No abstract

Purpose of Review Lung tissues are highly susceptible to airway inflammation as they are inevitably exposed to inhaled pathogens and allergens. In the lungs, clearance of infectious agents and regulation of inflammatory responses are important for the first-line defense, where surfactants play a role in host defense mechanisms. In this review, clinical significance of pulmonary surfactants in asthma has been highlighted. Recent Findings Surfactants, such as surfactant protein A (SP-A) and SP-D released from alveolar epithelium, reduce pathogen infection and control immune-cell activation. Especially, SP-D directly binds to eosinophil surface, leading to inhibition of extracellular trap formation and reduction in airway inflammation. Production of surfactants is commonly determined by both genetic (single nucleotide polymorphisms) and environmental factors influencing processes involved in the development of asthma. In addition, nintedanib (an intracellular inhibitor of tyrosine kinases) could increase SP-D levels and is used in patients with idiopathic pulmonary fibrosis. These findings may provide a possible application of SP-D in asthma. Summary Surfactants are key players contributing to host defense through maintaining the immune system. As clinical implications of surfactants involved in asthma have been suggested, further translational studies are needed to apply surfactants as an effective therapeutic target in patients with asthma.

Purpose There have been autoimmune mechanisms for the pathogenesis of severe asthma (SA) involving epithelial autoantigen-specific antibodies. This study aimed to find the function of these antibodies in the formation of eosinophil extracellular traps (EETs), contributing to the development of SA. Methods Patients with SA (n = 11), those with patients with nonsevere asthma (NSA, n = 41), and healthy controls (HCs, n = 26) were recruited to evaluate levels of epithelial antigens and autoantigen-specific antibodies. Moreover, the significance of epithelial autoantigen-specific antibodies in association with EET production was investigated ex vivo and in vivo . Results Significantly higher levels of serum cytokeratin (CK) 18 and CK18-specific IgG were observed in patients with SA than in those with NSA ( P = 0.001 and P = 0.031, respectively), while no differences were found in serum CK19 or CK19-specific immunoglobulin G (IgG). Moreover, levels of serum CK18 were positively correlated with total eosinophil counts ( r = 0.276, P = 0.048) in asthmatics, while a negative correlation was noted between levels of serum CK18 and forced expiratory volume in 1 second (FEV1) %. In the presence of CK18-specific IgG, peripheral eosinophils from asthmatics released EETs, which further increased CK18 production from airway epithelial cells. In severe asthmatic mice, CK18 expression and CK18-specific IgG production were enhanced in the lungs, where EET treatment enhanced CK18 expression and CK18-specific IgG production, either of which was not suppressed by dexamethasone. Conclusions These suggest that EETs could enhance epithelial autoantigen (CK18)-induced autoimmune responses, further stimulating EET production and type 2 airway responses, which is a new therapeutic target for SA.

Patients with severe eosinophilic asthma (SEA) suffer from frequent asthma exacerbations, where eosinophils are major effector cells in airway inflammation, and anti-interleukin (IL)-5 becomes an effective treatment modality to control eosinophilic inflammation of SEA. Fifteen patients with SEA who had been treated with anti-IL5 (reslizumab, 100 mg monthly intravenously) for 6 months at Ajou University Hospital (Suwon, Korea) were enrolled in this study. Clinical parameters, including total blood eosinophil count (TEC), FEV1%, fractional exhaled nitric oxide (FeNO) levels, and serum biomarkers such as eosinophil-derived neurotoxin (EDN), periostin (PON), and transforming growth factor-β1 (TGF-β1), were analyzed. EDN levels and TEC decreased significantly after 1 month of treatment ( P < 0.05 for both), while no changes were noted in FeNO/PON/TGF-β1 levels. FEV1% increased after 2 months of treatment ( P < 0.05). A positive correlation was observed between TEC and EDN levels ( r = 0.60, P = 0.02). Significant negative correlations were noted between age and TEC/EDN levels ( r = −0.57, P = 0.02 and r = −0.56, P = 0.03, respectively). Baseline TEC was higher in the EDN-responder group (≥75% decrease) than in the non-responder group ( P = 0.06) with a positive correlation between %reduction in EDN and TEC ( r = 0.67, P = 0.01). The onset age was younger and asthma duration was longer in the FEV1%-non-responder group (<12% increase) than in the FEV1%-responder group ( P = 0.07 and P = 0.007, respectively). In conclusion, changes in the serum EDN level may be a potential biomarker for monitoring eosinophilic inflammation after anti-IL5 treatment in SEA, which is affected by onset age and asthma duration.

Background: It has been known that a high serum total immunoglobulin E (IgE) level is a predisposing factor of allergic asthma; however, there are considerable limitations to apply it in clinical practice. Objective: To determine the clinical significance of the serum-free IgE level in patients with adult asthma. Methods: We measured free IgE levels using our homemade enzyme-linked immunosorbent assay by applying a novel IgE TRAP protein (GI innovation, Seoul, Republic of Korea) in sera of adults with asthma (n = 116) compared with healthy controls (n = 32); enzyme-linked immunosorbent assay inhibition test was performed to validate its binding specificity. Associations between asthma-related clinical and laboratory parameters were analyzed. The diagnostic value and cutoff point for detecting atopy and type 2 asthma were determined using receiver operating characteristic curve analysis. Results: The serum-free IgE levels were significantly higher in adults with asthma than in healthy controls and were significantly associated with atopic status and type 2 asthma (all P < .001). In the receiver operating characteristic analysis, serum-free IgE had a significantly greater area under the curve (AUC) than serum total IgE for assessing asthma, especially type 2 asthma (AUC, 0.810 vs 0.743; P = .006 and AUC, 0.729 vs 0.572; P < .001). The optimal cutoff points for predicting atopy and type 2 asthma were 82.8 and 120.8 ng/mL, respectively. Conclusion: It is suggested that a higher serum-free IgE level may be a useful biomarker of atopy and type 2 asthma in adults with asthma.