Digestive System Diseases

Symptoms and General Pathology

All Conditions

Neoplasms

Liver Cirrhosis

Carcinoma

Carcinoma, Hepatocellular

Liver Diseases

Fibrosis

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

Healthy Controls with or without risk factors for Chronic Liver Disease (i.e. patients referred due to concerns re: liver disease but found to have no evidence of chronic liver disease following assessment)

Patients with evidence of Liver Fibrosis on the basis of current diagnostic techniques / expert opinion.

Patients with evidence of Compensated Cirrhosis on the basis of current diagnostic techniques / expert opinion.

Patients with evidence of Decompensated Cirrhosis on the basis of current diagnostic techniques / expert opinion.

Patients with evidence of Hepatocellular Carcinoma on the basis of current diagnostic techniques / expert opinion.

Participants will be asked to provide 500mls of exhaled breath which will be loaded on to thermal desorption tubes and analysed via Mass Spectrometry.

Breath Analysis

Michael J Hewitt, MBBS BSc

Michael J Hewitt, MBBS

George B Hanna, FRCS

This study aims to determine whether a breath test could be used for early detection of hepatic fibrosis, cirrhosis or hepatocellular carcinoma.

Patients who are attending for a planned liver outpatient services or investigations will be approached to provide a breath sample.

Multi platform mass spectrometry analysis will be performed to establish volatile biomarkers that can discriminate between fibrosis, cirrhosis and hepatocellular carcinoma.

Volatile organic compound (VOCs) emitted from the human body have been of interest to researchers for several decades. In 1971, Pauling et al reported that breath and urine contained approximately 250 and 280 VOCs respectively in normal human subjects. VOCs are traditionally measured in food industry and counter-terrorism. Routine clinical applications include the alcohol breathalyser, 13-C urea breath test for H. pylori, nitric oxide in asthma, and hydrogen/methane test for bacteria overgrowth.

Preliminary work has suggested that there is alteration in the VOC profile of patients with liver disease. It is suggested that as fibrosis increases, liver function is impaired, resulting in increased levels of certain compounds. These compounds are then present at higher levels within the blood stream and when they reach the lungs, they are exhaled. There has also been work demonstrating a change in the profile of VOCs within cancers, demonstrating specific "breath signatures" in patients with oesophageal cancer. At Imperial College London, Marker et al have developed a breath test as screening test for oesophageal cancer with comparable sensitivity and specificity to other screening methods (e.g. faecal occult blood testing). The investigators would aim to achieve similar with hepatobiliary disease via a prospective cross-sectional study aimed at determining the diagnostic accuracy of exhaled breath volatile organic compounds (VOC) for the detection of liver disease.

Patients will be recruited from outpatient clinics and hospital wards based across Imperial College Healthcare Trust. They may also be recruited from the radiology department when attending for liver biopsies or hepatocellular carcinoma surveillance ultrasound scans. When attending for their appointment, a member of the research team will discuss the research project with the patient, explain that is requires the patient to provide a breath +/- urine sample. Patients will be provided with a patient information leaflet. If the patient is to agree to this, they will be asked to sign a written consent form. If a recent PHES test has not been performed, one will be conducted otherwise no additional investigations, invasive or otherwise will be required of the patients.

For patients under regular follow up within the trust, they may be asked to consent to further breath samples being taken at future appointments to facilitate longitudinal follow up. Patients will be entitled to withdraw at any point.

Patients attending for endoscopy, fibroscan or liver biopsy will have been nil by mouth for 4-6 hours prior to the procedure as per local guidelines. For those attending outpatient appointments, if identified prior to their appointment by their clinical team, the investigators will aim to contact the patients and request that they fast. Should they not be fasted, they may be asked to perform basic oral hygiene techniques (e.g. rinsing mouth with water), prior to the breath sample being taken. A food diary of the preceding 24 hours will be taken as part of the pre-sampling questionnaire.

As part of the consent process, patients will also be asked permission to access their hospital records for the purpose of the research study only, including their blood tests, radiology and pathology results. All data will be anonymised and all hospital records shall be handled with strict confidentiality in accordance with the Data Protection Act 1998 and the General Data Protection Regulation (GDPR).

