Carbocysteine Modifies Circulating miR-21, IL-8, sRAGE, and fAGEs Levels in Mild Acute Exacerbated COPD Patients: A Pilot Study.

Maria Ferraro,Serena Di Vincenzo,Stefania Leto Barone,Sebastiano Gangemi,Elisabetta Pace,Luigi Lanata,Claudia Sangiorgi

doi:10.3390/ph15020218

Abstract

Patients with Chronic Obstructive Pulmonary Disease (COPD) periodically experience acute exacerbation (AECOPD). Carbocysteine represents a valid add on therapy in COPD by exerting antioxidant and anti-inflammatory activities. The in vivo effects of carbocysteine on inflammatory markers are not yet fully understood. The aims of this study were to assess: (i) miR-21, IL-8, soluble Receptor for Advanced Glycation End Products (sRAGE), and fluorescent Advanced Glycation End Products (fAGEs) in control subjects (n = 9), stable (n = 9), and AECOPD patients (n = 24); and (ii) whether carbocysteine modifies these markers and the functional parameters in mild AECOPD patients. Mild AECOPD patients received or not carbocysteine along with background inhalation therapy for 20 days. At the onset and at the end of the observation period, the following parameters were evaluated: FEV1, FEF25–75%, CAT questionnaire; miR-21 by Real Time PCR; IL-8 and sRAGE by ELISA; and fAGEs by spectro-fluorescence method. COPD patients showed higher levels of miR-21, IL-8, fAGEs and lower levels of sRAGE compared to that of controls. miR-21 inversely correlated with FEV1. IL-8 and fAGEs were significantly different in stable and exacerbated COPD patients. Carbocysteine improved symptoms, FEV1 and FEF25–75%, increased sRAGE, and reduced miR-21, IL-8, and fAGEs in mild AECOPD patients. The present study provides compelling evidence that carbocysteine may help to manage mild AECOPD by downregulating some parameters of systemic inflammation.

Highlights

Chronic Obstructive Pulmonary Disease (COPD) is characterized by chronic inflammation that leads to airflow limitation and remodeling of the airways
Stable and Exacerbated COPD Show Increased Levels of Circulating miR-21, IL-8 and Fluorescent advanced glycation end products (AGEs) (fAGEs) and Lower Levels of soluble Receptor for Advanced Glycation End Products (sRAGE) Compared to Healthy Controls
Results are expressed as 2ˆ-delta CT (A). measurement of IL-8 and sRAGE in serum were determined by enzyme-linked immunosorbent assays (ELISA)

Summary

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is characterized by chronic inflammation that leads to airflow limitation and remodeling of the airways. Oxidative stress plays an important role in the pathogenesis of COPD, and oxidative stress markers are increased in exhaled breath condensate, sputum, and blood of patients with COPD [1]. COPD patients periodically experience acute exacerbations (AECOPD), periods of acute worsening of respiratory symptoms due to inflammatory processes generally triggered by viral or bacterial infections. Frequent exacerbations are associated with a more rapid decline in lung function, a poorer quality of life, and an increase in mortality. For this reason, AECOPD have strong clinical and economic consequences, and it is important

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