Rationale: Lung transplantation offers great promise for otherwise terminal lung diseases, but the development of bronchiolitis obliterans syndrome (BOS) continues to limit survival. Although acute rejection and lymphocytic bronchiolitis have been identified as risk factors for the development of BOS, it is unclear whether largeairway lymphocytic inflammation conveys the same risk. Objectives: We evaluated lymphocytic bronchitis on endobronchial biopsies as a risk factor for BOS and mortality. Methods: Endobronchial biopsies were collected and graded during surveillance after lung transplantation. We assessed samples with negative cultures collected in the first 90 days from 298 subjects and compared large-airway lymphocytic bronchitis assessed by a 0-2 "E-score" and with standard A and BR pathology scores for acute rejection and small-airway lymphocytic bronchiolitis, respectively. Measurements and Main Results: We found surprisingly little association between large-and small-airway lymphocytic inflammation scores from a given bronchoscopy. Endobronchial lymphocytic bronchitis was more prevalent in subjects in BOS stage 0p and BOS stages 1-3 at the time of biopsy. Within 90 days after transplantation, increasing maximum E-score was associated with greater risk of BOS (adjusted hazard ratio, 1.76; 95% confidence interval, 1.11-2.78; P ¼ 0.02) and in this analysis 90-day maximum E-scores were the only score type predictive of BOS (P , 0.01). Conclusions: These results support a multicenter study to evaluate endoscopic biopsies for the identification of patients at increased risk for BOS. The association of endobronchial lymphocytic inflammation and BOS may have mechanistic implications.Keywords: bronchiolitis obliterans; graft rejection; bronchoscopy; lung transplantation Lung transplantation can offer improved quality of life and survival from otherwise terminal lung diseases. However, the development of chronic rejection, manifested as bronchiolitis obliterans syndrome (BOS), is a major barrier to long-term patient survival (1). BOS can cause death from graft failure and can occur despite potent immunosuppression (2, 3). One risk factor for BOS is symptomatic acute rejection (4). When confirmed by transbronchial biopsy, acute rejection generally is treated with additional immunosuppressive medications (5). Most lung transplantation centers also use surveillance bronchoscopy to identify otherwise silent episodes of acute rejection (6), presuming that untreated acute rejection increases the risk of BOS (7,8).Previous studies revealed that small-airways lymphocytic bronchiolitis in transbronchial biopsy specimens also is associated with increased risk of BOS (9). Endobronchial biopsies have been evaluated in lung transplant recipients, in whom acute rejection and current BOS were associated with largeairway lymphocytosis (10). This lymphocytosis is predominantly CD4 1 and CD45 1 (10). Work from the present laboratory showed differential expression of gene transcripts in patients with large-airway, but not small-ai...

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BackgroundCulture of bronchoalveolar lavage (BAL) specimens takes time to report. We tested whether a molecular diagnostic test could accelerate donor lung assessment and treatment.MethodsWe compared BioFire Film Array Pneumonia Panel (BFPP) with standard of care (SOC) tests on lung allograft samples at three time points: (1) donor BAL at organ recovery, (2) donor bronchial tissue and airway swab at implantation, and (3) first recipient BAL following lung implantation. Primary outcomes were the difference in time to result (Wilcoxon signed‐ranked tests) and the agreement in results between BFPP and SOC assays (Gwet's agreement coefficient).ResultsWe enrolled 50 subjects. In donor lung BAL specimens, BFPP detected 52 infections (14 out of 26 pathogens in the panel). Viral and bacterial BFPP results were reported 2.4 h (interquartile range, IQR 2.0–6.4) following BAL versus 4.6 h (IQR 1.9–6.0, p = 0.625) for OPO BAL viral SOC results and 66 h (IQR 47–87, p < .0001) for OPO BAL bacterial SOC results. Although there was high overall agreement of results between BAL–BFPP versus OPO BAL–SOC tests (Gwet's AC p < .001 for all), the level of agreement differed among 26 pathogens designed in BFPP and differed by types of specimens. BFPP could not detect many infections identified by SOC assays.ConclusionsBFPP decreased time to detection of lung pathogens among donated lungs, but it cannot replace SOC tests due to the limited number of pathogens in the panel. image

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