Validation of Systematic Histologic Reporting of Transbronchial Biopsy Eosinophils for Sensitivity of Detection and Associations with Early Outcomes After Lung Transplant

Abstract

<h3>Purpose</h3> Eosinophils are reported in 8% of transbronchial biopsies (TBBx) and their presence is associated with an increased risk of CLAD and death. We aimed to validate a systematic reporting scheme for the presence, gradation, and pattern of TBBx eosinophils. <h3>Methods</h3> A prospective reporting scheme for TBBx eosinophils was introduced at St Vincent's Sydney in Jan-20. All TBBx were reported by blinded pathologists for the presence of eosinophils, histologic pattern (peribronchial, interstitial, perivascular) and count/high power field (HPF). Standardised reporting was compared with a historic TBBx cohort from Jan-Dec 2019. TBBx were classified for cellular rejection as per ISHLT guidelines and positive bronchoalveolar lavage (BAL) microbiology/eosinophils and blood eosinophil count was recorded. Multivariable logistic regression measured associations with an increased risk of TBBx eosinophils. <h3>Results</h3> A total of 213 TBBx from 93 lung transplant recipients were systematically reviewed, with 61.5% as surveillance procedures. The mean (SD) recipient age was 52 (13), with 96 (45%) males, at median (IQR) 85 (475) days after transplant. TBBx eosinophils were detected in greater proportions with systematic (27.7%) compared to historic reporting (5.6%) p<0.001. When present, eosinophils were detected in median (IQR) 18.0% (19) biopsy specimens with median (IQR) 2 (5) cell/HPF. TBBx eosinophil patterns were reported in the following proportions; Interstitial 64%, perivascular 7%, peribronchial 25%. In univariable analysis, A grade (OR 3.11 p<0.01), blood eosinophils (OR 13.28 p=0.04) and BAL microbiology (OR 2.15 p=0.02) were associated with increased risk of TBBx eosinophils, however BAL eosinophils (OR 1.75 p=0.31) were not. In multivariable analysis, A grade (OR 2.93 95%CI 1.65-5.20) and positive BAL microbiology (OR 2.18 95%CI 1.10-4.31) were associated with an increased risk of TBBx eosinophils. <h3>Conclusion</h3> Systematic reporting of TBBx eosinophils improves sensitivity for detection compared with historic reporting. Acute vascular rejection grades and positive BAL microbiology were independently associated with an increased risk of TBBx eosinophils after adjustment for blood eosinophil count. Systematic reporting of TBBx eosinophils may identify patients at risk of poor outcomes.