Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation

Study Overview
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Brief Summary
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This study investigates the role of azithromycin treatment for lymphocytic bronchitis/bronchiolitis after lung transplantation.

Detailed Description
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Lymphocytic bronchitis/bronchiolitis is one of the major risk factors for development of chronic rejection/BOS after lung transplantation. There is currently no established treatment available for this condition. There is now mounting evidence that IL-17 producing lymphocytes (TH17) not only participate in chronic allograft rejection/BOS, but are also present within the airway wall during lymphocytic bronchiolitis and that IL-17 mRNA-levels in bronchoalveolar lavage fluid of these patients are upregulated. As such, TH17 may account for the increased BAL neutrophilia seen in these patients, as IL-17 may be responsible for driving IL-8 secretion (a neutrophil-attracting chemokine) from various cell types in the airways. Since azithromycin has previously been shown to reduce both IL-17 induced IL-8 production by human airway smooth muscle cells 'in vitro' and bronchoalveolar IL-8/neutrophil levels in LTx recipients with established BOS, we believe that azithromycin has great potential for treating lymphocytic bronchi(oli)tis by attenuating this TH17/IL-17/IL-8-mediated airway inflammation, possibly even halting the subsequent development of chronic rejection/BOS after lung transplantation. In this study, histologic, spirometric, bronchoalveolar an radiologic features will be investigated in patients treated with confirmed lymphocytic bronchitis/bronchiolitis treated with azithromycin.

Official Title
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A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation

Conditions
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Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation

Intervention / Treatment
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* Drug: Azithromycin Dihydrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Adult (age at least 18 years old at moment of transplantation) Able to take oral medication Histologic diagnosis of lymphocytic bronchiolitis or bronchitis ('grade B') without concurrent acute cellular allograft rejection 'grade A' ≥2 Exclusion Criteria: Severe suture problems (e.g. airway stenosis) requiring lasering or stenting

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin<br>Add-on of study-drug (azithromycin) to 'standard of care': 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment). | Drug: Azithromycin Dihydrate<br>* Add-on of study-drug (azithromycin) to 'standard of care' at diagnosis of lymphocytic bronchi(oli)tis. Study-drug regime: 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment).<br>* Other names: Azithromycin 250 mg, ZTM250, Zitromax TM (ATC J01FA10);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histology on bronchial and/or transbronchial biopsies | Evolution of lymphocytic airway inflammation after 3 months of treatment | after 3 months of treatment | 
| Pulmonary function (FEV1) | Evolution of FEV1 after 3 months of treatment | after 3 months of treatment | 
| Bronchoalveolar cellularity and protein levels (IL-8, IL-17) | Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment | after 3 months of treatment | 
| Radiologic features | Evolution of radiologic features (e.g. tree-in-bud, consolidation, bronchiectasis, air trapping, etc.) on chest X-ray or HRCT after 3 months of treatment | after 3 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function (FEV1) | Evolution of FEV1 after 6 months of treatment | after 6 months of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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azithromycin, lymphocytic bronchitis or bronchiolitis, lung transplantation, acute allograft rejection, chronic allograft rejection, bronchiolitis obliterans syndrome