Figure 5
Graphical depiction of the study design. Serum samples were selected of LTX patients diagnosed with CLAD (BOS (n = 30) and RAS (n = 11)), ARAD (n = 22) and Stable-LTX (n = 56), patients with end-stage pulmonary disease [IPF (n = 31) and CF (n = 15)] listed for LTX and healthy volunteers (n = 63). CLAD phenotypes, Stable-LTX and ARAD patients were diagnosed via spirometry. Prototypical spirometric volume changes over time and flow volume loops of stable lung transplanted patients/healthy people and patients with BOS and RAS are depicted. Enzyme-linked immunosorbent assays were employed for measuring cytokine serum concentrations of Lipocalin-2, MMP-9, TIMP-1, Activin-A and Follistatin. MMP-9/TIMP-1 and Activin-A/Follistatin ratios were calculated. Immunohistochemical stainings were performed in specimens of 20 patients who underwent re-transplantation for either BOS (n = 11) or RAS (n = 9), 20 patients who underwent primary LTX for either IPF (n = 10) or CF (n = 10), and 10 patients who served as healthy controls. Further, the correlation of cytokine serum concentrations and clinical outcome, including OS, future onset of CLAD and re-transplantation was analysed by performing Kaplan–Meier analysis. LTX Lung transplantation, CLAD chronic lung allograft dysfunction, BOS bronchiolitis obliterans syndrome, RAS restrictive allograft syndrome, ARAD azithromycin-reversible allograft dysfunction, IPF idiopathic pulmonary fibrosis, CF cystic fibrosis, MMP-9 matrix metalloproteinase-9, TIMP-1 tissue inhibitors of metalloproteinase-1.
