Surveillance Bronchoscopy in Lung Transplant Recipients

Kukafka, David S.; O’Brien, Gerard; Furukawa, Satoshi; Criner, Gerard J.

doi:10.1378/chest.111.2.377

Cited by 59 publications

(29 citation statements)

References 16 publications

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“…Owing to the impact of acute rejection on the development of chronic rejection and, thus, survival (see below), 66% of centres, which report data to the ISHLT registry, perform surveillance TBB at fixed intervals during the first postoperative year, in addition to TBB in the setting of new symptoms or signs [15]. The role of regularly scheduled TBB in completely asymptomatic lung transplant recipients, however, remains controversial.…”

Section: The Diagnosis Of Acute Rejectionmentioning

confidence: 99%

Immunosuppressive therapy after human lung transplantation

Knoop¹,

Haverich²,

Fischer³

2004

European Respiratory Journal

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numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin-2-receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival.The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation.The superiority of Tac over CsA as a maintenance agent has not been established to date, and the administration of MMF instead of Aza in combination with CsA and steroids did not improve graft or patient survival in a recent international, prospective, randomised, controlled trial.Shift from cyclosporin A to tacrolimus has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis. The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, addition of inhaled immunosuppressants and/or total lymphoid irradiation and photopheresis. Eur Respir J 2004; 23: 159-171.

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Section: The Diagnosis Of Acute Rejectionmentioning

confidence: 99%

Immunosuppressive therapy after human lung transplantation

Knoop¹,

Haverich²,

Fischer³

2004

European Respiratory Journal

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“…Clinically, acute rejection can present as a syndrome indistinguishable from pulmonary infection or can be asymptomatic. As a result, a number of transplant centers, including ours, perform surveillance transbronchial biopsies via flexible bronchoscopes to identify and treat clinically occult acute rejection, with the goal of decreasing the long‐term risk for BOS . Other centers reserve transbronchial biopsies for patients with findings consistent with acute rejection, such as dyspnea, cough or decline in forced expiratory volume in 1 s (FEV 1 ) .…”

Section: Introductionmentioning

confidence: 99%

“…As a diagnostic test, however, it has limitations. These biopsies are invasive, carrying a risk of bleeding and pneumothorax , and are hampered by sampling error and low interobserver reliability . Further, the clinical significance of low grade (A1) rejection is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Bronchoalveolar Lavage Cell Immunophenotyping Facilitates Diagnosis of Lung Allograft Rejection

Greenland

Jewell

Gottschall

et al. 2014

American Journal of Transplantation

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Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2,939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies. We randomly assigned 317 subjects to a derivation or validation cohort. BAL samples were classified into four groups: infection, rejection grade ≥A1, both, or neither. We employed generalized estimating equation and survival modeling to identify clinical predictors of rejection and infection. We found that CD25+ and NK cell percentages identified a two-fold increased odds of rejection compared to either the infection or the neither infection nor rejection groups. Also, monocytes, lymphocytes, and eosinophil percentages were independently associated with rejection. A four-predictor scoring system had high negative predictive value (96–98%) for grade ≥A2 rejection, predicted future rejection in the validation cohort, and predicted increased risk of bronchiolitis obliterans syndrome in otherwise benign samples. In conclusion, BAL cell immunophenotyping discriminates between infection and acute rejection and predicts future outcomes in lung transplant recipients. Although it cannot replace histopathology, immunophenotyping may be a clinically useful adjunct.

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“…When confirmed by transbronchial biopsy, acute rejection generally is treated with additional immunosuppressive medications (5). Most lung transplantation centers also use surveillance bronchoscopy to identify otherwise silent episodes of acute rejection (6), presuming that untreated acute rejection increases the risk of BOS (7,8).…”

mentioning

confidence: 99%

Association of Large-Airway Lymphocytic Bronchitis with Bronchiolitis Obliterans Syndrome

Greenland

Jones²,

Hays³

et al. 2013

Am J Respir Crit Care Med

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Rationale: Lung transplantation offers great promise for otherwise terminal lung diseases, but the development of bronchiolitis obliterans syndrome (BOS) continues to limit survival. Although acute rejection and lymphocytic bronchiolitis have been identified as risk factors for the development of BOS, it is unclear whether largeairway lymphocytic inflammation conveys the same risk. Objectives: We evaluated lymphocytic bronchitis on endobronchial biopsies as a risk factor for BOS and mortality. Methods: Endobronchial biopsies were collected and graded during surveillance after lung transplantation. We assessed samples with negative cultures collected in the first 90 days from 298 subjects and compared large-airway lymphocytic bronchitis assessed by a 0-2 "E-score" and with standard A and BR pathology scores for acute rejection and small-airway lymphocytic bronchiolitis, respectively. Measurements and Main Results: We found surprisingly little association between large-and small-airway lymphocytic inflammation scores from a given bronchoscopy. Endobronchial lymphocytic bronchitis was more prevalent in subjects in BOS stage 0p and BOS stages 1-3 at the time of biopsy. Within 90 days after transplantation, increasing maximum E-score was associated with greater risk of BOS (adjusted hazard ratio, 1.76; 95% confidence interval, 1.11-2.78; P ¼ 0.02) and in this analysis 90-day maximum E-scores were the only score type predictive of BOS (P , 0.01). Conclusions: These results support a multicenter study to evaluate endoscopic biopsies for the identification of patients at increased risk for BOS. The association of endobronchial lymphocytic inflammation and BOS may have mechanistic implications.Keywords: bronchiolitis obliterans; graft rejection; bronchoscopy; lung transplantation Lung transplantation can offer improved quality of life and survival from otherwise terminal lung diseases. However, the development of chronic rejection, manifested as bronchiolitis obliterans syndrome (BOS), is a major barrier to long-term patient survival (1). BOS can cause death from graft failure and can occur despite potent immunosuppression (2, 3). One risk factor for BOS is symptomatic acute rejection (4). When confirmed by transbronchial biopsy, acute rejection generally is treated with additional immunosuppressive medications (5). Most lung transplantation centers also use surveillance bronchoscopy to identify otherwise silent episodes of acute rejection (6), presuming that untreated acute rejection increases the risk of BOS (7,8).Previous studies revealed that small-airways lymphocytic bronchiolitis in transbronchial biopsy specimens also is associated with increased risk of BOS (9). Endobronchial biopsies have been evaluated in lung transplant recipients, in whom acute rejection and current BOS were associated with largeairway lymphocytosis (10). This lymphocytosis is predominantly CD4 1 and CD45 1 (10). Work from the present laboratory showed differential expression of gene transcripts in patients with large-airway, but not small-ai...

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Surveillance Bronchoscopy in Lung Transplant Recipients

Cited by 59 publications

References 16 publications

Immunosuppressive therapy after human lung transplantation

Immunosuppressive therapy after human lung transplantation

Bronchoalveolar Lavage Cell Immunophenotyping Facilitates Diagnosis of Lung Allograft Rejection

Association of Large-Airway Lymphocytic Bronchitis with Bronchiolitis Obliterans Syndrome

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