Prognostic Value of Bronchoalveolar Lavage Neutrophilia in Stable Lung Transplant Recipients

Neurohr, Claus; Huppmann, Patrick; Samweber, Benedikt; Leuschner, S.; Zimmermann, G.; Leuchte, Hanno; Baumgärtner, R; Hatz, Rudolf; Frey, Ludwig; Ueberfuhr, Peter; Bittmann, Iris; Behr, Jüergen

doi:10.1016/j.healun.2009.01.014

Cited by 79 publications

(63 citation statements)

References 37 publications

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“…The prevalence of LAD was much higher in patients who later on developed BOS compared to those who remained stable, hence confirming the association between LAD and BOS which has been described previously (5). This might be explained by the high BAL neutrophilia found during LAD (8), which, as already demonstrated in other studies, is an important risk factor towards the development of BOS (15). Our study suggests that at least part of the LAD and BAL neutrophilia is explained by exposure to PM 10 .…”

Section: Discussionsupporting

confidence: 88%

Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

Verleden

Scheers

Nawrot

et al. 2012

American Journal of Transplantation

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Section: Discussionsupporting

confidence: 88%

Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

Verleden

Scheers

Nawrot

et al. 2012

American Journal of Transplantation

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“…The mechanisms by which IL-17 leads to fibrosis will require more investigation, but they are most likely multifold and involve many cell types. The potential role of neutrophils in the pathogenesis of murine obliterative airways disease also requires further study because several earlier studies in lung transplant recipients have shown BAL neutrophilia to be correlated with BOS (37)(38)(39). Here, we show increased allograft neutrophilia in T-bet-deficient recipients of lung transplant that is abolished with anti-CD154 and anti-IL-17 therapy, suggesting that this effect is mediated by CD8 CXCL1 in this model of lung allograft rejection and to elucidate the cellular pathways involved linking IL-17 to CXCL1 and neutrophilia.…”

Section: Cd8mentioning

confidence: 99%

CD8⁺IL-17⁺T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients

Lendermon

Dodd‐o

Coon

et al. 2015

Am J Respir Cell Mol Biol

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Acute cellular rejection is a known risk factor for the development of obliterative bronchiolitis, which limits the long-term survival of lung transplant recipients. However, the T cell effector mechanisms in both of these processes remain incompletely understood. Using the mouse orthotopic lung transplant model, we investigated whether C57BL/6 T-bet 2/2 recipients of major histocompatibility complex (MHC)-mismatched BALB/c lung grafts develop rejection pathology and allospecific cytokine responses that differ from wild-type mice. T-bet2/2 recipients demonstrated vigorous allograft rejection at 10 days, characterized by neutrophilic inflammation and predominantly CD8 1 T cells producing allospecific IL-17 and/or IFN-g, in contrast to IFN-g-dominant responses in WT mice. CD41 T cells produced IL-17 but not IFN-g responses in T-bet 2/2 recipients, in contrast to WT controls. Costimulation blockade using anti-CD154 Ab significantly reduced allospecific CD81 IFN-g 1 responses in both T-bet 2/2 and WT mice but had no attenuating effect on lung rejection pathology in T-bet 2/2 recipients or on the development of obliterative airway inflammation that occurred only in T-bet 2/2 recipients. However, neutralization of IL-17A significantly attenuated costimulation blockade-resistant rejection pathology and airway inflammation in T-bet 2/2 recipients. In addition, CXCL1 (neutrophil chemokine) was increased in T-bet 2/2 allografts, and IL-17 induced CXCL1 from mouse lung epithelial cells in vitro.Taken together, our data show that T-bet-deficient recipients of complete MHC-mismatched lung allografts develop costimulation blockade-resistant rejection characterized by neutrophilia and obliterative airway inflammation that is predominantly mediated by CD81 IL-17 1 T cells. Our data support T-bet-deficient mouse recipients of lung allografts as a viable animal model to study the immunopathogenesis of small airway injury in lung transplantation.

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“…Nitric oxide and carbon monoxide concentrations in exhaled breath have been correlated with airway neutrophilia in subjects with BOS, but their sensitivity is lower than SBNW [115]. Neutrophilia (.20%) in bronchoalveolar lavage is predictive for future BOS in stable lung transplant recipients [116]. Exhaled breath condensates, induced sputum, bronchoalveolar lavage, and CT scans have all been evaluated for early detection of BOS.…”

Section: Bronchiolitis Obliterans After Lung Transplantationmentioning

confidence: 99%

Small airways diseases, excluding asthma and COPD: an overview

Burgel¹,

Bergeron²,

Blic³

et al. 2013

Eur Respir Rev

105

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This review is the summary of a workshop on small airways disease, which took place in Porquerolles, France in November 2011. The purpose of this workshop was to review the evidence on small airways (bronchiolar) involvement under various pathophysiological circumstances, excluding asthma and chronic obstructive pulmonary disease. Histopathological patterns associated with small airways disease were reviewed, including cellular and obliterative bronchiolitis. Many pathophysiological conditions have been associated with small airways disease including airway infections, connective tissue diseases and inflammatory bowel diseases, bone marrow and lung transplantation, common variable immunodeficiency disorders, diffuse panbronchiolitis, and diseases related to environmental exposures to pollutants, allergens and drugs. Pathogenesis, clinical presentation, a computed tomography scan and pulmonary function test findings are reviewed, and therapeutic options are described with the objective of providing an integrative approach to these disorders.

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Prognostic Value of Bronchoalveolar Lavage Neutrophilia in Stable Lung Transplant Recipients

Cited by 79 publications

References 37 publications

Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

CD8⁺IL-17⁺T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients

Small airways diseases, excluding asthma and COPD: an overview

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Prognostic Value of Bronchoalveolar Lavage Neutrophilia in Stable Lung Transplant Recipients

Cited by 79 publications

References 37 publications

Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

CD8+IL-17+T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients

Small airways diseases, excluding asthma and COPD: an overview

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CD8⁺IL-17⁺T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients