Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
Information source: Katholieke Universiteit Leuven
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation
Intervention: Azithromycin Dihydrate (Drug)
Phase: Phase 4
Sponsored by: Katholieke Universiteit Leuven
Official(s) and/or principal investigator(s):
Geert M Verleden, MD, PhD, Principal Investigator, Affiliation: KULeuven and UZ Leuven
This study investigates the role of azithromycin treatment for lymphocytic
bronchitis/bronchiolitis after lung transplantation.
Official title: A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Histology on bronchial and/or transbronchial biopsies
Pulmonary function (FEV1)
Bronchoalveolar cellularity and protein levels (IL-8, IL-17)
Secondary outcome: Pulmonary function (FEV1)
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.
Minimum age: 18 Years.
Maximum age: N/A.
- 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
- Severe suture problems (e. g. airway stenosis) requiring lasering or stenting
Locations and Contacts
University Hospital Gasthuisberg, Leuven, Vlaams-Brabant B-3000, Belgium
Vanaudenaerde BM, De Vleeschauwer SI, Vos R, Meyts I, Bullens DM, Reynders V, Wuyts WA, Van Raemdonck DE, Dupont LJ, Verleden GM. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2008 Sep;8(9):1911-20. doi: 10.1111/j.1600-6143.2008.02321.x.
Vanaudenaerde BM, Wuyts WA, Geudens N, Dupont LJ, Schoofs K, Smeets S, Van Raemdonck DE, Verleden GM. Macrolides inhibit IL17-induced IL8 and 8-isoprostane release from human airway smooth muscle cells. Am J Transplant. 2007 Jan;7(1):76-82. Epub 2006 Oct 25.
Vanaudenaerde BM, Dupont LJ, Wuyts WA, Verbeken EK, Meyts I, Bullens DM, Dilissen E, Luyts L, Van Raemdonck DE, Verleden GM. The role of interleukin-17 during acute rejection after lung transplantation. Eur Respir J. 2006 Apr;27(4):779-87.
Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2006 Sep 1;174(5):566-70. Epub 2006 Jun 1.
Starting date: April 2010
Last updated: July 3, 2013