#METABOLOMICS WORKBENCH hormel101_20170407_134330 DATATRACK_ID:883 STUDY_ID:ST000587 ANALYSIS_ID:AN000902 PROJECT_ID:PR000430 VERSION 1 CREATED_ON April 12, 2017, 12:11 pm #PROJECT PR:PROJECT_TITLE Mayo Metabolomics Pilot and Feasibility Award: Metabolomics of Exhaled Breath PR:PROJECT_TITLE Condensate in Decompensated Heart Failure PR:PROJECT_SUMMARY Metabolomics is a large-scale approach to monitoring as many as possible of the PR:PROJECT_SUMMARY compounds involved in cellular processes in a single assay to derive metabolic PR:PROJECT_SUMMARY profiles. Compared with genomics or proteomics, metabolomics reflects changes in PR:PROJECT_SUMMARY phenotype and therefore function. Nearly all the blood volume-cardiac output in PR:PROJECT_SUMMARY humans flows through the lungs at a rate of 5L/min and traverses through PR:PROJECT_SUMMARY capillaries with a very thin blood-gas barrier (approximately 2μm, 600–800 PR:PROJECT_SUMMARY nm; in some places <200 nm) to allow sufficient gas diffusion. However, there is PR:PROJECT_SUMMARY evidence that many other biochemicals from the blood can be found in the exhaled PR:PROJECT_SUMMARY air. Collection of exhaled breath condensate (EBC) is a relatively new, PR:PROJECT_SUMMARY noninvasive method that allows assessment of biochemical profiles that may not PR:PROJECT_SUMMARY only link to airway physiology, but also to other changing processes in the PR:PROJECT_SUMMARY body. The aims of this study are: (1) Working with the Mayo Clinic Metabolomics PR:PROJECT_SUMMARY Resource Core Laboratory to develop the optimal method for performing PR:PROJECT_SUMMARY metabolomics of EBC, (2) Collecting and metabolomic profiling of the EBCs from PR:PROJECT_SUMMARY patients with heart failure; (2) Comparing the profiles of these patients PR:PROJECT_SUMMARY obtained during stable and acute exacerbation periods as well as during recovery PR:PROJECT_SUMMARY from a decompensation; (3) Comparing the profiles of these patients with age and PR:PROJECT_SUMMARY gender matched controls; (4) Correlation of EBC metabolomic profiles with PR:PROJECT_SUMMARY clinical phenotypes. The proposed metabolomics profiles would be obtained from PR:PROJECT_SUMMARY patients involved in IRB approved, ongoing, primarily NIH funded studies focused PR:PROJECT_SUMMARY on understanding pulmonary congestion in heart failure patients. This includes a PR:PROJECT_SUMMARY recently started project capturing patients as they present in the emergency PR:PROJECT_SUMMARY room with decompensated heart failure. Phenotyping for this study includes novel PR:PROJECT_SUMMARY measures of pulmonary capillary recruitment, alveolar-capillary conductance, PR:PROJECT_SUMMARY pulmonary capillary blood volume, thoracic CT imaging combined with in-hospital PR:PROJECT_SUMMARY clinical data, including blood biomarkers such as BNP and catecholamines. PR:PROJECT_SUMMARY Measurements are performed upon admission (within 24hours) and then repeated PR:PROJECT_SUMMARY just prior to dismissal. In addition, we would collect EBC on stable HF patients PR:PROJECT_SUMMARY and in age and gender matched controls healthy controls from our other ongoing PR:PROJECT_SUMMARY studies. The overall aim will be to identify novel patterns or biomarkers for PR:PROJECT_SUMMARY developing a point-of-care test (POC) for tracking disease status in HF PR:PROJECT_SUMMARY patients. PR:INSTITUTE Mayo Clinic PR:DEPARTMENT Cardiovascular Diseases PR:LABORATORY Mayo Metabolomics Core PR:LAST_NAME Johnson PR:FIRST_NAME Bruce PR:ADDRESS 200 First St. SW, Rochester, Minnesota, 55905, USA PR:EMAIL johnson.bruce@mayo.edu PR:PHONE 507-284-4441 #STUDY ST:STUDY_TITLE Metabolomics of Exhaled Breath Condensate in Decompensated Heart Failure ST:STUDY_SUMMARY The aim of the study was to test weather characteristic differences or changes ST:STUDY_SUMMARY in metabolic profile exist between exhaled breath condensate (EBC) and saliva of ST:STUDY_SUMMARY healthy individuals and heart failure patients. EBC NMR profiling was performed. ST:INSTITUTE Mayo Clinic ST:DEPARTMENT Cardiovascular Diseases ST:LABORATORY Mayo Metabolomics Core ST:LAST_NAME Johnson ST:FIRST_NAME Bruce ST:ADDRESS 200 First Street SW, Rochester, MN 55905 ST:EMAIL johnson.bruce@mayo.edu ST:PHONE 507-284-4441 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - HF01 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF02 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF03 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF04 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF05 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF06 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF07 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF09 