Patients will be asked to give a number of exhalations into a breath sampling device until a defined volume of breath has been sampled. This may be done via one of several techniques. The investigators preferred option is that they breathe into a custom designed nalophan bag which is attached to thermal desorption tubes and a breath sampling device. Alternatively, patient may be asked to perform normal tidal breathing whilst wearing a face mask, which takes around 2 minutes on average. Patients located at St Mary's Hospital may also be asked to breathe directly into a mass spectrometer machine (SYFT Voice200Ultra). This mass spectrometer instrument is a self-contained mobile device which can be moved between clinical areas within St Mary's Hospital. Sampling by this method will involve a single deep nasal inhalation followed by complete exhalation via their mouth into a plastic cylinder connected to a tube leading to the mass spectrometer itself. This is repeated three times within a 60 second window. The investigators expect the breath sampling process to take no longer than 5-10 minutes in total. Patients will be requested to pass urine into a standardised 60ml urine specimen vial, which will be immediately sealed. 20ml of urine will be aliquoted into a standard 60ml specimen vial.

The VOCs from the breath will be trapped onto adsorbent tubes inserted into the breath taking device. After sampling the adsorbent tube is removed from the device, capped and transported back to the laboratory at St Mary's Hospital London for analysis. Samples will be transported by courier or by a member of the research team. The sample(s) shall undergo analysis via mass spectrometry instruments, at St Mary's Hospital London.

Breath VOCs sampled on adsorbent tubes will be analysed within 48 hours of collection. The sample constituents are destroyed within the mass spectrometer for detection meaning that no clinical material will remain after analysis by the mass spectrometry instruments. Urine samples will be stored within a registered tissue bank in accordance with the Human Tissue Act and disposed of following analysis.

As part of the study, the investigators will aim to follow patients up longitudinally to ascertain if a participant's VOC profile changes with progression or regression of liver disease. At each appointment, before sample is taken, the participant's consent will be reviewed and if the participant is still willing to continue in the study, further breath and urine samples will then be collected. This would be for a maximum of 24 months.

Breath VOCs sampled on adsorbent tubes will be analysed within 48 hours of collection. The sample constituents are destroyed within the mass spectrometer for detection meaning that no clinical material will remain after analysis by the mass spectrometry instruments. Urine samples will be stored within a registered tissue bank (REC Ref no. 04/Q0403/119, custodian Prof G Hanna) in accordance with the Human Tissue Act and disposed of following analysis.

Volatile Organic Compounds for the Assessment of Liver Disease

Volatile Organic Compounds for the Assessment of Liver Disease: Assessment of Hepatobiliary Disease Through Non-Invasive Detection of Exhaled Volatile Organic Compounds

Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of fibrosis / cirrhosis / hepatocellular carcinoma. Sensitivity and specificity values are represented by a number between 0 to 1 indicating the test's ability to pick up true positive results and true negative results respectively, where a number closer to one indicates a greater detection ability.

Imperial College London

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Participants will provide two breath samples by exhaling into the breath sampling apparatus and complete the Medical Questionnaire (medications, lifestyle, demographics, smoking history) and survey (lung health). Information related to LC diagnosis (histologic sub-type, tumor stage) will be collected.

Participants will provide two breath samples by exhaling into the breath sampling apparatus and complete the Medical Questionnaire (medications, lifestyle, demographics, smoking history) and survey (lung health).

Ali Mahtabifard, MD

The aim of this study is to sample and analyze volatile organic compounds (VOCs) from lung cancer patients and individuals without lung cancer ("healthy" controls). The breath sample analysis will help investigators describe and identify profiles of VOCs found in the breath of patients with lung cancer when compared to normal breath profiles using infrared spectroscopy. This work will help validate early proof of concept results conducted with prototype technology and later stage NSCLC breath samples, and inform future breath testing analysis.

Globally, lung cancer accounts for the most cancer deaths in both sexes combined. It is believed to develop slowly through progressive accumulation of genetic mutations, hence the disease allows time for diagnosis and curative surgical treatment. Five year survival rates for non-small-cell lung carcinoma (NSCLC) can range from 57-61% when detected in the early stages of disease. This is compared with a survival rate of approximately 6% once distant metastases are present. However, disease diagnosis typically occurs when it has progressed to an advanced stage when patients present with signs and symptoms. Therefore, technologies capable of asymptomatic disease detection will significantly impact lung cancer specific mortality. Metabolomic profiling of cancer measures compounds produced as a result of cellular activity including volatile organic compounds (VOCs) in exhaled breath. Infrared spectroscopy is a proven technique for breath analysis that can measure chemical concentrations in the parts per trillion range for certain VOCs. When coupled with machine learning techniques, this has the potential to be a novel approach for disease detection using exhaled breath.

