Separating smoking-related diseases using NMR-based metabolomics of exhaled breath condensate.

Nuclear magnetic resonance (NMR)-based metabolomics separates exhaled breath condensate (EBC) profiles of patients affected by pulmonary disease from those of healthy subjects. Here we show the discriminatory ability of NMR-based metabolomics in separating patients exposed to the same risk factor, namely, smoking habit in smoking-related diseases. Fifty duplicated EBC samples from a cohort of current smokers without chronic obstructive pulmonary disease (COPD, henceforth HS), COPD smokers, and subjects with established pulmonary Langerhans cell histiocytosis (PLCH) were analyzed by means of NMR spectroscopy followed by principal component analysis (PCA) and projection to latent structures discriminant analysis (PLS-DA). Clusterization of EBC spectra was disease-specific. COPD and PLCH samples present a profile different from that of HS, showing acetate increase and 1-methylimidazole reduction. An inverse behavior of 2-propanol and isobutyrate characterized COPD with respect to PLCH (high/low in COPD, low/high in PLCH). Both the 2-component and the 3-component PLS-DA models showed a 96% cross-validated accuracy, presenting R(2) and Q(2) values in the ranges of 0.97-0.87 and 0.91-0.78, respectively, and R(2) = 0.87 and Q(2) = 0.78, indicating that data variation is well explained by each model (R(2)), with a good predictivity (Q(2)). NMR spectra of EBC discriminate COPD and PLCH patients from HS and between them, with well-defined metabolic profiles for each class. The specificity of EBC profiles suggests that disease itself drives metabolic separation overwhelming the "common background" due to smoking habit. EBC-NMR investigation offers a powerful tool for assessing the evolution of airway diseases even in the presence of a strong common factor.

Asthma prevalence and risk factors among children and adolescents living around an industrial area: a cross-sectional study.

BACKGROUND: The exposure to air pollution has negative effects on human health, increasing the risk of respiratory diseases, such as asthma. Few data are yet available on the epidemiology of childhood asthma in some areas of Italy. The aim of the study was to estimate asthma prevalence and related risk factors in children and adolescents residents around the industrial area of Termoli, Molise region, Central-South Italy. METHODS: Prevalence was assessed through the administration of modified ISAAC questionnaires filled out by parents of 89 children and adolescents for the identification of confirmed and probable cases, and by analyzing pediatricians' databases on drug prescriptions for symptoms control and treatment of assisted population in the study area (n = 1,004), compared to a control area (n = 920) with lower industrialization. The association of asthma with risk factors was evaluated by univariate (Chi-square or Fisher's Exact test) and regression logistic analysis. RESULTS: A total of 22 (24.7%) asthmatics were identified, including both confirmed (n = 7; 7.9%) and probable cases (n = 15; 16.8%), most of them (n = 17; 77.3%) resident of Termoli town. All asthma cases were georeferenced based on the residence, however clusters were not found. Using drug prescriptions analysis, a higher prevalence (n = 138; 13.7%) of diagnosed cases was found. Lifetime history of both atopic dermatitis and bronchitis were significantly relateds to asthma cases, as well as an elevated body mass index, whose association is consistent with prevalence data of overweight/obese children living in the study area. Moreover, being resident of the town of Termoli was associated to the occurrence of cases. CONCLUSIONS: Although our data indicated a prevalence concordance with previous national studies in pediatric population, a definitive correlation with environmental industrial factors present in the study area was not established. However, asthma outcome was significantly associated to individuals living in the town of Termoli that, despite the industrial/manufacturing activities, is also subjected to a higher environmental pressure due to the presence of toll road, state highway, railroad, and seaport which may cause air pollution from motor vehicle traffic and increase asthma induction. This study provides hitherto unavailable data on asthma in childhood population living in an industrialized area which was never investigated before, could be part of a systematic review or meta-analysis procedure, might suggest significant findings for larger observational studies, and contribute to complete the frame of disease epidemiology in Italy.

Exploring airway diseases by NMR-based metabonomics: a review of application to exhaled breath condensate.

