Pulmonary Sarcoidosis with Predominant Ground Glass Opacities: a Case-Control Study

Background: Sarcoidosis is a systemic granulomatous inflammatory disease that has heterogeneous features. Hilar lymph nodes and lungs are interested in 90% of cases. Pulmonary sarcoidosis with predominant ground glass opacities (SPGGOs) is a rare and not well characterized presentation of the disease. Research Question: Is SPGGOs associated to a particular phenotype, especially to a worse initial respiratory function and poorer prognosis? Study Design and Methods: it is a retrospective monocentric case-control study. 1169 patients with sarcoidosis managed in clinic between April 2006 and February 2025 were searched. Every SPGGOs case was matched, by age (± 5 years) and baseline (± 2 years) (the last corresponds to the date of the first CT scan with lung abnormalities), to a control presenting lung involvement without predominant GGOs. The primary endpoint is forced vital capacity (FVC) at baseline, expressed as percentage of predicted; secondary endpoints are composite physiological index (CPI) >40, fibrotic progression and clinical outcomes. Statistical analyses were done using Chi² or Fischer’s exact test, t-student or Mann Whitney test, and linear mixed regression model as appropriate. Results: 79 cases (6.8%) with SPGGOs were identified (mean age was 47 years, 60% males and 49% afro-caribbean). Compared to 79 controls, cases resulted more exposed to tobacco (66% vs 32%, P < .001), cannabis (14% vs 4%, P = .03), and mold (14% vs 4%, P = .03). At baseline, FVC was significantly worse in cases (71% vs 81% of predicted, P = .006), and CPI was >40 in 58% of cases versus 25% of controls (P < .001). Pulmonary hypertension was more frequent (23% vs 3%, P = .03). Treatment was administered in 65% of patients at baseline (71% of cases vs 60% of controls, P = .15). During follow-up, pulmonary fibrosis was more frequent in cases (37% vs 17%, P = .006), recovery was less achieved (5% vs 18%, P = .02), and more relapses occurred (1 vs 0.7, P = .05). Interpretation: patients presenting SPGGOs have more severe respiratory function and are more exposed to tobacco, cannabis, and/or mold. They are more susceptible to develop pulmonary fibrosis, pulmonary hypertension and poorer outcomes, in particular more relapses and less recoveries, with respect to typical patterns. Same basic characteristics and systemic involvement are noticed.