A novel approach to the assessment of lymphocytic bronchiolitis after lung transplantation—transbronchial brush

Chambers, Daniel C.; Hodge, Sandra; Hodge, Greg; Yerkovich, Stephanie T.; Kermeen, F.; Reynolds, Paul N.; Holmes, Mark; Hopkins, Peter

doi:10.1016/j.healun.2010.10.018

Cited by 16 publications

(11 citation statements)

References 27 publications

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“…Moreover the number of T-cells in this infiltrate correlated with the BAL neutrophilia. 45 BAL neutrophilia is indeed the most typical characteristic of NRAD patients, but BAL neutrophilia can also be found during episodes of LB. Vos et al indeed demonstrated that the percentage of BAL neutrophils is significantly higher during LB compared with that of control patients and patients suffering from acute perivascular rejection.…”

Section: Lymphocytic Bronchiolitis and Nrad: Different Entities Or Not?mentioning

confidence: 93%

Neutrophilic Reversible Allograft Dysfunction (NRAD) and Restrictive Allograft Syndrome (RAS)

Verleden

Vandermeulen

Ruttens

et al. 2013

Semin Respir Crit Care Med

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Lung transplantation is currently considered as an ultimate live-saving treatment for selected patients suffering from end-stage pulmonary disease. Long-term survival, however, is hampered by chronic rejection, or chronic lung allograft dysfunction (CLAD). Recently, various phenotypes within CLAD have been identified, challenging the established clinical definition of bronchiolitis obliterans syndrome (BOS). Some patients with presumed BOS, for instance, demonstrate an important improvement in forced expiratory volume in the first second of expiration (FEV1) after treatment with azithromycin. These patients are characterized by the presence of excess (≥ 15%) bronchoalveolar lavage (BAL) neutrophils, in absence of concurrent infection. This phenotype of CLAD has been redefined as neutrophilic reversible allograft dysfunction (NRAD), and these patients generally have a very good prognosis after diagnosis. Another group of patients with CLAD develop a restrictive rather than an obstructive pulmonary function defect (defined as a decline in total lung capacity of at least 10%) and demonstrate persistent interstitial and ground-glass opacities on chest computed tomographic (CT) scan. This phenotype is called restrictive allograft syndrome (RAS), and patients with RAS have a much worse prognosis after diagnosis. This review further discusses both of these CLAD phenotypes that do not fit the classical definition of BOS. Potential pathophysiological mechanisms, etiology, diagnosis, prognosis, and treatments are discussed.

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Section: Lymphocytic Bronchiolitis and Nrad: Different Entities Or Not?mentioning

confidence: 93%

Neutrophilic Reversible Allograft Dysfunction (NRAD) and Restrictive Allograft Syndrome (RAS)

Verleden

Vandermeulen

Ruttens

et al. 2013

Semin Respir Crit Care Med

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“…Transbronchial brushing provides distal airway cells that can be analyzed by flow cytometry and differentiate infective and alloimmune drivers of lymphocytic bronchiolitis following LTx . Probe‐based confocal laser endomicroscopy provides real‐time imaging of the pulmonary acini and distinctive cell profiles have been shown to be associated with acute rejection .…”

Section: Other Bronchoscopic Proceduresmentioning

confidence: 99%

“…71,72 Other Bronchoscopic Techniques Transbronchial brushing provides distal airway cells that can be analyzed by flow cytometry and differentiate infective and alloimmune drivers of lymphocytic bronchiolitis following LTx. 73 Probe-based confocal laser endomicroscopy provides real-time imaging of the pulmonary acini and distinctive cell profiles have been shown to be associated with acute rejection. 74 Autofluorescence imaging bronchoscopy can detect areas of abnormal mucosal thickening and following LTx may identify subtle airway ischemic damage.…”

Section: Research Applicationsmentioning

confidence: 99%

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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“…after processing by recipient APC) recognize donor epithelial MHC class I or II antigens . Involvement of IL‐17‐producing lymphocytes, including CD4 + T helper 17 cells (Th17) and CD8 + T effector 17 cells (Tc17), is thought to be crucial for the evolution from acute to chronic allograft rejection . Th17 are characterized by production of IL‐17, IL‐22 and IL‐21, whereas Tc17 are mainly characterized by IL‐17 secretion and no IL‐21 or IL‐22 co‐secretion .…”

Section: Introductionmentioning

confidence: 99%

Azithromycin and the Treatment of Lymphocytic Airway Inflammation After Lung Transplantation

Vos

Verleden

Ruttens

et al. 2014

American Journal of Transplantation

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Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1, FEF25–75, Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL‐17+ cells/mm2 lamina propria) and broncho‐alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C‐reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL‐1β, IL‐8/CXCL‐8, IP‐10/CXCL‐10, RANTES/CCL5, MIP1‐α/CCL3, MIP‐1β/CCL4, Eotaxin, PDGF‐BB, total cell count, neutrophils and eosinophils, as well as plasma C‐reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.

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A novel approach to the assessment of lymphocytic bronchiolitis after lung transplantation—transbronchial brush

Cited by 16 publications

References 27 publications

Neutrophilic Reversible Allograft Dysfunction (NRAD) and Restrictive Allograft Syndrome (RAS)

Neutrophilic Reversible Allograft Dysfunction (NRAD) and Restrictive Allograft Syndrome (RAS)

Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients

Azithromycin and the Treatment of Lymphocytic Airway Inflammation After Lung Transplantation

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