No abstract

The finding that oral NO is increased in OSA and is related to upper airway obstructive episodes and to hypoxemia severity, strengthens the clinical and pathogenic role of oral inflammation in OSA.

Inflammation mediated by the immune system is known to be important in carcinogenesis and, specifically, T helper 17 cells have been reported to play a role in tumor progression by promoting neo-angiogenesis. The aim of this study was to investigate whether inflammatory cytokines and vascular endothelial growth factor (VEGF) levels in exhaled breath condensate (EBC) and in serum were related to tumor size in patients with non-small cell lung cancer (NSCLC). Il-6, IL-17, TNF-α and VEGF levels were measured in EBC and serum of 15 patients with stage I-IIA NSCLC and in 30 healthy controls by immunoassay. The tumor size was measured by a CT scan. The concentrations of IL-6, IL-17 and VEGF were significantly higher in EBC of patients with lung cancer, compared with controls, while only serum IL-6 concentration was higher in patients compared to controls. A significant correlation (r = 0.78, p = 0.001) was observed between EBC levels of IL-6 and IL-17; IL-17 was also correlated to EBC levels of the VEGF (r = 0.83, p < 0.001) and TNF-α (r = 0.62, p = 0.014). The tumor diameter was significantly correlated with EBC concentrations of VEGF (r = 0.58, p = 0.039), IL-6 (r = 0.67, p = 0.013) and IL-17 (r = 0.66, p = 0.017). Our results show a significant relationship between inflammatory and angiogenic markers, measured in EBC by a non-invasive method, and tumor mass.

In women with unexplained chronic cough unresponsive to targeted treatment, airway and cough hyperresponsiveness may be sustained by iron deficiency. Healthy women with chronic cough should be checked for iron deficiency as iron repletion may resolve such disturbing symptom.

This study suggests that Cbl-D may contribute to chronic cough by favoring sensory neuropathy as indicated by laryngeal hyperresponsiveness and increased NGF expression in pharyngeal biopsies of Cbl-D patients. Cbl-D should be considered among factors that sustain chronic cough, particularly when cough triggers cannot be identified.

Introduction: Upper airway inflammation and narrowing are characteristics of obstructive sleep apnoea (OSA). Inflammatory markers have been found to be increased in exhaled breath and induced sputum of patients with OSA. Objectives: The aim of this study was to investigate if the measurement of exhaled nitric oxide (FENO), as marker of airway inflammation, together with the forced mid-expiratory/mid-inspiratory airflow ratio (FEF50/FIF50), as marker of upper airway narrowing, may help to predict OSA. Methods: Two hundred one consecutive outpatients with suspected OSA were prospectively studied between January 2004 and December 2005. All patients underwent clinical examination, spirometry with measurement of FEF50/FIF50, maximum inspiratory pressure, arterial blood gas analysis, exhaled nitric oxide (FENO) and overnight polysomnography. Linear regression models were used to evaluate the effect of measured variables on the apnoea-hypopnoea index (AHI). Models were cross-validated by bootstrapping. Results: Most of the patients were obese and had severe OSA. FEF50/FIF50, FENO and an interaction term between smoking and FENO contributed significantly to the predictive model for AHI, in addition to age, neck circumference, body mass index and carboxyhaemoglobin saturation. A nomogram to predict AHI was obtained, which converted the effect of each covariate in the model to a 0-100 scale. The nomogram showed a good predictive ability for AHI values between 25 and 64. Conclusions: The measurement of FENO and of FEF50/FIF50 improves the ability to predict OSA and may be used to identify patients who require a sleep study. EthicsThe study was approved by the local ethics committee, and patients gave their informed consent to the study.

Introduction: Lung cancer is the second most frequent malignancy worldwide, but its aetiology is still unclear. Inflammatory cytokines and Th cells, including Th17, are now emerging as being involved in NSCLC pathways, thus postulating a role of IL-17 in tumour angiogenesis by stimulating the vascular endothelial growth factor and the release of nitric oxide. Despite the fact that many biomarkers are used for chest malignancy diagnosis, data on FeNO levels and inflammatory cytokines in NSCLC are still few. Our study aimed to evaluate the relationship between pulmonary nitric oxide production and VEGF and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. Methods: FeNO measurement and lung function tests were performed in both patients affected by NCSLC and controls; EBC samples were also taken, and Th1 (IL-1, IL-6, IL-12, IFN-g, TNF-a), Th17 (IL-17, IL-23) and Th2 (IL-4, IL-5, IL-13) related cytokines were measured. Results: Th1 and Th17-related cytokines in EBC, except for IFN-gamma and TNF-alpha, were significantly higher in patients than in healthy controls, whereas no differences were seen for Th2-related cytokines. FeNO at the flow rate of 50 mL/s, JawNO and CalvNO levels were significantly higher in patients affected by NSCLC compared to controls. Significant correlations were found between FeNO 50 mL/s and IL-17, IL-1 and VEGF. JawNO levels positively correlated with IL-6, IL-17 and VEGF. No correlations were found between FeNO and Th2-related cytokines. Conclusion: This is the first report assessing a relationship between FeNO levels and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. IL-17, which could promote angiogenesis through the VEGF pathway, might be indirectly responsible for the increased lung production of NO in patients with NSCLC.

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 Nitric oxide (NO) is an intracellular and intercellular signalling molecule involved in the regulation of the immunological mechanisms, that, as free oxygen radical, takes part in inflammatory disorders (1). NO is synthesized from L-arginine by nitric oxide synthase (NOS) that exists in several isoforms: constitutive (eNOS) (endothelial NOS and neuronal NOS) and inducible (iNOS). Increased iNOS expression can be induced by immunostimulatory cytokines and has been found in many tumours, including B cell lymphoid neoplasms (2-3).Hodgkin's disease (HD) is a malignant lymphoma originating from B cells, characterized by typical malignant cells, Hodgkin cells (HC) and Reed-Stenberg cells (HRS) (4). These cells represent less than I% of the total tumour mass, and are surrounded by an extensive inflammatory infiltrate, characterized by lymphocytes, histiocytes, eosinophils, fibroblasts, neutrophils and plasma cells