TY - JOUR
T1 - Molecular Assessment of Single-Piece Mucosal Biopsies is Highly Reproducible Compared to Transbronchial Biopsies in Lung Transplantation
AU - Parkes, M. D.
AU - Halloran, P. F.
AU - Timofte, I. L.
AU - Snell, G. I.
AU - Westall, G. P.
AU - Roux, A.
AU - Havlin, J.
AU - Hachem, R.
AU - Kreisel, D.
AU - Levine, D.
AU - Juvet, S.
AU - Keshavjee, S.
AU - Jaksch, P.
AU - Klepetko, W.
AU - Hirji, A.
AU - Weinkauf, J.
AU - Halloran, K. M.
N1 - Conference code: 40th
PY - 2020/4
Y1 - 2020/4
N2 - PURPOSE: Histologic assessment for rejection on transbronchial biopsies (TBB) has poor reproducibility. Mucosal biopsies are safer than TBBs but their histologic assessment has not been systematically studied or standardized. We developed molecular platforms to assess TBBs and mucosal biopsies from the third airway bifurcation (3BMB). We examined the reproducibility of scores assigned by molecular assessment of both biopsy types in lung transplant patients from 9 international centers. METHODS: We trained machine learning models (archetypal analysis, principal component analysis) on microarray data from 457 TBBs and 243 3BMBs. We processed 14 pairs of TBB pieces (28 total) taken during the same procedure and 13 pairs of 3BMBs (26 total). The models assigned each biopsy sets of archetype scores (denoted by "R") and principal component scores (denoted by "PC") describing injury and rejection phenotypes. We studied within-score agreement between biopsy pairs using intraclass correlations (ICC). RESULTS: Most scores had excellent reproducibility in 3BMB pairs compared to TBBs (Table 1). In 3BMBs the R1 (normal), R2 (rejection), R3 (late injury), PC1 (inflammation/rejection), and PC2 (late injury) scores were highly reproducible, but R4 and PC3 (both recent injury) were not. In TBBs the R2 (rejection) and PC1 (inflammation/rejection) scores were moderately reproducible; other scores had poor reproducibility. CONCLUSION: Molecular assessment of paired, single piece 3BMBs achieves excellent reproducibility in its key scores. TBB scores were less reproducible likely because of tissue heterogeneity and greater anatomic distance between samples. Measurements could be stabilized by combining ≥2 pieces per microarray. Importantly, molecular assessment with 3BMBs or TBBs requires fewer pieces (2-3) than TBB histology, which requires up to ten. These data support continued study of the diagnostic and prognostic utility of 3BMBs in lung transplantation.
AB - PURPOSE: Histologic assessment for rejection on transbronchial biopsies (TBB) has poor reproducibility. Mucosal biopsies are safer than TBBs but their histologic assessment has not been systematically studied or standardized. We developed molecular platforms to assess TBBs and mucosal biopsies from the third airway bifurcation (3BMB). We examined the reproducibility of scores assigned by molecular assessment of both biopsy types in lung transplant patients from 9 international centers. METHODS: We trained machine learning models (archetypal analysis, principal component analysis) on microarray data from 457 TBBs and 243 3BMBs. We processed 14 pairs of TBB pieces (28 total) taken during the same procedure and 13 pairs of 3BMBs (26 total). The models assigned each biopsy sets of archetype scores (denoted by "R") and principal component scores (denoted by "PC") describing injury and rejection phenotypes. We studied within-score agreement between biopsy pairs using intraclass correlations (ICC). RESULTS: Most scores had excellent reproducibility in 3BMB pairs compared to TBBs (Table 1). In 3BMBs the R1 (normal), R2 (rejection), R3 (late injury), PC1 (inflammation/rejection), and PC2 (late injury) scores were highly reproducible, but R4 and PC3 (both recent injury) were not. In TBBs the R2 (rejection) and PC1 (inflammation/rejection) scores were moderately reproducible; other scores had poor reproducibility. CONCLUSION: Molecular assessment of paired, single piece 3BMBs achieves excellent reproducibility in its key scores. TBB scores were less reproducible likely because of tissue heterogeneity and greater anatomic distance between samples. Measurements could be stabilized by combining ≥2 pieces per microarray. Importantly, molecular assessment with 3BMBs or TBBs requires fewer pieces (2-3) than TBB histology, which requires up to ten. These data support continued study of the diagnostic and prognostic utility of 3BMBs in lung transplantation.
UR - http://www.scopus.com/inward/record.url?scp=85085675952&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2020.01.785
DO - 10.1016/j.healun.2020.01.785
M3 - Meeting Abstract
C2 - 32465032
AN - SCOPUS:85085675952
SN - 1053-2498
VL - 39
SP - S191-S192
JO - The Journal of Heart and Lung Transplantation
JF - The Journal of Heart and Lung Transplantation
IS - 4
T2 - Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation 2020
Y2 - 22 April 2020 through 25 April 2020
ER -