Calcineurin inhibitor ( CNI ) therapy after lung transplantation increases risk of kidney failure. Early everolimus‐based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open‐label, 12‐month multicenter trial was conducted at 8 German sites. Patients 3‐18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate ( eGFR ). In the quadruple low CNI regimen, patients received everolimus (target trough level 3‐5 ng/mL) with reduced CNI (tacrolimus 3‐5 ng/mL or cyclosporine 25‐75 ng/mL) and a cell cycle inhibitor plus prednisone. In the standard triple CNI regimen, patients received tacrolimus (target trough level >5 ng/mL) or cyclosporine (>100 ng/mL) and a cell cycle inhibitor plus prednisone. Of the 180 patients screened, 130 were randomized: 67 in the quadruple low CNI group and 63 in the standard triple CNI group. The primary endpoint ( eGFR after 12 months) demonstrated superiority of the quadruple low CNI regimen: 64.5 mL/min vs 54.6 mL/min for the standard triple group (least squares mean, analysis of covariance; P < .001). Key efficacy parameters (biopsy‐proven acute rejection, chronic lung allograft dysfunction, and death) and safety endpoints were similar between both groups. Quadruple low CNI immunosuppression early after lung transplantation was demonstrated to be efficacious and safe. Clinical trials registry: ClinicalTrials.gov NCT 01404325.

Background Osteopontin (OPN) is a glycoprotein that has been associated with inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an intense inflammatory and remodelling process. The aim of this study was to investigate the levels of OPN in sputum supernatants of patients with SRA, to compare them with milder forms of the disease and to investigate their possible association with mediators and cells involved in the inflammatory and remodelling process. Methods 33 patients with SRA, 29 with moderate asthma, 21 with steroid-naïve asthma and 20 healthy subjects were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of OPN, vascular endothelial growth factor, transforming growth factor b1 (TGF-b1), cysteinyl leukotrienes, interleukin 13 (IL-13), eosinophilic cationic protein (ECP) and IL-8 in sputum supernatants. Results Median (IQR) OPN levels (pg/ml) were significantly higher in patients with SRA than in those with moderate asthma, steroid-naive asthma and healthy control subjects (1840 (1125e11000) vs 130 (100e210) vs 100 (67e130) vs 50 (42e70), respectively, p<0.001). Regression analysis showed a significant association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL-13, TGF-b1 and ECP. TGF-b1 represented the strongest association with OPN. The above associations were not observed in milder forms of the disease or in healthy subjects. Conclusions The results indicate that OPN levels are higher in SRA than in less severe forms of the disease. Moreover, OPN is associated with mediators involved in both the inflammatory and remodelling process such as TGF-b1, IL-13 and cysteinyl leukotrienes only in SRA.

No abstract