Utility of a Molecular Classifier as a Complement to HRCT to Identify Usual Interstitial Pneumonia

Rationale Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy (SLB) for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A 'molecular diagnosis of UIP' in transbronchial lung biopsy (TBBx), the Envisia Genomic Classifier, accurately predicted histopathologic UIP. Objectives We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern. Methods Ninety-six patients who had diagnostic lung pathology, as well as a TBBx for molecular testing with Envisia Genomic Classier, were included in this analysis. The classifier results were scored against reference pathology. UIP identified on HRCT as documented by features in local radiologists' reports was compared to histopathology. Measurements and Main Results In 96 patients, the Envisia classifier achieved a specificity of 92.1% [CI:78.6%-98.3%] and a sensitivity of 60.3% [CI:46.6%-73.0%] for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology with a sensitivity of 34.0% [CI:21.5%-48.3%], and a specificity of 96.9% [CI:83.8 - 100]). In conjunction with HRCT patterns of UIP, the Envisia classifier results identified 24 additional UIP patients (sensitivity 79.2% specificity 90.6%). Conclusions In 96 patients with suspected ILD, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an ILD (especially IPF) diagnosis without the need for SLB.