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Background: We evaluated survival and hospitalization rates in patients with group 1 portopulmonary hypertension (PoPH) in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry).Methods: The REVEAL Registry is a multicenter, observational, US-based study evaluating demographics and management of patients with pulmonary arterial hypertension (PAH). Outcomes were examined using Kaplan-Meier time-to-event estimates and compared with patients with idiopathic PAH (IPAH) or familial PAH (FPAH).Results: One hundred seventy-four patients with PoPH were enrolled in the REVEAL Registry (IPAH/FPAH; n = 1,478) from March 2006 to December 2009. Mean age was 53 ± 10 years, 52% were female, 32% were newly diagnosed, and 6% were New York Heart Association/World Health Organization functional class IV. Outcome parameters were worse for PoPH vs IPAH/FPAH, respectively: 2-year survival from enrollment (67% vs 85%, P < .001), 5-year survival from time of diagnosis (40% vs 64%, P < .001), and 2-year freedom from all-cause hospitalization (49% vs 59%, P = .019). However, despite worse outcomes, hemodynamic parameters at diagnosis were better for PoPH vs IPAH/FPAH, respectively: mean pulmonary artery pressure (49 mm Hg vs 53 mm Hg, P < .001), mean right atrial pressure (9 mm Hg vs 10 mm Hg, P = .005), pulmonary vascular resistance (8 Wood units vs 12 Wood units, P < .001), and cardiac output (5 L/min vs 4 L/min, P < .001). Compared with patients with IPAH/FPAH, patients with PoPH were less likely to be on a PAH-specific therapy at enrollment (P < .001), suggesting potential delays in therapy for patients with PoPH.Conclusions: Patients with PoPH had significantly poorer survival and all-cause hospitalization rates compared with patients with IPAH/FPAH, despite having better hemodynamics at diagnosis. Further studies should investigate such outcomes and differences in treatment patterns.Trial Registry: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals with severe asthma. SARP collaboration has led to a rapid recruitment of subjects and efficient sharing of samples among participating sites to conduct independent mechanistic investigations of severe asthma. Enrolled SARP subjects underwent detailed clinical, physiologic, genomic, and radiological evaluations. In addition, SARP investigators developed safe procedures for bronchoscopy in participants with asthma, including those with severe disease. SARP studies revealed that severe asthma is a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features and unique structure-function abnormalities. Priorities for future studies include recruitment of a larger number of subjects with severe asthma, including children, to allow further characterization of anatomic, physiologic, biochemical, and genetic factors related to severe disease in a longitudinal assessment to identify factors that modulate the natural history of severe asthma and provide mechanistic rationale for management strategies. [ABSTRACT FROM AUTHOR]

Background: Measurement of fractional nitric oxide (NO) concentration in exhaled breath (Fe(NO)) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While Fe(NO) measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of Fe(NO) in clinical practice.Purpose: To develop evidence-based guidelines for the interpretation of Fe(NO) measurements that incorporate evidence that has accumulated over the past decade.Methods: We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach.Results: The evidence related to the use of Fe(NO) measurements is reviewed and clinical practice recommendations are provided.Conclusions: In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV(1) reversibility or provocation tests are only indirectly associated with airway inflammation. Fe(NO) offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy. [ABSTRACT FROM AUTHOR]

The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FeNO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FeNO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness. Recently, five randomized controlled algorithm asthma trials reported only equivocal benefits of adding measurements of FeNO to usual clinical guideline management including spirometry; however, significant design issues may exist. Overall, FeNO measurement at a single expiratory flow rate of 50 mL/s may be an important adjunct for diagnosis and management in selected cases of asthma. This may supplement standard clinical asthma care guidelines, including spirometry, providing a noninvasive window into predominantly large-airway-presumed eosinophilic inflammation. In COPD, large/central airway maximal NO flux and peripheral/small airway/alveolar NO concentration may be normal and the role of FeNO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FeNO. Monitoring FeNO in pulmonary hypertension and cystic fibrosis has opened up a window to the role NO may play in their pathogenesis and possible clinical benefits in the management of these diseases. [ABSTRACT FROM AUTHOR]

