Clinico-radiological features and efficacy of anti-fibrotic agents in atypical idiopathic pulmonary fibrosis

Background: Atypical idiopathic pulmonary fibrosis (IPF) including multiple cysts or markedly atelectatic induration in upper lung predominance occasionally can confirm the diagnosis of IPF through a multidisciplinary discussion (MDD) between clinician, radiologist and, pathologist in clinical practice. The aim of this study was to clarify the differences in clinico-radiological characteristics and the efficacy of antifibrotic agents between atypical IPF and typical IPF. Methods: We retrospectively evaluated the differences in clinico-radiological characteristics between patients with atypical IPF (n=44) and those with typical IPF (n=87) and examined efficacy of anti-fibrotic agents in atypical IPF. Atypical IPF was characterized by the presence of markedly atelectatic induration in upper lung predominance (pleuroparenchymal fibroelastosis; PPFE like lesion) with and without multiple thick-walled large cysts (TWLC), so-called macrocystic honeycombing (TWLC; >2.5 cm in diameter with 1-3 mm thickness) in addition to honeycombing in the bilateral lower lobes predominance. Results: There was no difference in the baseline disease severity for IPF between both groups. The annual change value of fibrotic score and traction bronchiectasis (TBE) score, and decreased changes in forced vital capacity (FVC) during 6 months were significantly higher in atypical IPF than those in typical IPF. Survival time was significantly lower in patients with atypical IPF (MST: 33.4 vs. 47.9 months, P=0.03). The multivariate Cox regression model demonstrated that the prognostic predictors were presence of atypical IPF and increased Gender-Age-Physiology (GAP) staging. Moreover, the rate of decrease in FVC value 6 months after treatment with anti-fibrotic agents was significantly higher in atypical IPF than those in typical IPF (-11.8%+/- 14.0% vs. -1.0%+/- 12.7%; P=0.01). Conclusions: This study demonstrated that the prognosis for atypical IPF was significantly worse than that for typical IPF. Future studies are required prospective analyses of efficacy of anti-fibrotic agents for patients with atypical IPF.