*4.1. Study Subjects*

ACPA-positive subjects referred to the Early Arthritis Clinic of Policlinico Umberto I Hospital/ "Sapienza" University of Rome were consecutively enrolled. Participants were divided into three groups. The first group included ACPA-positive subjects without clinical evidence of arthritis (no disease subjects, ND). The second group included ACPA-positive Early Rheumatoid Arthritis (ERA) patients, diagnosed according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, naïve to treatment and with a disease duration shorter than 6 months. The third group included established, ACPA-positive Rheumatoid Arthritis patients (long-standing Rheumatoid Arthritis, LSRA), with a disease duration shorter than 36 months, on treatment with disease-modifying antirheumatic drugs (DMARDs). Subjects of both sexes and aged between 18 and 65 years were included in the study. Exclusion criteria were: any persistent respiratory complains, personal history of any kind of lung disease (e.g., asthma, chronic obstructive pulmonary disease) chronic heart failure NHYA class II-III-IV, overlap autoimmune syndromes, ongoing treatment with glucocorticoids, presumed or established pregnancy. Finding of Usual Interstitial Pneumonia (UIP) patterns at HRCT was also considered an exclusion criterion (see below).

Each subject underwent clinical and clinimetric, laboratory, functional and imaging evaluation. Age- and sex-matched healthy controls (HC) were also enrolled for comparison concerning laboratory assessment. Written informed consent was obtained from all patients and the study was approved by the local Ethics Committee (Comitato Etico Policlinico Umberto I, Sapienza Università di Roma, study reference number 815/13).

#### *4.2. Clinic and Clinimetric Evaluation*

Detailed medical history was taken for each subject. Every ACPA-positive subject without evidence of arthritis was evaluated to assess the absence of current or previous arthritis. General and musculoskeletal physical examination was performed, and counts of involved joints were registered for all participants.

Clinimetric scales were administered at the time of enrolment to evaluate global disease activity (i.e., Visual Analog Scale, VAS) and to calculate the composite index of disease activity (i.e., Disease Activity Score 28, DAS28). Moreover, disease onset and laboratory data regarding erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and ACPA levels were collected for each subject.