Rationale: High-density lipoprotein cholesterol (HDL-C) promotes healthy vascular function, and it is decreased in insulin resistance. Insulin resistance predisposes to pulmonary vascular disease.Objectives: We hypothesized that HDL-C is associated with clinical outcomes in pulmonary arterial hypertension (PAH).Methods: Plasma HDL-C concentrations were measured in 69 patients with PAH (age, 46.7 +/- 12.9 yr; female, 90%) and 229 control subjects (age, 57 +/- 13 yr; female, 48%). Clinical outcomes of interest included hospitalization for PAH, lung transplantation, and all-cause mortality. Survival and time to clinical worsening curves were derived by the Kaplan-Meier method. Cox regression modeling of outcome versus HDL-C with individual covariate adjustments was performed.Measurement and Main Results: HDL-C was low in subjects with PAH compared with control subjects (median, interquartile range: PAH: 36, 29-40 mg/dl; control subjects: 49, 40-60 mg/dl; P < 0.001). An HDL-C level of 35 mg/dl discriminated survivors from nonsurvivors, with a sensitivity of 100% and specificity of 60%. After a median follow-up of 592 days, high HDL-C was associated with decreased mortality (hazard ratio for every 5-mg/dl increase in HDL-C, 0.643; 95% confidence interval, 0.504-0.822; P = 0.001) and less clinical worsening (hazard ratio for every 5-mg/dl increase in HDL-C, 0.798; 95% confidence interval, 0.663-0.960; P = 0.02). HDL-C remained a significant predictor of survival after adjusting for cardiovascular risk factors, C-reactive protein, indices of insulin resistance, and severity of PAH (all P < 0.05).Conclusions: Low plasma HDL-C is associated with higher mortality and clinical worsening in PAH. This association does not appear to be explained by underlying cardiovascular risk factors, insulin resistance, or the severity of PAH. [ABSTRACT FROM AUTHOR]

Rationale: Exhaled nitric oxide (Fe(NO)) is a biomarker of airway inflammation in mild to moderate asthma. However, whether Fe(NO) levels are informative regarding airway inflammation in patients with severe asthma, who are refractory to conventional treatment, is unknown. Here, we hypothesized that classification of severe asthma based on airway inflammation as defined by Fe(NO) levels would identify a more reactive, at-risk asthma phenotype.Methods: Fe(NO) and major features of asthma, including airway inflammation, airflow limitation, hyperinflation, hyperresponsiveness, and atopy, were determined in 446 individuals with various degrees of asthma severity (175 severe, 271 non-severe) and 49 healthy subjects enrolled in the Severe Asthma Research Program.Measurements and Main Results: Fe(NO) levels were similar among patients with severe and non-severe asthma. The proportion of individuals with high Fe(NO) levels (>35 ppb) was the same (40%) among groups despite greater corticosteroid therapy in severe asthma. All patients with asthma and high Fe(NO) had more airway reactivity (maximal reversal in response to bronchodilator administration and by methacholine challenge), more evidence of allergic airway inflammation (sputum eosinophils), more evidence of atopy (positive skin tests, higher serum IgE and blood eosinophils), and more hyperinflation, but decreased awareness of their symptoms. High Fe(NO) identified those patients with severe asthma characterized by the greatest airflow obstruction and hyperinflation and most frequent use of emergency care.Conclusions: Grouping of asthma by Fe(NO) provides an independent classification of asthma severity, and among patients with severe asthma identifies the most reactive and worrisome asthma phenotype. [ABSTRACT FROM AUTHOR]

