Systemic oxidative stress in patients with pulmonary sarcoidosis☆
Introduction
Sarcoidosis is a systemic disease of unknown aetiology, characterized by the presence of noncaseating granulomas which affect the lungs in up to 90% of all cases. Although, diagnosis based on a compatible clinical and histological picture is usually straightforward, sarcoidosis still remains an enigmatic disorder [1]. Its diverse manifestations and its variable natural course, which is characterized by episodic recrudescence and remissions, render impossible the prediction of the long-term outcome of any individual patient. Targeting towards better disease understanding and improved patient care, investigators have focused on the identification of biomarkers [2] which would assist diagnosis or disease monitoring and would partly reveal the underlying mechanisms of disease.
The role of oxidative stress has been well documented in several lung diseases, including acute lung injury, asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis [3], [4], [5]. The sequence of events that lead to an increased oxidative burden is considered to commence when a usually unknown triggering factor activates an acute inflammatory response. The recruited inflammatory cells produce and release cytotoxic substances, such as reactive oxygen species (ROS), which perpetuate a vicious circle of amplified tissue destruction and cytotoxic mediator generation.
Oxidative stress has also been implicated in the pathogenesis of sarcoidosis. Although no study has yet described a systemic redox imbalance in this context, several investigators have demonstrated that alveolar macrophages isolated from the bronchoalveolar lavage (BAL) of patients with sarcoidosis are locally activated to produce oxygen radicals in vitro [6], [7]. This enhanced oxidative activity is also expressed in vivo as inferred by the elevation of 8-isoprostane, an oxidative product of arachidonic acid, in BAL [8] and exhaled breath condensate (EBC) [9] of sarcoidosis patients. The aim of the present study was to evaluate the systemic levels of oxidative stress in the serum of patients with sarcoidosis using a commercially available and easy to perform assay, and to explore the relationship between these levels, the severity of dyspnoea and the impairment of lung function in such patients. In addition, the present study also assessed whether oxidative stress levels are influenced by treatment with corticosteroids.
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Study population
Patients with histologically proven pulmonary sarcoidosis were considered for entry into the study if they presented during a stable phase of their disease. Patients with active sarcoidosis, those receiving corticosteroids for less than six months, smokers and subjects with co-morbidities, a respiratory tract infection during the past two months, allergies or asthma were excluded. Healthy volunteers, matched in age and gender with the patients, were used as controls. The study protocol was
Statistical analysis
Analysis was performed and graphs were drawn with the use of SPSS 15.0 for Windows. Data's normality of distribution was examined with the use of the Kolmogorov–Smirnov test. As D-ROMS test was normally distributed, comparison of the two main groups of subjects (normal subjects and sarcoidosis patients) was assessed with the unpaired t test, whether One-way analysis of variance (ANOVA) was used to compare multiple groups of subjects and Bonferroni's correction was applied to compare selected
Results
In this clinical study we investigated 35 patients with histologically proven pulmonary sarcoidosis during a stable phase of their disease and 13 healthy volunteers that served as controls. Disease duration prior to the study was 2 ± 1years (mean ± SD). The clinical characteristics of the 48 subjects who participated in this study are summarized in Table 1. The study populations did not differ significantly in terms of sex and age.
All patients reported stability of their symptoms during the last 6
Discussion
In the current study we have demonstrated that patients with sarcoidosis, assessed during a stable phase of their disease, have higher systemic oxidative stress levels compared to controls, whereas patients receiving systemic corticosteroids have systemic oxidative stress levels similar to that of normal subjects. According to our knowledge, this is the first study to demonstrate a systemic Redox imbalance in the context of sarcoidosis and to provide evidence of a sustained oxidative burden
Conclusions
Patients with stable sarcoidosis that do not receive corticosteroids have elevated systemic oxidative stress levels. This finding advocates towards a potential key role of oxidative stress in the pathogenesis of the disease and implies that the underlying pathophysiological events that occur during the course of sarcoidosis persist even when clinical, functional and radiological criteria indicate disease stability. Although so far there is no available biomarker sensitive enough to monitor
Conflicts of interest
All authors declare that they have no conflicts of interest related to the present study.
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The present work was performed at the Department of Respiratory Medicine, University of Thessaly Medical School, Larissa, Greece.