Exhaled Nitric Oxide and Nitric Oxide Synthase Expression in Hodgkin's Disease

Abstract

Hodgkin's disease (HD) is a malignant lymphoma with frequent mediastinal involvement, characterized by a significant inflammatory infiltration. Exhaled nitric oxide (FENO), is present in healthy humans, and has been proven to be increased in eosinophilic diseases such as allergic asthma. We investigated whether FENO is increased in mediastinal HD and whether NO is produced by lymphoma tissue. To this aim FENO was measured in 56 HD patients, 17 with and 39 without bulky mediastinal involvement, in the period from January 2007 to December 2008. Thirty-seven patients were reassessed after remission. Lymph node biopsies of 10 patients were evaluated for inducible (iNOS) and constitutive (eNOS) nitric oxide synthase expression by immunohistochemistry. FENO resulted significantly related to the mediastinal mass maximum diameter (p=0.009) and was significantly higher in patients with as compared to those without bulky mediastinal disease (38.7 ppb, CI 95% 19.3-58.0, versus 20.7 ppb, CI 95% 16.6-24.7; p=0.009). iNOS and eNOS immunoreactivity was observed in tumour and inflammatory cells (eosinophils and histiocytes). Only in patients with bulky mediastinal HD there was a significant decrease in FENO (from 50.4 ppb CI 95% 18.0-82.8 to 11.1 ppb CI 95% 4.4-17.8, p=0.011). In conclusion, high FENO and NOS expression in lymph-nodes indicate that NO is a component of the inflammatory network of HD. FENO may be proposed for the assessment and follow up of bulky mediastinal HD patients.