Longitudinal multimodal assessment of pulmonary nodules in fibrosing interstitial lung diseases: a retrospective study

Background: Pulmonary nodules are increasingly detected during high-resolution computed tomography (HRCT) surveillance in patients with fibrosing interstitial lung diseases (fILD). However, nodule risk stratification is challenging in fibrotic lungs, and evidence guiding clinical management remains limited. We aimed to characterize the longitudinal behaviour of HRCT-detected nodules in fILD and identify predictors of malignancy. Methods: We conducted a retrospective observational study at a tertiary ILD referral centre. All HRCT examinations performed between January 2018 and January 2022 in patients with multidisciplinary-diagnosed fILD were reviewed. Nodules (≤ 30 mm) were classified as low- or high-risk according to the 2017 Fleischner Society Guidelines. Nodules were adjudicated as malignant based on histopathology; benign nodules were defined by histological confirmation or long-term radiological stability (≥ 24 months). Clinical, functional, and radiological variables were analysed using univariate and multivariable logistic regression. Results: Among 789 screened fILD patients, 91 (11.5%) had at least one pulmonary nodule, yielding 153 nodules (123 low-risk [80.4%] and 30 high-risk [19.6%]). Four patients were excluded due to incomplete diagnostic work-up, leaving 87 patients (mean age 73.3 ± 10.7 years; 71.3% male) with definitively characterized nodules. Thirteen patients were diagnosed with lung cancer (9 squamous cell carcinomas; 4 adenocarcinomas). All malignant nodules occurred in the high-risk group (13/30, 43.3%), whereas none of the low-risk nodules were malignant (p < 0.001). In univariate analysis, nodule size was significantly associated with malignancy (OR 1.18; 95% CI 1.07–1.29; p = 0.031). Among the variables assessed, nodule size was the only variable independently associated with malignancy in multivariable analysis (OR 1.17; 95% CI 1.01–1.35; p = 0.041). Smoking exposure, HRCT pattern (UIP vs. non-UIP), ILD subtype, pulmonary function parameters, antifibrotic therapy, morphology, number of nodules, symptoms, and radiological progression were not independently associated with malignancy. Conclusions: In fILD, conventional nodule risk features may be less informative than in non-fibrotic lungs. Among the variables assessed, nodule size was the only variable independently associated with malignancy in multivariable analysis, supporting the need for ILD-specific strategies to optimize surveillance and avoid unnecessary invasive procedures. Clinical trial registration: Clinical trial number: not applicable.