Breathomics in lung disease

Volatile organic compounds (VOCs) are produced by virtually all metabolic processes of the body. As such, they have potential to serve as noninvasive metabolic biomarkers. Since exhaled VOCs are either derived from the respiratory tract itself or have passed the lungs from the circulation, they are candidate biomarkers in the diagnosis and monitoring of pulmonary diseases in particular. Good examples of the possibilities of exhaled volatiles in pulmonary medicine are provided by the potential use of VOCs to discriminate between patients with lung cancer and healthy control subjects and to noninvasively diagnose infectious diseases and the association between VOCs and markers of disease activity that has been established in obstructive lung diseases. Several steps are, however, required prior to implementation of breath-based diagnostics in daily clinical practice. First, VOCs should be studied in the intention-to-diagnose population, because biomarkers are likely to be affected by multiple (comorbid) conditions. Second, breath collection and analysis procedures need to be standardized to allow pooling of data. Finally, apart from probabilistic analysis for diagnostic purposes, detailed examination of the nature of volatile biomarkers not only will improve our understanding of the pathophysiologic origins of these markers and the nature of potential confounders but also can enable the development of sensors that exhibit maximum sensitivity and specificity toward specific applications. By adhering to such an approach, exhaled biomarkers can be validated in the diagnosis, monitoring, and treatment of patients in pulmonary medicine and contribute to the development of personalized medicin

A European Respiratory Society technical standard: exhaled biomarkers in lung disease

Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10\u2005years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)