Single Exhaled Breath Metabolomic Analysis Identifies Unique Breathprint in Patients With Acute Decompensated Heart Failure

Acute decompensated heart failure (ADHF) is the most common indication for hospital admission, particularly in the elderly, yet the identification of those with impending decompensation using conventional clinical methods is unreliable and frequently leaves insufficient lag time for therapeutic interventions (1). Exhaled breath constitutes a complex mixture of hundreds of volatile organic compounds (VOCs) that could potentially be used as a safe and noninvasive method of diagnostic and therapeutic monitoring (2). Previous research studies have identified elevated acetone, pentane, and nitric oxide levels in exhaled breath in the setting of HF correlated with disease severity (3–5). Selected ion-flow tube mass-spectrometry (SIFT-MS) combines a fast flow tube technique with quantitative mass spectrometry that is ideally suited for exhaled breath analysis because it allows for the analysis of small and humid samples without the need for cumbersome sample preparation or calibration (6). Scan times are relatively brief, thus facilitating high throughput and serial comparisons. Using this technology, we conducted a prospective, single-center cohort study to assess the feasibility of exhaled breath analysis to identify patients admitted for ADHF. The study protocol was approved by the Cleveland Clinic Institutional Review Board. We recruited 25 consecutive patients admitted with ADHF as their primary diagnosis (mean left ventricular ejection fraction 27 ± 13%, median N-terminal pro–B-type natriuretic peptide level 954 pg/ml) and a control group of 16 subjects admitted with non-ADHF cardiovascular diagnoses and who had no clinical evidence of systemic or venous congestion at the time of enrollment. Indications for hospitalization in the control group included unstable angina or non–ST-segment elevation myocardial infarction (6 of 16), conduction disorders (3 of 16), hypertensive emergency (3 of 16), atrial tachyarrhythmia (2 of 16), or stable angina (2 of 16). All analyses were performed using JMP Pro 9.0 (SAS Institute, Cary, North Carolina). As expected, there were significant (p \u3c 0.01) baseline differences in the frequency of hypertension (54% vs. 100%) and baseline estimated glomerular filtration rate (68 ± 43 ml/min/1.73 m2 vs. 102 ± 44 ml/min/1.73 m2), which were significantly worse in the ADHF versus control group. Nevertheless, there were no significant differences between groups in age, body mass index, or several comorbidities (i.e., diabetes mellitus, chronic obstructive pulmonary disease, active smoking) theorized to result in alterations in the exhaled metabolome

A pilot study on the kinetics of metabolites and microvascular cutaneous effects of nitric oxide inhalation in healthy volunteers

RATIONALE: Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation of hemodynamics in the body. A detailed investigation into the generation of these metabolites has been overlooked. OBJECTIVES: We investigated the kinetics of nitrite and S-nitrosothiol-hemoglobin (SNO-Hb) in plasma derived from inhaled NO subjects and how this modifies the cutaneous microvascular response. FINDINGS: We enrolled 15 healthy volunteers. Plasma nitrite levels at baseline and during NO inhalation (15 minutes at 40 ppm) were 102 (86-118) and 114 (87-129) nM, respectively. The nitrite peak occurred at 5 minutes of discontinuing NO (131 (104-170) nM). Plasma nitrate levels were not significantly different during the study. SNO-Hb molar ratio levels at baseline and during NO inhalation were 4.7E-3 (2.5E-3-5.8E-3) and 7.8E-3 (4.1E-3-13.0E-3), respectively. Levels of SNO-Hb continued to climb up to the last study time point (30 min: 10.6E-3 (5.3E-3-15.5E-3)). The response to acetylcholine iontophoresis both before and during NO inhalation was inversely associated with the SNO-Hb level (r: -0.57, p = 0.03, and r: -0.54, p = 0.04, respectively). CONCLUSIONS: Both nitrite and SNO-Hb increase during NO inhalation. Nitrite increases first, followed by a more sustained increase in Hb-SNO. Nitrite and Hb-SNO could be a mobile reservoir of NO with potential implications on the systemic microvasculature

Detrimental Effects of Environmental Tobacco Smoke in Relation to Asthma Severity

Background: Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown. Methods: In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity. Findings: From 2002-2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage. Interpretation: ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma. © 2011 Comhair et al

Asthma Is More Severe in Older Adults

Background: Severe asthma occurs more often in older adult patients. We hypothesized that the greater risk for severe asthma in older individuals is due to aging, and is independent of asthma duration. Methods: This is a cross-sectional study of prospectively collected data from adult participants (N=1130; 454 with severe asthma) enrolled from 2002 – 2011 in the Severe Asthma Research Program. Results: The association between age and the probability of severe asthma, which was performed by applying a Locally Weighted Scatterplot Smoother, revealed an inflection point at age 45 for risk of severe asthma. The probability of severe asthma increased with each year of life until 45 years and thereafter increased at a much slower rate. Asthma duration also increased the probability of severe asthma but had less effect than aging. After adjustment for most comorbidities of aging and for asthma duration using logistic regression, asthmatics older than 45 maintained the greater probability of severe asthma [OR: 2.73 (95 CI: 1.96; 3.81)]. After 45, the age-related risk of severe asthma continued to increase in men, but not in women. Conclusions: Overall, the impact of age and asthma duration on risk for asthma severity in men and women is greatest over times of 18-45 years of age; age has a greater effect than asthma duration on risk of severe asthma