BAL neutrophilia in azithromycin-treated lung transplant recipients: Clinical significance

Elly Vandermeulen, Stijn E Verleden, David Ruttens, Eva Moelants, Anneleen Mortier, Jana Somers, Hannelore Bellon, Davide Piloni, Lieven J Dupont, Dirk E Van Raemdonck, Paul Proost, Dominique Schols, Robin Vos, Geert M Verleden, Bart M Vanaudenaerde

Onderzoeksoutput: Articlepeer review

13 Citaten (Scopus)


BACKGROUND: Azithromycin decreases airway neutrophilia and can prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx). It also can be used to treat lymphocytic bronchiolitis, as it decreases the submucosal infiltrating IL-17 positive lymphocytes. Some patients, while receiving azithromycin, (re)develop increased airway neutrophilia, which we hypothesize to result in worse outcome and to be regulated by an IL-17-independent mechanism.

METHODS: LTx recipients, transplanted between 2001 and 2012, were investigated and categorized in a study group of patients with increased broncho-alveolar lavage (BAL) neutrophilia (≥15%) and a matched control group with low BAL neutrophilia (<15%), both groups while already being on azithromycin treatment. CLAD-free and overall survival were compared between groups. Cell differentials and 33 proteins in BAL were analyzed to identify underlying mechanisms.

RESULTS: The study group (n=72) demonstrated a significantly lower CLAD-free (p=0.015) and overall survival (p=0.041) compared to the control group (n=37). Absolute BAL neutrophils and eosinophils were increased in the study group, which was paralleled by elevated inflammatory cytokines (IL-1β/IL-1Ra, IL-4 and IL-6) and chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL11/eotaxin) concentrations compared to the control group (all p<0.05).

CONCLUSION: Patients with elevated airway neutrophilia despite azithromycin, experience worse CLAD-free and overall survival. In these patients, IL-1β might play a central role giving rise to neutrophils, eosinophils, macrophages and B-cells. This provides an opportunity to further investigate the modulation of this pathway.

Originele taal-2English
Pagina's (van-tot)37-44
Aantal pagina's8
TijdschriftTransplant immunology
Nummer van het tijdschrift1
StatusPublished - sep 2015

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Copyright © 2015 Elsevier B.V. All rights reserved.


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