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Microparticles and Bronchiolitis Obliterans Syndrome

Completed
Conditions
Bronchiolitis Obliterans
Interventions
Other: Dosage of Microparticles (MPs) in broncho-alveolar lavage fluid (BALF)
Registration Number
NCT02458274
Lead Sponsor
University Hospital, Strasbourg, France
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Patient with bronchiolitis obliterans syndromeDosage of Microparticles (MPs) in broncho-alveolar lavage fluid (BALF)Patient with bronchiolitis obliterans syndrome three years after lung transplantation.
Patient without bronchiolitis obliterans syndromeDosage of Microparticles (MPs) in broncho-alveolar lavage fluid (BALF)Lung transplanted patient without bronchiolitis obliterans syndrome
Primary Outcome Measures
NameTimeMethod
Correlation between total concentration of MPs in broncho-alveolar lavage fluid (BALF) and occurrence of bronchiolitis obliterans syndrome at three year post lung transplantationLung 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 Outcome Measures
NameTimeMethod
Total concentration MPs and characterization of cellular origin of MPs in BALF and in plasma of patients at three year post lung transplantation.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).

Trial Locations

Locations (1)

CHU Strasbourg

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Strasbourg, France

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