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A consecutive RA patients hospitalized in the Department of Internal Medicine and Rheumatology, Military Institute of Medicine in Warsaw between December 2006 and April 2010, fulfilling inclusion and exclusion criteria, were recruited to the study. The inclusion criteria were as follows: (i) the diagnosis of RA established on the basis of 1987 ACR criteria; (ii) age ≥18 years; (iii) written informed consent to the study. The exclusion criteria included the following: (i) presence of malignancy; (ii) history of pulmonary thromboembolism; (iii) severe left ventricular failure; (iv) pneumonia; (v) previous diagnosis of ILD. The reason to exclude patients with pre-existing ILD was to avoid channeling bias, as the presence of this complication could affect choice of RA treatment regimen (i.e. avoidance of MTX and preferring other drugs, such as leflunomide) and our main goal was to assess the influence of DMARDs on ILD risk.

A structured questionnaire was used to collect data regarding age, gender, smoking habits, body mass index (BMI) and previous treatment S1 and S2 Files. All conventional and biologic DMARDs and glucocorticosteroids (GCS) used for at least 3 months were reported. Based on treatment history patients were divided into group treated (present and in the past) and not-treated with an individual medication. Additionally, on the basis of history of MTX treatment patients were divided into three groups: i) patients not treated with MTX (N-MTX group), ii) patients treated with a mean MTX dose<15 mg/week (0<MTX<15 group), iii) patients treated with a mean MTX dose ≥15 mg/week (MTX≥15 group).

The laboratory work-up included: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). In order to assess disease activity and physical dysfunction DAS28 (disease activity score 28) and HAQ (health assessment questionnaire) were used, respectively.

HRCT of chest was performed in each patient included in the study. HRCT was scored by an experienced radiologist, who was aware of the RA diagnosis but was blinded to the clinical and laboratory data. ILD was diagnosed based on typical tomography pattern, defined as presence of diffuse peripheral or subpleural reticulation with or without honeycombing and ground-glass opacities [2, 3, 37]. On the basis of HRCT patients were classified as having ILD (ILD group) or not (N-ILD group). The ILD was graded using the semi-quantitative Warrick scale of fibrosis from 0 to 30 [37]. Warrick extent score (WES) and Warrick severity score (WSS) were calculated separately for each patient, then combined to obtain a global score (WGS). ILD was classified as mild (WGS <8 points), moderate (WGS 8–15 points) and severe (WGS >15 points), similarly as in the study by Fessi et al. [37].

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