SummaryBackground Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. Objectives We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). Methods Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)-8 (100 ng/mL). Autophagy (light chain 3-II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = À0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups. Conclusions and Clinical Relevance Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.

Autophagy could play a role in the pathogenesis of severe asthma. Autophagy modulation may be a novel therapeutic target for conventional therapy-resistant severe asthma.

Background: Increasing evidence suggests that adipokines affect immune responses and chronic urticaria (CU) is associated with an altered immune response related to chronic systemic inflammation. Our objectives were to investigate whether adipokines are involved in CU pathogenesis and to outline relationships between adipokines and urticaria severity and quality of life. Methods: Serum adiponectin, leptin, lipocalin-2 (LCN2), interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α concentrations were measured by enzyme-linked immunosorbent assays in 191 CU patients and 89 healthy controls. The effect of LCN2 on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced neutrophil chemotaxis was assessed using migration assays. CU severity was assessed based on the urticaria activity score (UAS). To explore relationships between adipokines and UAS and the chronic urticaria-specific quality of life (CU-QoL) questionnaire, a structural equation model was used. Results: Mean levels of serum LCN2, TNF-α, IL-6, and IL-10 were significantly higher in CU patients than in controls. Adiponectin levels were significantly lower in patients with CU than in controls. While serum IL-6 levels were significantly higher in refractory CU patients, compared to responsive CU individuals, LCN2 levels were significantly lower. LCN2 inhibited fMLP-induced neutrophil migration. LCN2 showed a direct relationship with UAS (β = -0.274, p < 0.001), and UAS was found to contribute to CU-QoL (β = 0.417, p < 0.001). Conclusions: Our results highlighted an imbalance in pro- and anti-inflammatory adipokines in CU patients. We suggest that LCN2 could be a differential marker for disease activity and the clinical responses to antihistamine treatment in CU patients. Modulation of systemic inflammation may be a therapeutic strategy for treating severe, refractory CU.

These findings suggest that circulating IgG autoantibody to FcεRIα in a subset of patients may be involved in the autoimmune mechanism of CSU. Further studies are needed to clarify its clinical significance.

Background/AimsChronic urticaria (CU) is a common skin disorder characterized by wheals and pruritus lasting more than 6 weeks. Due to its long duration and changeable symptoms, the quality of life (QOL) of patients with CU can be impaired substantially. We evaluated the CU-QOL, a previously validated CU-specific QOL measure, and investigated factors influencing QOL in chronic spontaneous urticaria (CSU) patients.MethodsA hospital-based cross-sectional study was performed on 390 adult patients diagnosed with CSU from March 2009 to December 2012 at the Allergy and Clinical Immunology Clinic at Ajou University Hospital. The CU-QOL questionnaire, urticaria activity score (UAS), combined angioedema, and serum total immunoglobulin E (IgE) levels were investigated.ResultsThe average CU-QOL score obtained from the questionnaire was 70.6 (of 100 points). The CU-QOL scores correlated significantly with the UAS, particularly with the 15-point UAS (UAS-15; coefficient –0.532, p < 0.01) rather than the 6-point UAS (–0.502, p < 0.01). The patients presenting with angioedema and urticaria had poorer scores in the urticaria symptom domain than those with urticaria alone (37.4 vs. 46.9, p = 0.004). Log-transformed serum total IgE levels correlated significantly with CU-QOL (–0.131, p < 0.05). Multivariate regression models indicated that severe CU (UAS-15 score ≥ 13), log (total IgE), and the presence of angioedema were significant predictors of impaired CU-QOL (< 85 points).ConclusionsCU has a substantial negative impact on QOL. The assessment of UAS-15, total IgE, and the presence of angioedema can be useful to predict QOL of the patients with CSU.