Breath Analysis in Early Stage Lung Cancer Using Infrared Spectroscopy

Analysis of Volatile Chemicals in the Breath of Lung Cancer Patients Using Infrared Spectroscopy

VOC spectral profiles will be compared between cohorts to identify statistical differences.

University of California, Irvine

Picomole Inc

High-risk for lung cancer population who meet the USPSTF eligibility. One 10-L breath sample will be collected from each subject. During breath collection, subjects will be asked to exhale into a portable breath sampling device through a single use filter. Subjects will not be contacted to donate additional/serial breath specimens after the initial breath samples. Subjects will fill out a medical questionnaire and medical records will also be reviewed to extract low-dose CT scan (LDCT) screening results and any additional tumour-related information including histologic subtype, tumor stage, and sites of disease.

Kyle Chapman, MD

The aim of this study is to sample and analyze volatile organic compounds (VOCs) from a high-risk population of subjects eligible for lung cancer screening as defined by the US Preventive Services Task Force (USPSTF) guidelines. The breath sample analysis will help investigators describe and identify real-world breath profiles from individuals at high risk of developing lung cancer and to use this to test machine learning (ML) algorithms for lung cancer screening. This study will also evaluate the feasibility and usability of Picomole's breath sampling technology in a mobile platform.

with lung cancer when compared to normal breath profiles using infrared spectroscopy. This work will help validate early proof of concept results conducted with prototype technology and later stage NSCLC breath samples, and inform future breath testing analysis.

Lung cancer is the most common malignancy in the world in terms of both incidence and mortality (1.1 million new cases per year and 0.95 million deaths in males and 0.51 million new cases per year and 0.43 million deaths in females). The highest rates of lung cancer are found in Europe and North America. In addition, lung cancer is the leading cause of cancer death in Canada. Lung cancer is believed to develop slowly via a progressive accumulation of genetic mutations, hence the disease allows time for diagnosis and curative surgical treatment. When detected in the early stages, the 5-year survival rate for NSCLC is 57% to 61%, compared with a survival rate of approximately 6% once distant metastases are present. Unfortunately, most patients do not experience any signs or symptoms of lung cancer until the disease has progressed to an advanced stage. Therefore, technologies that facilitate detection of lung cancer in the earliest asymptomatic stages have significant potential to reduce lung cancer-specific mortality.

Malignant transformation is facilitated by deregulation of fundamental cellular processes, including alterations in metabolism. Thus, metabolomic profiling may be a promising strategy for identifying lung cancer before it is detectable via conventional methods such as CT scans. Breathomics is a field of study dedicated to deconstructing the metabolomic profile or biological components of volatile organic compounds (VOC) in breath. To date, various analytical techniques including gas chromatography combined with mass spectrometry, ion mobility spectrometry, proton transfer reaction spectrometry, and selected ion flow tube mass spectrometry have been used to study breath VOCs. In a recent study, ion mobility spectrometry discriminated between lung cancer and chronic obstructive lung disease with 79% accuracy, 76.8% sensitivity, and 85.7% specificity. Furthermore, breath analysis can be used to not only identify lung cancer but also distinguish between lung cancers with particular somatic mutations. For example, electronic nose technology demonstrated 79% and 85% sensitivity and specificity, respectively, for identifying EGFR-mutant lung cancer. These studies suggest that breath analysis is a highly sensitive and specific approach to detecting lung cancer.

This study will evaluate the performance characteristics of infrared spectroscopy for breath analysis. The spectrometer used to analyze breath gases is optimized to measure chemical concentrations down to the parts per trillion range. In a pilot study of 165 (67 newly diagnosed Non-Small Cell Lung Cancer (NSCLC) subjects which used infrared spectroscopy to analyze breath specimens from subjects with lung cancer and subjects without cancer, sensitivity and specificity for detecting lung cancer was 88.7% and 80%, respectively, with an accuracy of 86%. These preliminary results compare very favorably to mass spectrometry (the analytical platform that has been used in most breath analysis studies).

This study will analyze breath VOCs from 300 subjects who meet the USPSTF eligibility guidelines for lung cancer screening. The study aims to better understand the VOC breath profiles in a larger group of subjects at high risk for developing lung cancer. By restricting the population to screen-eligible subjects, this study will approximate the potential future "real world" use of this screening strategy and better approximate its utility in the field, sampling high risk populations in rural settings. It is envisioned that this study will generate preliminary data that will inform the performance of machine learning algorithms developed to detect the presence of lung cancer in unselected populations.

