A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
Overview
- Phase
- Phase 4
- Intervention
- Azithromycin Dihydrate
- Conditions
- Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation
- Sponsor
- KU Leuven
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Histology on bronchial and/or transbronchial biopsies
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This study investigates the role of azithromycin treatment for lymphocytic bronchitis/bronchiolitis after lung transplantation.
Detailed Description
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.
Investigators
GM. Verleden
Medical Director Leuven Lung Transplant Programme
KU Leuven
Eligibility Criteria
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
Arms & Interventions
Azithromycin
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).
Intervention: Azithromycin Dihydrate
Outcomes
Primary Outcomes
Histology on bronchial and/or transbronchial biopsies
Time Frame: after 3 months of treatment
Evolution of lymphocytic airway inflammation after 3 months of treatment
Pulmonary function (FEV1)
Time Frame: after 3 months of treatment
Evolution of FEV1 after 3 months of treatment
Bronchoalveolar cellularity and protein levels (IL-8, IL-17)
Time Frame: after 3 months of treatment
Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment
Radiologic features
Time Frame: after 3 months of treatment
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
Secondary Outcomes
- Pulmonary function (FEV1)(after 6 months of treatment)