Lung Ultrasound to Phenotype Chronic Lung Allograft Dysfunction in Lung Transplant Recipients. A Prospective Observational Study.

Jesper Rømhild Davidsen,Jørn Carlsen,Elisabeth Bendstrup,Thomas Kromann Lund,Anna Kalhauge,Daniel Pilsgaard Henriksen,Martin Iversen,Michael Perch,Christian B Laursen,Mikkel Højlund,Hans Henrik Lawaetz Schultz,Klaus Nielsen Jeschke

doi:10.3390/jcm10051078

Abstract

Background: Bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) are two distinct phenotypes of chronic lung allograft dysfunction (CLAD) in lung transplant (LTx) recipients. Contrary to BOS, RAS can radiologically present with a pleuroparenchymal fibroelastosis (PPFE) pattern. This study investigates lung ultrasound (LUS) to identify potential surrogate markers of PPFE in order to distinguish CLAD phenotype RAS from BOS. Methods: A prospective cohort study performed at a National Lung Transplantation Center during June 2016 to December 2017. Patients were examined with LUS and high-resolution computed tomography of the thorax (HRCT). Results: Twenty-five CLAD patients (72% males, median age of 54 years) were included, corresponding to 19/6 BOS/RAS patients. LUS-identified pleural thickening was more pronounced in RAS vs. BOS patients (5.6 vs. 2.9 mm) compatible with PPFE on HRCT. LUS-identified pleural thickening as an indicator of PPFE in RAS patients’ upper lobes showed a sensitivity of 100% (95% CI; 54–100%), specificity of 100% (95% CI; 82–100%), PPV of 100% (95% CI; 54–100%), and NPV of 100% (95% CI; 82–100%). Conclusion: Apical pleural thickening detected by LUS and compatible with PPFE on HRCT separates RAS from BOS in patients with CLAD. We propose LUS as a supplementary tool for initial CLAD phenotyping.

Highlights

Chronic lung allograft dysfunction (CLAD) is the leading cause of morbidity and mortality in adult lung transplant recipients, affecting more than 50% surviving beyond five years after lung transplantation (LTx) [1]
Twenty-five patients with chronic lung allograft dysfunction (CLAD) were included corresponding to Bronchiolitis obliterans syndrome (BOS):restrictive allograft syndrome (RAS) of 19:6 with an overall male predominance of 72.0% and a median age of 54 years
In BOS and RAS patients, the lung physiology was represented by an average decline from best obtained post-LTx FEV1 and total lung capacity (TLC) of 49% and 38%, respectively

Summary

Introduction

Chronic lung allograft dysfunction (CLAD) is the leading cause of morbidity and mortality in adult lung transplant recipients, affecting more than 50% surviving beyond five years after lung transplantation (LTx) [1]. In 2011 a novel CLAD phenotype-restrictive allograft dysfunction (RAS)-was introduced and characterized by a combined decline in FEV1 and TLC with concurrent presence of pleuroparenchymal fibrotic changes on a high-resolution computed tomography (HRCT) [8,9,10,11]. Bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) are two distinct phenotypes of chronic lung allograft dysfunction (CLAD) in lung transplant (LTx) recipients. This study investigates lung ultrasound (LUS) to identify potential surrogate markers of PPFE in order to distinguish CLAD phenotype RAS from BOS. LUS-identified pleural thickening was more pronounced in RAS vs BOS patients (5.6 vs 2.9 mm) compatible with PPFE on HRCT. LUS-identified pleural thickening as an indicator of PPFE in RAS patients’ upper lobes showed a sensitivity of 100% (95% CI; 54–100%), specificity of 100% (95% CI; 82–100%), PPV of 100% (95% CI; 54–100%), and NPV of 100%

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