Unraveling unclassifiable interstitial lung disease – a multicenter approach

Abstract

Background: Unclassifiable interstitial lung disease (uILD) is defined as ILD where multidisciplinary team discussion cannot secure a specific diagnosis with a diagnostic confidence > 50%. Yet, as understanding the nature of uILD is still obscure, we aim to explore uILD by a multicenter approach further.

Methods: The databases of two tertiary referral centers for ILD were reviewed for uILD. Clinical, functional, radiological and treatment data were analyzed retrospectively.

Results: 211 patients were identified. Mean age was 66 years, 58% male, 63% ever-smokers, mean FVC 72%, mean DLCO 48%, mean ILD-GAP score 3.29. Reasons for classification of uILD were: 75.4% due to missing histology data (mainly due to comorbidities); 1.8% due to overlapping of histological features; 14.1% due to major discordance between clinical, radiologic or pathological data and 8% due to uncertain etiology. On HRCT, 75.1% showed reticulations, 80% traction bronchiectasis and 16.9% honeycombing (50% NSIP pattern, 17% probable or typical UIP pattern). Treatments were mainly based on immunomodulation with 63% receiving monosteroid (CS) therapy, while 23% received azathioprine, 12% methotrexate, 5% cyclophosphamide on top of CS, 19% received antifibrotic therapy (11% pirfenidone, 7% nintedanib). After a median follow-up of 14.2 months acute exacerbations were observed in 17.9% with a median time to first AE of 359 days.

Conclusions: uILD represents a heterogeneous group of diseases with different clinical and radiological characteristics associated with a significant limitation for appropriate therapy selection. Future approaches have to clarify outcomes with different therapeutic approaches.