analysis of exhaled breath fingerprints and volatile organic compounds in copd

Exhaled air contains many volatile organic compounds (VOCs) produced during human metabolic processes, in both healthy and pathological conditions. Analysis of breath allows studying the modifications of the profile of the exhaled VOCs due to different disease states, including chronic obstructive pulmonary disease (COPD). The early diagnosis of COPD is complicated and the identification of specific metabolic profiles of exhaled air may provide useful indication to better identify the disease. The aim of our study was to characterize the specific exhaled VOCs by means of the electronic nose and by solid phase micro-extraction associated to gas chromatography–mass spectrometry (SPME GC-MS). Exhaled air was collected and measured in 34 subjects, 7 healthy and 27 former smokers affected by COPD (GOLD 1–4). The signals of the electronic nose sensors were higher in COPD patients with respect to controls, and allowed to accurately classify the studied subjects in healthy or COPD. GC-MS analysis identified 37 VOCs, nine of which were significantly correlated with COPD. In particular the concentration of two of these were positively correlated whereas seven were negatively correlated with COPD. The partial least squares discriminant analysis (PLS-DA) carried out with these nine VOCs produced a significant predictive model of disease. This study shows that COPD patients exhibit qualitative and quantitative differences in the chemical compositions of exhale. These differences are detectable both by the GC-MS and the six-sensor e-nose. The use of electronic nose may represent a suitable, non-invasive diagnostic tool for characterization of COPD

Simultaneous presence of Brugada and overgrowth syndromes

In the present article, we describe the case of a 21-year-old male presenting to the Emergency Department following a syncopal episode. Physical examination revealed a distinctive facial appearance in the context of an overgrowth syndrome. Also, an ajmaline test was performed because of the evidence of an incomplete right bundle branch block with ST-T segment elevation in the right precordial derivations, revealing a type-1 Brugada electrocardiographic pattern. Considering the high cardiovascular risk phenotype, the patient underwent subcutaneous cardiac defibrillator implantation. The subsequent comprehensive genomic testing analysis led to the diagnosis of a variant of an uncertain significance of the nuclear receptor binding SET domain protein 1 (NSD1) gene and a heterozygous mutation of the calsequestrin 2 (CASQ2) gene. NSD1 gene alterations are usually responsible for the Sotos syndrome, characterized by distinctive facial appearance, learning disability, and overgrowth, in addition to cardiac anomalies, ranging from single self-limiting alterations to more severe, complex cardiac abnormalities. On the contrary, a compound heterozygous or homozygous alteration of the CASQ2 gene is usually associated with catecholaminergic polymorphic ventricular tachycardia; however, the significance of a merely heterozygous alteration in CASQ2 gene, as in the present case report, is not yet clear. In conclusion, to the best of our knowledge, this is the first description of the coexisting presence of Brugada and overgrowth syndromes in a single patient

New developments in the combination treatment of COPD: focus on umeclidinium/vilanterol

An increasing body of evidence suggests that the long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination appears to play an important role in maximizing bronchodilation, with studies to date indicating that combining different classes of bronchodilators may result in significantly greater improvements in lung function compared to the use of a single drug, and that these combinations are well tolerated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). An inhaled, fixed-dose combination of two 24-hour bronchodilators, the LAMA umeclidinium and the LABA vilanterol, is under development as a once-daily treatment for COPD. The efficacy of both mono-components has already been demonstrated. The information currently available suggests that umeclidinium/vilanterol is an effective once-daily dual bronchodilator fixed-dose combination in the treatment of COPD. However, it remains to be seen if it compares favorably with current therapies. Moreover, the question remains whether umeclidinium/vilanterol fixed-dose combination, which significantly improves FEV1, is also associated with improvements in other outcome measures that are important to COPD patients

Pharmacological assessment of the onset of action of aclidinium and glycopyrronium versus tiotropium in COPD patients and human isolated bronchi

Preclinical studies suggested that aclidinium and glycopyrronium might have a faster onset of action than tiotropium. In this study we assessed the onset of action of aclidinium and glycopyrronium versus tiotropium, all administered at the approved clinical doses, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and in human isolated bronchi by using different concentrations. Sixteen COPD patients inhaled single doses of aclidinium 400µg, glycopyrronium 50μg and tiotropium 18µg and FEV1 was measured to assess their onset of action. In human isolated bronchi the time to evoke half maximal relaxation of transmural stimulation was tested from 10nM to 1µM for each drug. Nine, eight and twelve patients did not achieve 15% increase of FEV1 after inhalation of aclidinium, glycopyrronium and tiotropium, respectively. Aclidinium (15.6±7.5min) and glycopyrronium (17.9±10.4min) enhanced 15% FEV1 more rapidly than tiotropium (42.5±19.4min), with no significant difference (P>0.05). In isolated airways, glycopyrronium elicited a dose-dependent onset of action (10nM: 8.2±1.3min, 100nM: 7.1±2.1min, 1μM: 3.4±0.4min) that was faster compared to that induced by aclidinium (1μM: 6.4±0.5min) and tiotropium (1μM: 8.4±1.1min) (P0.05). In isolated airways, glycopyrronium elicited a dose-dependent onset of action (10nM: 8.2±1.3min, 100nM: 7.1±2.1min, 1μM: 3.4±0.4min) that was faster compared to that induced by aclidinium (1μM: 6.4±0.5min) and tiotropium (1μM: 8.4±1.1min) (P<0.05), that halved the contractile tone only at the highest concentration. Bronchodilation induced by aclidinium and glycopyrronium was faster than that induced by tiotropium, but since our analysis was restricted to the acute effect of these LAMAs and the inhaled doses were not isoeffective, the real differences in their impact on the onset of bronchodilation will be definitely determined after a long-term challenge of these treatments at isoeffective doses in COPD patients