Volatile organic compounds (VOC) in breath are organic chemicals that are diffused or suspended at a room temperature. Breath samples will be collected into sorbent tubes that will be placed immediately (within ten minutes) after collection and stored in a freezer maintained at -1 to -10 degrees Fahrenheit and shipped on to Picomole headquarters for volatile chemical analysis using infrared spectroscopy.

Analysis of Volatile Chemicals in Lung Cancer Screen-Eligible Subjects Using Infrared Spectroscopy

VOC spectral profiles will be compared between cohorts to identify statistical differences

West Virginia University

Anti-Infective Agents

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Bacterial Agents

Bleomycin

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Methotrexate

Melphalan

Lomustine

Ifosfamide

Antibiotics, Antitubercular

Busulfan

Thiotepa

Carmustine

Carbon Monoxide

Isophosphamide mustard

All lung function tests are non-invasive and last about 60 minutes per child:

* Multiple Breath Washout: The nitrogen multiple-breath-washout test (N2MBW) measures ventilation inhomogeneity of the lung that occurs when smaller airways are damaged.
* Spirometry/Bodyplethysmography/DLCO: Spirometry measures dynamic air flows to quantify airway obstruction of large airways and pulmonary restriction. Plethysmography assesses static lung volumes. Diffusing capacity of the lung for carbon monoxide (DLCO) evaluates diffusion deficits.

Lung function measurements

Patients will exhale into a secondary electrospray-ionization-mass spectrometry (SESI-MS) breath analysis platform. SESI-MS allows real-time breath-printing by detection of both volatile and non-volatile trace components.

Functional MRI scan assessing regional fractional lung ventilation and relative perfusion, followed by a morphological MRI scan. This technique allows simultaneous assessment of all affected lung components, the airways, alveoli and pulmonary vasculature.

Magnetic resonance imaging (MRI)

Short questions on current airway symptoms, recent colds, exercise-related respiratory symptoms, and passive smoking exposure will be assessed. The interview takes about 10 minutes.

Standardized interview to assess respiratory symptoms

Assessment of clinical parameters and cumulative doses to chemotherapy, radiation, surgery and hematopoietic stem cell transplantation (HSCT). Data on cumulative doses of pulmotoxic chemotherapy (carmustine, lomustine, busulfan, bleomycin, methotrexate and cyclophosphamide, fludarabine, ifosfamide, melphalan and thiotepa) and radiation therapy at the region of the chest from patient's hospital charts will be collected. Information on chest wall and lung surgery will be retrieved from the surgical reports. Information about conditioning regimens including cumulative chemotherapy doses and total body irradiation of patients undergoing HSCT will be collected. Further information on the health state of the patient and interventions (e.g. development of pneumonia, antibiotic treatment) will be collected from the hospital charts.

Data collection for assessment of clinical parameters and cumulative doses to chemotherapy, radiation, surgery and HSCT

Germline DNA is collected (e.g. through saliva or buccal cell sampling) for later analysis on genetic risk factors for pulmonary complications.

Collection of genetic samples

Jakob Usemann, PD Dr. med.

Christine Schneider

Nicolas Von der Weid, Prof. Dr. med.

Christina Schindera, Dr. med.

Jochen Roessler, Prof. Dr. med.

Christine Schneider, Dr. med.

Philipp Latzin, Prof. Dr. med.

Marc Ansari, Prof. Dr. med.

Manuel Diezi, Dr. med.

Laura Crosazzo, Dr. med.

Sylvain Blanchon, Dr. med.

Jean- Pierre Bourquin, Prof. Dr. med.

Alexander Moeller, Prof. Dr. med.

This longitudinal, prospective, multicentre study is to monitor lung function prospectively in childhood cancer patients after diagnosis. The impact of cancer treatment on pulmonary dysfunction non-invasively using lung function, lung imaging and breath analysis as well as clinical symptoms using a questionnaire will be assessed at different time points.

For study participants who signed further the general consent form, biological materials and health-related data will be coded and stored in a secure biobank/database (BaHOP). The biological material and genetic data are kept in the BaHOP biobank for an indefinite period of time for further, until now not defined research questions.

