Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation

Condition(s) targeted: Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation

Intervention: Azithromycin Dihydrate (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Katholieke Universiteit Leuven

Official(s) and/or principal investigator(s):
Geert M Verleden, MD, PhD, Principal Investigator, Affiliation: KULeuven and UZ Leuven

Overall contact:
Geert M Verleden, MD, PhD, Phone: +32 16 34 68 08, Ext: Prof. Dr., Email: geert.verleden@uzleuven.be

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: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Histology on bronchial and/or transbronchial biopsies

Pulmonary function (FEV1)

Bronchoalveolar cellularity and protein levels (IL-8, IL-17)

Radiologic features

Secondary outcome:

Pulmonary function (FEV1)

Bronchoalveolar cellularity and protein levels

Radiologic features

Pulmonary function (FEV1)

Bronchoalveolar cellularity and protein levels

Radiologic features

Prevalence of chronic rejection (diagnosed as bronchiolitis obliterans syndrome, BOS)

Prevalence of chronic rejection (diagnosed as bronchiolitis obliterans syndrome or BOS)

Overall survival

Overall survival

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Geert M Verleden, MD, PhD, Phone: +32 16 34 68 08, Ext: Prof. Dr., Email: geert.verleden@uzleuven.be

University Hospital Gasthuisberg, Leuven, Vlaams-Brabant B-3000, Belgium; Recruiting
Geert M Verleden, Md, PhD, Phone: +32 16 34 68 08, Ext: Prof. Dr., Email: geert.verleden@uzleuven.be
Bart M Vanaudenaerde, PhD, Phone: +32 16 33 01 95, Ext: Dr., Email: bart.vanaudenaerde@med.kuleuven.be
Geert M Verleden, MD, PhD, Principal Investigator
Bart M Vanaudenaerde, PhD, Sub-Investigator
Robin Vos, MD, Sub-Investigator
Lieven J Dupont, MD, PhD, Sub-Investigator

Related publications:

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.

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: April 22, 2010