Organizing Pneumonia in Lung Transplant Recipients, a Restrospective Exploratory Study (OPIL-Study)

The aim of this study is to generate evidence regarding organizing pneumonia in lung transplant recipients.

Allograft failure remains the leading cause of morbidity and mortality in lung transplant recipients (LTR) accounting for 40% of deaths beyond the first year after transplantation. The current median survival over all LTRs is 6.0 years. Chronic allograft dysfunction (CLAD) is defined as a substantial and persistent decline in the measured forced expiratory volume in 1 second (FEV1) with ≥ 20% from the baseline value. The consensus statement from the International Society for Heart and Lung Transplantation in 2019 classified CLAD into two main phenotypes: Bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Based on respiratory function and computed tomography (CT) findings, CLAD is classified into four groups: BOS, RAS, mixed (BOS and RAS), and undefined. Definite CLAD-BOS is defined as persistent decline of ≥ 20% from the reference value after more than 3 months without a restriction and without persistent radiologic pulmonary opacities.

The main histologic findings of BOS include obliterative bronchiolitis (OB) accompanying chronic inflammation and fibrosis in the respiratory tract.

Up to 30 % of patients with CLAD present a restrictive pattern stated as CLAD-RAS. CLAD-RAS is physiologically defined as a persistent decline in FEV1 (± FVC) of ≥20% compared with the reference or baseline value, a decrease in total lung capacity (TLC) to ≤90% compared with baseline and the presence of persistent opacities on chest imaging. The pathology of RAS is nearly identical to that observed in the entity of pleuroparenchymal fibroelastosis. It features severe alveolar fibrosis organized around the pleura and the interlobular septa with concomitant obliterative bronchiolitis lesions. Von der Thüsen et al. analysed tissue samples of 21 patients with RAS describing not only patterns consistent with pleuroparenchymal fibroelastosis but also nonspecific interstitial pneumonia, irregular emphysema, organizing pneumonia (OP) and acute fibrinous organizing pneumonia (AFOP).

Some authors have advocated acute fibrinoid and organizing pneumonia (AFOP) as a third potential form of chronic allograft dysfunction, with decline of lung functions as for CLAD but with distinct histopathology and imaging findings. Paraskeva et al. identified AFOP as a novel entity in 22 out of 194 (11%) lung transplant recipients, invariably associated with a rapid decline in respiratory function and death after a median time of 101 days. AFOP is a unique pathological entity with intra-alveolar fibrin in the form of "fibrin balls" and organizing pneumonia.

While AFOP and its clinical impact is getting more and more recognized as a pattern of RAS, little is known about OP and its clinical impact in LTRs. OP per se is a pattern of lung tissue repair after injury. It can be a response to a specific lung injury (secondary OP) or cryptogenic (COP). COP has no identifiable cause and is classified as a form of idiopathic diffuse parenchymal lung disease (DPLD). So far it is not clear if OP is a form of the RAS spectrum and if the presence of OP might also predict a rapid decline in lung function and survival comparable with AFOP.

The aim of this study is to investigate the prevalence of OP forms in lung transplant recipients, possible risk factors for OP and the impact of OP itself on the course of lung allograft function.

Eligibility Criteria:
Inclusion Criteria:

* All lung transplant recipients treated in the lung transplantation department of the USZ will be included in this analysis with documented tissue sampling or autopsy between 01.01.2012 and 01.06.2023

Exclusion Criteria:

* Denied general consent or any statement verbal or in writing by patient that precludes research