Serum KL-6 level and the development of bronchiolitis obliterans syndrome in lung transplant recipients.

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.

Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1.

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common beta chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR alpha chain, encoded in the X-chromosome pseudoautosomal region 1.

Treatment of adenovirus pneumonia with cidofovir in pediatric lung transplant recipients.

BACKGROUND: Adenovirus pneumonia results in significant morbidity and mortality in lung transplant recipients. Cidofovir allows for directed therapy but can result in nephrotoxicity. We report our experience with cidofovir for the treatment of adenovirus pneumonia in pediatric lung transplant recipients. METHODS: In a retrospective review, we identified four cases of culture-proven adenovirus pneumonia in children who underwent lung transplantation at Texas Children's Hospital (TCH). All patients received cidofovir 1 mg/kg every other day or three times a week for a total of 4 weeks. Probenecid and intravenous hydration were administered in conjunction with the cidofovir. Intravenous immunoglobulin (IVIg) was given as adjunctive therapy, and immunosuppression was not modified during the treatment course. RESULTS: The four cases of adenovirus pneumonia comprised 4 of the 54 (7%) lung transplantations performed at TCH from 2002 to 2006, and all were in children <3 years of age. All patients developed pneumonia within 2 months after transplantation. With cidofovir treatment, three of the four children survived. Among the survivors, two developed early bronchiolitis obliterans within 1 year after transplant, and one has continued to have good graft function at 2 years after transplant. All patients maintained normal renal function throughout the treatment course. CONCLUSIONS: Pediatric lung transplant recipients <3 years of age are at increased risk of adenovirus pneumonia early after transplantation. Cidofovir, when used in the modified dosing regimen and in combination with IVIg and renal protection measures, is a safe and potentially effective treatment option for adenovirus pneumonia in lung transplant recipients.