Early Pulmonary Dysfunction in Childhood Cancer Patients

Prospective Multicentre Cohort Study of Early Pulmonary Dysfunction in Childhood Cancer Patients (SWISS-Pearl Study)

Dynamic lung function parameter: Forced expiratory volume in 1 second (FEV1)

Dynamic lung function parameter: ratio of FEV1/forced vital capacity (FVC) for airway obstruction

Static lung function parameter: total lung capacity (TLC) to assess lung restriction

Static lung function parameter: residual volume (RV)/TLC to assess hyperinflation

Global ventilation inhomogeneity assessed by lung clearance index (LCI)

Functional MRI: the primary outcome of functional lung imaging is the percentage portion of the lung volume with impaired ventilation or perfusion.

Change in lung morphology assessed by MRI (description of structural changes: ground glass changes, thickened septal lines, interstitial infiltrates, diffuse alveolar infiltrates, haemorrhage, focal consolidation, fibrosis, pulmonary hypertension, pleural effusion, nodular changes, vasculitis (wall thickening) and thrombosis will be assessed)

Breath analysis: 4-hydroxy-2-nonenal is regarded as a surrogate marker for oxidative stress in the human body.

Untargeted explorative approach to assess volatile organic compounds (VOCs) in exhaled breath

Genetic variants associated with susceptibility to cancer therapy or related to lung development. Assessed in the Germline DNA Biobank Switzerland for childhood cancer and blood disorders (BISKIDS, as part of the Paediatric Biobank for Research in Haematology and Oncology \[BaHOP\], ethics approval PB_2017-00533 to assess genetic determinants of pulmonary toxicity.

University Children's Hospital Basel

Multiple Pulmonary Nodules

Solitary Pulmonary Nodule

Antibodies

Autoantibodies

Immunoglobulins

Douglas W Johnson, MD

Recent studies have shown that low-dose chest CT scans can detect lung cancers in high-risk populations (age \>50yo, \>30 pack-years of tobacco use), and can lower cancer mortality. Unfortunately, the vast majority of "positive" findings on these CT scans are benign (\>95%). Currently, an inordinate amount of expensive follow-up testing is required for these patients to try to prove who among them truly has a cancer.

Several new emerging non-invasive and potentially cheaper tests are now being investigated to help differentiate patients with cancers versus just benign lung nodules. These new tests include a new type of sputum analysis, a breath analysis, a blood test measuring certain tumor markers, a blood test looking for auto-antibodies, and a standard PET/CT scan. Each of these tests have different sensitivity and specificity rates when looking for lung cancer, and it is unclear which test is best.

This study will employ a panel of all 5 of these non-invasive tests on an initial cohort of 50 patients with recently diagnosed lung cancer to try to measure the sensitivity of the tests. A follow-on study will then perform the same panel of tests on 300 lung nodule patients to see which test, or combination of tests, gives the best overall accuracy in terms of predicting who really has lung cancer. It is hoped that the use of such a panel could lead to dramatically decreased need for expensive and morbid invasive testing for this population.

The study revolves around specifying the exact signatures and accuracy associated with discriminating between benign and malignant SPNs for each of the biomarkers in the specific high risk cohort under the NLST screening protocol. To help identify and quantify these signatures, we will evaluate specifically the volatile signature in the exhaled breath, the accuracy of LuCED sputum detection, the profile of tumor markers and the specifications of auto-antibodies through immunoassays and Orbitrap technology, and the PET/CT in patients already diagnosed with lung cancer.

Non-Invasive Biomarkers For Early Detection Of Lung Cancers

NON-INVASIVE BIOMARKERS FOR EARLY DETECTION OF LUNG CANCERS: ELEMENT 1: NON-RANDOMIZED PHASE II EVALUATION AND VALIDATION IN NEWLY DIAGNOSED LUNG CANCER PATIENTS

Douglas W. Johnson MD, FACR

Principal Investigator

Rare Diseases

Esophageal Neoplasms

Stomach Neoplasms

Barrett Esophagus

Head and Neck Neoplasms

Esophageal Diseases

Precancerous Conditions

Esophageal Cancer

Stomach Cancer

Participants with gastroesophageal cancer providing a breath and blood sample for biomarker identification

Participants with Barrett's esophagus providing a breath and blood sample for biomarker identification

Healthy controls providing a breath and blood sample for biomarker identification

Detection of proteins and volatile organic compounds (oncometabolites) in the exhaled breath

Breath analysis

Detection of proteins and circulating tumor DNA (oncometabolites) in the peripheral blood

Blood analysis

Stijn Vanstraelen, MD

Philippe Nafteux, MD, PhD

The goal of this minimally invasive interventional study is to learn if oncometabolic biomarkers, detected in the exhaled breath and blood can identify early-stage gastro-oesophageal cancer in patient at risk for gastro-oesophageal cancer.

