Cytological monitoring of peripheral blood, bronchoalveolar lavage fluid, and transbronchial biopsy specimens during acute rejection and cytomegalovirus infection in lung and heart--lung allograft recipients.
OBJECTIVE
Acute rejection and cytomegalovirus (CMV) infection are important complications after lung and heart--lung transplantation. We sought to investigate whether acute rejection and CMV infection demonstrated as CMV antigenemia had an effect on the cell profiles of peripheral blood (PB), bronchoalveolar lavage fluid (BAL-F), or TBB histology.


METHODS
In this prospective study, composition of cells in PB, BAL-F, and TBB samples from 20 lung or heart-lung transplantation patients were analyzed during episodes of acute rejection or CMV antigenemia. Rejection was graded according to the International Society for Heart and Lung Transplantation criteria. As controls, samples with no evidence of rejection or infection were used. To evaluate the effect of time on cellular findings, samples were divided into three groups according to time after transplantation: 1--30, 31--180, and more than 180 d after transplantation.


RESULTS
Acute rejection was associated with mild blood basophilia (p<0.05; specificity 94%, sensitivity 42%). In BAL-F during rejection, the number of basophils (p<0.05), eosinophils (p<0.05), and lymphocytes (p<0.05; specificity 77%, sensitivity 64%) was increased compared to controls during the post-operative month 1. Later-occurring rejections were associated with increased amounts of neutrophils in BAL-F (p<0.05; specificity 82%, sensitivity 74%). In TBB histology, acute rejections were associated with perivascular and/or peribronchial infiltration of lymphocytes (p<0.001) and plasma cells (p<0.05) compared to controls. In our patients receiving gancyclovir prophylaxis, CMV antigenemia did not significantly alter the cell profiles in PB and BAL-F nor the inflammatory cell picture in TBB histology.


CONCLUSIONS
TBB histology remains the 'gold standard' for diagnosing rejection in lung and heart-lung transplantation patients, as the inflammatory cell findings in TBB specimens are highly specific for rejection. The cellular changes associated with rejection, mild PB basophilia and increased proportions of lymphocytes in early- and neutrophils in later-occurring rejection, observed in BAL-F cannot be considered specific for rejection, but may warrant clinical suspicion of rejection.
Tikkanen
J
J
Cardiopulmonary Research Group of Transplantation, Laboratory, University of Helsinki and Helsinki University Central Hospital, Finland. jussi.tikkanen@helsinki.fi
Lemström
K
K
Halme
M
M
Pakkala
S
S
Taskinen
E
E
Koskinen
P
P
D000208:Acute Disease; D000328:Adult; D000956:Antigens, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000627:therapeutic use; D001491:Basophils; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D004804:Eosinophils; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D016041:Heart-Lung Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology*; D016040:Lung Transplantation; D016131:Lymphocyte Subsets; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D000956:Antigens, Viral; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D015774:Ganciclovir