Pulmonary Pharmacology & Therapeutics 21 (2008) 26–31 Serum levels of oxidative stress as a marker of disease severity in idiopathic pulmonary fibrosis Zoe D. Daniil , Evangelia Papageorgiou, Agela Koutsokera, Konstantinos Kostikas, Theodoros Kiropoulos, Andriana I. Papaioannou, Konstantinos I. Gourgoulianis Department of Respiratory Medicine, University Hospital of Larissa, University of Thessaly, Larissa, Greece Received 15 March 2006; received in revised form 27 June 2006; accepted 10 October 2006 Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a fatal illness characterized by progressive fibrosis resulting in severe dyspnea and impairment of lung function. Although the mechanisms by which lung fibrosis develops are not fully ascertained, recent findings suggest that oxidative stress may play an important role in the pathogenesis of tissue fibrosis. Aim: To evaluate the oxidative stress in the serum of patients with IPF and to explore the relationship between oxidative stress levels, dyspnea and impairment of lung function. Material and methods: Blood samples from 21 untreated patients with IPF, sequentially recruited over a period of 2 years, and 12 controls were analyzed. The level of oxidative stress in the blood was determined through a spectrophotometric procedure (D-ROMs test). FVC and DLCO were measured in all patients. The level of dyspnea was assessed by the Medical Research Council (MRC) chronic dyspnea scale. Results: Serum levels of oxidative stress were significantly increased in patients with IPF compared to controls (mean7SEM: 356.8714 and 201710 Carratelli units respectively, po0.001). Oxidative stress was negatively associated with FVC (po0:01, r ¼0:79) and with DLCO (po0:01, r ¼0:75). Furthermore, oxidative stress was significantly correlated with MRC dyspnea score (po0:01, r ¼ 0:87). Oxidative stress measurements were highly reproducible on two consecutive measurements in the same patients. Conclusion: The levels of systemic oxidative stress are enhanced in patients with IPF and could provide useful information about the classification of IPF severity. Strategies to reduce the oxidant burden in IPF may be beneficial in reducing the progressive deterioration of these patients. r 2006 Elsevier Ltd. All rights reserved. Keywords: Idiopathic pulmonary fibrosis; Oxidative stress; Medical research council chronic dyspnea scale; Lung function 1. Introduction Idiopathic pulmonary fibrosis (IPF) is a devastating condition that leads to progressive lung destruction and scarring. The diagnosis of IPF requires compatible clinical history, functional and high-resolution computed tomo- graphy (HRCT) findings, and the exclusion of other known causes of interstitial lung disease [1]. Usual interstitial pneumonia (UIP) is the histopathologic pattern that identifies patients with IPF in lung biopsy specimens [1]. UIP has patchy lung involvement with a variable stage of fibrosis (active fibrogenesis occurring in the so-called fibroblastic foci) and a low grade of inflammation [2]. It has been widely held that pulmonary fibrosis begins with alveolar inflammation and that chronic inflammation modulates fibrogenesis [3]. However, recent observations have led to new concepts in the pathogenesis of IPF. Several key observations suggest that inflammation does not play a prominent pathogenetic role, and that alveolar epithelial injury directly results in lung fibrosis [4]. Furthermore, ultrastructural studies have demonstrated alveolar type II cell injury and apoptosis in lung biopsies from patients with IPF [5]. A mechanism proposed to explain epithelial cell apoptosis is an increased production of oxidants in IPF. Additionally, free radicals activate ARTICLE IN PRESS www.elsevier.com/locate/ypupt 1094-5539/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.pupt.2006.10.005 Corresponding author. Tel.:++30 2410682898. E-mail address: zdaniil@med.uth.gr (Z.D. Daniil).