Genomic Classifier Aids Diagnosis and Management of Interstitial Lung Disease
Presenter: Joseph A. Lasky, MD, Professor of Medicine, Pulmonary/Critical Care Section Chief, Tulane University School of Medicine, New Orleans, LA.
A summary of The impact of the Envisia genomic classifier in the diagnosis and management of patients with interstitial lung disease, presented October 18, 2021.
The diagnosis of idiopathic pulmonary fibrosis (IPF), a progressive fibrosis of interstitial lung disease, is challenging and often results in delayed or missed diagnoses that can lead to worse outcomes. A diagnosis of IPF is based on the presence of either a radiographic or histologic pattern of usual interstitial pneumonia (UIP) in the absence of an identifiable cause.
The Envisia genomic classifier is a commercially available, clinically validated molecular diagnostic test that can detect a UIP pattern using whole transcriptome sequencing of transbronchial biopsies. The classifier analyzes the gene expression of 190 genes, and it was developed to provide a “rule in” test for UIP pattern. It generates and sequences a single whole-transcriptome library from RNA pooled from transbronchial biopsy samples, which are used to designate either positive or negative molecular UIP pattern.
It has high specificity for detecting UIP patterns in transbronchial biopsies. Combined results from two published validation trials of the genomic classifier show specificity and sensitivity of 91% and 63%, respectively.
To determine whether the clinical use of the genomic classifier would improve the diagnosis of ILD, Lasky and colleagues surveyed practitioners regarding the impact of a positive UIP result from the genomic classifier. They hypothesized that positive UIP pattern results would have the following effects:
- Increase the number of IPF diagnoses consistent with a centrally adjudicated multidisciplinary team IPF diagnosis
- Increase practitioners’ ILD diagnostic confidence level
- Increase the recommendations to initiate antifibrotic therapy.
This prospective, randomized decision-impact survey included 11 patient cases with undiagnosed ILD identified through expert panels. None of the cases were reviewed more than once by the same physician.
“There was a pre- and post-Envisia cohort of 84 physicians who were given the case to review, then given the genomic classifier, and then given the case again,” Lasky explained. “They did 172 case reviews. Two independent cohorts were either given the genomic classifier (89 physicians who did 171 case reviews) or no genomic classifier (91 physicians who did 172 case reviews).”
Results showed that the number of IPF diagnosis increased with the genomic classifier. “The pre- and post-Envisia cohort more than doubled their diagnoses of IPF,” Lasky said. “There was also an increase with the independent cohort, but not to the same extent. Both results were statistically significant.”
Overall, they found that physicians’ high confidence in their ILD diagnosis (≥ 90%) was significantly increased when the genomic classifier results were included. Results were significant in both in the pre- and post-results cohorts (P < .001) and the independent cohorts (P < .008) (Raghu 2019; Richeldi 2021).
Lasky added that the initiation of treatment recommendations were also increased by the including the genomic classifier. “In regard to these cases, we saw an increase in the use of antifibrotic therapy in patients with IPF, and also a decrease in patients treated with immunosuppressive drugs, which may be harmful,” he said.
In conclusion, Lasky said, “The genomic classifier had a significant impact on physician’s clinical decision making in the diagnosis and management of patients with ILD. The Envisia UIP-positive results increased the number of IPF diagnoses, the confidence of physicians’ in these diagnoses, and the appropriate use of antifibrotic therapy. By facilitating an IPF diagnosis, the genomic classifier will enable physicians to more effectively to manage patients with ILD, leading to improved patient outcomes.”
Disclosure
Joseph A. Lasky, MD: Veracyte (Educational presentations)
Reference
Lasky JA, Case A, Unterman A, et al. The impact of the Envisia genomic classifier in the diagnosis and management of patients with interstitial lung disease. Presented virtually at: Chest Annual Meeting 2021; October 18, 2021.
Raghu G, Flaherty KR, Lederer RL, et al. Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study. Lancet Respir Med 2019;7(6):487–496. doi: 10.1016/S2213-2600(19)30059-1
Richeldi L, Scholand MB, Lynch DA, et al. Utility of a molecular classifier as a complement to high-resolution computed tomography to identify usual interstitial pneumonia. Am J Respir Crit Care Med 2021;203(2):211–220. doi: 10.1164/rccm.202003-0877OC