BACKGROUND: Chronic lung allograft dysfunction (CLAD) remains a major risk factor for death after lung transplantation. Previous data suggested that within CLAD at least 2 phenotypes are present: a neutrophilic type (nCLAD or neutrophilic reversible allograft dysfunction [NRAD]), reversible with azithromycin therapy, vs a low neutrophilic type, non-responsive to azithromycin (fibrotic bronchiolitis obliterans syndrome [fBOS]). We aimed to further characterize this dichotomy by measuring multiple proteins in the bronchoalveolar lavage (BAL) fluid of 28 lung recipients. METHODS: Patients were retrospectively subdivided by the absence or presence of CLAD and subsequently by their response to azithromycin, resulting in 3 groups: 10 stable, 9 responsive (nCLAD/NRAD), and 9 non-responsive (fBOS). Enzyme-linked immunosorbent assay was used to measure 32 different proteins. RESULTS: Protein variations were predominantly present in the nCLAD/NRAD group, whereas no differences were observed in the fBOS group compared with control. MCP-1 (p < 0.01), RANTES (p < 0.05), IL-1β (p < 0.01), IL-8 (p < 0.01), TIMP-1 (p < 0.01), MMP-8 (p < 0.01), MMP-9 (p < 0.01), HGF (p < 0.001), MPO (p < 0.01), and bile acid (p < 0.05) concentrations were upregulated in nCLAD/NRAD compared with fBOS, whereas PDGF-AA (p < 0.05) was downregulated. CONCLUSIONS: These data provide further evidence that within CLAD there is a heterogeneity of phenotypes with different mechanisms involved. Further investigation is warranted to unravel the pathophysiology of both phenotypes.
BACKGROUND:Chronic lung allograft dysfunction (CLAD) remains a major risk factor for death after lung transplantation. Previous data suggested that within CLAD at least 2 phenotypes are present: a neutrophilic type (nCLAD or neutrophilic reversible allograft dysfunction [NRAD]), reversible with azithromycin therapy, vs a low neutrophilic type, non-responsive to azithromycin (fibrotic bronchiolitis obliterans syndrome [fBOS]). We aimed to further characterize this dichotomy by measuring multiple proteins in the bronchoalveolar lavage (BAL) fluid of 28 lung recipients. METHODS:Patients were retrospectively subdivided by the absence or presence of CLAD and subsequently by their response to azithromycin, resulting in 3 groups: 10 stable, 9 responsive (nCLAD/NRAD), and 9 non-responsive (fBOS). Enzyme-linked immunosorbent assay was used to measure 32 different proteins. RESULTS: Protein variations were predominantly present in the nCLAD/NRAD group, whereas no differences were observed in the fBOS group compared with control. MCP-1 (p < 0.01), RANTES (p < 0.05), IL-1β (p < 0.01), IL-8 (p < 0.01), TIMP-1 (p < 0.01), MMP-8 (p < 0.01), MMP-9 (p < 0.01), HGF (p < 0.001), MPO (p < 0.01), and bile acid (p < 0.05) concentrations were upregulated in nCLAD/NRAD compared with fBOS, whereas PDGF-AA (p < 0.05) was downregulated. CONCLUSIONS: These data provide further evidence that within CLAD there is a heterogeneity of phenotypes with different mechanisms involved. Further investigation is warranted to unravel the pathophysiology of both phenotypes.
Authors: Monika I Suwara; Bart M Vanaudenaerde; Stijn E Verleden; Robin Vos; Nicola J Green; Chris Ward; Lee A Borthwick; Elly Vandermeulen; Jim Lordan; Dirk E Van Raemdonck; Paul A Corris; Geert M Verleden; Andrew J Fisher Journal: Transpl Int Date: 2014-06-17 Impact factor: 3.782
Authors: Andreacarola Urso; Miguel M Leiva-Juárez; Domenica F Briganti; Beatrice Aramini; Luke Benvenuto; Joseph Costa; Renu Nandakumar; Estela Area Gomez; Hilary Y Robbins; Lori Shah; Meghan Aversa; Joshua R Sonnet; Selim Arcasoy; Serge Cremers; Frank D'Ovidio Journal: J Heart Lung Transplant Date: 2021-05-28 Impact factor: 13.569
Authors: Hrishikesh S Kulkarni; Kristy Ramphal; Lina Ma; Melanie Brown; Michelle Oyster; Kaitlyn N Speckhart; Tsuyoshi Takahashi; Derek E Byers; Mary K Porteous; Laurel Kalman; Ramsey R Hachem; Melanie Rushefski; Ja'Nia McPhatter; Marlene Cano; Daniel Kreisel; Masina Scavuzzo; Brigitte Mittler; Edward Cantu; Katrine Pilely; Peter Garred; Jason D Christie; John P Atkinson; Andrew E Gelman; Joshua M Diamond Journal: JCI Insight Date: 2020-09-03