Improving P. Aeruginosa Detection With Breath-based Diagnostics (IMPACT-Breath)

Study Overview
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Brief Summary
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The study is a breath biomarker validation study. It is anticipated that 300 patients with cystic fibrosis (CF) from 5 clinical sites in the USA will be enrolled. The study is funded by the US NIH and the US Cystic Fibrosis Foundation. Enrollment commenced in May 2019. Sputum, induced sputum, and oropharyngeal swabs will be collected and evaluated at each clinic as part of standard clinical practice. Excess sputum will be sent to Children's Colorado Hospital for molecular analysis. No swabs will be sent anywhere (other than the clinic from which they originate). Breath samples will be taken from all study participants.

Detailed Description
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AIM 1: Refine and validate volatile biomarkers in the breath of adult and pediatric CF patients for detecting established P. aeruginosa lung infections. For each expectorating subject (n ≥ 288; 5 centers), the diagnostic accuracy of the volatile biomarker panel will be tested, with sputum culture as the standard. AIM 2: Quantify intra-subject breath variability of the target pediatric population. We will collect longitudinal breath samples for two years from P. aeruginosa-negative subjects (n ≥ 58;  60% non-expectorating) at 4 pediatric CF clinical centers. We will measure intra-subject variance in the breath signatures of expectorating and non-expectorating subjects, with the latter being the target population for the clinical trial. Two to 8 breath samples will be collected per patient.

Official Title
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Improving P. Aeruginosa Detection With Breath-based Diagnostics (IMPACT-Breath)

Conditions
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Cystic Fibrosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aim 1, Cross-Sectional IInclusion Criteria: Male or female, ages 8 years and older Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations @ BC Children's Hospital only- Non-expectorators are eligible if having a clinically indicated OP swab. FEV1 ≥ 30% predicted for spontaneous expectorators or FEV1 ≥ 40% predicted for subjects undergoing sputum induction Either P. aeruginosa (Pa) negative or chronically infected with P. aeruginosa (Pa positive) as defined below: a. P. aeruginosa negative: must meet one of the following criteria: i: No growth of Pa in previous 12 months and ≥ 4 consecutive Pa-negative cultures, OR ii: No history of Pa positive airway cultures (sputum, OP, Bronchoalveolar lavage) b. P. aeruginosa positive i: Over 50% of cultures positive and at least 2 cultures positive for Pa in previous 18 months Willing to participate in and comply with the study procedures and willingness of the subject, parent or legally authorized representative to provide written informed consent. Exclusion criteria: Age < 8 years Intermittently infected with Pa FEV1 < 30% History of lung transplant Presence of a condition or abnormality that in the opinion of the Principal Investigator would compromise the safety of the subject or the quality of the data. Aim 2, Longitudinal Inclusion Criteria, Expectorating Cohort (n=48): Male or female, ages 8-16 years Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations @ BC Children's Hospital only- Non-expectorators are eligible if having a clinically indicated OP swab. FEV1 ≥ 30% predicted for spontaneous expectorators or FEV1 ≥ 40% predicted for subjects undergoing sputum induction P. aeruginosa negative, based on one of the following criteria: No growth of Pa in previous 12 months and ≥ 4 consecutive Pa-negative cultures No history of Pa positive airway cultures (sputum, OP, bronchoalveolar lavage) Willing to participate in and comply with the study procedures and willingness of the subject, parent or legally authorized representative to provide written informed consent. Exclusion criteria: Age < 8 years Intermittently or chronically infected with Pa Unable to expectorate sputum or undergo sputum induction FEV1 < 30% History of lung transplant Presence of a condition or abnormality that in the opinion of the Principal Investigator would compromise the safety of the subject or the quality of the data. Inclusion Criteria, Non-Expectorating Cohort (n=10): Male or female, ages 3-8 years Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations 3. FEV1 ≥ 30% 4. Unable to expectorate sputum 5. P. aeruginosa negative, based on one of the following criteria: No growth of Pa in previous 12 months and ≥ 4 consecutive Pa-negative cultures No history of Pa positive airway cultures (sputum, OP, bronchoalveolar lavage) 6. Willing to participate in and comply with the study procedures and willingness of the subject, parent or legally authorized representative to provide written informed consent. Exclusion criteria: Age < 3 years Intermittently or chronically infected with Pa FEV1 < 30% History of lung transplant Presence of a condition or abnormality that in the opinion of the Principal Investigator would compromise the safety of the subject or the quality of the data.

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AIM 1<br>No-Intervention. Participants in this group will have 1 study visit only. During that visit, breath and sputum samples will be collected. | |
| AIM 2<br>No-Intervention. Participants in this group will have up to 8 study visits over a 2 year period. During the study visits, breath and sputum samples will be collected. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples obtained from persons with and without P. aeruginosa lung infections | Measured using comprehensive two-dimensional gas chromatography of exhaled breath compared to sputum culture (gold standard) | Enrollment thru 2023. Last Longitudinal Study Visit will be 24 months after last AIM 2 enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-subject changes in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples | Breath samples obtained over a duration of two years, measured using comprehensive two-dimensional gas chromatography of exhaled breath | Thru end of 2025 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breath, IMPACT