Gene Expression Profiling of Bronchoalveolar Lavage Cells During Aspergillus Colonization of the Lung Allograft

Weigt, S. Samuel; Wang, Xiaoyan; Palchevskiy, Vyacheslav; Patel, Neil; Derhovanessian, Ariss; Shino, Michael Y.; Sayah, David M.; Lynch, Joseph P.; Saggar, Rajan; Ross, David J.; Kubak, B.; Ardehali, A.; Palmer, Scott M.; Husain, Shahid; Belperio, John A.

doi:10.1097/tp.0000000000002058

Cited by 15 publications

(7 citation statements)

References 43 publications

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“…We are not aware of other studies differentiating endobronchial from alveolar samples. 23 - 25 This higher prevalence of endobronchial sample positivity may suggest that IA mainly occurred as tracheobronchitis, in keeping with earlier data. 10 Interestingly, small-conidia Aspergillus species (eg, Aspergillus fumigatus ) predominated in our patients and have been reported to be associated with a higher BOS rate compared to large-conidia species.…”

Section: Discussionsupporting

confidence: 86%

Risk of Lung Allograft Dysfunction Associated With Aspergillus Infection

Pavec

Pradère

Gigandon

et al. 2021

Transplantation Direct

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Background. We sought to determine whether invasive aspergillosis (IA) during the first year after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD). Methods. We retrospectively reviewed the records of 191 patients who underwent lung transplantation at our institution between January 2013 and December 2017. Screening for Aspergillus was with bronchial aspirates, bronchoalveolar lavage if indicated or during surveillance bronchoscopy, radiography, and computed tomography. We used Fine and Gray multivariable regression to identify potential risk factors for CLAD. Results. During the first posttransplant year, 72 patients had at least 1 deep-airway sample positive for Aspergillus ; 63 were classified as having IA and were included in the study. Median number of endoscopies per patient during the first year was 9 (range, 1–44). Median time from transplantation to first Aspergillus -positive sample was 121 d. Bronchial aspirate samples and bronchoalveolar lavage fluid were positive in 71 and 44 patients, respectively. Aspergillus fumigatus (n = 36, 50%) predominated; bacterial samples were also positive in 22 (31%) patients. IA within 4 mo after transplantation was independently associated with CLAD development (subdistribution hazard ratio, 3.75; 95% confidence interval [CI], 1.61-8.73; P < 0.01) by regression analysis. Survival at 3 and 5 y conditional on 1-y CLAD-free survival was 37% (95% CI, 24%-58%), and 24% (95% CI, 11%-52%) in the IA <4 mo group compared to 65% (95% CI, 57%-73%) and 54% (95% CI, 43%-66%) in the non-IA group and to 69% (95% CI, 58%-83%) and 54% (95% CI, 35%-82%) in the IA ≥4 mo group, respectively ( P < 0.01, logrank test). Conclusions. Our evaluation of de novo IA showed that this infection was most strongly associated with CLAD when found within 4 mo after transplantation.

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Section: Discussionsupporting

confidence: 86%

Risk of Lung Allograft Dysfunction Associated With Aspergillus Infection

Pavec

Pradère

Gigandon

et al. 2021

Transplantation Direct

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“…Despite the lack of association with DSA, we do note with interest that Aspergillus isolation was associated with worse CLAD‐free survival in this study. A previous study at the University of California, Los Angeles showed that, whereas innate immune responses were common to all Aspergillus cases, those Aspergillus cases that progressed to CLAD expressed gene profiles related to wounding and to adaptive engagement of both T cells and B cells . Although Aspergillus was not a focus of the current study, the association of Aspergillus with CLAD is consistent with our prior published observations and contradicts a recent retrospective multicenter study that found neither Aspergillus nor Pseudomonas was associated with CLAD .…”

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confidence: 82%

Demystifying “bad luck”: Seemingly unrelated risk factors for CLAD may be connected by a common pathway

Weigt

Snyder

2020

American Journal of Transplantation

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“…23 recipients. 24,25 While molecular diagnostics have been developed for fungal pathogens, extracting nucleic acids through fungal cell walls and excluding fungal contamination in reagents can be challenging. 26 Of note, revised guidelines for invasive fungal disease incorporate fungal PCR testing.…”

Section: Discussionmentioning

confidence: 99%

Rapid molecular detection of airway pathogens in lung transplant recipients

Hoover

Mintz

Deiter

et al. 2021

Transplant Infectious Dis

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Background: Airway 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. Methods: In 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. Results: For the 150 enrolled subjects, BFPP results were available 3.8 hours (IQR 2.8-5.1) following bronchoscopy, compared to 13 hours for viral SOC (IQR 10-34, P <0.001) results and 48 hours for bacterial SOC (IQR 46-70, P <0.001) results. Positive BFPP were interpreted in 9 hours (IQR 5-20) following bronchoscopy, compared to 74 hours for SOC (IQR 37-110, P <0.001). Assays agreed for 138 (92%) of the 150 subjects. Of 22 BFPP diagnoses, 5 (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. Conclusions: This 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. Trial Registration: NCT03933878

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Gene Expression Profiling of Bronchoalveolar Lavage Cells During Aspergillus Colonization of the Lung Allograft

Cited by 15 publications

References 43 publications

Risk of Lung Allograft Dysfunction Associated With Aspergillus Infection

Risk of Lung Allograft Dysfunction Associated With Aspergillus Infection

Demystifying “bad luck”: Seemingly unrelated risk factors for CLAD may be connected by a common pathway

Rapid molecular detection of airway pathogens in lung transplant recipients

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