Usefulness of Exhaled Nitric Oxide to Guide Risk Stratification for Bronchiolitis Obliterans Syndrome After Lung Transplantation

Neurohr, Claus; Huppmann, Patrick; Leuschner, S.; Wulffen, Werner von; Meis, Tobias; Leuchte, Hanno; Ihle, Franziska; Zimmermann, G.; Baezner, Carlos; Hatz, Rudolf; Winter, Hauke; Frey, Lorenz; Ueberfuhr, Peter; Bittmann, Iris; Behr, Jüergen

doi:10.1111/j.1600-6143.2010.03327.x

Cited by 26 publications

(30 citation statements)

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“…31 Many physiological and pathological factors can determine exhaled NO levels. 32,33 Concentrations of exhaled NO are easily detectable by non-invasive measures and as an association between BO syndrome after lung transplantation and the levels of fractional exhaled NO was reported 34 we tried to identify any changes regarding FeNO in BO after hematopoietic SCT. Surprisingly, in contrast to the Munich Lung Transplant Group we found decreased levels of FeNO in our BO-patients and regardless of the time point during the course of the disease it was possible to differentiate between BO-and non-BO-patients post-hematopoietic SCT by using a threshold level for FeNO.…”

Section: Discussionmentioning

confidence: 99%

Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight—new perspectives?

Ditschkowski

Elmaagacli

Koldehoff

et al. 2013

Bone Marrow Transplant

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Bronchiolitis obliterans (BO) is a late non-infectious pulmonary complication after allogeneic hematopoietic SCT. Among 982 patients after myeloablative hematopoietic SCT between January 2000 and October 2010, 68 were diagnosed with BO according to NIH criteria. The median onset of BO was 18 months post transplant, 5-year cumulative incidence was 5.8% and 5-year mortality 41%. BO prevalence rate was 10% among all long-term surviving hematopoietic SCT recipients and 12% among chronic GVHDpatients. Chronic GVHD, peripheral SCT and ABO blood group incompatibility were identified as risk factors associated with BO. IgG levels were significantly decreased at the onset of BO (6.7 g/L ± 0.7, P ¼ 0.001), the mean exhaled NO concentrations were lower in BO-patients than in stem cell recipients without BO (14 p.p.b.±0.9 vs 20 p.p.b.±2.1) or healthy controls (25 p.p.b.±2.4, Po0.001). Hypoxia-inducible factor 1 alpha (HIF-1a) was significantly elevated in BO as compared with healthy controls or GVHD-patients without lung involvement (340 ± 61 vs 127 ± 22 vs 140 ± 32, P ¼ 0.02). Calculated 5-year survival was superior in female than in male BO-patients (86 vs 45%, P ¼ 0.04). These results emphasize the relevance of BO as serious late complication with substantial mortality and point to essential pathophysiological changes due to regulatory responses to hypoxia. Keywords: bronchiolitis obliterans; nitric oxide; allogeneic; GVHD; HIF-1a; SCT INTRODUCTION Allogeneic hematopoietic SCT has been shown to provide longterm disease-free survival for otherwise fatal malignant or nonmalignant hematological disorders. With increasing survival rates due to toxicity reduced hematopoietic SCT methods, advanced GVHD-management and improved anti-infectious therapy and prophylaxis, a distinct increment in late transplant related complications can be observed. Pulmonary complications develop in 30-60% of allogeneic hematopoietic SCT recipients and are considered as a major cause of morbidity and mortality. 1,2 Late-onset non-infectious pulmonary complications 3 beginning 3 months after transplantation with an incidence of 10-15% are considered as life-threatening complications significantly limiting the quality of life. 4,5 Although late-onset non-infectious pulmonary complications classification is rather undefined, the most common categorizations include bronchiolitis obliterans (BO), bronchiolitis obliterans organizing pneumonia and interstitial pneumonia. 6,7 According to the NIH consensus criteria, BO is considered to be the only pulmonary manifestation of chronic GVHD. 8 The reported incidence of BO in allogeneic hematopoietic SCT recipients ranges from 2-10% and mortality rates have been assessed between 13 and 23%. 9,10 BO is prevalent in 2-5.5% of hematopoietic SCT recipients and in up to 14% of hematopoietic SCT recipients with chronic GVHD. 11 Patients diagnosed with BO have a 5-year survival rate of only 45% vs 75% in patients without BO. 9 Advanced disease stages at transplantation, preceding GVHD, older donor and recipient age, M...

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Section: Discussionmentioning

confidence: 99%

Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight—new perspectives?

Ditschkowski

Elmaagacli

Koldehoff

et al. 2013

Bone Marrow Transplant

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“…In a recent study with adult patients after lung transplantation, FeNO has been shown to be a valuable tool for risk stratification for bronchiolitis obliterans syndrome [21]. In contrast to immunocompetent children [7,19], no data exist on normal FeNO levels in immunosuppressed children or on the predictive value of elevated FeNO for pulmonary complications after paediatric allogeneic HSCT.…”

Section: Discussionmentioning

confidence: 98%

Exhaled nitric oxide and pulmonary complications after paediatric stem cell transplantation

et al. 2012

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“…Increased FE NO has been noted with acute rejection [170], pulmonary infection [171], and development of bronchiolitis obliterans syndrome (BOS) [172,173] in adult lung transplant recipients. However, no elevated FE NO is also reported in pulmonary infection or BOS in human lung transplantation [170].…”

Section: Transplantationmentioning

confidence: 99%

Fractional Exhaled Nitric Oxide: Indications and Interpretation

Kim

Kercsmar

Davis

2014

Respiratory Medicine

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Exhaled nitric oxide (NO) is a marker for eosinophilic airway inflammation. The correlations between fraction of exhaled NO (FE NO ) and eosinophils in blood, sputum, bronchoalveolar lavage, and mucosal biopsies of the airway have been well studied. A quantitative, noninvasive, and simple methodology has been developed to determine how best to assess FE NO as a measure of airway inflammation. FE NO measurement has been standardized by the American Thoracic Society/ European Respiratory Society (Am J Respir Crit Care Med 171(8): [912][913][914][915][916][917][918][919][920][921][922][923][924][925][926][927][928][929][930] 2005). The gold standard for measuring FE NO is the single-breath online method, which can be performed in young children from the age of 4-5 years. A chemiluminescencebased analyzer or a portable analyzer using an electrochemical sensor can be used to measure FE NO . Many studies have shown that FE NO has potential diagnostic and therapeutic roles in various respiratory diseases, particularly asthma. In asthma, FE NO is useful to diagnose and monitor eosinophilic airway inflammation, and predict steroid responsiveness. It also can be helpful in supporting the diagnosis of asthma and in guiding adjustment of anti-inflammatory medication. ATS Clinical Practice Guidelines have been published for interpretation and clinical applicability of FE NO (Dweik et al., 184(5):602-615, 2011). FE NO can provide additional information on underlying airway inflammation, and is complementary to respiratory symptoms, lung function tests, and bronchial provocation tests for asthma and other respiratory diseases in the clinical setting.

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Usefulness of Exhaled Nitric Oxide to Guide Risk Stratification for Bronchiolitis Obliterans Syndrome After Lung Transplantation

Cited by 26 publications

References 32 publications

Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight—new perspectives?

Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight—new perspectives?

Exhaled nitric oxide and pulmonary complications after paediatric stem cell transplantation

Fractional Exhaled Nitric Oxide: Indications and Interpretation

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