Rheumatoid Arthritis–Associated Interstitial Lung Disease in a Single Center Cohort: Be Vigilant in Older Male Smokers Who Are Seropositive and Have a Low DLCO at Baseline

Objectives To characterize serologic, inflammatory, and pulmonary function profiles of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) in a tertiary Canadian cohort, and to identify early markers of physiologic decline following ILD diagnosis.

Methods This retrospective case series included 98 patients with confirmed RA-ILD followed in Hamilton, Ontario. Demographics, including sex, smoking history, autoantibody titers, inflammatory biomarkers, and pulmonary function test (PFT) results were abstracted from clinical records. Clinically meaningful progression was defined as ≥10% absolute decline in forced vital capacity (FVC %) or diffusing capacity for carbon monoxide (DLCO %) predicted. Patients with ≥2 PFTs within 2 years of ILD diagnosis (n = 54) were assessed, of whom 14 (26%) exhibited >10% functional change.

Results Of 98 patients, 82 had pulmonary data and 54 had serial PFTs within 2 years; 14 (25.9%) demonstrated >10% change in FVC and/or DLCO, indicating progression. Of the progressors, 9 were male (64%), suggesting greater susceptibility to functional decline among men. Compared with the broader cohort, the progression group showed higher autoantibody titers (mean RF 280 IU/mL vs 164 IU/mL; anti-CCP 147 vs 131 U/mL) and greater smoking exposure (mean 48.4 vs 38.3 pack-years). Despite greater physiologic decline, they exhibited lower inflammatory markers (CRP 11.5 vs 15.6 mg/L; ESR 21.4 vs 31.8 mm/hr), necessitating further analysis to determine whether decline occurs independently of systemic inflammation. Functionally, the progression group had higher FVC (82.9% vs 75.9%) but lower DLCO (46.9% vs 50.7%), potentially suggesting disproportionate impairment in gas transfer and early fibrotic or microvascular injury. Radiographically, 11 of 16 patients with available HRCT follow-up demonstrated disease progression, 8 of whom exhibited a usual interstitial pneumonia (UIP) pattern, consistent with previously described aggressive fibrosing phenotypes.[2] The rate and pattern of progression are comparable to those reported in previous RA-ILD studies,[3] reinforcing the established link between seropositivity, smoking, and pulmonary decline.[1]

Conclusion Approximately 1 in 4 RA-ILD patients experienced clinically significant pulmonary function decline within 2 years of diagnosis. Progression occurred predominantly among male patients, who were highly seropositive, heavily smoking-exposed, and more likely to exhibit a UIP pattern with reduced DLCO, even in the absence of elevated systemic inflammation. These findings delineate a distinct high-risk RA-ILD phenotype that warrants early, proactive monitoring and timely therapeutic intervention, including consideration of antifibrotic or immunomodulatory strategies, to prevent irreversible pulmonary decline and respiratory failure.[1-3]

References [1.] Assayag D. Respir Med 2014;108:857-64. [2.] Kim EJ. Chest 2010;138:1275-83. [3.] Zamora-Legoff JA. Eur Respir J 2017;49:1601796.