Bronchiectasis
Conditions
Keywords
bronchiectasis, breathomics, exhaled breath
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTAn 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.
Sponsors
Shanghai Pulmonary Hospital, Shanghai, China
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Ability of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Sensitivity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 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. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Specificity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 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. | 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Bronchiectasis 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.
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. | 215 |
| Healthy Control Group Control group is healthy participants.
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. | 221 |
| Unhealthy Control Group 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 .
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. | 74 |
| Total | 510 |
Baseline characteristics
| Characteristic | Total | Healthy Control Group | Patients With Bronchiectasis | Unhealthy Control Group |
|---|---|---|---|---|
| Age, Continuous | 56 years | 52 years | 57 years | 65 years |
| Alcohol Drinker | 20 Participants | 11 Participants | 6 Participants | 3 Participants |
| Alcohol Non-drinker | 448 Participants | 173 Participants | 204 Participants | 71 Participants |
| Alcohol No record | 42 Participants | 37 Participants | 5 Participants | 0 Participants |
| BMI(Body Mass Index) | 22.9 kg/m^2 | 23.9 kg/m^2 | 21.1 kg/m^2 | 24.2 kg/m^2 |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Sex: Female, Male Female | 328 Participants | 145 Participants | 150 Participants | 33 Participants |
| Sex: Female, Male Male | 182 Participants | 76 Participants | 65 Participants | 41 Participants |
| Smoking Non-smoker | 391 Participants | 162 Participants | 183 Participants | 46 Participants |
| Smoking No record | 24 Participants | 19 Participants | 5 Participants | 0 Participants |
| Smoking Smoker | 95 Participants | 40 Participants | 27 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 215 | 0 / 221 | 0 / 74 |
| other Total, other adverse events | 5 / 215 | 0 / 221 | 2 / 74 |
| serious Total, serious adverse events | 0 / 215 | 0 / 221 | 0 / 74 |
Outcome results
Primary
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.
Time frame: 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.
Population: All participants were randomly divided to a discovery cohort (n=252), an internal validation cohort (n=103) and a blinded test cohort (n=155). The main outcomes were assumed by the data analysed from the blinded test cohort which was mentioned above.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bronchiectasis Participants | The Ability of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 65 Participants |
| Healthy Controls | The Ability of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 67 Participants |
| Unhealthy Controls | The Ability of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 23 Participants |
Comparison: 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.p-value: <0.0595% CI: [0.932, 0.996]Wilcoxon (Mann-Whitney)
Comparison: 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.p-value: <0.0595% CI: [0.879, 0.982]Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 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.
Population: All participants were randomly divided to a discovery cohort (n=252), an internal validation cohort (n=103) and a blinded test cohort (n=155). The main outcomes were assumed by the data analysed from the blinded test cohort which was mentioned above.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bronchiectasis Participants | The Sensitivity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 65 Participants |
| Healthy Controls | The Sensitivity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 67 Participants |
| Unhealthy Controls | The Sensitivity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 23 Participants |
Comparison: 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.95% CI: [77.1, 95.2]
Comparison: 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.95% CI: [77.1, 95.2]
Other Pre-specified
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.
Time frame: 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.
Population: All participants were randomly divided to a discovery cohort (n=252), an internal validation cohort (n=103) and a blinded test cohort (n=155). The main outcomes were assumed by the data analysed from the blinded test cohort which was mentioned above.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bronchiectasis Participants | The Specificity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 65 Participants |
| Healthy Controls | The Specificity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 67 Participants |
| Unhealthy Controls | The Specificity of the Breath Test Model to Distinguish Bronchiectasis From Healthy People | 23 Participants |
Comparison: 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.95% CI: [86.2, 98.8]
Comparison: 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.95% CI: [56, 91.9]