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Bernadette R. Gochuico, MD; Nilo A. Avila, MD; Catherine K. Chow, MD; Levi J. Novero, MD; Hai-Ping Wu, BS; Ping Ren, MD, PhD; Sandra D. MacDonald, RN; William D. Travis, MD; Mario P. Stylianou, PhD; Ivan O. Rosas, MD

Arch Intern Med. 2008;168(2):159-166.

Background  Early detection and treatment for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objective of this study was to identify asymptomatic lung disease and potential therapeutic targets in patients having RA and preclinical ILD (RA-ILD).

Methods  Sixty-four adults with RA and 10 adults with RA and pulmonary fibrosis (RAPF) were referred to the National Institutes of Health, Bethesda, Maryland, and underwent high-resolution computed tomography (HRCT) and pulmonary physiology testing. Proteins capable of modulating fibrosis were quantified in alveolar fluid.

Results  Twenty-one of 64 patients (33%) having RA without dyspnea or cough had preclinical ILD identified by HRCT. Compared with patients without lung disease, patients with RA-ILD had statistically significantly longer histories of cigarette smoking (P < .001), increased frequencies of crackles (P = .02), higher alveolar-arterial oxygen gradients (P = .004), and higher HRCT scores (P < .001). The HRCT abnormalities progressed in 12 of 21 patients (57%) with RA-ILD. The alveolar concentrations of platelet-derived growth factor–AB and platelet-derived growth factor–BB were statistically significantly higher in patients having RA-ILD (mean [SE], 497.3 [78.6] and 1473 [264] pg/mL, respectively) than in patients having RA without ILD (mean [SE], 24.9 [42.4] and 792.7 [195.0] pg/mL, respectively) (P < .001 and P =.047, respectively). The concentrations of interferon gamma and transforming growth factor β₂ were statistically significantly lower in patients having RAPF (mean [SE], 5.59 [1.11] pg/mL and 0.94 [0.46] ng/mL, respectively) than in patients having RA without ILD (mean [SE], 14.1 [1.9] pg/mL and 2.30 [0.39] ng/mL, respectively) (P =.001 and P =.006, respectively) or with preclinical ILD (mean [SD], 11.4 [2.6] pg/mL and 3.63 [0.66] ng/mL, respectively) (P =.04 and P =.007, respectively). Compared with patients having stable RA-ILD, patients having progressive RA-ILD had statistically significantly higher frequencies of treatment using methotrexate and higher alveolar concentrations of interferon gamma and transforming growth factor β₁ (P =.046, P =.04, and P =.04, respectively).

Conclusions  Asymptomatic preclinical ILD, which is detectable by HRCT, may be prevalent and progressive among patients having RA. Cigarette smoking seems to be associated with preclinical ILD in patients having RA, and treatment using methotrexate may be a risk factor for progression of preclinical ILD. Quantification of alveolar proteins indicates that potential pathogenic mechanisms seem to differ in patients having RA-ILD and symptomatic RAPF.

Author Affiliations: Pulmonary–Critical Care Medicine Branch (Drs Gochuico, Novero, Ren, and Rosas and Mss Wu and MacDonald) and Office of Biostatistics Research (Dr Stylianou), National Heart, Lung, and Blood Institute, and Department of Diagnostic Radiology, Clinical Center (Drs Avila and Chow), National Institutes of Health, Bethesda, Maryland; and Pulmonary and Mediastinal Department, Armed Forces Institute of Pathology, Washington, DC (Dr Travis).