The main questions this study aims to answer:

Are oncometabolites proficient and reproducible enough to function as diagnostic biomarkers? Can these biomarkers identify early-stage gastro-esophageal cancer? Researchers will compare participants with gastro-oesophageal cancer to healthy controls and participants with Barrett's esophagus to detect meaningful differences between the groups.

Participants will provide a breath and blood sample during their routine standard of care visits.

Participants with gastro-esophageal cancer, participants with Barrett's esophagus and Healthy controls will be monitored in parallel to identify oncometabolic biomarkers related to cancer

Molecular Assessment for Gastro-Esophageal Cancer

Data will be shared upon reasonable request with the principal investigator.

Identify the concentrations of cancer-related metabolites (oncometabolites) in the exhaled breath and blood compared to healthy controls

Distinguish early-stage gastro-oesophageal cancer from Barrett's esophagus and healthy controls based on sensitivity, specificity and accuracy of the oncometabolite concentration

Predict and assess therapy response prior to surgery, based on sensitivity, specificity and accuracy of the oncometabolite concentration

Assess changes in the concentrations of the oncometabolites related to treatment.

Predict and assess recurrence, based on sensitivity, specificity and accuracy of the oncometabolite concentration

KU Leuven

Principal investigator

Infections

Nervous System Diseases

Communicable Diseases

Apnea

Sleep Apnea Syndromes

Lung Diseases, Interstitial

Pleural Neoplasms

pulmonary disorders with pleural infusions

Michael Westhoff, MD

Patric Litterst, MD

Recognition of disease specific clusters of volatile organic compounds in patients with different lung diseases, using breath analysis with ion mobility spectrometry. Lung diseases of interest are:

* COPD
* tumors
* airway infection
* interstitial lung disease
* sleep apnea Hypothesis: Breath analysis with ion mobility spectrometry can differentiate pulmonary disorders.

Recruitment of patients with different lung diseases goes on. First sub-group analysis of patients with COPD,lung cancer and sarcoidosis is done in order to create a training set of VOC-clusters for further validation in a bigger population of patients.

breath, pleural fluid (only in patients with therapeutic pleurocentesis)

Breath Analysis by Ion Mobility Spectrometry

Detection of Clusters of Volatile Organic Compounds (VOC)in Patients With Different Lung Disorders by Ion Mobility Spectrometry. Different Clusters of VOC in the Diagnosis of Different Lung Disorders Using Ion Mobility Spectrometry

Lung Clinic Hemer

Dr. Michael Westhoff

Ulcer

Stomach Diseases

Stomach Ulcer

Hu Liu, M.D.

The investigators study the feasibility of a novel method in oncology based on breath analysis with a nanosensors array for identifying gastric diseases. Alveolar exhaled breath samples collected from volunteers referred for upper endoscopy or surgery are analyzed using a custom-designed array of chemical nanosensors based on organically functionalized gold nanoparticles and carbon nanotubes. Predictive models are built employing discriminant factor analysis (DFA) pattern recognition method. Classification accuracy, sensitivity and specificity are determined using leave-one-out cross-validation or an independent blind test set. The chemical composition of the breath samples is studied using gas chromatography coupled with mass spectrometry (GC-MS).

A pilot study is conducted first (enlistment of 160 subjects at the Department of Oncology, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.)

The pilot study is followed by a large-scale clinical trial to confirm the preliminary results of the Chinese pilot study (enlistment of 800 subjects at the Digestive Diseases Centre GASTRO, Riga East University Hospital, 6 Linezera iela, LV1006 Riga, Latvia). 25% of the samples are used as independent blind test set. The samples are blinded by the medical team and are not disclosed until prediction of blind sample identity is complete.

To further prove the diagnosis of GC from exhaled breath and seek the interrelationship among Breathomics, metabolomics and transcriptomics, saliva samples from about 200 patients are collected from volunteers referred for upper endoscopy or surgery are analyzed using Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Simultaneously, RNA sequencing are preformed on gastric cancer tissue samples and paracancerous tissue samples collected from same group of volunteers. The data of salivary metabonomics and transcriptomics were integrated and analyzed on the on Kyoto Encyclopedia of Genes and Genomes to confirm the diagnostic validity of salivary metabonomics.

