Chronic Rejection of Lung Transplant

Chronic rejection, more commonly called bronchiolitis obliterans syndrome (BOS), is the leading cause of death beyond the first year post lung transplantation. The diagnosis of BOS is typically made by clinical, physiological, and radiographic parameters. Early detection would be desirable since it allows treatment modification to stop or delay the process. In the last few years there has been a growing interest in lung clearance index (LCI), a measure of lung physiology derived from multiple breath washout tests. LCI is derived from Multiple Breath Washout (MBW) tests. Early detection of BOS with LCI measurement will allow the investigators early recognition of this chronic rejection form and with early institution of the enhanced treatment survival will increase. All paticipants who underwent bilateral lung transplantation at Zurich University Hospital will be included. The measurement will be done 3 months after lung transplantation. Approximately 90 paticipants will be included. The follow-up will be 5 years. If the investigators could detect the development of BOS with this novel method before the clinical deterioration (fall in lung function) the investigators can start the available treatment options before irreversible damage occurs. This might increase overall survival in the study cohort.

Lung transplantation (LTx) is the only effective treatment for patients with end stage lung disease. Of the major organs transplanted, survival following LTx is the lowest with a mean of 5 years. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and contributes to the development of chronic lung allograft dysfunction (CLAD) that remains the leading cause of late mortality. Earlier detection of rejection after LTx is of substantial importance as it would improve the possibilities of treatment and could increase survival. The investigators have shown in previous work that exhaled breath particles (EBP) reflect the composition of respiratory tract lining fluid (RTLF). EBP and particle flow rate (PFR) can be used as non-invasive methods for early detection and monitoring of airway diseases such as acute respiratory distress syndrome (ARDS). It has also been shown that the particle flow prolife after lung transplantation differs between patients who develop PGD and those who do not and that the composition of EBP differs between patients with and without bronchiolitis obliterans syndrome (BOS), an obstructive form of CLAD. Samples of EBP and measurements of PFR will be collected from lung transplanted patients. Membranes with EBP will be saved for molecular analysis. The investigators aim to identify potential particle flow patterns and biomarkers for earlier detection of rejection after lung transplantation.