Elissavet Konstantellou

Increased levels of osteopontin in sputum supernatant of smoking asthmatics.

Smoking may modify the inflammatory pattern of the asthmatic airways. Osteopontin (OPN) has been associated with inflammation and fibrosis. In asthma, sputum levels of OPN are elevated and have been related to the underlying severity and to mediators expressing remodeling and inflammation. To evaluate the levels of OPN in sputum supernatants of asthmatic patients and to investigate the possible role of smoking as well as associations with mediators and cells involved in the inflammatory and remodeling process. We studied 103 asthma patients (49 smokers) and 40 healthy subjects (20 smokers) who underwent lung function tests, bronchial hyperresponsiveness to methacholine, and sputum induction for cell count identification and measurement of OPN, TGF-β1, IL-8, IL-13 and ECP in sputum supernatants. The concentrations of all mediators were measured using enzyme immunoassays. OPN levels (pg/ml) were significantly higher in smoking asthmatics compared to non-smoking asthmatics, and both non-smoking and smoking controls [median (interquartile ranges) 1120 (651,1817) vs. 197 (118,341) vs. 50 (42,70) vs. 102 (77,110) pg/ml, respectively; p<0.001]. Regression analysis provided significant associations between OPN and sputum neutrophils, IL-8 and TGF-β1, the most significant being the one with TGF-β1. These associations were present only in smoking asthmatics. Smoking habit significantly affects sputum OPN levels in asthma. The associations of OPN with sputum neutrophils, TGF-β1 and IL-8 in smoking asthmatics suggest a possible role for OPN in the neutrophilic inflammation and remodeling process in this phenotype of asthma.

Increased Levels of Osteopontin in Sputum Supernatant in Patients With COPD

BACKGROUND Osteopontin (OPN) is a phosphorylated acidic glycoprotein that can function as both an extracellular matrix molecule and a cytokine. Published data support that OPN is upregulated in surgical lung tissue samples of patients with COPD. The aim of this study was to determine the levels of OPN in sputum supernatants of patients with COPD and to investigate possible associations with mediators and cells involved in the inflammatory and remodeling process as well as with the extent of emphysema. METHODS Seventy-seven patients with COPD and 40 healthy subjects (20 smokers) were studied. All subjects underwent lung function tests, sputum induction for cell count identification, and OPN, transforming growth factor-β1, matrix metalloproteinase (MMP)-2, IL-8, and leukotriene-4 measurement in sputum supernatants. High-resolution CT (HRCT) scan of the chest was performed for quantification of emphysema. RESULTS OPN levels (pg/mL) were significantly higher in patients with COPD compared with healthy smokers and nonsmokers (median [interquartile range], 1,340 [601, 6,227] vs 101 [77, 110] vs 68 [50, 89], respectively; P < .001). Regression analysis showed a significant association between OPN and sputum neutrophils, IL-8, MMP-2, and the extent of emphysema. The associations previously listed were not observed in healthy subjects. CONCLUSIONS OPN levels are higher in patients with COPD compared with healthy subjects. OPN may play a role in the neutrophilic inflammation and in the pathogenesis of emphysema.

Angiopoietins 1 and 2 in sputum supernatant of optimally treated asthmatics: the effect of smoking

Angiopoietin‐1 (Ang‐1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin‐2 (Ang‐2) acts as its natural inhibitor.

Predictors of future exacerbation risk in patients with asthma

ABSTRACT Objectives: Although modern treatment of asthma improves asthma control, some patients still experience exacerbations. The aim of the present study was to detect predictors of asthmatic exacerbations Methods: We included patients with asthma followed up in asthma clinics of 2 tertiary University hospitals. Demographic and functional characteristics, levels of exhaled NO, and inflammatory biomarkers (IL-13, ΕCP και IL-8) and cell counts in induced sputum were recorded at baseline. Measurements were performed with the patients in stability and were considered as their personal best. Patients received optimal treatment with good compliance and were followed up for 1 year for asthma exacerbations occurrence. Evaluation of the effect of recorded parameters on asthma exacerbations was performed with univariate and multivariate Poisson regression analysis. Results: 171 patients (118 female) with bronchial asthma (mean age 51.6 ± 13.2 years) were included in the study. The mean number of exacerbations in 1 year of follow up was 0.4 ± 0.8 while the majority of patients (71.9%) did not experience any exacerbation. In multivariate Poisson Regression analysis only 3 characteristics were predictors of future exacerbations: FEV1 [IRR(95% CI)], [0.970(0.954–0.987)], p = 0.001, high BMI [1.078(1.030–1.129)], p = 0.001, and the need for permanent treatment with oral corticosteroids for asthma control maintenance [2.542(1.083–5.964)], p = 0.032 Conclusion: Optimal guideline-based asthma management results in minimal occurrence of exacerbations in the majority of patients. Predictors of exacerbations are low FEV1 levels in stability, high BMI and the need for permanent treatment with oral corticosteroids.

Sputum interleukin-13 as a biomarker for the evaluation of asthma control.

Asthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin‐13 (IL‐13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control.

Clinical, functional and inflammatory characteristics in patients with paucigranulocytic asthma

Introduction: According to induced sputum cell count,4 different asthma phenotypes have been recognised(eosinophilic, neutrophilic,mixedand paucigranulocytic). Aim: To detect the differences in functional and inflammatory characteristics of asthmatic patients according to the phenotype. Methods: 240(169 female)optimally treated asthmatic patients underwent pulmonary function tests, sputum induction and measurement of FeNO. The levels ofIL-8,IL-13, and ECP were measured in sputum supernatant. Patients treatment, asthma control [using the Asthma Control Test, (ACT)] and the presence of Severe Refractory Asthma(SRA) (according to the ATS workshop consensus) were also recorded. Results: Although ACT did not differ between the groups(p=0.288)patients with paucigranulocytic asthma had better lung function (i.e FEV1%74.2±19.8 vs 69.7±18.2 vs72.2±20.2 vs 81.9±20.4 for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma respectively, p=0.009).SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7% respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7% respectively) (p=0.01).As expected,FeNO and ECP were higher in eosinophilic and mixed asthma while IL-8 was increased in patients with neutrophilic and mixed asthma (p Conclusion: According to our results,paucigranulocyticasthma is characterised bylower levels of inflammatory cells and inflammatory biomarkers,better pulmonary function and lower frequency of SRA which might reflect a better response to therapy in these patients.