There is increasing evidence that biomarkers of exhaled gases or exhaled breath condensate (EBC) may help in detecting abnormalities in respiratory diseases mirroring increased, oxidative stress, airways inflammation and endothelial dysfunction. Beside the traditional techniques to investigate biomarker profiles, "omics" sciences have raised interest in the clinical field as potentially improving disease phenotyping. In particular, metabonomics appears to be an important tool to gain qualitative and quantitative information on low-molecular weight metabolites present in cells, tissues, and fluids. Here, we review the potential use of EBC as a suitable matrix for metabonomic studies using nuclear magnetic resonance (NMR) spectroscopy. By using this approach in airway diseases, it is now possible to separate specific EBC profiles, with implication in disease phenotyping and personalized therapy.

Exhaled nitric oxide in severe obesity: effect of weight loss.

Exhaled nitric oxide (NO) is a recognized biomarker in the lower respiratory tract. The effect of large variation in body mass on exhaled NO in the same individuals is not well known. The aim of the study was to evaluate both the effect of severe obesity and the influence of weight reduction on exhaled NO. A consecutive series of 24 uncomplicated obese patients (OB), who had laparoscopic adjustable gastric banding (LAGB) and 15 healthy controls (HC) were studied. Body mass index (BMI), exhaled NO and respiratory function tests were assessed. Exhaled NO was lower in obese in comparison to HC (12.0+/-3.6ppb versus 15.8+/-4.0ppb, p=0.0035). A significant positive correlation was found between exhaled NO and BMI in HC, which was not evident in OB. Among the respiratory indexes, functional residual capacity was significantly associated to exhaled NO. After 1 year, 12 obese patients undergone to LAGB were re-evaluated. Mean BMI (kg/m(2)) decreased from 44.8 before surgery to 32.3 post-operatively. The exhaled NO increased from 11.8+/-3.2ppb before surgery to 14.9+/-3.1ppb 1 year post-operatively (p=0.0023, n=12). In conclusion exhaled NO is consistently reduced in severe obesity and it is restored after weight reduction. The relationship between exhaled NO, large body mass excess and decrease of resting lung volume in severe obesity deserves further studies.

Nocturnal continuous positive airway pressure in severe non-apneic asthma. A pilot study.

INTRODUCTION: It has been demonstrated that brief periods of nocturnal continuous positive airway pressure (nCPAP) reduce airway reactivity in animal models and in patients with asthma. The effects of nCPAP in severe uncontrolled non-apneic asthmatic patients are not well known. AIM: In this open pilot study, we aimed to assess the effect nCPAP on peak flow (PEF) variability and asthma control in this type of patients. METHODS: CPAP was applied to 10 patients with severe long-standing asthma without obstructive sleep apnea for seven consecutive nights. CPAP was titrated in auto setting and applied to the patients. Daily PEF, was measured from 2 weeks before the intervention to 2 weeks after the end of nCPAP treatment. PEF amplitude and PEF morning dip (MD) over 24-h periods averaged over 1 week were calculated as indexes of PEF variability. Asthma control test (ACT) and European quality of life (EuroQol) questionnaire were measured at baseline and after 1 month, and at baseline and at the end of CPAP period, respectively. RESULTS: The PEF amplitude significantly decreased both during CPAP period and in the first week after nCPAP discontinuation as compared with the baseline (19.8 ± 7.5%, 23.9 ± 9.1% and 28.9 ± 11.5%, respectively, always P < 0.05). PEF MD significantly decreased during nCPAP in comparison with the baseline (P < 0.001). The ACT and EuroQol significantly improved after nCPAP in comparison with the basal value. CONCLUSIONS: In this preliminary report, brief period of nCPAP reduces PEF variability and improves control in severe non-apneic asthma at a short-term evaluation. Further studies with longer-term evaluation and larger number of patients are warranted.

Adiponectin oligomerization state and adiponectin receptors airway expression in chronic obstructive pulmonary disease.

