Single-institution Study Evaluating the Utility of Surveillance Bronchoscopy After Lung Transplantation

Valentine, Vincent G.; Gupta, Meera; Weill, David; Lombard, G; LaPlace, S.G.; Seoane, Leonardo; Taylor, David E.; Dhillon, Gundeep

doi:10.1016/j.healun.2008.10.010

Cited by 62 publications

(48 citation statements)

References 32 publications

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“…In a further more recent study by Benden et al acute cellular rejection (≥A2) or subclinical infection was reported at 4% and 29%, respectively, in specimens taken from asymptomatic pediatric patients during the first post‐LTx year . Notwithstanding these reports, there has been a single, again relatively recent, adult study where surveillance bronchoscopy did not find any ≥A2 rejection . In this study there were 2.4 times more procedures done for clinical indications, and with an overall rejection (≥A2) rate of a low 4.6%.…”

Section: Indications For Bronchoscopy In Pediatric Ltxmentioning

confidence: 50%

Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients

2015

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Bronchoscopy remains a pivotal diagnostic and therapeutic intervention in pediatric patients undergoing lung transplantation (LTx). Whether performed as part of a surveillance protocol or if clinically indicated, fibre-optic bronchoscopy allows direct visualization of the transplanted allograft, and in particular, an assessment of the patency of the bronchial anastomosis (or tracheal anastomosis following heart-lung transplantation). Additionally, bronchoscopy facilitates differentiation of infective processes from rejection episodes through collection and subsequent assessment of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBx) samples. Indeed, the diagnostic criteria for the grading of acute cellular rejection is dependent upon the histopathological assessment of biopsy samples collected at the time of bronchoscopy. Typically, performed in an out-patient setting, bronchoscopy is generally a safe procedure, although complications related to hemorrhage and pneumothorax are occasionally seen. Airway complications, including stenosis, malacia, and dehiscence are diagnosed at bronchoscopy, and subsequent management including balloon dilatation, laser therapy and stent insertion can also be performed bronchoscopically. Finally, bronchoscopy has been and continues to be an important research tool allowing a better understanding of the immuno-biology of the lung allograft through the collection and analysis of collected BAL and TBBx samples. Whilst new investigational tools continue to evolve, the simple visualization and collection of samples within the lung allograft by bronchoscopy remains the gold standard in the evaluation of the lung allograft. This review describes the use and experience of bronchoscopy following lung transplantation in the pediatric setting.

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Section: Indications For Bronchoscopy In Pediatric Ltxmentioning

confidence: 50%

Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients

2015

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“…For a patient with a clinical suspicion of rejection, transbronchial biopsy is preferred to confirm the diagnosis. However, in the context of data suggesting that detection of silent acute rejection may not affect long-term outcomes (22)(23)(24), the use of surveillance bronchoscopy in otherwise asymptomatic patients may be to identify those at increased risk for BOS (25). A strategy that avoids transbronchial biopsy in surveillance of asymptomatic patients could reduce risk of procedural complications (26,27).…”

Section: Discussionmentioning

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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“…Some practitioners advocate for treatment of asymptomatic low-grade acute cellular rejection with high-dose corticosteroids 30 , based on the observation that a single episode of A1-grade rejection confers increased risk for chronic lung allograft dysfunction 31 and that grade A1 rejection may progress to more severe rejection if untreated 32 . On the other hand, many transplant centers do not treat A1- or even A2-grade rejection with high doses of corticosteroids in the absence of symptoms or other clinical findings 33 and 1 study found no benefit of performing surveillance bronchoscopic biopsies in individuals lacking symptoms to suggest rejection or infection 34 . High Treg frequencies during acute cellular rejection are consistent with a self-limiting process.…”

Section: Discussionmentioning

confidence: 99%

Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts

et al. 2016

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Background Acute cellular rejection is a major cause of morbidity following lung transplantation. Because regulatory T cells (Treg) limit rejection of solid organs, we hypothesized that donor-reactive Treg increase after transplantation with development of partial tolerance and decrease relative to conventional CD4+ (Tconv) and CD8+ T cells during acute cellular rejection. Methods To test these hypotheses, we prospectively collected 177 peripheral blood mononuclear cell (PBMC) specimens from 39 lung transplant recipients at the time of transplantation and during bronchoscopic assessments for acute cellular rejection. We quantified the proportion of Treg, CD4+ Tconv, and CD8+ T cells proliferating in response to donor-derived, stimulated B cells. We used generalized estimating equation-adjusted regression to compare donor-reactive T cell frequencies with acute cellular rejection pathology. Results An average of 16.5±9.0% of pretransplantation PBMC Treg were donor-reactive, compared with 3.8%±2.9% of CD4+ Tconv and 3.4±2.6% of CD8+ T cells. These values were largely unchanged following transplantation. Donor-reactive CD4+ Tconv and CD8+ T cell frequencies both increased 1.5-fold (95% CI 1.3-1.6, P <0.001 and 95% CI 1.2-1.6, P = 0.007, respectively) during A2-grade rejection compared with no rejection. Surprisingly, donor-reactive Treg frequencies increased by 1.7-fold (95% CI 1.4-1.8, P <0.001). Conclusions Contrary to prediction, overall proportions of donor-reactive Treg are similar before and after transplantation and increase during A2-grade rejection. This suggests how A2 rejection can be self-limiting. The observed increases over high baseline proportions in donor-reactive Treg were insufficient to prevent acute lung allograft rejection.

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Single-institution Study Evaluating the Utility of Surveillance Bronchoscopy After Lung Transplantation

Cited by 62 publications

References 32 publications

Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients

Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients

Association of Large-Airway Lymphocytic Bronchitis with Bronchiolitis Obliterans Syndrome

Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts

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