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15-F2t-Isoprostane, a reliable biomarker of oxidative stress, has been found elevated in exhaled breath condensate (EBC), a non-invasive technique for sampling of airway secretions, in patients with cystic fibrosis (CF). Azithromycin has antioxidant properties in experimental models of CF, but its effects on oxidative stress in CF patients are largely unknown. Primary objective of this pilot, proof-of-concept, prospective, parallel group, pharmacological study, was investigating the potential antioxidant effects of azithromycin in CF patients as reflected by EBC 15-F2t-isoprostane. Secondary objectives included studying the effect of azithromycin on EBC and serum metabolic profiles, and on serum 15-F2t-isoprostane. In CF patients who were on maintenance treatment with oral vitamin E (200 UI once daily), treatment with oral azithromycin (250 or 500 mg depending on body weight) plus vitamin E (400 UI once daily) (group A) (n = 24) or oral vitamin E alone (400 UI once daily) (group B) (n = 21) was not associated with changes in EBC 15-F2t-isoprostane compared with baseline values after 8–week treatment or 2 weeks after treatment suspension. Likewise, no within- or between-group differences on serum 15-F2t-isoprostane or metabolites were observed in both study groups. NMR spectroscopy-based metabolomics of EBC shows that suspension of both azithromycin plus vitamin E and vitamin E alone has a striking effect on metabolic profiles in EBC. Between-group comparisons show that EBC metabolite distribution after treatment and two weeks after treatment suspension is different. Quantitative differences in ethanol, saturated fatty acids, acetate, acetoin/acetone, and methanol are responsible for these differences. Our study was unable to show antioxidant effect of azithromicyn as add-on treatment with doubling the dose of oral vitamin E as reflected by 15-F2t-isoprostane concentrations in EBC. Add-on therapy with azithromycin itself does not induce EBC metabolite changes, but it

The respiratory phenotypes of cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are different, with PCD showing much slower progression. Nuclear magnetic resonance (NMR)-based metabolomics of exhaled breath condensate (EBC) recognizes markers separating children with asthma or adults with chronic obstructive pulmonary disease from healthy subjects and unstable from stable CF. No NMR studies in PCD have been reported, and whether EBC metabolic profiles in PCD differ from CF is unknown. In thuis cross-sectional stud we aimed to determine if NMR might be useful in discriminating between PCD and CF and possibly identify selective metabolites accounting for their differing prognoses.

Metabolomic analysis of exhaled breath condensate in patients with asthma and COPD

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.

NMR spectroscopy-based metabolomics of exhaled breath condensate in inflammatory respiratory diseases

Metabolomics could provide new insights into the pathophysiology of cystic fibrosis (CF) by identifying profiles of endogenous metabolites., BACKGROUND: Metabolomics could provide new insights into the pathophysiology of cystic fibrosis (CF) by identifying profiles of endogenous metabolites. OBJECTIVES: To investigate whether metabolomics of exhaled breath condensate could discriminate between patients with unstable CF, stable CF and healthy subjects, and whether selected metabolites were responsible for between-group differences. METHODS: Twenty-nine patients with stable CF, 24 with unstable CF and 31 healthy subjects (age 9-24 years) participated in a cross-sectional study. Metabolomics was performed with high-resolution nuclear magnetic resonance spectroscopy. Partial least squares-discriminant analysis was used as classifier. The results were validated in a second independent study. RESULTS: Intraclass correlation coefficients for between-day and technical repeatability were 0.93 and 0.96, respectively. Bland-Altman analysis showed good within-day repeatability. Correct classification rate of CF (n=53) vs. healthy subjects (n=31) was 96% (R2=0.84; Q2=0.79). Model validation with a testing sample set obtained from subjects not included in the primary analysis (23 CF and 25 healthy subjects) showed a sensitivity of 91% and a specificity of 96%. The classification rate of stable CF (n=29) vs. unstable CF patients (n=24) was 95% (R2=0.82; Q2=0.78). Model external validation in 14 patients with stable CF and 16 with unstable CF showed a sensitivity of 86% and a specificity of 94%. Ethanol, acetate, 2-propanol and acetone were most discriminant between patients with CF and healthy subjects, whereas acetate, ethanol, 2-propanol and methanol were the most important metabolites for discriminating between patients with stable and unstable CF. CONCLUSIONS: Nuclear magnetic resonance spectroscopy of exhaled breath condensate is reproducible, discriminates patients with CF from healthy subjects and patients with unstable CF from those with stable CF, and identifies the metabolites responsible for between-group di

The lack of standardized procedures for exhaled breath condensate (EBC), a noninvasive technique for investigating lung inflammatory mediators, makes it difficult between-laboratory comparison of results. Moreover, different collecting devices have been reported to influence the EBC content. Analysis of metabolic profiles (“metabolomics”) of EBC with nuclear magnetic resonance (NMR) spectroscopy discriminates between chronic obstructive pulmonary disease (COPD) patients and healthy subjects (HS), between asthmatic children and HS, and between patients with stable cystic fibrosis, unstable cystic fibrosis and HS. This approach has recently been questioned, as NMR-based metabolomics of EBC collected using a condenser with reusable parts was reported to be affected by cleaning procedures, generating artificial signals not related to the endogenous metabolites of the lungs. In this study, we assessed: the effects of a different cleaning procedure of a reusable-part condenser on EBC metabolomics; the possible time and carry-over effects when the same device is repeatedly used; technique sensitivity; the ability of NMR spectroscopy of EBC to discriminate between COPD patients and HS; its potential for identifying selective EBC metabolites.

This paper reports the chemical study of a sample of Fasciospongia sp. collected along the Atlantic Portuguese coast. Three new isomeric furanosesquiterpenes, isomicrocionin-3 (1), (−)-microcionin-1 (2), and (−)-isomicrocionin-1 (3), were isolated along with the known (−)-ent-pallescensin A (4) and (−)-pallescensin-1 (5) from the ethyl acetate-soluble portion of the methanolic extract. The structures of the new compounds were elucidated by extensive spectroscopic studies. (−)-Microcionin-1 (2) tested positive against several Gram-negative bacteria.