Rationale: The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma.Objectives: To identify novel asthma phenotypes using an unsupervised hierarchical cluster analysis.Methods: Reduction of the initial 628 variables to 34 core variables was achieved by elimination of redundant data and transformation of categorical variables into ranked ordinal composite variables. Cluster analysis was performed on 726 subjects.Measurements and Main Results: Five groups were identified. Subjects in Cluster 1 (n = 110) have early onset atopic asthma with normal lung function treated with two or fewer controller medications (82%) and minimal health care utilization. Cluster 2 (n = 321) consists of subjects with early-onset atopic asthma and preserved lung function but increased medication requirements (29% on three or more medications) and health care utilization. Cluster 3 (n = 59) is a unique group of mostly older obese women with late-onset nonatopic asthma, moderate reductions in FEV(1), and frequent oral corticosteroid use to manage exacerbations. Subjects in Clusters 4 (n = 120) and 5 (n = 116) have severe airflow obstruction with bronchodilator responsiveness but differ in to their ability to attain normal lung function, age of asthma onset, atopic status, and use of oral corticosteroids.Conclusions: Five distinct clinical phenotypes of asthma have been identified using unsupervised hierarchical cluster analysis. All clusters contain subjects who meet the American Thoracic Society definition of severe asthma, which supports clinical heterogeneity in asthma and the need for new approaches for the classification of disease severity in asthma. [ABSTRACT FROM AUTHOR]

Rationale: Angiogenesis is a defining pathologic feature of airway remodeling and contributes to asthma severity. Women experience changes in asthma control over the menstrual cycle, a time when vessels routinely form and regress under the control of angiogenic factors. One vital function modulated over the menstrual cycle in healthy women is gas transfer, and this has been related to angiogenesis and cyclic expansion of the pulmonary vascular bed.Objectives: We hypothesized that changes in gas transfer and the pulmonary vascular bed occur in women with asthma over the menstrual cycle and are associated with worsening airflow obstruction.Methods: Twenty-three women, 13 with asthma and 10 healthy control subjects, were evaluated over the menstrual cycle with weekly measures of spirometry, gas transfer, nitric oxide, hemoglobin, factors affecting hemoglobin binding affinity, and proangiogenic factors.Measurements and Main Results: Airflow and lung diffusing capacity varied over the menstrual cycle with peak levels during menses that subsequently declined to nadir in early luteal phase. In contrast to healthy women, changes in lung diffusing capacity (DL(CO)) were associated with changes in membrane diffusing capacity and DL(CO) was not related to proangiogenic factors. DL(CO) did not differ between the two groups, although methemoglobin and carboxyhemoglobin were higher in women with asthma than in healthy women.Conclusions: Women with asthma experience cyclic changes in airflow as well as gas transfer and membrane diffusing capacity supportive of a hormonal effect on lung function. [ABSTRACT FROM AUTHOR]

Rationale: As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation.Objectives: We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity.Methods: Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated.Measurements and Main Results: Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma.Conclusions: Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma. [ABSTRACT FROM AUTHOR]

Background Published reports consistently describe incomplete delivery of prescribed enteral nutrition. Which specific step in the process delays or interferes with the administration of a full dose of nutrients is unclear. Objectives To assess factors associated with interruptions in enteral nutrition in critically ill patients receiving mechanical ventilation. Methods An observational prospective study of 59 consecutive patients who required mechanical ventilation and were receiving enteral nutrition was done in an 18-bed medical intensive care unit of an academic center. Data were collected prospectively on standardized forms. Steps involved in the feeding process from admission to discharge were recorded, each step was timed, and delivery of nutrition was quantified. Results Patients received approximately 50% (mean, 1106.3; SD, 885.9 Cal) of the prescribed caloric needs. Enteral nutrition was interrupted 27.3% of the available time. A mean of 1.13 interruptions occurred per patient per day; enteral nutrition was interrupted a mean of 6 (SD, 0.9) hours per patient each day. Prolonged interruptions were mainly associated with problems related to small-bore feeding tubes (25.5%), increased residual volumes (13.3%), weaning (11.7%), and other reasons (22.8%). Placement and confirmation of placement of the small-bore feeding tube were significant causes of incomplete delivery of nutrients on the day of admission. Conclusions Delivery of enteral nutrition in critically ill patients receiving mechanical ventilation is interrupted by practices embedded in the care of these patients. Evaluation of the process reveals areas to improve the delivery of enteral nutrition. [ABSTRACT FROM AUTHOR]

