Prevalence and clinical features of progressive pulmonary fibrosis in patients with unclassifiable idiopathic interstitial pneumonia: A post hoc analysis of prospective multicenter registry.

Background: Idiopathic interstitial pneumonias (IIPs) may remain unclassifiable owing to inadequate, nonspecific, or conflicting clinical, radiological, or histopathological findings despite multidisciplinary discussion (MDD). Unclassifiable IIP (UCIIP) is a heterogeneous disease that can present with progressive pulmonary fibrosis (PPF). This study aimed to investigate the prevalence and clinical features of PPF in patients with UCIIP.

Methods: In this post hoc analysis of a prospective multicenter registry of 222 patients with IIPs, 71 with UCIIP diagnosed using MDD were enrolled. PPF was defined based on worsening symptoms and radiological and physiological progression using the guideline criteria within 12 months or the criteria from the INBUILD trial within 24 months.

Results: The median age was 72 years, and surgical lung biopsy was performed in 19.7%. Of the 66 patients with adequate follow-up data, 30 (45.5%) met either criterion and were diagnosed with PPF. UCIIP patients with PPF had significantly higher serum surfactant protein-D level and percentage of bronchoalveolar fluid neutrophils, lower %forced vital capacity and %diffusing capacity for carbon monoxide, and a higher proportion of honeycombing on high-resolution computed tomography and desaturation on exertion than those without PPF. Additionally, they had significantly more anti-fibrotic therapy and long-term oxygen therapy, a higher incidence of acute exacerbation, and a poorer prognosis than those without PPF. Cox proportional hazards analysis revealed that PPF was a significant poor prognostic factor, regardless of the criteria.

Conclusions: PPF is common and associated with poor prognosis in patients with UCIIP. Appropriate evaluation and management of PPF are essential for UCIIP.