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF12 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF13 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - HF17 factor:heart failure type=EBC SUBJECT_SAMPLE_FACTORS - C10 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C11 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C14 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C15 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C16 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C18 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C19 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C20 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C21 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C22 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C23 factor:control type=EBC SUBJECT_SAMPLE_FACTORS - C24 factor:control type=EBC #COLLECTION CO:COLLECTION_SUMMARY The samples were collected in Dr. Bruce Johnson lab, at the Department of CO:COLLECTION_SUMMARY Cardiovascular Diseases, Mayo Clinic. EBC samples were collected using Jaeger CO:COLLECTION_SUMMARY EcoScreen cooling unit (-20°C). Patients were breathing through mouth piece CO:COLLECTION_SUMMARY while wearing a nose clip during 30 minutes. Saliva was collected from the same CO:COLLECTION_SUMMARY patients during last 15 minutes. The samples were frozen immediately after CO:COLLECTION_SUMMARY collection. #TREATMENT TR:TREATMENT_SUMMARY We will focus initially on patients with classic systolic HF who are admitted to TR:TREATMENT_SUMMARY St Mary’s Hospital with decompensated disease. These patients are currently TR:TREATMENT_SUMMARY being studied to quantify changes in lung water during the “recompensation” TR:TREATMENT_SUMMARY diuresis in the hospital and the related changes in alveolar gas conductance and TR:TREATMENT_SUMMARY breathing pattern to develop a predictive algorithm for likelihood of TR:TREATMENT_SUMMARY readmission, but also to obtain a better understanding of fluid regulation in TR:TREATMENT_SUMMARY the lungs. As these subjects are recruited, we will recruit age and sex matched TR:TREATMENT_SUMMARY stable HF patients going through similar testing in parallel running studies as TR:TREATMENT_SUMMARY well as age and sex matched control subjects. We will target 12 subjects per TR:TREATMENT_SUMMARY group and in addition to the EBC collection we will obtain saliva samples and TR:TREATMENT_SUMMARY blood at the same time points. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY EBC: Transfer 800μl aliquots of EBC samples into a 1.5ml microcentrifuge tubes SP:SAMPLEPREP_SUMMARY and dry down (lyophilize) each sample in a centrifugal vacuum evaporator for 4-6 SP:SAMPLEPREP_SUMMARY h. Apply no heating during the drying process. In the dried EBC samples add SP:SAMPLEPREP_SUMMARY 250μl of phosphate buffer and 250μl of 4mM TSP-d4 solution. Vortex for 20 s. SP:SAMPLEPREP_SUMMARY Transfer the solution to 5mm NMR tube. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE - CH:INSTRUMENT_NAME - CH:COLUMN_NAME - #ANALYSIS AN:ANALYSIS_TYPE NMR #NMR NM:INSTRUMENT_NAME Bruker 600 MHz Avance III HD spectrometer NM:INSTRUMENT_TYPE FT-NMR NM:NMR_EXPERIMENT_TYPE 1D-1H NM:SPECTROMETER_FREQUENCY 600 MHz #NMR_METABOLITE_DATA NMR_METABOLITE_DATA:UNITS uM NMR_METABOLITE_DATA_START Samples HF01 HF02 HF03 HF04 HF05 HF06 HF07 HF09 HF12 HF13 HF17 C10 C11 C14 C15 C16 C18 C19 C20 C21 C22 C23 C24 Factors factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:heart failure factor:control factor:control factor:control factor:control factor:control factor:control factor:control factor:control factor:control factor:control factor:control factor:control Acetate 73.8 193.8 47.7 123.9 142.2 80.6 64.2 67.7 57.6 19.6 179.7 69.4 201.4 203.1 40.1 183.7 290.8 55.8 33.4 199.4 152.5 132.3 168.6 Acetone 1.1 0.9 0.6 0 0.8 0.9 0 0.9 1.9 1.8 1 0 0.8 0 0.7 1.7 4.3 2 1.6 0 1.6 1.6 1.9 Ethylene glycol 4.5 3.7 2.4 7.2 2.6 2.1 3.8 1.8 1.7 1.6 0 4.2 2.7 0 1.4 2.3 0 3.1 1.4 0 3.7 1.9 6.7 Formate 36.2 19.5 19.7 53.6 26.6 17.1 27.5 17 21.9 18.7 0 25.8 24.2 45.5 22.6 55.7 59 19.3 17 44.5 51.1 26.3 48.9 Isopropanol 0 1.2 0.7 0 0 0.8 0 0 0.9 0 0 0 0 0 0.8 0 0 0 0 0 1.4 0 0 Lactate 4.3 3.3 3.1 10.6 49.7 20.4 5.7 3.2 4.4 4.2 11.3 19.9 7 0 6.9 4 43.2 7.6 4 91.2 4.4 5.2 141.1 Methanol 20.7 20.5 0 19.9 21 20.5 20.7 20.4 22.7 22.7 13 20.2 20.6 20.1 20.9 24.2 21.2 22.4 21.4 13.9 22.4 22.5 23.2 Propionate 12.1 43.8 4.2 8.3 15.4 14.7 4.8 14.1 7.9 0 0 0 55.8 54.7 5.1 17.9 43.7 7.2 0 26.1 17 21.5 22.6 Pyruvate 0 7.9 7.4 0 1.8 0 8.7 8.5 0 0 6.4 8.2 0 0 7.6 10.6 0 12.8 9.3 0 0 0 4.7 NMR_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Acetate Acetone Ethylene glycol Formate Isopropanol Lactate Methanol Propionate Pyruvate METABOLITES_END #END