Microparticles and Bronchiolitis Obliterans Syndrome

The main long-term complication of lung transplantation is chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS) is the most frequent presentation of CLAD. BOS leads to a progressive loss of lung allograft function, with recurrence of dyspnea and airflow limitation. In some advanced cases, patients need a lung re transplantation. The mechanisms of BOS are not completely elucidated, and there are no early markers or specific treatment available for this condition.

Microparticles (MPs) are submicron plasma membrane fragments released into the vascular compartment or the pericellular space in response to cell activation, injury or apoptosis. Broncho alveolar and circulating MPs may reflect cellular insults of the lung allografts. Therefore, MPs could be viewed either as biomarkers or as effectors of the chronic inflammatory or procoagulant processes leading to bronchiolitis obliterans syndrome.

The investigators plan to include 60 patients before lung transplantation at our centre in Strasbourg (France). Follow-up will be requested at the base of usual care (spirometry, blood sampling, bronchoscopy with broncho-alveolar lavage [BAL]). The investigators will measure at one month, one, two and three year post transplantation, the total concentration of MPs in plasma and BAL and characterize their phenotype.

The investigators objective is to demonstrate correlation between total MPs concentration in broncho-alveolar lavage fluid (BALF) and the occurrence of bronchiolitis obliterans syndrome at three years post lung transplantation.

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Key information

Conditions

Bronchiolitis Obliterans Bronchial Diseases Bronchiolitis Bronchitis Lung Diseases Lung Diseases, Obstructive Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU Strasbourg

Strasbourg, +67000, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Every adult (>18 years) patient on lung transplant waiting list
Patients who give a written informed consent
Patients affiliated to a social security regimen

Exclusion criteria

Patients on lung transplant waiting list for BOS
Patients who cannot sign an informed consent form (emergency situation, patient with understanding difficulties…)

Treatment and study plan

Dosage of Microparticles (MPs) in broncho-alveolar lavage fluid (BALF)

Other

Primary outcomes

Correlation between total concentration of MPs in broncho-alveolar lavage fluid (BALF) and occurrence of bronchiolitis obliterans syndrome at three year post lung transplantation

Time frame: Lung transplanted patients will be followed up with usual care. Spirometry and bronchoscopy with BALF at three years after transplantation will be used in the present study.

We will measure at three years post transplantation, the total concentration of MPs in plasma and BAL and characterize their phenotype Bronchiolitis Obliterans Syndrome (BOS) will be graded according to guidelines of the the International Society for Heart and Lung transplantation. Percentage of decrease of lung function based on actual FEV1 compared to the average of the two best FEV1, distant for three week, post lung transplantation.

BOS 0 : FEV1 > 90% BOS 0-p : 90 >FEV1 > 81% BOS 1 : 80 >FEV1 > 66% BOS 0-p : 65 >FEV1 > 51% BOS 0-p : FEV1 < 50% If BOS is present, we usually do CT-scan and bronchoscopy with BALF to confirm BO and eliminate alternative diagnosis.

Secondary outcomes

Total concentration MPs and characterization of cellular origin of MPs in BALF and in plasma of patients at three year post lung transplantation.

Time frame: Lung transplanted patients will have spirometry and bronchoscopy with BALF at three years after transplantation as it's usually done for each lung transplanted.

MPs expose to the surface phosphatidylserine (PhtdSer), tissue factor and membrane antigens from the parental cells.

MPs collected from plasma and BALF will have differential centrifugation and concentrations of MPs will be measured using original functional multiwell assays.

MPs will be captured onto annexin-5 (total MPs) or onto specific antibodies directed against membrane antigens borne by MPs and testifying their cell origin (CD104, CD66b, CD62E, CD62P, CD35, E105, CD14, CD3, CD20).

Sponsors and collaborators

Lead sponsor

University Hospital, Strasbourg, France

Other

Registry information

Official study title

Circulating and Pulmonary Microparticles for Early Diagnosis of Bronchiolitis Obliterans Syndrome After Lung Transplantation

Acronym: MIBO

Important dates

Study start: 2014
Primary completion: 2020
Study completion: 2020
First posted: Jun 1, 2015
Registry last updated: Aug 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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