Rationale: Increased oxidative stress and decreased superoxide dismutase (SOD) activity in the asthmatic airway are correlated to airflow limitation and hyperreactivity. We hypothesized that asthmatic individuals with higher levels of oxidative stress may have greater loss of SOD activity, which would be reflected systemically in loss of circulating SOD activity and clinically by development of severe asthma and/or worsening airflow limitation.Methods: To investigate this, serum SOD activity and proteins, the glutathione peroxidase/glutathione antioxidant system, and oxidatively modified amino acids were measured in subjects with asthma and healthy control subjects.Results: SOD activity, but not Mn-SOD or Cu,Zn-SOD protein, was lower in asthmatic serum as compared with control, and activity loss was significantly related to airflow limitation. Further, serum SOD activity demonstrated an inverse correlation with circulating levels of 3-bromotyrosine, a posttranslational modification of proteins produced by the eosinophil peroxidase system of eosinophils. Exposure of purified Cu,Zn-SOD to physiologically relevant levels of eosinophil peroxidase-generated reactive brominating species, reactive nitrogen species, or tyrosyl radicals in vitro confirmed that eosinophil-derived oxidative pathways promote enzyme inactivation.Conclusion: These findings are consistent with greater oxidant stress in asthma leading to greater inactivation of SOD, which likely amplifies inflammation and progressive airflow obstruction. [ABSTRACT FROM AUTHOR]

Rationale: Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry.Objectives: We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma.Methods: In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer.Main Results: Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively.Conclusion: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. Methods We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography. Results Both DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p CO of PAH patients did not change over time, DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers. Conclusions The findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion.

Objective:  This study aimed to assess the volatile organic compounds (VOC)s in breath samples collected noninvasively from pregnant women during pregnancy and postpartum and compare it with nonpregnant controls., Study Design:  This pilot study included 50 subjects: 10 pregnant patients in their first trimester, 10 in second trimester, 10 in third trimester, 10 in the first postpartum week, and 10 nonpregnant subjects as a control. We collected exhaled breath from subjects who reported to be healthy and free of any respiratory symptoms. Clinical and demographic data were collected. The samples were analyzed for VOCs using a selected-ion flow-tube mass spectrometer., Results:  The VOCs monitored were 22 compounds selected for their common presence in exhaled breath. During pregnancy and postpartum period, there were differences in five compounds mainly: 2-propanol, acrylonitrile, 1-nonene, 2-nonene, and hydrogen sulfide. Significant differences in VOCs were identified during each trimester compared with controls., Conclusion:  VOCs could be measured safely and noninvasively in pregnant women. VOCs differed significantly among nonpregnant, pregnant women, and postpartum period. The utilization of this novel assay to identify fetal conditions or identifying women at risk of premature delivery, which should be further investigated in future studies., Key Points: · This study demonstrated that VOCs could be measured noninvasively in exhaled breath of pregnant women.. · VOCs differed significantly among women who were nonpregnant, pregnant, and in postpartum period.. · These findings might serve as a base to look for potential markers for maternal or fetal conditions.., Competing Interests: None declared., (Thieme. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressures that can lead to right heart failure and death. No cure exists for this disease, but therapeutic advancements have extended its median survival from 2 to 7 years. Mechanistic research in PAH has been limited by factors including that a) animal models do not fully recapitulate the disease or provide insights into its pathogenesis, and b) cellular material from PAH patients is primarily obtained from donor lungs during autopsy or transplantation, which reflect end-stage disease. Therefore, there is a need to identify tools that can elucidate the specific mechanisms of human disease in individual patients, a critical step to guide treatment decisions based on specific pathway abnormalities. Here we demonstrate a simple method to isolate and culture circulating endothelial cells (CECs) obtained at the time of right heart catheterization in PAH patients. We tested these CECs using transcriptomics and found that they have typical traits of PAH, including those involving key treatment pathways, i.e. nitric oxide, endothelin, prostacyclin and BMP/activin pathways. CECs show important gene expression changes in other central PAH disease pathways. In summary, we present a new cellular model for the ex-vivo mechanistic evaluation of critical PAH pathways that participate in the pathogenesis of the disease and may help personalized therapeutic decisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aulak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To assess volatile organic compounds (VOCs) in breath samples collected non-invasively from preterm and full-term infants., Methods: This was a pilot study included preterm and full-term infants who were not intubated or suspected or diagnosed with metabolic or gastrointestinal disorders. The samples were analyzed for VOCs using a selected-ion flow-tube mass spectrometer., Results: Twenty infants were included; ten preterm and ten full-term infants. Twenty-two VOCs were detected and measurable in all samples. There was a significant difference between preterm and full-term infants for the 2-propanol, acetaldehyde, acetone, acetonitrile, benzene, ethanol, isoprene, pentane, 3-methylhexane, 2-nonene, ethane, triethylamine, and trimethylamine compounds., Conclusion: It is feasible to measure VOCs in breath samples of preterm and full-term non-intubated infants. Full-term infants express different concentrations than preterm infants. Further studies are needed to examine the utility and reproducibility of measuring VOCs to identify neonatal diseases and predict outcomes., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired infective diarrhea. Current methods for diagnosing CDI have limitations; enzyme immunoassays for toxin have low sensitivity and Clostridioides difficile polymerase chain reaction cannot differentiate infection from colonization. An ideal diagnostic test that incorporates microbial factors, host factors, and host-microbe interaction might characterize true infection. Assessing volatile organic compounds (VOCs) in exhaled breath may be a useful test for identifying CDI. To identify a wide selection of VOCs in exhaled breath, we used thermal desorption-gas chromatography-mass spectrometry to study breath samples from 17 patients with CDI. Age- and sex-matched patients with diarrhea and negative C.difficile testing (no CDI) were used as controls. Of the 65 VOCs tested, 9 were used to build a quadratic discriminant model that showed a final cross-validated accuracy of 74%, a sensitivity of 71%, a specificity of 76%, and a receiver operating characteristic area under the curve of 0.72. If these findings are proven by larger studies, breath VOC analysis may be a helpful adjunctive diagnostic test for CDI., (© 2024 IOP Publishing Ltd.)

