Cystic Fibrosis
Conditions
Keywords
Breath, IMPACT
Brief summary
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
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.
Interventions
None listed
Sponsors
Arizona State University
Children's Hospital Colorado
National Heart, Lung, and Blood Institute (NHLBI)
Cystic Fibrosis Foundation
University of British Columbia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aim 1, Cross-Sectional IInclusion Criteria: 1. Male or female, ages 8 years and older 2. Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations 3. @ BC Children's Hospital only- Non-expectorators are eligible if having a clinically indicated OP swab. 4. FEV1 ≥ 30% predicted for spontaneous expectorators or FEV1 ≥ 40% predicted for subjects undergoing sputum induction 5. 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 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
1. Age \< 8 years 2. Intermittently infected with Pa 3. FEV1 \< 30% 4. History of lung transplant 5. 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): 1. Male or female, ages 8-16 years 2. Diagnosis of CF based on sweat chloride ≥ 60 mmol/L and/or 2 known CF mutations 3. @ BC Children's Hospital only- Non-expectorators are eligible if having a clinically indicated OP swab. 4. FEV1 ≥ 30% predicted for spontaneous expectorators or FEV1 ≥ 40% predicted for subjects undergoing sputum induction 5. P. aeruginosa negative, based on one of the following criteria: 1. No growth of Pa in previous 12 months and ≥ 4 consecutive Pa-negative cultures 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples obtained from persons with and without P. aeruginosa lung infections | Enrollment thru 2023. Last Longitudinal Study Visit will be 24 months after last AIM 2 enrollment | Measured using comprehensive two-dimensional gas chromatography of exhaled breath compared to sputum culture (gold standard) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intra-subject changes in concentrations of individual volatile biomarkers and combinations of biomarkers in breath samples | Thru end of 2025 | Breath samples obtained over a duration of two years, measured using comprehensive two-dimensional gas chromatography of exhaled breath |
Countries
Canada, United States
Contacts
Primary ContactJane E Hill, PhD
Backup ContactNina Nouribakikomarolya, PhD
Outcome results
None listed