Assessment of an Exhaled Breath Test to Detect Bronchiectasis

Assessment of an Exhaled Breath Test Using High-Pressure Photon Ionization Time-of-Flight Mass Spectrometry to Detect Bronchiectasis

To investigate whether the breath test is able to detect bronchiectasis using breathomics. This study was conducted with a prospective specimen collection, evaluator-blinded, case-controlled clinical study designed to evaluate the accuracy of breathomics to diagnosis of bronchiectasis in adults.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis
• Intervention / Treatment: Diagnostic test: An exhaled breath test

Detailed Description

Bronchiectasis is a chronic airway inflammation with irreversible expansion of bronchial walls, which is characteristic by chronic cough, mucinous sputum, dyspnea and wheezing. High resolution CT (HRCT) combined with clinical manifestations is the main diagnostic method of bronchiectasis, but HRCT is expensive and radioactive. Therefore, it is urgent to develop a new technology to diagnose bronchiectasis. Exhaled breath may be a better tool for bronchiectasis detection because of its noninvasive nature. Many efforts have been made to develop breath tests for lung cancer, asthma and Helicobacter pylori infection. However, little studies pay attention to bronchiectasis. High-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) is a promising tool for breath testing, because it is highly sensitive, does not require pretreatment of exhaled breath, and holds great tolerance for humidity. In our case-control diagnostic study, we investigated whether a breath test combining HPPI-TOFMS and a support vector machine (SVM) algorithm was able to distinguish patients with bronchiectasis from control individuals.

• Study Type: Observational
• Enrollment (Actual): 544

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The age of all subjects were all older than 18 . The study population was recruited from Shanghai pulmonary hospital. Diagnosis of bronchiectasis was performed using chest HRCT scans in suspected patients with coughing and expectoration, or long durations of haemoptysis. Idiopathic bronchiectasis patients with acute exacerbation were included in the study. Healthy participants (HC) and unhealthy participants(UHC) were as control.

Description

Inclusion Criteria:

BE Patients were recruited according to the following inclusion criteria: (1) Age>18 years; (2) the diagnosis of BE was according to European Respiratory Society guidelines for the management of adult bronchiectasis; (3) Willing to join in and sign the informed consent form.

Healthy control subjects were recruited according to the following inclusion criteria:(1) Age>18 years; (2) No history of any lung disease (according to pulmonary imaging and physical examinations); (3) Willing to join in and sign the informed consent form.

Unhealthy control subjects were recruited according to the following inclusion criteria: (1) Age>18 years; (2) The diagnosis of ILD was according to HRCT and clinical symptoms by two experts' consensus; (3) The diagnosis of Sarcoidosis (SA) was according to American Thoracic Society Clinical Practice Guideline;(4) Willing to join in and sign the informed consent form.

Exclusion Criteria:

