immunosorbant assay and genotyped 4 single nucleotide polymorphisms of the MBL2 gene (226G>A in exon 1, -554G>C, -431A>C, and -225G>C in the promoter) by using TaqMan assays. Fifty-nine subjects (15.5%) were previously diagnosed with AR/BA, and 64 subjects (16.8%) complained of WRS. No significant differences were found in serum MBL levels between groups I and II. However, in group II subjects, but not in group I subjects, the serum MBL levels were significantly higher in bakery workers with WRS than in those without. In addition, the serum MBL levels were significantly different according to genetic polymorphisms of the MBL2 gene and its haplotypes. In conclusion, serum MBL, affected by genetic polymorphisms, may be associated with WRS in bakery workers with no previous history of AR/BA.

Purpose: The prevalence of pollinosis is increasing, and it is expected to increase further with climate change. Mugwort and ragweed pollens are well known as prevalent allergenic weed pollens in Korea. However, the clinical significance of dandelion pollen as an inhalant allergen has not yet been studied. The purpose of this study was to evaluate the clinical significance and cross allergenicity between dandelion and major weed pollens. Methods: Ninety-seven patients with allergic rhinitis and asthma or with allergic rhinitis alone who were sensitized to dandelion pollens on skin prick tests (allergen/histamine ratio>3) were enrolled between December, 2012 and November, 2013. Serum specific IgE levels to dandelion pollen extracts were measured by using enzyme-linked immunosorbent assay (ELISA). ELISA inhibition tests were performed to evaluate cross allergenecity with other weed pollens. Results: When the positive cutoff value for serum specific IgE was set at the mean±3 standard deviation of absorbance values, 52 patients (53.6%) had a high serum specific IgE antibody level. ELISA inhibition tests showed significant inhibitions with serial addition of dandelion pollen extracts, and 5 different inhibition patterns were noted with addition of 4 weed pollen extracts: significant inhibitions with pollens of mugwort, ragweed, chenopodium and Hop J (25%, 13 of 52), inhibitions with pollens of mugwort, ragweed and chenopodium (17.3%, 9 of 52), inhibitions with 2 pollens of mugwort and ragweed (32.6%, 17 of 52), inhibitions with mugwort pollen (21.1%, 11 of 52), and inhibitions with dandelion pollen alone (4%, 2 of 52). Conclusion: These findings suggest that dandelion pollen may be a causative inhalant allergen to induce pollinosis in the autumn season. Cross-allergenicity with other weed pollens showed individual differences; most patients had cross-reactivity with mugwort, ragweed, and chenopodium pollens, while some with Hop J pollen. Few patients were sensitized to dandelion pollen alone. (Allergy Asthma Respir Dis 2015;3:358-364)