Open AccessMechanistic differences between phenotypes of chronic lung allograft dysfunction after lung transplantation
Author(s) -
Suwara Monika I.,
Vanaudenaerde Bart M.,
Verleden Stijn E.,
Vos Robin,
Green Nicola J.,
Ward Chris,
Borthwick Lee A.,
Vandermeulen Elly,
Lordan Jim,
Van Raemdonck Dirk E.,
Corris Paul A.,
Verleden Geert M.,
Fisher Andrew J.
Publication year - 2014
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12341
Subject(s) - neutrophilia , bronchiolitis obliterans , medicine , bronchoalveolar lavage , lung transplantation , bronchiolitis , immunology , lung , transplantation , pathology , virus
Summary Distinct phenotypes of chronic lung allograft dysfunction ( CLAD ) after lung transplantation are emerging with lymphocytic bronchiolitis ( LB )/azithromycin reversible allograft dysfunction ( ARAD ), classical or fibrotic bronchiolitis obliterans syndrome ( BOS ), and restrictive allograft syndrome ( RAS ) proposed as separate entities. We have additionally identified lung transplant recipients with prior LB , demonstrating persistent airway neutrophilia ( PAN ) despite azithromycin treatment. The aim of this study was to evaluate differences in the airway microenvironment in different phenotypes of CLAD . Bronchoalveolar lavage ( BAL ) from recipients identified as stable (control), LB / ARAD , PAN , BOS , and RAS were evaluated for differential cell counts and concentrations of IL ‐1α, IL ‐1β, IL ‐6, IL ‐8, and TNF ‐α. Primary human bronchial epithelial cells were exposed to BAL supernatants from different phenotypes and their viability measured. BOS and RAS showed increased BAL neutrophilia but no change in cytokine concentrations compared with prediagnosis. In both LB / ARAD and PAN , significant increases in IL ‐1α, IL ‐1β, and IL ‐8 were present. BAL IL ‐6 and TNF ‐α concentrations were increased in PAN and only this phenotype demonstrated decreased epithelial cell viability after exposure to BAL fluid. This study demonstrates clear differences in the airway microenvironment between different CLAD phenotypes. Systematic phenotyping of CLAD may help the development of more personalized approaches to treatment.