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Background: The activated complement cascade is involved in asthmatic airway inflammation. Ficolins are essential for innate immunity and can activate the complement lectin pathway. Despite this, the significance of ficolins in asthma has yet to be determined. This study aimed to explore the presence of ficolins in individuals with asthma and to determine the relationship between ficolins and clinical characteristics., Methods: For the study, 68 asthmatic patients and 30 healthy control subjects were recruited. Enzyme-linked immunosorbent assay was used to determine plasma ficolin-1, ficolin-2, and ficolin-3 concentrations both before and after inhaled corticosteroid (ICS) therapy. Further, the associations of plasma ficolin-1 level with pulmonary function and asthma control questionnaire (ACQ) score were examined in the asthma patients., Results: Patients with asthma exhibited significantly elevated plasma ficolin-1 levels (median, 493.9 ng/mL; IQR, 330.2-717.8 ng/mL) in comparison to healthy controls (median, 330.6 ng/mL; IQR, 233.8-371.1 ng/mL). After ICS treatment, plasma ficolin-1 (median, 518.1 ng/mL; IQR, 330.2-727.0 ng/mL) in asthmatic patients was significantly reduced (median, 374.7 ng/mL; IQR, 254.8-562.5 ng/mL). Additionally, ficolin-1 expressions in plasma were significantly correlated with pulmonary function parameters and ACQ score in asthmatic patients. Asthma patients with higher plasma ficolin-1 levels demonstrated poorer lung function than those with lower plasma ficolin-1 levels., Conclusions: The results revealed that asthmatic patients had higher plasma ficolin-1 concentrations, which decreased after ICS treatment and were linked to their lung function, implying a potential involvement of ficolin-1 in asthma pathogenesis., (© 2023. The Author(s).)

Patients with eosinophilic asthma react well to conventional treatment of asthma while individualized therapy for non-eosinophilic endotypes have yet to be developed. Dysregulated sphingosine metabolites are associated with the pathophysiology of different asthma endotypes with their receptors involved. However, whether the sphingosine-1-phosphate receptor 4 (S1PR4) contributes to disease progression of asthma remains underappreciated. In this study, we demonstrated that sphingosine metabolism was disturbed in asthma while it could not be used to distinguish between different endotypes of asthma. S1PR4, a vital receptor of bioactive sphingosine metabolites and mainly expressed in macrophages, exhibited lower expression both in patients and experimental mice with neutrophilic airway inflammation. Additionally, S1pr4 deficiency aggravated the OVA/LPS-induced pulmonary inflammation in mice along with a significant up-regulation in M1 macrophage activation. Mechanistic studies showed that S1PR4 was strongly connected to bioactive oxylipins concurrent with bounding to formyl peptide receptor 2 to influence the phosphorylation of JNK and contributed to the macrophage M1 program, which in turn secreted amounts of inflammatory cytokines associated to the inflammatory response of neutrophilic asthma. Furthermore, treating mice with S1PR4 agonist CYM50308 was characterized by less pulmonary inflammatory infiltration. Our research indicates S1PR4 a promising therapeutic target for non-eosinophilic phenotypes of asthma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Club cell 10-kDa protein (CC10) is a documented biomarker for airway obstructive diseases. Primarily produced by nonciliated club cells in the distal airway and in nasal epithelial cells, CC10 suppresses Th2 cell differentiation and Th2 cytokine production. In this study, we aimed to determine whether CC10 can also be used as an alternative biomarker for identifying Type 2 (T2) asthma., 74 patients with asthma, and 24 healthy controls were enrolled in the study. T2-high asthma was defined as elevation in two or more biomarkers, such as sputum eosinophilia ≥ 3%, high blood eosinophils ≥ 300/µL, or high FeNO ≥ 30 ppb. T2-low asthma was defined as no elevation in biomarkers. Enzyme-linked immunosorbent assay (ELISA) was used to assess the CC10 levels in plasma., The plasma CC10 level in patients with T2-high asthma was lower than that of patients with T2-low asthma and healthy controls ( P  < 0.05). To distinguish between T2-high and T2-low phenotype in patients with asthma, a receiver-operating characteristic (ROC) analysis was performed. It showed a sensitivity of 58.1% and specificity of 78.0% when using 22.74 ng/ml of plasma CC10. Correlation analysis indicated that the plasma CC10 level was inversely correlated with sputum eosinophil, blood eosinophil, and FeNO, and positively correlated with log PD20. However, no correlation with sputum neutrophil percentages, macrophage percentages, IgE, or lung function was found., Plasma CC10 is potentially useful in predicting T2-high and T2-low asthma. Lower plasma CC10 was associated with enhanced airway hyperresponsiveness, and Type 2 inflammation.

Lipid mediators play an essential role in the pathogenesis of asthma. Many studies on the differential expression of sphingolipids and fatty acid exist, but relatively few concerned about glycerophospholipid (GP) metabolites in asthma. Here, plasma samples from 20 healthy controls and 24 asthmatic patients were collected and analyzed. High-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) revealed that 29 GPs were identified and relatively quantified as differential metabolites for discriminating asthma patients and healthy subjects, consisting of six major subclasses of GPs. Moreover, a significant relevance was found between the selected metabolites and diagnostic and prognostic indicators of asthma. Remarkably, in subgroup analyses, plasma phosphatidic acid (PA), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) levels were higher in patients with eosinophilic asthma than non-eosinophilic asthma. Receiver-operating characteristic curve analysis revealed that the power of plasma PA and PG levels to distinguish between asthmatic patients and healthy subjects was strong (all areas under the curves > 0.9; P < 0.05). Our study characterized circulating GP metabolites in patients with asthma and explored their clinical relevance which may help to develop reliable biomarkers for early and accurate diagnosis based on lipid metabolites and provide novel insight into the role of GPs in asthma., (Copyright © 2020. Published by Elsevier B.V.)