(1) Patients combined with serious comorbidities (chronic renal failure, hepatic disease, etc.); (2) Patients who are diagnosed with asthma, pneumonia, malignant tumor, and COPD; (3) Women who are pregnant or preparing for pregnancy or breastfeeding; (4) Participated in other clinical trials within three months; (5) Refused to join in and sign the informed consent form.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult patients with bronchiectasis (BE); Diagnosis of bronchiectasis was performed using chest HRCT scans in suspected patients with coughing and expectoration, or long durations of haemoptysis. High-resolution images were obtained during full inspiration at 1-mm collimation and 10-mm intervals from the apex to the base of the lungs. The presence of bronchiectasis was confirmed based on the following criteria: 1) lack of tapering in the bronchi; 2) dilation of the bronchi where the internal diameter was larger than that of the adjacent pulmonary artery; or 3) visualisation of the peripheral bronchi within 1 cm of the costal pleural surface or the adjacent mediastinal pleural surface.	Diagnostic test: An exhaled breath test; All exhaled breath samples were collected by trained investigators following the same protocol. All participants fasted for at least 6 hours before breath collection. To reduce potential confounding factors, all participants were asked to not ingest spicy food, alcohol, or coffee the night before exhaled breath collection. Exhaled breath was collected in Tedlar air bags (DuPont de Nemours). The night before breath collection, the Tedlar bags were baked at 60 °C for 3 hours to fully release possible contaminants and continuously purged with high-purity nitrogen 4 times. Participants first gargled with pure water and then performed a single deep nasal inhalation followed by complete exhalation via their mouth into Tedlar bags. A total of 1000 mL of exhaled breath was collected from each participant. Breath sample detection was based on the HPPI-TOFMS platform.
Healthy control group (HC); Control group is healthy participants.	Diagnostic test: An exhaled breath test; All exhaled breath samples were collected by trained investigators following the same protocol. All participants fasted for at least 6 hours before breath collection. To reduce potential confounding factors, all participants were asked to not ingest spicy food, alcohol, or coffee the night before exhaled breath collection. Exhaled breath was collected in Tedlar air bags (DuPont de Nemours). The night before breath collection, the Tedlar bags were baked at 60 °C for 3 hours to fully release possible contaminants and continuously purged with high-purity nitrogen 4 times. Participants first gargled with pure water and then performed a single deep nasal inhalation followed by complete exhalation via their mouth into Tedlar bags. A total of 1000 mL of exhaled breath was collected from each participant. Breath sample detection was based on the HPPI-TOFMS platform.
Unhealthy control group (UHC); Patients with interstitial lung disease or patients with Sarcoidosis. Interstitial lung disease is a heterogeneous pulmonary disease characterized with lung fibrosis and manifest with breathlessness. Sarcoidosis is a systemic disease of unknown etiology characterized by the formation of granulomas in various organs, mostly involved is the lungs and intrathoracic lymph nodes .	Diagnostic test: An exhaled breath test; All exhaled breath samples were collected by trained investigators following the same protocol. All participants fasted for at least 6 hours before breath collection. To reduce potential confounding factors, all participants were asked to not ingest spicy food, alcohol, or coffee the night before exhaled breath collection. Exhaled breath was collected in Tedlar air bags (DuPont de Nemours). The night before breath collection, the Tedlar bags were baked at 60 °C for 3 hours to fully release possible contaminants and continuously purged with high-purity nitrogen 4 times. Participants first gargled with pure water and then performed a single deep nasal inhalation followed by complete exhalation via their mouth into Tedlar bags. A total of 1000 mL of exhaled breath was collected from each participant. Breath sample detection was based on the HPPI-TOFMS platform.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Ability of the Breath Test Model to Distinguish Bronchiectasis From Healthy People	Evaluate the ability of the breath test model to distinguish bronchiectasis from healthy individuals by measuring the area under the receiver operating characteristic (ROC) curves. The maximum value in the area below the receiver is 1. The closer the value is to 1, the higher the prediction accuracy of the model.	One week.Exhaled breath samples were collected on the first day of patients' hospitalization and sent to detect VOCs.The entire process will take one week.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Sensitivity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People	Sensitivity=number of true positives/(number of true positives+number of false negatives) * 100% Sensitivity is the rate of correctly judging patients.We calculated the sensitivity of the breath test model to distinguish bronchiectasis from healthy people.The maximum percentage of the sensitivity is 100%. The higher the percentage is , the more sensitive of the model.	One week.Exhaled breath samples were collected on the first day of patients' hospitalization and sent to detect VOCs.The entire process will take one week.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Specificity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People	Specificity=number of true negative cases/(number of true negative cases+number of false positive cases) * 100% The specificity is the rate of correctly judging non patients.We calculated the specificity of the breath test model to distinguish bronchiectasis from healthy people.The maximum percentage of the specificity is 100%. The higher the percentage is , the more specificity of the model.	One week.Exhaled breath samples were collected on the first day of patients' hospitalization and sent to detect VOCs.The entire process will take one week.

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China
• Investigators: Study Director: Jin-fu Xu, MD, Department of Respiratory and Critical Care

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): May 1, 2023
• Study Completion (Actual): May 20, 2023

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: September 16, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: bronchiectasis; exhaled breath; breathomics
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: 20220303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No