Utility of a Molecular Classifier as a Complement to High-Resolution Computed Tomography to Identify Usual Interstitial Pneumonia

Richeldi, Luca; Scholand, Mary Beth; Lynch, David A.; Colby, Thomas V.; Myers, Jeffrey L.; Groshong, Steve D.; Chung, Jonathan H.; Benzaquen, Sadia; Nathan, Steven D.; Davis, John R.; Schmidt, Shelley L.; Hagmeyer, Lars; Sonetti, David A.; Hetzel, Jürgen; Criner, Gerard J.; Case, Amy Hajari; Ramaswamy, Murali; Calero, Karel; Gauhar, Umair; Patel, Nina; Lancaster, Lisa; Choi, Yoonha; Pankratz, Daniel G.; Walsh, P. Sean; Lofaro, Lori; Huang, Jing; Bhorade, Sangeeta; Kennedy, Giulia C.; Martínez, Fernando J.; Raghu, Ganesh

doi:10.1164/rccm.202003-0877oc

Cited by 59 publications

(34 citation statements)

References 27 publications

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“…Finally, it may be necessary to combine this kind of analysis with newer technologies including image analysis and biomarkers to create the desired result. Such technologies are in development but are not yet routinely incorporated into clinical practice [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

et al. 2021

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Background Current interstitial lung disease (ILD) diagnostic guidelines assess criteria across clinical, radiologic and pathologic domains. Significant interobserver variation in histopathologic evaluation has previously been shown but the specific source of these discrepancies is poorly documented. We sought to document specific areas of difficulty and develop improved criteria that would reduce overall interobserver variation. Methods Using an internet-based approach, we reviewed selected images of specific diagnostic features of ILD histopathology and whole slide images of fibrotic ILD. After an initial round of review, we confirmed the presence of interobserver variation among our group. We then developed refined criteria and reviewed a second set of cases. Results The initial round reproduced the existing literature on interobserver variation in diagnosis of ILD. Cases which were pre-selected as inconsistent with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) were confirmed as such by multi-observer review. Cases which were thought to be in the spectrum of chronic fibrotic ILD for which UIP/IPF were in the differential showed marked variation in nearly all aspects of ILD evaluation including extent of inflammation and extent and pattern of fibrosis. A proposed set of more explicit criteria had only modest effects on this outcome. While we were only modestly successful in reducing interobserver variation, we did identify specific reasons that current histopathologic criteria of fibrotic ILD are not well defined in practice. Conclusions Any additional classification scheme must address interobserver variation in histopathologic diagnosis of fibrotic ILD order to remain clinically relevant. Improvements to tissue-based diagnostics may require substantial resources such as larger datasets or novel technologies to improve reproducibility. Benchmarks should be established for expected outcomes among clinically defined subgroups as a quality metric.

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Section: Discussionmentioning

confidence: 99%

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

et al. 2021

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“…However, next-generation RNA sequencing of TBLB specimens has potential to be a less invasive approach to confirm the presence of UIP histopathology. In two recent trials, genomic classification (GC) of lung biopsies improved the ability to differentiate IPF from other ILDs [ 93 , 94 ]. Thus, GC may be useful to identify patients with significant senescence burden and benefit from senotherapeutics [ 95 ].…”

Section: Ipf Clinical Presentation Diagnosis and Senescent Cell Burdenmentioning

confidence: 99%

Cellular Senescence in Idiopathic Pulmonary Fibrosis

2021

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Cellular senescence (CS) is increasingly implicated in the etiology of age-related diseases. While CS can facilitate physiological processes such as tissue repair and wound healing, senescent cells also contribute to pathophysiological processes involving macromolecular damage and metabolic dysregulation that characterize multiple morbid and prevalent diseases, including Alzheimer’s disease, osteoarthritis, atherosclerotic vascular disease, diabetes mellitus, and idiopathic pulmonary fibrosis (IPF). Preclinical studies targeting senescent cells and the senescence-associated secretory phenotype (SASP) with “senotherapeutics” have demonstrated improvement in age-related morbidity associated with these disease states. Despite promising results from these preclinical trials, few human clinical trials have been conducted. A first-in-human, open-label, pilot study of the senolytic combination of dasatinib and quercetin (DQ) in patients with IPF showed improved physical function and mobility. In this review, we will discuss our current understanding of cellular senescence, its role in age-associated diseases, with a specific focus on IPF, and potential for senotherapeutics in the treatment of fibrotic lung diseases.

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“…The Envisia® genomic classifier (Veracyte, South San Francisco, CA) predicts the presence of histologic usual interstitial pneumonia using a proprietary gene expression-based signature ( 196 ). This tool has been shown to predict histologic UIP with good test performance and increases diagnostic confidence for IPF when positive ( 197 , 198 ).…”

Section: Parenchymal Lung Biomarkersmentioning

confidence: 99%

Biomarkers in Progressive Fibrosing Interstitial Lung Disease: Optimizing Diagnosis, Prognosis, and Treatment Response

2021

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Interstitial lung disease (ILD) comprises a heterogenous group of diffuse lung disorders that commonly result in irreversible pulmonary fibrosis. While idiopathic pulmonary fibrosis (IPF) is the prototypical progressive fibrosing ILD (PF-ILD), a high proportion of patients with other ILD subtypes develop a PF-ILD phenotype. Evidence exists for shared pathobiology leading to progressive fibrosis, suggesting that biomarkers of disease activity may prove informative across the wide spectrum of ILDs. Biomarker investigation to date has identified a number of molecular markers that predict relevant ILD endpoints, including disease presence, prognosis, and/or treatment response. In this review, we provide an overview of potentially informative biomarkers in patients with ILD, including those suggestive of a PF-ILD phenotype. We highlight the recent genomic, transcriptomic, and proteomic investigations that identified these biomarkers and discuss the body compartments in which they are found, including the peripheral blood, airway, and lung parenchyma. Finally, we identify critical gaps in knowledge within the field of ILD biomarker research and propose steps to advance the field toward biomarker implementation.

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Utility of a Molecular Classifier as a Complement to High-Resolution Computed Tomography to Identify Usual Interstitial Pneumonia

Cited by 59 publications

References 27 publications

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

Cellular Senescence in Idiopathic Pulmonary Fibrosis

Biomarkers in Progressive Fibrosing Interstitial Lung Disease: Optimizing Diagnosis, Prognosis, and Treatment Response

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