Effect of an additional dose of indacaterol in COPD patients under regular treatment with indacaterol

SummaryAimIn this randomized, double-blind, crossover study, we explored the acute effects on respiratory function and safety of an additional dose of indacaterol 150 μg in stable COPD patients regularly treated with a conventional dose of indacaterol 150 μg.MethodsOn two non-consecutive days, patients inhaled indacaterol 150 μg. After 180 min, they inhaled an additional dose of indacaterol 150 μg or placebo. Lung function, oxygen saturation by pulse oximetry (SpO2) and heart rate were measured before the first drug administration and up to 360 min thereafter.ResultsIn both treatment groups, indacaterol induced a significant (P < 0.05) bronchodilation during all the study time. The difference between the FEV1 AUCs0–180 min was not statistically significant (P = 0.971). On the contrary, the difference between the FEV1 AUCs180–360 min was significant (P < 0.0001). However, only 8 out of 20 patients showed a further increase of at least 100 ml from the peak obtained after the first administration of indacaterol 150 μg with the second dose of 150 μg. Indacaterol 150 μg induced a modest but significant decrease in SpO2 up to 60 min and a second dose of indacaterol 150 μg significantly decreased the SpO2 mean value up to 360 min.ConclusionThis study suggests that it is reasonable and safe to increase the dose of indacaterol in those stable COPD patients who are under regular therapy with indacaterol 150 μg from which they do not draw the maximum benefit because they are unable to perceive bronchodilation. However, only a minority of patients seem to benefit from this dose escalation, at least in terms of spirometric improvement

Large, single-center experience in transvenous coronary sinus lead extraction: procedural outcomes and predictors for mechanical dilatation

Background: The aim of this study was to evaluate procedural outcomes of coronary sinus (CS) lead extraction, focusing on predictors and need for mechanical dilatation (MD) in the event that manual traction (MT) is ineffective.Methods: The study assessed results in 145 consecutive patients (age 69 +/- 10 years; 121 men)-a total of 147 CS pacing leads-who underwent transvenous CS lead removal between January 2000 and March 2010.Results: All leads but one (99%) (implantation time 29 +/- 25 months) were successfully removed. MT was effective in 103 (70%), and MD was necessary in the remaining 44 (30%) procedures. In multivariate analyses, unipolar design (odds ratio [OR] 3.22, 95% confidence interval [CI] 1.43-7.7; P = 0.005) and noninfective indication (OR 4.8, 95% CI 1.8-13, P = 0.002) were independent predictors for MD (P &lt; 0.0001), with a predictive trend for prior cardiac surgery (OR 2.2, 95% CI 0.98-5.26; P = 0.06). Five (3.4%) complex procedures required a transfemoral vein approach (TFA) or repeat procedure. No deaths occurred, and there was one major complication (0.7%), cardiac tamponade, after MT. No complication predictors were identified.Conclusions: CS leads were safely and effectively removed in nearly all patients, and 70% were removed with MT alone; 30% required MD. Preoperative predictors suggesting the need for MD or TFA were noninfective indication and unipolar lead design. Complications were rare, and there was no predictable pattern among MT or MD removal techniques. (PACE 2012; 35:215-222

Transvenous Removal of Pacing and Implantable Cardiac Defibrillating Leads using Single Sheath Mechanical Dilatation and Multiple Venous Approaches

Introduction Device related complications are raising the need for transvenous lead removal (TLR). Transvenous extraction of pacing (PL) and defibrillating leads (DL) is a highly effective technique. The aim of this chapter is to describe an 18 year single-center experience in pacing and defibrillating leads removal using an effective and safe modified mechanical dilatation technique. Methods We developed a single mechanical dilating sheath extraction technique with multiple venous entry site approaches. We performed a venous entry site approach (VEA) in cases of exposed leads, and an alternative transvenous femoral approach (TFA) combined with an internal transjugular approach (ITA) in the presence of very tight binding sites causing failure of VEA extraction or in cases of free-floating leads. Results From January 1997 to December 2014, we managed 2250 consecutive patients (1718 men, mean age 65.3 years) with 4114 leads (mean pacing period 71.8 months, range 1-576). PL were 3228 (1582 ventricular, 1391 atrial, 355 coronary sinus leads), DL were 786 (765 ventricular, 6 atrial, 15 superior vena cava leads). Removal was attempted in 4105 leads, since the technique was not applicable in 9 PL. Among these, 4019 leads were completely removed (97.9%), 44 (1.1%) partially removed, and 42 (1.0%) not removed. Among 4020 exposed leads, 625 were removed by manual traction (15.5%), 2998 by mechanical dilatation using the venous entry site (74.6%), 32 by femoral approach (FA) (0.8%), and 279 by ITA. Major complications occurred in 13 cases (0.6%): cardiac tamponade (12 cases, 2 deaths), hemotorax (1 death). Conclusion Mechanical single sheath extraction technique with multiple venous entry site approaches is effective, safe and has a good cost effective profile for pacing and ICD leads removal. TLR through the ITA increases the effectiveness and safety of the procedure in case of challenging leads