Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation
Conditions
Keywords
azithromycin, lymphocytic bronchitis or bronchiolitis, lung transplantation, acute allograft rejection, chronic allograft rejection, bronchiolitis obliterans syndrome
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.
Interventions
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).
Sponsors
Fund for Scientific Research, Flanders, Belgium
KU Leuven
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Histology on bronchial and/or transbronchial biopsies | after 3 months of treatment | Evolution of lymphocytic airway inflammation after 3 months of treatment |
| Pulmonary function (FEV1) | after 3 months of treatment | Evolution of FEV1 after 3 months of treatment |
| Bronchoalveolar cellularity and protein levels (IL-8, IL-17) | after 3 months of treatment | Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment |
| Radiologic features | 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
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary function (FEV1) | after 6 months of treatment | Evolution of FEV1 after 6 months of treatment |
Countries
Belgium
Outcome results
None listed