Anastasia Papaporfyriou

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.

Decreased Serum Sirtuin-1 in COPD

Background The protein deacetylase sirtuin‐1 (SIRT1) is an antiaging molecule that is decreased in the lung in patients with COPD. Recently, SIRT1 was reported to be detectable in serum, but serum SIRT1 (s120S) levels have not yet been reported in patients with COPD. Methods Serum SIRT1 protein of all samples was measured by Western blot, and the SIRT1 protein band densities were calculated and compared with clinical parameters. Results Several molecular sizes of SIRT1, including 120 kDa (actual size) and fragments (102 and 75 kDa) were quantified by Western blot. Among them, only the 120‐kDa s120S was significantly decreased in patients with COPD compared with the control subjects without COPD (s120S ratio in healthy subjects = 0.90 ± 0.34 vs those with COPD = 0.68 ± 0.24; P = .014) and was positively correlated with airway obstruction (FEV1/FVC, r = 0.31; P = .020); its severity measured by FEV1 % predicted (r = 0.29; P = .029). s120S also showed a positive correlation with BMI (r = 0.36; P = .0077) and diffusing capacity of the lung per unit volume (the carbon monoxide transfer coefficient: KCO%) (r = 0.32; P = .025). It was also significantly decreased with increasing severity of lung emphysema (r = –0.40; P = .027) and with a clinical history of frequent COPD exacerbations (infrequent vs frequent, 0.76 ± 0.20 vs 0.56 ± 0.26; P = .027). SIRT1 was not detected in supernatant of A549 and primary epithelial cells in normal culture conditions. Conclusions s120S was decreased in the patients with COPD, potentially as reflected by the reduced SIRT1 within cells as a result of oxidative stress, and might be a potential biomarker for certain disease characteristics of COPD.

Pulmonary alveolar proteinosis: time to shift?

Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary and autoimmune PAP (aPAP) types. The common pathogenesis is the ability of the alveolar macrophages to catabolize phagocytized surfactant is affected. Hereditary PAP is caused by mutations involving the GM-CSF signaling, particularly in genes for the GM-CSF receptor and sometimes by GATA2 mutations. Secondary PAP occurs in hematologic malignancies, other hematologic disorders, miscellaneous malignancies, fume and dust inhalation, drugs, autoimmune disorders and immunodeficiencies. aPAP is related to the production of GM-CSF autoantibodies. PAP is characterized morphologically by the inappropriate and progressive ‘occupation’ of the alveolar spaces by an excessive amount of unprocessed surfactant, limiting gas exchange and gradually exhausting the respiratory reserve. Myeloid cells’ immunity deteriorates, increasing the risk of infections. Treatment of PAP is based on its etiology. In aPAP, recent therapeutic advances might shift the treatment option from the whole lung lavage procedure under general anesthesia to the inhalation of GM-CSF ‘as needed’.

Sputum and BAL Clara cell secretory protein and surfactant protein D levels in asthma

Clara cell secretory protein (CC16) is associated with Th2 modulation. Surfactant protein D (SPD) plays an important role in surfactant homeostasis and eosinophil chemotaxis. We measured CC16 and SPD in sputum supernatants of 84 asthmatic patients and 12 healthy controls. In 22 asthmatics, we additionally measured CC16 and SPD levels in BAL and assessed smooth muscle area (SMA), reticular basement membrane (RBM) thickness, and epithelial detachment (ED) in bronchial biopsies. Induced sputum CC16 and SPD were significantly higher in patients with severe asthma (SRA) compared to mild–moderate and healthy controls. BAL CC16 and SPD levels were also higher in SRA compared to mild–moderate asthma. CC16 BAL levels correlated with ED, while SPD BAL levels correlated with SMA and RBM. Severity represented a significant covariate for these associations. CC16 and SPD levels are upregulated in SRA and correlate with remodeling indices, suggesting a possible role of these biomarkers in the remodeling process.

Levels of prostaglandin E2 and Cysteinyl-leukotrienes in sputum supernatant of patients with asthma: the effect of smoking

Smoking is associated with worse asthma outcomes and may modify airway inflammation. Such modification may be mediated through an effect on prostaglandin E2 (PGE2) and cysteinyl leukotrienes (Cyst‐LTs).

