Clinical trial NCT01109160: Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
Official title: A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation
Keywords: azithromycin
lymphocytic bronchitis or bronchiolitis
lung transplantation
acute allograft rejection
chronic allograft rejection
bronchiolitis obliterans syndrome
Lead sponsor: KU Leuven
Sponsor class: OTHER
Collaborators: name: Fund for Scientific Research, Flanders, Belgium
First posted: 2010-04-23
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Histology on bronchial and/or transbronchial biopsies
timeFrame: after 3 months of treatment
measure: Pulmonary function (FEV1)
timeFrame: after 3 months of treatment
measure: Bronchoalveolar cellularity and protein levels (IL-8, IL-17)
timeFrame: after 3 months of treatment
measure: Radiologic features
timeFrame: after 3 months of treatment
Secondary outcomes:
measure: Pulmonary function (FEV1)
timeFrame: after 6 months of treatment
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
state: Vlaams-Brabant
Study officials:
affiliation: KULeuven and UZ Leuven
name: Geert M Verleden, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. doi: 10.1111/j.1600-6143.2006.01586.x. Epub 2006 Oct 25.
citation: 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. doi: 10.1183/09031936.06.00019405.
citation: 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. doi: 10.1164/rccm.200601-071OC. Epub 2006 Jun 1.