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BackgroundLung transplant recipients undergo bronchoalveolar lavage (BAL) to detect antecedents of chronic lung allograft dysfunction (CLAD), but routine assessment of BAL cytology is controversial. We hypothesized that inflammation on BAL cytology would predict CLAD-free survival.MethodsIn a single-center retrospective cohort, associations between cytology results and clinical characteristics were compared using generalized-estimating equation-adjusted regression. The association between BAL inflammation and CLAD or death risk was assessed using time-dependent Cox models.ResultsIn 3365 cytology reports from 451 subjects, inflammation was the most common finding (6.2%, 210 cases), followed by fungal forms (5.3%, 178 cases, including 24 cases of suspectedAspergillus). Inflammation on BAL cytology was more common in procedures for symptoms (8.5%) versus surveillance (3.2%, p&nbsp

Author(s): Hoover, Jonathan; Mintz, Michelle A; Deiter, Fred; Aminian, Emily; Chen, Joy; Hays, Steven R; Singer, Jonathan P; Calabrese, Daniel R; Kukreja, Jasleen; Greenland, John R | Abstract: BackgroundAirway infections are difficult to distinguish from acute rejection in lung transplant recipients. Traditional culture techniques take time that may delay treatment. We hypothesized that a rapid multiplex molecular assay could improve time to diagnosis and appropriate clinical decision making.MethodsIn a prospective observational study of recipients undergoing bronchoscopy, we assessed the BioFire® FilmArray® Pneumonia Panel (BFPP) in parallel to standard of care (SOC) diagnostics. Research clinicians performed shadow (research only) clinical decision making in real time. Time to report and interpretation were reported as median and interquartile ranges and compared by Wilcoxon signed-ranked test. Agreement was defined based on detection of any species targeted in the molecular assay.ResultsFor the 150 enrolled subjects, BFPP results were available 3.8nhours (IQR 2.8-5.1) following bronchoscopy, compared to 13nhours for viral SOC (IQR 10-34, Pnln.001) results and 48nhours for bacterial SOC (IQR 46-70, Pnln.001) results. Positive BFPP results were interpreted in 9nhours (IQR 5-20) following bronchoscopy, compared to 74nhours for SOC (IQR 37-110, Pnln.001). Assays agreed for 138 (92%) of the 150 subjects. Of 22 BFPP diagnoses, five (23%) resulted in a shadow antibiotic recommendation. Notable BFPP deficiencies included fungal species and H parainfluenzae, accounting for 15 (27%) and 13 (23%) of the 56 actionable SOC results, respectively.ConclusionsThis molecular diagnostic including bacterial targets has the potential to shorten time to diagnosis and augment current clinical decision making but cannot replace SOC culture methods.

Purpose Final culture results are often unavailable at the time of donor organ offers, despite their importance in the evaluation of donor organ quality. We hypothesized that a rapid multiplex molecular assay could improve time to results and facilitate treatment initiation in the donors prior to organ recovery. Methods The “Rapid Detection of Airway Pathogens for Lung Transplantation” trial (NCT03933878) is a prospective observational clinical trial investigating the efficiency and accuracy of the BioFire Pneumonia Panel in the context of donor bronchoscopy. This assay tests the presence and/or quantity for 26 common airway pathogens in 2 hours. Bronchoalveolar lavage was collected from brain dead donors at the time of lung procurement. Molecular assay results were compared to standard of care cultures. Time to result between molecular assay and standard of care was compared by Wilcoxon signed-rank test. Agreement between assays was assessed by Cohen's kappa. Results A total of 35 donor samples were included. From the time of sample collection to time to result, the median time was 7.01 hours [6.59–9.18] versus 57.7 hours [44.6–72.6] (p Conclusion Molecular detection of lower respiratory pathogens significantly reduces the time to result while maintaining agreement with standard of care clinical cultures in the context of candidate lung allografts. Such data could inform quality assessment and facilitate timely donor management prior to organ recovery.

Purpose Rejection and infection can be antecedents of chronic lung allograft dysfunction (CLAD), the major limitation to long term survival for lung transplant recipients. BAL cytology is routinely performed but recently some have advocated abandoning this practice because of the low diagnostic yield. We hypothesized that inflammation observed on BAL cytology would predict CLAD risk. Methods We categorized diagnostic findings on BAL cytology between 2012 and 2019. Bronchoscopy indication, infection treatment, BAL and biopsy results, and CLAD-free survival were abstracted from medical records. Cytology associations with clinical outcomes were compared using generalized-estimating equation-adjusted logistic regression. The association between BAL inflammation and CLAD or death were determined using time-dependent Cox proportional hazards models adjusted for age, gender, diagnosis, lung allocation score, and transplant type. Results We evaluated 3,578 cytology reports from 491 subjects. Inflammation was the most common finding (6.4%), followed by fungi (5.2%). There were 5 cases of malignancy and 2 cases of CMV. Inflammation on BAL cytology was more common in procedures performed for symptoms, associated with antimicrobial initiation (a proxy for clinically significant infection), associated with acute rejection, and linked to increased BAL neutrophil and lymphocyte concentrations (Figure 1A). Inflammation on BAL cytology was present for 32% of subjects on at least one sample, more frequent around the time of CLAD onset, and associated a 2.6-fold hazard ratio (CI 1.2-5.3) for CLAD or death (Figure 1B). However, this association was not significant after adjusting for BAL cell counts and acute rejection. Conclusion Inflammation on BAL cytology specimens is clinically significant, suggesting acute rejection or infection and increased risk of CLAD or death. However, other indicators of allograft inflammation can substitute for some of the information provided by BAL cytology.