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.

Activin A and follistatin in patients with asthma. Does severity make the difference

Activin A is a pleiotropic cytokine holding a fundamental role in inflammation and tissue remodelling. Follistatin can modulate the bioactivity of activin. We aimed to measure activin A and follistatin in sputum supernatants and bronchoalveolar lavage (BAL) of asthmatic patients and to determine the possible associations with severity as well as with inflammatory and remodelling indices.

Noninvasive evaluation of airway inflammation in patients with severe asthma

INSTRUCTIONS Credit can now be obtained, free for a limited time, by reading the review article in this issue and completing all activity components. Please note the instructions listed below: Review the target audience, learning objectives and all disclosures. Complete the pre-test online at http://www.annallergy.org (click on the CME heading). Follow the online instructions to read the full version of the article; reflect on all content as to how it may be applicable to your practice. Complete the post-test/evaluation and claim credit earned; at this time, you will have earned up to 1.0 AMA PRA Category 1 CreditTM. Please note that the minimum passing score on the post-test is 70%. Release Date: May 1, 2013 Expiration Date: April 30, 2015 Estimated Time to Complete: 60 minutes Target Audience: Physicians involved in providing patient care in the field of allergy/asthma/immunology Learning Objectives: At the conclusion of this activity, participants should be able to: Describe principles, procedures and challenges faced in the management of severe asthma Discuss the methodology, value and limitations associated with the non-invasive evaluation of airway inflammation Accreditation: The American College of Allergy, Asthma & Immunology (ACAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation: The American College of Allergy, Asthma & Immunology (ACAAI) designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Planning Committee Members: Petros Bakakos, MD (Author) Michael S Tankersley, MD (CME Series Editor) Gailen D. Marshall, Jr, MD, PhD (Editor-in-Chief) Disclosure of Relevant Financial Relationships: A. Papaporfyriou, E. Tseliou, S. Loukides, K. Kostikas, P. Bakakos, M.S. Tankersley, and G.D. Marshall, have nothing to disclose. Reviewers and Education/Editorial staff have no relevant financial relationships to disclose. No unapproved/investigative use of a product/device is discussed. Recognition of Commercial Support: This activity has not received external commercial support. Copyright Statement: 2013-2015 ACAAI. All rights reserved. CME Inquiries: Contact the American College of Allergy, Asthma & Immunology at education@acaai.org or 847-427-1200.

Serum periostin in patients hospitalized for COPD exacerbations

HighlightsSerum periostin is a surrogate biomarker of Th2 response in asthma.Periostin levels on COPD hospitalization were elevated compared to discharge.Periostin was not a good predictor of future risk for hospitalization or mortality. &NA; Serum periostin has been proposed as a surrogate biomarker of Th2 inflammatory response in patients with asthma, but its predictive role in hospitalized patients with COPD has not been evaluated. The aim of the present observational prospective cohort study was to evaluate the possible role of serum periostin as predictor of outcome in COPD patients hospitalized for AECOPD. Serum periostin was measured on admission and at discharge in patients admitted to the hospital for a COPD exacerbation. Patients were followed‐up for 1 year for future exacerbations, hospitalizations and mortality. 155 consecutive patients admitted to the hospital for AECOPD were included to the study. Periostin levels on admission were elevated compared to discharge [34.7 (25.2–52.2) vs. 25.9 (17.4–41.0) ng/mL, p = 0.003], but serum periostin levels did not differ between patients with or without prolonged hospitalization, or those who required non‐invasive ventilation, intubation, or died during hospitalization. Frequent exacerbators had higher serum periostin levels at the time of discharge compared to non‐frequent exacerbators [37.9 (26.6, 64.5) vs. 23.9 (16.2, 37.9), p < 0.001]. Periostin levels above the median value (25 ng/mL) were not related to the time of next exacerbation, time of next COPD hospitalization, (p = 0.858) or time to death. The role of serum periostin levels as a predictive biomarker of future risk in hospitalized patients with COPD is of limited value.