Inflammation Patterns in Allogeneic and Autologous Airway Tissue of Lung Transplant Recipients

Irani, Sarosh; Gaspert, Ariana; Vogt, Peter R.; Russi, Erich W.; Weder, Walter; Speich, Rudolf; Boehler, Annette

doi:10.1111/j.1600-6143.2005.01049.x

Cited by 6 publications

(6 citation statements)

References 18 publications

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“…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-airway, lymphocytic bronchitis (11).…”

mentioning

confidence: 78%

“…A small study including four patients with BOS suggested that patients with BOS are more likely to have lymphocytic bronchitis (10). At the same time, potential BOS stage (BOS-0p), as defined by FEV 1 81-90% of baseline or forced expiratory flow, midexpiratory phase, less than or equal to 75% of baseline, has been proposed as a predictor of patients who go on to develop BOS and has been validated in single-and double-lung allograft recipients (20,21).…”

Section: Association Between Large-airway Lymphocytic Bronchitis and mentioning

confidence: 99%

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confidence: 99%

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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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confidence: 78%

Section: Association Between Large-airway Lymphocytic Bronchitis and mentioning

confidence: 99%

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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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“…2,48 Although lymphocytic inflammation is frequently seen on endobronchial biopsies of large cartilaginous airways, its clinical and prognostic significance remain unclear, and there is no demonstrated link between lymphocytic inflammation seen on endobronchial biopsies and lymphocytic bronchiolitis or bronchitis seen on transbronchial biopsies. [49][50][51][52] Although eosinophils, 53 B-cells, 38 and mast cells 54 have been identified in acute rejection biopsies and have been correlated with worse prognosis, their exact clinical significance remains unclear.…”

Section: Clinical Significance Of Acute Rejectionmentioning

confidence: 99%

Acute Allograft Rejection: Cellular and Humoral Processes

Martinu

Pavlisko

Chen

et al. 2011

Clinics in Chest Medicine

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SYNOPSIS Acute cellular rejection affects greater than a third of lung transplant recipients. Alloreactive T lymphocytes, responding directly or indirectly to donor antigen, constitute the basis of lung allograft rejection, as diagnosed by well-established histopathological criteria that reflect the severity of perivascular or peribronchial inflammation in the lung allograft. Recent evidence supports a more complex immune response to the allograft with involvement of humoral mechanisms, characterized by circulating antibody to donor HLA and specific patterns of lung injury, occurring in parallel with T cell-based rejection. Emerging evidence further suggests that the interaction between recipient genetics, immunosuppression therapies, and allograft environmental exposures, including pulmonary infection, contributes to high rejection rates after lung transplantation. A greater understanding of the heterogeneous mechanisms of lung rejection is critical to developing effective therapies that target the precise pathophysiology of the disease and ultimately improve long-term lung transplant outcomes.

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“…Large airway inflammation, as determined by endobronchial biopsies, is by definition excluded from the B-grading of acute airway rejection. Although large airway inflammation can represent infectious tracheo-bronchitis (47), most studies of endobronchial biopsies have demonstrated the presence of noninfectious CD81 T cell rich inflammation, distinct from the inflammation seen on transbronchial biopsies and in the BAL (48,49). In addition, gene expression has been found to be discordant between endobronchial biopsy cells and transbronchial biopsy tissue, suggesting that A-grade rejection is a process different from large airway inflammation (50).…”

Section: Clinical Significance Of Acute Rejectionmentioning

confidence: 99%

Acute Rejection and Humoral Sensitization in Lung Transplant Recipients

Martinu¹,

Chen²,

Palmer³

2009

Proceedings of the American Thoracic Society

153

108

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Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that limits survival to only 50% at 5 years after lung transplantation. Recent evidence demonstrates that peribronchiolar mononuclear inflammation (also known as lymphocytic bronchiolitis) or even a single episode of minimal perivascular inflammation significantly increase the risk for BOS. We comprehensively review the clinical presentation, diagnosis, histopathologic features, and mechanisms of acute cellular lung rejection. In addition, we consider emerging evidence that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens (HLA). We discuss in detail methods for HLA antibody detection as well as the clinical relevance, the mechanisms, and the pathologic hallmarks of humoral injury. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. A greater mechanistic understanding of cellular and humoral forms of rejection and their role in the pathogenesis of BOS is critical in developing therapies that extend long-term survival after lung transplantation.

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Inflammation Patterns in Allogeneic and Autologous Airway Tissue of Lung Transplant Recipients

Cited by 6 publications

References 18 publications

Association of Large-Airway Lymphocytic Bronchitis with Bronchiolitis Obliterans Syndrome

Association of Large-Airway Lymphocytic Bronchitis with Bronchiolitis Obliterans Syndrome

Acute Allograft Rejection: Cellular and Humoral Processes

Acute Rejection and Humoral Sensitization in Lung Transplant Recipients

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