Exhaled breath volatile organic compounds (VOCs) are elevated in heart failure (HF). The ability of VOCs to predict long term cardiovascular mortality and morbidity has not been independently verified. In 55 patients admitted with acute decompensated heart failure (ADHF), we measured exhaled breath acetone and pentane levels upon admission and after 48 h of diuresis. In a separate cohort of 51 cardiac patients undergoing cardiopulmonary exercise testing (CPET), we measured exhaled breath acetone and pentane levels before and at peak exercise. In the ADHF cohort, admission acetone levels correlated with lower left ventricular ejection fraction (LVEF, r = -0.297, p = 0.035). Greater weight loss with diuretic therapy correlated with a greater reduction in both acetone levels (r = -0.398, p = 0.003) and pentane levels (r = -0.309, p = 0.021). In patients with above-median weight loss (≥4.5 kg), patients demonstrated significantly greater percentage reduction in acetone (59% reduction vs. 7% increase, p < 0.001) and pentane (23% reduction vs. 2% reduction, p = 0.008). In the CPET cohort, admission acetone and pentane levels correlated with higher VE/VCO2 (r = 0.39, p = 0.005), (r = 0.035, p = 0.014). However, there were no significant correlations between baseline or peak exercise acetone and pentane levels and peak VO2. In longitudinal follow-up with a median duration of 33 months, patients with elevated exhaled acetone and pentane levels experienced higher composite adverse events of death, ventricular assist device implantation, or orthotopic heart transplantation. In patients admitted with ADHF, higher exhaled breath acetone levels are associated with lower LVEF and poorer outcomes, and greater reductions in exhaled breath acetone and pentane tracked with greater weight loss. Exhaled acetone and pentane may be novel biomarkers in heart failure worthy of future investigation.