Short summary

Lung ultrasound has not previously been investigated in the perspective of phenotyping chronic lung allograft dysfunction after lung transplantation. The purpose of this study was to explore whether LUS is usable in a clinical setting to differentiate subtypes of chronic lung allograft dysfunction in lung transplanted patients.

Rationale

Lung ultrasound (LUS) has during the past 20 years undergone an enormous development and is now used in a number of specialties such as respiratory medicine, emergency medicine, anesthesiology and traumatology due to a high sensitivity to diagnose pleura pulmonary conditions involving diffuse interstitial edema, pulmonary edema, hemo- and pneumothorax, ARDS, pleural effusion, interstitial inflammation and fibrosis.

Lung transplantation (LTx) is a well-established treatment in a variety of end-stage lung diseases where surgery improves survival and quality of life. The average number of annually performed LTx' in Denmark approximates 35 with a total of 700 transplants carried out since 1992 at the national LTx centre at Rigshopitalet. The one-year survival is approximately 90%, 60-70% at five years and 40-50% at ten years. However, most patients die from chronic rejection or the so-called chronic lung allograft dysfunction (CLAD), a condition that affects about 50% of lung transplanted patients after 5 years. CLAD can be divided into bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). BOS represents a progressive airway obstruction, whereas RAS is characterized by the presence of pleuraparenchymal fibrosis and other interstitial lung findings with a poorer survival than in BOS. As other studies have shown that interstitial lung involvement can be identified with use of LUS, the specific RAS characteristics are also expected to present similar LUS findings. Yet, there are no studies of LUS after LTx to assess CLAD or the possibility of using LUS for CLAD phenotyping.

This pilot project is expected to result in an increased knowledge of potential pathognomonic LUS findings for BOS and RAS. Such knowledge would contribute to initiate an adequate and faster approach to specific CLAD treatment. 

Description of the cohort

At clinical follow-up after double LTx (DLTx) at Rigshospitalet (Copenhagen University Hospital, Heart Centre, Divison of Lung Transplantation), South Danish Centre of Interstitial Lung Diseases (Department of Respiratory Medicine, Odense University Hospital), and West Danish Centre of Interstitial Lung Diseases (Department of Respiratory Medicine and Allergy, Aarhus University Hospital) patients fulfilling criteria for CLAD will, upon acceptance, be included.

Data and biological material

Inclusion period will be due to 1 June 2016 and 1 June 2017.

In patients with verified CLAD a baseline LUS will be performed at the time of CLAD diagnosis and three months after the baseline LUS. HRCT findings (used as golden standard) will be compared to assess LUS as a diagnostic and monitoring tool for specific CLAD findings/patterns. The LUS findings will be reviewed in consensus between two experienced pulmonologists in LUS. HRCT findings will be reviewed in consensus between one pulmonologists and one radiologist, both experienced in assessing LTx related HRCTs. The consensus findings from the LUS-group will be blinded to the HRCT-group and vice versa. 

Collaborating researchers and departments

Division of Lung Transplantation, Heart Centre, Copenhagen University Hospital, Rigshospitalet

• PhD-Fellow Hans Henrik Schultz, MD
• Associate Professor Martin Iversen, MD, DMSci
• Michael Perch, MD
• Associate Professor Thomas Kromann Lund, MD, PhD
• Associate Professor Jørn Carlsen, MD, DMSci

Department of Radiology, Copenhagen University Hospital, Rigshospitalet

• Anna Kalhauge, MD

West Danish Centre of Interstitial Lung Diseases, Aarhus University Hospital

• Associate Professor Elisabeth Bendstrup, MD, PhD

Research Unit of Respiratory Medicine, Department of Respiratory Medicine, Odense University Hospital

• Clinical Associate Professor Christian Borbjerg Laursen, MD, PhD
• Daniel Pilsgaard Henriksen, MD, PhD

Publications associated with the project

Davidsen JR, Laursen CB, Højlund M, Lund TK, Jeschke KN, Iversen M, Kalhauge A, Bendstrup E, Carlsen J, Perch M, Henriksen DP, Schultz HHL. Lung Ultrasound to Phenotype Chronic Lung Allograft Dysfunction in Lung Transplant Recipients. A Prospective Observational Study. J Clin Med. 2021 Mar 5;10(5):1078. doi: 10.3390/jcm10051078. PMID: 33807615; PMCID: PMC7961975.