Interobserver variability in grading transbronchial lung biopsy specimens after lung transplantation.
BACKGROUND
Acute rejection remains a major source of morbidity after lung transplantation. Given the importance of this diagnosis, an international grading system was developed to standardize the diagnosis of acute lung-allograft rejection. The reliability of this grading system has not been adequately assessed by previous studies.


METHODS
We examined the level of agreement in grading transbronchial biopsy specimens obtained from a large multicenter study (AIRSAC [Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation] trial). Biopsy specimens were initially graded for acute rejection and lymphocytic bronchiolitis by the site pathologist and subsequently graded by a central pathologist. Reliability of interobserver grading was evaluated using Cohen κ coefficients.


RESULTS
A total of 481 transbronchial biopsy specimens were graded by both the site and central pathologists. The overall concordance rates were 74% and 89% for grade A and grade B biopsy specimens, respectively. When samples from biopsies performed at different time points after transplantation were assessed, there was a higher level of agreement early (≤ 6 weeks) after transplant compared with later time points for acute rejection. However, there was still only moderate agreement for both grade A (κ score 0.479; 95% CI, 0.29-0.67) and grade B (κ score 0.465; 95% CI, 0.08-0.85) rejection.


CONCLUSIONS
These results expand upon previous reports of interobserver variability in grading transbronchial biopsy specimens after lung transplantation. Given the variability in grading these specimens, we advocate further education of the histopathologic findings in lung transplant biopsy specimens, as well as revisiting the current criteria for grading transbronchial biopsy specimens to improve concordance among lung transplant pathologists.


BACKGROUND
ClinicalTrials.gov; No. NCT00321906; URL: www.clinicaltrials.gov.
University of Chicago Medical Center, Chicago, IL. Electronic address: sbhorade@medicine.bsd.uchicago.edu.
Sangeeta M
SM
Bhorade
University of Chicago Medical Center, Chicago, IL.
Aliya N
AN
Husain
University of Chicago Medical Center, Chicago, IL.
Chuanhong
C
Liao
University of Chicago Medical Center, Chicago, IL.
Lee Chuan
LC
Li
Hospital of the University of Pennsylvania, Philadelphia, PA.
Vivek N
VN
Ahya
University of Florida School of Medicine, Gainesville, FL.
Maher A
MA
Baz
University of Texas Medical Branch, Galveston, TX.
Vincent G
VG
Valentine
Loyola University Medical Center, Maywood, IL.
Robert B
RB
Love
Methodist Hospital System, Houston, TX.
Harish
H
Seethamraju
Loyola University Medical Center, Maywood, IL.
Charles G
CG
Alex
Emory University School of Medicine, Atlanta, GA.
Remzi
R
Bag
University of Wisconsin School of Medicine, Madison, WI.
Nilto C
NC
DeOliveira
University of Chicago Medical Center, Chicago, IL.
Wickii T
WT
Vigneswaran
University of Chicago Medical Center, Chicago, IL.
Edward R
ER
Garrity
Columbia University Medical Center, New York, NY.
Selim M
SM
Arcasoy
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy / Q000379:methods*; D001999:Bronchoscopy; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008168:Lung / Q000473:pathology*; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011446:Prospective Studies; D014481:United States