Adiponectin (Acrp30) shows several beneficial properties and circulates as different oligomers. The role of Acrp30 in lung is not fully clear, but a link with chronic obstructive pulmonary disease (COPD) has been highlighted. In this study, we analyzed the anthropometrical and biochemical features and evaluated total Acrp30 levels of a COPD cohort without metabolic complications compared to healthy controls. In addition, being the oligomerization state critical for its biological activities, we characterized the pattern of Acrp30 circulating oligomers focusing on the high molecular weight (HMW) oligomers to verify whether it correlates to COPD. Finally, we investigated AdipoR1 and AdipoR2 expression in lung from COPD. Interestingly, we found for the first time that the oligomerization state of Acrp30 is altered in COPD; particularly, we observed that the higher levels of Acrp30 are associated with a significant and specific increase of HMW. In addition, we demonstrated the presence of AdipoRs with a lower expression of AdipoR2 compared to AdipoR1. In conclusion, we demonstrated that in COPD, the higher levels of Acrp30 are associated with the significantly increase of HMW representing the most biologically active forms. The important role of Acrp30 in pathophysiological conditions of lung is supported also by the modulation of AdipoRs with the down regulation of AdipoR2. The low expression of AdipoR2 could suggest a specific role of this receptor, mainly implicated in Acrp30 effects on inflammation and oxidative stress. Thus, total Acrp30, HMW and its receptors could be considered critical targets to improve diagnostic and therapeutic strategies for lung diseases.

Exhaled nitric oxide monitoring in COPD using a portable analyzer.

BACKGROUND: The exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation in asthma. A very recent statement has suggested FeNO as potential outcome in chronic obstructive pulmonary disease (COPD). Recently, a new hand-held FeNO analyzer (NIOX MINO) has been developed. PATIENTS AND METHODS: We have evaluated the NIOX MINO in COPD patients and monitored FeNO levels during 1-year assessment in the outpatient setting. Short-term variability in FeNO was compared using a NIOX MINO and a stationary chemiluminescence analyzer (NOA, Sensormedics) in healthy volunteers and COPD patients on two consecutive months. Long-term FeNO variability was assessed on a cohort of 70 COPD outpatients measuring FeNO for 1 year. The intra-individual FeNO coefficient of variation (eNOCoV) was taken as index FeNO long-term variability. RESULTS: In COPD there were no significant differences between NIOX MINO and NOA FeNO values recorded at baseline and 1 month later. Ninety five percent limits of agreement between NIOX MINO and NOA were-2.7 and 1.9ppb with significant reliability (r=0.96, p<0.0001). Mean FeNO at baseline was 15.0+/-9.5ppb. Over the 1-year period the overall mean FeNO was 15.5+/-10.1ppb. The long-term eNOCoV was 33.9+/-16.4% (range 8.1-83.1%), and it was significantly associated with exacerbation rate (r=0.57, p<0.0001). CONCLUSION: FeNO electrochemical hand-held analyzer is feasible in COPD showing good agreement with stationary chemiluminescence analyzer. COPD patients exhibit a wide range of FeNO levels and a high variability of FeNO over time, which was positively associated with the number of exacerbations.

Association of Adams-Oliver syndrome with pulmonary arterio-venous malformation in the same family: a further support to the vascular hypothesis.

Adams-Oliver syndrome (AOS) is a rare disease characterized by congenital scalp defects, terminal transverse limb defects and cutis marmorata telangiectatica. A significant incidence of cardiac and vascular malformations has been reported, leading to the hypothesis of a vascular defect early involved in the pathogenesis. We report two members of the same family with previously diagnosed AOS based on clinical phenotype and later recognized to have pulmonary arterio-venous malformation (PAVM). None of the subjects fulfilled current diagnostic criteria of hereditary hemorrhagic telangiectasia, which is the most common cause of PAVM. The occurrence of PAVM in AOS lends support to the hypothesis that endothelial specific abnormalities could be a patho-physiological mechanism in its development. Therefore, the role of screening for PAVM in clinical management of subjects with AOS should deserve further studies.