Usefulness of gene expression profiling of bronchoalveolar lavage cells in acute lung allograft rejection.

BackgroundChronic lung allograft dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Because effective therapies are lacking, early identification and mitigation of risk factors is a pragmatic approach to improve outcomes. Acute cellular rejection (ACR) is the most pervasive risk factor for CLAD, but diagnosis requires transbronchial biopsy, which carries risks. We hypothesized that gene expression in the bronchoalveolar lavage (BAL) cell pellet (CP) could replace biopsy and inform on mechanisms of CLAD.MethodsWe performed RNA sequencing on BAL CPs from 219 lung transplant recipients with A-grade ACR (n = 61), lymphocytic bronchiolitis (n = 58), infection (n = 41), or no rejection/infection (n = 59). Differential gene expression was based on absolute fold difference >2.0 and Benjamini-adjusted p-value ≤0.05. We used the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resource for pathway analyses. For classifier modeling, samples were randomly split into training (n = 154) and testing sets (n = 65). A logistic regression model using recursive feature elimination and 5-fold cross-validation was trained to optimize area under the curve (AUC).ResultsDifferential gene expression identified 72 genes. Enriched pathways included T-cell receptor signaling, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction. A 4-gene model (AUC = 0.72) and classification threshold defined in the training set exhibited fair performance in the testing set; accuracy was 76%, specificity 82%, and sensitivity 60%. In addition, classification as ACR was associated with worse CLAD-free survival (hazard ratio = 2.42; 95% confidence interval = 1.29-4.53).ConclusionsBAL CP gene expression during ACR is enriched for immune response pathways and shows promise as a diagnostic tool for ACR, especially ACR that is a precursor of CLAD

RSV prevention and treatment in pediatric lung transplant patients: a survey of current practices among the International Pediatric Lung Transplant Collaborative

RSV infection can be severe after pediatric lung transplantation. Strategies to prevent and treat RSV in this population are underreported. To assess the current practices, we surveyed the members of the IPLTC regarding RSV prevention and treatment strategies. Twenty-eight programs were surveyed; 18 (64.3%) responded at least partially. A median of 53 transplants (range, 8-355) occurred since inception. RSV testing occurs in asymptomatic (6/17) and symptomatic (17/17) patients. Diagnostic method is polymerase chain reaction at 13 sites and DFA at 8. Transplant candidates were received prophylaxis at 10 sites, with nine following national (5) or local (4) guidelines. All use palivizumab IM and/or IV. Recipients were received prophylaxis with palivizumab at eight centers (eight IM, one IV). Fourteen were treated for RSV (seven all patients; seven age-related). Medications include inhaled (6), oral (4), or IV (4) ribavirin, plus IVIG (9), steroids (8), and IV (2) or IM (3) palivizumab. Prevention and treatment barriers include insurance/hospital concerns, such as institutional reluctance to use inhaled ribavirin. RSV prevention and treatment strategies are diverse at pediatric lung transplant programs. Many centers offer prophylaxis (9/17) and treatments (14/17), but strategies are not uniform

Antifungal prophylaxis in pediatric lung transplantation: An international multicenter survey

Fungal infections create a significant risk to pediatric lung transplant recipients. However, no international consensus guidelines exist for fungal infection prevention strategies. It was the aim to describe the current strategies of antifungal prophylaxis in pediatric lung transplant centers. A self-administered, web-based survey on current practices to prevent fungal infection was circulated to centers within the IPLTC. Twenty-one (88%) IPLTC centers participated, predominantly from Europe and the US. More than 50% of respondents perform adult and pediatric lung transplant operations. Twenty-four percent use universal prophylaxis, 28% give prophylaxis to all patients but stratify the antifungal coverage based on pretransplant risk, and 48% target prophylaxis to only the children with CF or pretransplantation fungal colonization. Commonly, centers aim to target Aspergillus and Candida infection. Monotherapy with either voriconazole or inhaled amphotericin B is used in the majority of centers. Institutions utilize prophylactic therapy for variable time periods (40% 3-6 months; 30% ≥12 months). Alternative drugs were prescribed for lack of tolerance, toxicity, or positive surveillance culture. TDM (itraconazole/voriconazole) was used in 86% of centers. The survey revealed a wide range of antifungal prophylaxis strategies as current international practice in pediatric lung transplant recipients