High-dose vitamin D after lung transplantation: A randomized trial.

BACKGROUND: Vitamin D may have innate immunomodulatory functions with potentially beneficial therapeutic effects in lung transplant recipients. METHODS: This was a single-center, double blind, randomized, placebo-controlled, prevention trial of once-monthly oral vitamin D (cholecalciferol; 100,000 IU, n = 44) vs placebo (n = 43) during 2 years in adult lung transplant recipients enrolled from October 2010 to August 2013. Primary outcome was prevalence of chronic lung allograft dysfunction (CLAD) 3 years after transplantation. Secondary outcomes included overall survival, prevalence of acute rejection, lymphocytic bronchiolitis and infection, lung function, pulmonary and systemic inflammation, and bone mineral density. RESULTS: All included patients underwent bilateral lung transplantation and were mostly middle-aged men with prior smoking-related emphysema. Levels of 25-hydroxy vitamin D after 1 year (p < .001) and 2 years (p < .001) were significantly higher in the vitamin D group compared with the placebo group. No difference was observed for CLAD prevalence (p = 0.7) or CLAD-free survival between both groups (p = 0.7). Secondary outcomes were overall comparable between both groups (all p > 0.05). CONCLUSIONS: Once-monthly oral vitamin D supplementation after lung transplantation fails to demonstrate a significant difference in CLAD prevalence, innate immunomodulatory, or a beneficial clinical effect compared with placebo.

Interleukin-1α induced release of interleukin-8 by human bronchial epithelial cells in vitro: assessing mechanisms and possible treatment options.

Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK1/2 , Iκß) and targets known to be involved in tumor formation (PI3K, Akt) were investigated. Finally, different treatment options were tested for their potential inhibitory effect. IL-1α induced IL-8 in bronchial epithelial cells, which was dose-dependently inhibited by dexamethasone but not by azithromycin. IL-1α induced p38 and Akt phosphorylation, but activation of these MAPK was not inhibited by dexamethasone. JNK, ERK1/2 , Iκß and PI3K were not activated. None of the tested drugs reduced the IL-1α induced IL-8 production. We established an in vitro model wherein steroids inhibit the IL-1α-induced IL-8 production, while azithromycin was ineffective. Despite using this simple in vitro model, we could not identify a new treatment option for azithromycin-resistant airway neutrophilia.

Vitamin D deficiency in lung transplant patients: is it important?

BACKGROUND: Vitamin D deficiency has been reported in different chronic pulmonary diseases like asthma and chronic obstructive pulmonary disease, but little is known in lung transplant recipients. METHODS: Serum 25-hydroxyvitamin D (25-OHD) levels and pulmonary function (forced expiratory volume in 1 sec [FEV(1)] %predicted) were measured in 131 lung transplant patients during their yearly posttransplant check-up hospital stay, and the total number of infections and perivascular/peribronchiolar rejections were assessed from transplantation on. RESULTS: Vitamin D deficiency (<30 ng/mL) occurred in 62 of 131 patients (47.3%), of whom 26 (19.8%) were severely deficient (<20 ng/mL). The FEV(1) was significantly lower in the deficient group compared with the group with normal levels (P=0.019). Moreover, we could find an association between FEV(1) and 25-OHD levels in univariate analysis (P=0.018), which remained significant in multivariate analysis (P=0.012). The same holds true for the association between 25-OHD levels and the peak postoperative FEV(1) (P=0.021 in multivariate analysis). We also identified significantly more patients with moderate to severe B-grade rejections in the deficient group (P=0.0038). CONCLUSION: Vitamin D deficiency is present in 47% of our lung transplant patients and seems independently associated with a lower FEV(1) and more severe B-grade rejections. This study raises the potential need for additional vitamin D treatment in lung transplantation and clearly indicates the role of a randomized placebo-controlled trial with vitamin D supplementation, which is ongoing in our center.