Clinical trial NCT06203964: Organizing Pneumonia in Lung Transplant Recipients, a Restrospective Exploratory Study (OPIL-Study)
Official title: Organizing Pneumonia in Lung Transplant Recipients, a Restrospective Exploratory Study (OPIL-Study)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Organizing Pneumonia
Lung Transplant Rejection
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2024-01-12
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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

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

Detailed description: 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

Primary outcomes:
measure: Prevalence of organizing pneumonia
timeFrame: 01.01.2012-01.06.2023
Secondary outcomes:
measure: Body Mass Index
timeFrame: date of organizing pneumonia
measure: Forced expiratory volume in 1 second
timeFrame: 1 year before and after organizing pneumonia
measure: Total lung capacity
timeFrame: 1 year before and after organizing pneumonia
measure: Vital capacity
timeFrame: 1 year before and after organizing pneumonia
measure: Prevalence of primary graft dysfunction
timeFrame: 01.01.2012-01.06.2023
measure: Cell count of eosinophils in blood
timeFrame: 1 year before and after organizing pneumonia
measure: Cell count of lymphocytes in blood
timeFrame: 1 year before and after organizing pneumonia
measure: Cell count of neutrophils in blood
timeFrame: 1 year before and after organizing pneumonia
measure: Level of rhematoid factor in blood
timeFrame: date of organizing pneumonia
measure: Level of anti-nuclear antibodies in blood
timeFrame: date of organizing pneumonia
measure: Level of antineutrophil cytoplasmic antibodies in blood
timeFrame: date of organizing pneumonia
measure: Prevalence of infection
timeFrame: date of organizing pneumonia
measure: C-reactive proteine
timeFrame: date of organizing pneumonia
measure: Histopathological patterns beside organising pneumonia
timeFrame: date of organizing pneumonia
measure: Radiological findings in CT scan
timeFrame: date of organizing pneumonia
measure: Medication associated with organizing pneumonia
timeFrame: date of organizing pneumonia
measure: NTproBNP
timeFrame: date of organizing pneumonia
measure: Echocardiography
timeFrame: 1 year before and after organizing pneumonia
measure: Cellcount in the bronchoalveolar lavage
timeFrame: 1 year before and after organizing pneumonia
measure: Level of donor specific antibodies
timeFrame: 1 year before and after organizing pneumonia
measure: Time to death
timeFrame: after diagnosis of organizing pneumonia
measure: Reason for death according to biopsy results od physician declared cause of death
timeFrame: after diagnosis of organizing pneumonia (- 01.06.2023)
measure: Number of patients with therapeutic interventions due to organizing pneumonia
timeFrame: 01.01.2012-01.06.2023
measure: Prevalence of risk factors of OP
timeFrame: 01.01.2012-01.06.2023
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
References: