TY - JOUR
T1 - Donor derived cell free DNA% is elevated with pathogens that are risk factors for acute and chronic lung allograft injury
AU - Bazemore, Katrina
AU - Rohly, Michael
AU - Permpalung, Nitipong
AU - Yu, Kai
AU - Timofte, Irina
AU - Brown, A. Whitney
AU - Orens, Jonathan
AU - Iacono, Aldo
AU - Nathan, Steven D.
AU - Avery, Robin K.
AU - Valantine, Hannah
AU - Agbor-Enoh, Sean
AU - Shah, Pali D.
N1 - Funding Information:
K.B. has received funding from the NIH. N.P. has received research funding from Health Systems Research Institute (Thailand), NIH, Cystic Fibrosis Foundation, and Fisher Center Discovery Program, Johns Hopkins University. R. K. Avery has received study grant support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, and Takeda/Shire. P.S. has received funding from the NIH and Cystic Fibrosis Foundation.This manuscript was funded by the National Heart, Lung, and Blood Institute, award HHSN268201800082P (I.T, A.B., J.O., S.D.N., H.V., S.A-E., P.S.). S.A-E. also received support through the Lasker Clinical Research Program, NIH Distinguished Scholar Program and Cystic Fibrosis Foundation (Grant # AGBORE20Q10)
Funding Information:
This manuscript was funded by the National Heart, Lung, and Blood Institute , award HHSN268201800082P (I.T, A.B., J.O., S.D.N., H.V., S.A-E., P.S.). S.A-E. also received support through the Lasker Clinical Research Program, NIH Distinguished Scholar Program and Cystic Fibrosis Foundation (Grant # AGBORE20Q10 )
Publisher Copyright:
© 2021 International Society for Heart and Lung Transplantation
PY - 2021/11
Y1 - 2021/11
N2 - Background: Acute and chronic forms of lung allograft injury are associated with specific respiratory pathogens. Donor-derived cell free DNA (ddcfDNA) has been shown to be elevated with acute lung allograft injury and predictive of long-term outcomes. We examined the %ddcfDNA values at times of microbial isolation from bronchoalveolar lavage (BAL). Methods: Two hundred and six BAL samples from 51 Lung Transplant Recipients (LTRs) with concurrently available plasma %ddcfDNA were analyzed along with microbiology and histopathology. Microbial species were grouped into bacterial, fungal, and viral and “higher risk” and “lower risk” cohorts based on historical association with downstream allograft dysfunction. Analyses were performed to determine pathogen category association with %ddcfDNA, independent of inter-subject variability. Results: Presence of microbial isolates in BAL was not associated with elevated %ddcfDNA compared to samples without isolates. However, “higher risk” bacterial and viral microbes showed greater %ddcfDNA values than lower risk species (1.19% vs. 0.65%, p < 0.01), independent of inter-subject variability. Histopathologic abnormalities concurrent with pathogen isolation were associated with higher %ddcfDNA compared to isolation episodes with normal histopathology (medians 1.23% and 0.66%, p = 0.05). Assessments showed no evidence of correlation between histopathology or bronchoscopy indication and presence of higher risk vs. lower risk pathogens. Conclusion: %ddcfDNA is higher among cases of microbial isolation with concurrent abnormal histopathology and with isolation of higher risk pathogens known to increase risk of allograft dysfunction. Future studies should assess if %ddcfDNA can be used to stratify pathogens for risk of CLAD and identify pathogen associated injury prior to histopathology.
AB - Background: Acute and chronic forms of lung allograft injury are associated with specific respiratory pathogens. Donor-derived cell free DNA (ddcfDNA) has been shown to be elevated with acute lung allograft injury and predictive of long-term outcomes. We examined the %ddcfDNA values at times of microbial isolation from bronchoalveolar lavage (BAL). Methods: Two hundred and six BAL samples from 51 Lung Transplant Recipients (LTRs) with concurrently available plasma %ddcfDNA were analyzed along with microbiology and histopathology. Microbial species were grouped into bacterial, fungal, and viral and “higher risk” and “lower risk” cohorts based on historical association with downstream allograft dysfunction. Analyses were performed to determine pathogen category association with %ddcfDNA, independent of inter-subject variability. Results: Presence of microbial isolates in BAL was not associated with elevated %ddcfDNA compared to samples without isolates. However, “higher risk” bacterial and viral microbes showed greater %ddcfDNA values than lower risk species (1.19% vs. 0.65%, p < 0.01), independent of inter-subject variability. Histopathologic abnormalities concurrent with pathogen isolation were associated with higher %ddcfDNA compared to isolation episodes with normal histopathology (medians 1.23% and 0.66%, p = 0.05). Assessments showed no evidence of correlation between histopathology or bronchoscopy indication and presence of higher risk vs. lower risk pathogens. Conclusion: %ddcfDNA is higher among cases of microbial isolation with concurrent abnormal histopathology and with isolation of higher risk pathogens known to increase risk of allograft dysfunction. Future studies should assess if %ddcfDNA can be used to stratify pathogens for risk of CLAD and identify pathogen associated injury prior to histopathology.
KW - cfDNA
KW - chronic lung allograft dysfunction
KW - lung transplantation
KW - transplant infection
UR - http://www.scopus.com/inward/record.url?scp=85111569594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111569594&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2021.05.012
DO - 10.1016/j.healun.2021.05.012
M3 - Article
C2 - 34344623
AN - SCOPUS:85111569594
SN - 1053-2498
VL - 40
SP - 1454
EP - 1462
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 11
ER -