Serum KL-6 level and the development of bronchiolitis obliterans syndrome in lung transplant recipients.
ABSTRACT KL-6 is a glycoprotein expressed by pulmonary epithelial cells, and its serum level has been used as a marker of disease activity in a variety of respiratory illnesses. Previously, we showed that KL-6 was elevated in lung transplant recipients diagnosed with BOS. In this study, we followed serum KL-6 levels and lung functions prospectively in lung transplant recipients who were within the first five-yr post-transplant and had no evidence of BOS at the time of study entry. Mean peak KL-6 levels were 596.16 ± 309.32 U/mL in the nine recipients who developed BOS compared to 352.41 ± 140.68 in 36 recipients who did not (p = 0.05). Six of the nine patients with BOS had an absolute rise in KL-6 above baseline level >200 U/mL compared to two of the 37 who had the same increase in KL-6 but did not develop BOS. Using the 200 U/mL elevation of KL-6 from baseline as a threshold for a positive test would produce a sensitivity of 67%, specificity of 95%, PPV of 75%, and a NPV of 92%. In addition, mean KL-6 levels of patients during acute rejection were not significantly elevated compared to the prerejection mean KL-6 levels (p = 0.71). We conclude that serum KL-6 is a relatively specific marker of BOS in lung transplant recipients.
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ABSTRACT: The success of pediatric lung transplantation continues to be limited by long-term graft dysfunction. Historically this has been characterized as an obstructive spirometric defect in the form of the bronchiolitis obliterans syndrome (BOS). It is recognized, however, that this does not reflect many of the other acknowledged etiologies of chronic lung dysfunction-noting it is the sum of the parts that contribute to respiratory morbidity and mortality after transplant. The term chronic lung allograft dysfunction (CLAD) has been coined to reflect these other entities and, in particular, a group of relatively recently described lung disorders called the restrictive allograft syndrome (RAS). RAS is characterized by a restrictive spirometric defect. Although these entities have not yet been studied in a pediatric setting their association with poor compliance, antibody-mediated rejection (AMR), and post-infectious lung damage (particularly viral) warrants attention by pediatric lung transplant teams. Current therapy for the BOS subset of CLAD is otherwise limited to changing immunosuppressants and avoiding excessive infectious risk by avoiding over-immunosuppression. Long-term macrolide therapy in lung transplantation is not of proven efficacy. Reviewing previous BOS studies to explore restrictive spirometric cases and joint projects via groups like the International Pediatric Lung Transplant Collaborative will be the way forward to solve this pressing problem.Paediatric Drugs 04/2013; · 1.72 Impact Factor
- Lung Diseases - Selected State of the Art Reviews, 03/2012; , ISBN: 978-953-51-0180-2
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ABSTRACT: The enduring success of lung transplantation is built on the use of immunosuppressive drugs to stop the immune system from rejecting the newly transplanted lung allograft. Most patients receive a triple-drug maintenance immunosuppressive regimen consisting of a calcineurin inhibitor, an antiproliferative and corticosteroids. Induction therapy with either an antilymphocyte monoclonal or an interleukin-2 receptor antagonist are prescribed by many centres aiming to achieve rapid inhibition of recently activated and potentially alloreactive T lymphocytes. Despite this generic approach acute rejection episodes remain common, mandating further fine-tuning and augmentation of the immunosuppressive regimen. While there has been a trend away from cyclosporine and azathioprine towards a preference for tacrolimus and mycophenolate mofetil, this has not translated into significant protection from the development of chronic lung allograft dysfunction, the main barrier to the long-term success of lung transplantation. This article reviews the problem of lung allograft rejection and the evidence for immunosuppressive regimens used both in the short- and long-term in patients undergoing lung transplantation.Drugs 10/2013; · 4.13 Impact Factor