Clinical Features and Immunological Markers Associated with Invasive Pulmonary Fungal Disease in Organizing Pneumonia: A Matched Case–Control Study

Background/Objectives: Invasive pulmonary fungal disease (IPFD) is a serious complication of organizing pneumonia (OP), but associated clinical and immunological features remain poorly defined. Methods: We conducted a retrospective 1:2 age- and sex-matched case–control study of 126 adults with OP, including 42 with concomitant IPFD and 84 controls. Clinical, radiological, immunosuppressive exposure and admission lymphocyte-subset data were analyzed using a full-cohort clinical model and an immunological subgroup model (n = 39). Results: Pre-infection glucocorticoid and immunosuppressant exposure did not differ between groups. Invasive mechanical ventilation was more frequent with IPFD (59.5% vs. 21.4%, p < 0.001). Pleural effusion was associated with higher odds of IPFD (OR = 3.263, 95% CI: 1.237–8.607), whereas coexisting interstitial lung disease was associated with lower odds (OR = 0.168, 95% CI: 0.066–0.426). In the immunological subgroup, a lower CD4+ T-cell percentage was associated with IPFD (OR = 0.914, 95% CI: 0.849–0.983, p = 0.015), although statistical significance was lost after exclusion of possible IPFD cases. Conclusions: Pleural effusion and lower CD4+ T-cell percentage were associated with IPFD in OP; the potential clinical utility of lymphocyte-subset assessment should be evaluated prospectively.