Number of patients that will have a definitive diagnosis and Alveolar exhaled breath samples collected from individuals with Tedlar® bags (Keika Ventures, LLC) after endoscopy.. Two breath samples were collected from each person tested.

Two-bed sorption tubes filled with the following sorbents were used as traps for sample collection with simultaneous preconcentration: 100mg matrix Tenax TA and 50mg matrix Tenax TA (35-60 mesh; purchased from Supelo, Bellefonte, PA). Sorbents were separated by glass wool. The samples were collected at a total flow through sorption trap of 200ml/min.

One sample was used for analysis with the nanosensors array, and the other sample was used for Gas Chromatography coupled with Mass Spectrometry (GC-MS) analysis.

Cancer tissue and paracancerous tissue samples were collected in the process of surgical resection. After collection in the operating room, the samples were immediately placed in - 5 ℃ dry ice and transferred to the laboratory. Then, the samples were frozen in liquid nitrogen for 30 minutes, and then placed in - 80℃ freezer for cold storage. After that, the samples were divided into several batches and transported in dry ice for subsequent transcriptome analysis. All the saliva samples were collected using 2ml cryopreservation tube during early morning before surgery or endoscopic resection. The patient had been told not to eat after 22 o'clock the night, and not to drink water, smoke, brush teeth or exercise violently one hour before the collection. The saliva samples were sealed in the -80 C refrigerator after collection and then transported in a foam box equipped with dry ice, followed by UHPLC-MS analysis.

exhaled breath of volunteers; saliva; tissue

Diagnosis of Gastric Lesions From Exhaled Breath and Saliva

Study of the Exhaled Breath and Salivary Metabolites of Patients With Malignant or Benign Gasctric Lesions

Salivary samples collected from 200 subjects referred for upper endoscopy or surgery are analyzed using Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Predictive models are built employing discriminant factor analysis (DFA). Classification accuracy, sensitivity and specificity were determined using leave-one-out cross-validation.

Data from breathomics, salivary metabonomics and transcriptomics are integrated to seek the proof of breath diagnosis at different levels.

Proof-of-concept:

Alveolar exhaled breath samples collected from 160 subjects referred for upper endoscopy at The First Affiliated Hospital of Anhui Medical University are analyzed using a custom-designed array of chemical nanosensors. Predictive models are built employing discriminant factor analysis (DFA). Classification accuracy, sensitivity and specificity were determined using leave-one-out cross-validation. The chemical composition is studied using gas chromatography coupled with mass spectrometry (GC-MS).

Confirmation of proof-of-concept:

Alveolar exhaled breath samples collected from 800 subjects referred for upper endoscopy at Riga East University Hospital are analyzed as was used in the pilot study. Predictive models are built as in the pilot study,using a training set of only 75% of the samples. Classification accuracy, sensitivity and specificity are determined using an independent blind test set (25% of the samples)

Specifically, to compare the VOCs that distinguish between malignant and benign gastric lesions in the Chinese and Latvian cohorts. The cohorts from China and Latvia are matched in terms of sample size, gender ratio, average age, and smoking habits.

Technion, Israel Institute of Technology

University of Latvia

Anhui Medical University

Associated Professor

These are the participants with identified stage 1 lung cancer.

These are participants who have similar clinical characteristics as our cases, but do not have any history of cancer.

These are housemates of the participants with stage 1 lung cancer (cases).

Breath will be analyzed in all three groups using gas chromatography mass spectrometry.

Lonny Yarmus, DO

This study will evaluate exhaled volatile organic compounds (VOC's) in the breath of participants with stage 1 lung cancer, their house-mates, and matched controls. The goal of the study is to identify VOC fingerprints that are only detectable in those with stage 1 lung cancer.

Lung cancer is by far the leading cause of cancer death in the United States. More people die annually of lung cancer than of colon, breast, and prostate cancers combined. Worldwide it is already the leading cause of cancer death among males, and with smoking rates substantially higher in developing countries relative to the United States the worldwide burden of lung cancer is projected to increase considerably in the future.