Background: Pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation. Recently, it has been reported that PTX3 deficiency enhances interleukin (IL)-17A-dominant pulmonary inflammation in an ovalbumin (OVA)-induced mouse asthma model. However, whether PTX3 treatment would provide protection against allergic airway inflammation has not been clearly elucidated. The goal of this study was to further investigate the effect of recombinant PTX3 administration on the phenotype of asthma., Methods: C57BL/6 J mice were sensitized and challenged with OVA to induce eosinophilic asthma model, as well as sensitized with OVA plus LPS and challenged with OVA to induce neutrophilic asthma model. We evaluated effect of recombinant PTX3 on asthma phenotype through both asthma models. The bronchoalveolar lavage fluid (BALF) inflammatory cells and cytokines, airway hyperresponsiveness, and pathological alterations of the lung tissues were assessed., Results: In both eosinophilic and neutrophilic asthma models, PTX3 treatment provoked airway hyperresponsiveness, concomitant with increased inflammatory cytokines IL-4, IL-17, eotaxin, and transforming growth factor (TGF)-β1 and aggravated airway accumulation of inflammatory cells, especially eosinophils and neutrophils. In histological analysis of the lung tissue, administration of PTX3 promoted inflammatory cells infiltration, mucus production, and collagen deposition. In addition, PTX3 also significantly enhanced STAT3 phosphorylation in lung tissue., Conclusion: Our results show that exogenous PTX3 can exacerbate multiple asthmatic features by promoting both eosinophils and neutrophils lung infiltration and provide new evidence to better understand the complex role of PTX3 in allergic airway inflammation.

Background: Innate immunity has been thought to be involved in asthma pathogenesis. Pentraxins, acting as soluble pattern recognition molecules, play an important role in humoral innate immunity. Asthma is a heterogeneous inflammatory disease of airways and can be classified as eosinophilic or non-eosinophilic asthma., Objective: To investigate whether pentraxin levels differ in subjects with eosinophilic versus non-eosinophilic asthma. Furthermore, to access the predictive performance of pentraxin levels for discriminating asthma inflammatory phenotypes., Methods: A total of 80 asthmatic patients and 24 healthy control subjects underwent sputum induction at study inclusion. Differential leucocyte counts were performed on selected sputum. Plasma C-reactive protein (CRP), serum amyloid P (SAP), pentraxin 3 (PTX3), and sputum SAP, PTX3, IL-8 levels were determined by enzyme-linked immunosorbent assay., Results: Subjects with non-eosinophilic asthma had significantly increased pentraxin levels compared with those with eosinophilic asthma and healthy controls, with median (interquartile range) plasma CRP levels of 0.86 (0.28-2.07), 0.26 (0.14-0.85), and 0.15 (0.09-0.45)mg/L (P < .001), respectively, plasma SAP levels of 33.69 (19.79-58.39), 19.76 (16.11-30.58), and 20.06 (15.68-31.11)mg/L (P = .003), respectively, and sputum PTX3 levels of 4.9 (1.35-18.72), 0.87 (0.30-2.07), and 1.08 (0.31-4.32)ng/mL (P < .001), respectively. Conversely, sputum SAP concentrations of eosinophilic asthmatics (median, 21.49 ng/mL; IQR, 6.86-38.79 ng/mL) were significantly higher than those of non-eosinophilic patients (median, 8.15 ng/mL; IQR, 2.82-18.01 ng/mL) and healthy controls (median, 8.79 ng/mL; IQR, 2.00-16.18 ng/mL). Asthma patients with high plasma CRP (P = .004), SAP (P = .005) and sputum PTX3 levels (P < 0.001) also had significantly lower sputum eosinophil percentages. Sputum PTX3 levels had the best power (11.18-fold, P < .001) to predict non-eosinophilic airway inflammation in asthma patients., Conclusion and Clinical Relevance: Pentraxin levels differed significantly between patients with non-eosinophilic asthma and those with eosinophilic asthma. Furthermore, elevated pentraxin expressions may predict non-eosinophilic airway inflammation in asthmatic patients., (© 2018 John Wiley & Sons Ltd.)

Background: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics., Methods: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment. Blood samples were collected from all patients during their first visit of the study. Neutrophils isolated from the blood were cultured with dexamethasone and/or atopic asthmatic serum for 18 h. The mRNA expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), a glucocorticoid transactivation target, and glucocorticoid-induced transcript 1 (GLCCI1), an early marker of glucocorticoid-induced apoptosis whose expression was associated with the response to inhaled glucocorticoids in asthma , was determined by real-time PCR, and ELISA was used to assess the pro-inflammatory cytokine IL-8 levels in the supernatant. Constitutive neutrophil apoptosis was detected by flow cytometry., Results: DEX significantly induced MKP-1 expression in both patients with SS and SR patients in a concentration-dependent manner, but greater induction was observed for SS patients at a low concentration (10 -6 M). Asthmatic serum alone showed no MKP-1expression, and there was impaired induction of MKP-1 by DEX in SR asthma patients. The expression of GLCCI1 was not induced in neutrophils with DEX or DEX/atopic asthmatic serum combination. Greater inhibition of IL-8 production was observed in neutrophils from patients with SS asthma treated with DEX/atopic asthmatic serum combination compared with SR asthma patients, though DEX alone showed the same effect on neutrophils from SS and SR asthma patients. Meanwhile, DEX dependent inhibition of constitutive neutrophil apoptosis was similar between SS asthma and SR asthma patients., Conclusions: DEX exerted different effects on neutrophils from patients with SS asthma and SR asthma, which may contribute to glucocorticoid insensitivity.