SESSION TITLE: Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis SESSION TYPE: Original Investigations PRESENTED ON: 10/08/2018 07:30 am - 08:30 am PURPOSE: Under the diagnostic criteria for idiopathic pulmonary fibrosis (IPF) recently proposed by the Fleischner Society, histologic confirmation of UIP by tissue biopsy is necessary for a confident diagnosis of IPF if high-resolution computed tomography (HRCT) does not show either definite or probable usual interstitial pneumonia (UIP), in the clinical context of an idiopathic interstitial pneumonia. If histopathology is not available or not definitive, a working IPF diagnosis may be appropriate. The Envisia Genomic Classifier (Envisia) detects UIP at the molecular level (‘molecular UIP’) in transbronchial biopsy samples, using a locked machine learning algorithm applied to the expression of 190 genes. In a prospective, multi-center validation study of 49 subjects undergoing clinical evaluation for new-onset interstitial lung disease (BRonchial sAmple collection for a noVel gEnomic test, BRAVE), Envisia shows 88% specificity and 70% sensitivity for histopathology-proven UIP. We report Envisia performance in validation cohort subjects who had HRCT patterns other than definite or probable UIP, determined by local radiology diagnoses and by central radiology review. METHODS: HRCT scans and diagnoses were obtained from BRAVE sites. Available scans were reviewed by an expert thoracic radiologist and diagnosed as definite UIP, probable UIP, possible UIP, non-UIP or ‘other’. For categorical comparison (Cohen’s kappa), specific non-UIP and ‘other’ diagnoses were defined as ‘inconsistent with UIP’. RESULTS: 46 of 49 validation subjects had available HRCT scans. Diagnostic agreement between local and central radiology was low (kappa= 0.28), but improved when confident UIP (definite or probable UIP) was compared to those with either possible UIP or a pattern inconsistent with UIP (kappa =0.49). We excluded 4 subjects with definite or probable UIP patterns by both local and central radiology, as these subjects would be considered already to have a confident diagnosis. Among 42 subjects without definite or probable UIP on HRCT (40% UIP prevalence by histopathology), Envisia showed specificity of 88% [CI:69%-97%], sensitivity of 76% [CI:50%-93%], positive predictive value of 81% [54%-96%] and negative predictive value of 85% [CI:65%-96%]. CONCLUSIONS: In a retrospective analysis of subjects with HRCT patterns other than definite or probable UIP, Envisia molecular UIP had >80% predictive value for histologically-proven UIP. CLINICAL IMPLICATIONS: Molecular UIP results may be useful in the multidisciplinary evaluation of subjects without high-confidence HRCT patterns, who are being considered for surgical biopsy. In the appropriate clinical context, the high predictive value of molecular UIP may support confident IPF diagnosis without surgery. 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