For lung cancer, as for many cancers, early diagnosis allowing for full resection offers the greatest chance for long-term survival, but unfortunately these individuals currently constitute only a minority of the lung-cancer population. Screening technologies that allow for the earliest detection of lung cancer would therefore have tremendous potential to substantially improve outcomes. Recently, and for the first time, a screening test for lung cancer of high risk individuals has been recommended by the US Preventive Services Task Force, as well as others, for the reduction of lung cancer mortality. This recommendation was based primarily on the results of the National Lung Screening Trial (NLST) that randomized over 53,000 individuals considered at high risk for lung cancer to 3 annual screenings with either low-dose CT (LDCT) or a chest x-ray and then followed for a median of 6.5 years. In this study LDCT scanning was associated with a statistically significant 20% relative decrease in lung cancer mortality, and a smaller, but still significant 6.7% decrease in overall mortality. Despite these encouraging results of LDCT, as a screening tool it has substantial limitations. Beyond the costs, inconvenience and radiation exposure associated with LDCT, its performance characteristics are far from optimal. For example, nearly a quarter of the LDCT population had a positive screening test, with the vast majority - 96.4% - proving to be false-positive. With a positive predictive value of \<4% LDCT screening will lead to a great number of unnecessary diagnostic procedures as well as substantial anxiety in the screened population and their family.

Breath analytics is a new and very promising tool for diagnosing lung cancer, as well as multiple other conditions. Previous studies identified that dog's heightened olfactory senses were able to detect cancer in an individual's breath with an accuracy of nearly 100%. Since then attempts have been made to mimic canine capabilities with "electronic noses" to detect and quantitate the nearly 3000 compounds, many in the parts per billion or even parts per trillion ranges, in exhaled breath. Early studies of these technologies support great potential as a diagnostic and screening tool. As a screening tool it could be ideal as it is noninvasive, painless and free of any undesirable side effects. In addition, new advances in nanotechnology have allowed these extremely sensitive detection technologies to be miniaturized to the point that they can be linked to a smartphone, providing future possibilities to almost continuously surveil individuals for the development of lung cancer and other life-threatening conditions. This study is concerned with comparing the concentrations of volatile organic compounds (VOCs) in the breath of lung cancer patients (cases) and lung-cancer-free individuals (controls).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Volatile Organic Compounds for the Assessment of Liver Disease	NCT04620538	Cirrhosis Cirrhosis, Live... Fibrosis, Liver Hepatocellular ... Hepatocellular ...	Breath Analysis	18 Years - 90 Years	Imperial College London
Breath Analysis in Early Stage Lung Cancer Using Infrared Spectroscopy	NCT04556435	Lung Cancer Non Small Cell ...		18 Years -	Picomole Inc
Analysis of Volatile Chemicals in Lung Cancer Screen-Eligible Subjects Using Infrared Spectroscopy	NCT05174468	Lung Cancer		50 Years - 80 Years	Picomole Inc
Early Pulmonary Dysfunction in Childhood Cancer Patients	NCT05427136	Pulmonary Dysfu...	Lung function m... Breath Analysis Magnetic resona... Standardized in... Data collection... Collection of g...	4 Years - 22 Years	University Children's Hospital Basel
Non-Invasive Biomarkers For Early Detection Of Lung Cancers	NCT01580332	Lung Cancer		18 Years -	Baptist Cancer Institute
Volatile Organic Compounds for the Assessment of Liver Disease	NCT04620538	Cirrhosis Cirrhosis, Live... Fibrosis, Liver Hepatocellular ... Hepatocellular ...	Breath Analysis	18 Years - 90 Years	Imperial College London
Molecular Assessment for Gastro-Esophageal Cancer	NCT06346054	Esophageal Canc... Gastric Cancer Barrett Esophag...	Breath analysis Blood analysis	18 Years - 100 Years	KU Leuven
Analysis of Volatile Chemicals in Lung Cancer Screen-Eligible Subjects Using Infrared Spectroscopy	NCT05174468	Lung Cancer		50 Years - 80 Years	Picomole Inc
Breath Analysis by Ion Mobility Spectrometry	NCT00632307	Lung Diseases		18 Years - 90 Years	Lung Clinic Hemer
Breath Analysis in Early Stage Lung Cancer Using Infrared Spectroscopy	NCT04556435	Lung Cancer Non Small Cell ...		18 Years -	Picomole Inc
Diagnosis of Gastric Lesions From Exhaled Breath and Saliva	NCT01420588	Stomach Disease...		18 Years - 75 Years	Anhui Medical University
NanoSpectrometer Biomarker Discovery and Confirmation Study	NCT03275688	Lung Cancer	Breath Analysis	18 Years -	Johns Hopkins University
Early Pulmonary Dysfunction in Childhood Cancer Patients	NCT05427136	Pulmonary Dysfu...	Lung function m... Breath Analysis Magnetic resona... Standardized in... Data collection... Collection of g...	4 Years - 22 Years	University Children's Hospital Basel

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