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

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.

Lung Ultrasound as a Promising Diagnostic Tool for Primary Graft Dysfunction after Lung Transplantation

“…So far, there is only limited experience with LUS after LTX [21,22,23,24,25]. In chronic lung allograft dysfunction pleura thickening identified by LUS was able to discriminate between the two phenotypes, bronchiolitis obliterans syndrome and restrictive allograft syndrome [22]. Further studies focusing on the earlier postoperative course showed that LUS after LTX is feasible and able to monitor typical postoperative pathologies such as pleural effusion, pneumonia, and atelectasis [21,25].…”

Thoracic Ultrasound in Lung Transplantation—Insights in the Field

“…In 2017, Davidsen et al published a case report proposing that TUS could be used as a novel tool to phenotype CLAD [ 31 ]. The same study group further investigated this hypothesis in a later observational study with the prospective inclusion of 25 lung transplant recipients with new-onset CLAD (n(BOS):n(RAS) = 19:6), who were examined with TUS and HRCT, performed within an average time window of ten days prior to or after TUS [ 12 ]. HRCT was used as the gold standard for the PPFE findings that would correspond to the TUS findings demonstrating pleural thickening.…”

“…( B ): Axial HRCT image of the upper lobes showing fibrotic pleural and septal thickening consistent with PPFE. The white arrow corresponds to TUS zone R1 presented in ( A ) [ 12 ].…”

“…Such training also contributes to understanding the commonly used terminology and knowledge of normal and pathological findings of the lung parenchyma, pleura, and thoracic wall, which is an essential prerequisite for the sufficient interpretation of TUS observations [ 6 , 7 ]. Several TUS scanning protocols with different scanning areas and zones are described, but the most frequently used in prospective clinical studies is the 14-zone approach, which accommodates the scanning of the thorax’s anterior, lateral, and posterior surfaces [ 8 , 9 , 10 , 11 , 12 ] ( Figure 1 ).…”

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective

“…In 2015, Davidsen et al demonstrated the utility of lung ultrasonography for identifying pleural thickening in CLAD patients, assuming pleural thickening to be a marker of RAS, absent in BOS [ 41 ]. They studied BOS and RAS prospectively by chest HRCT and lung ultrasonography.…”