Utility of Induced Sputum Using Hypertonic Saline to Evaluate Infection and Inflammation in Cystic Fibrosis

Study Overview
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Brief Summary
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The objective of the study is to evaluate the clinical utility and the feasibility, in an outpatient setting, of sputum induction using hypertonic saline. This study will also study pilot techniques on a sub using a sub-sample to assess the lower airway inflammatory cells and markers in relation to new emerging organisms in cystic fibrosis (CF) and antibiotic therapy in CF.

Detailed Description
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Chronic airway infection, mainly by Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA), is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Isolation of organisms from the respiratory tract is important to optimize treatment. The current recommended methods for bacterial evaluation are bronchoalveolar lavage (BAL) and expectorated sputum (ES) analysis. However, a significant proportion of young CF patients cannot produce sputum spontaneously. The method used most frequently therefore is to isolate respiratory organisms is to perform throat swabs (TS) which have poor sensitivity and specificity in the evaluation of respiratory pathogens in CF patients. Induced sputum (IS) using hypertonic saline has been used in a limited number of studies to evaluate respiratory organisms in CF patients. These studies have reported that IS may be a useful non-invasive diagnostic test to increase the yield of detection of respiratory pathogens. Beside its use as a diagnostic test to identify bacterial pathogens induced sputum has been used to assess lower airway inflammation in CF. While numerous studies have clarified the role of S. aureus and P. aeruginosa in CF lung disease, the role of other emerging bacteria such as Stenotrophomonas maltophilia (SM) and Achromobacter xylosoxidans (AX) species remains largely unclear. IS offers the potential to possibly differentiate between colonisation and infection for the emerging pathogens and to help clarify their role in CF lung disease.

Official Title
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Diagnostic Utility of Induced Sputum Using Hypertonic Saline to Evaluate Airway Infection and Inflammation in Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Hypertonic Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children diagnosed with CF (by sweat chloride ≥60 and/or genetic testing) Children ages between 6-18 years Ability to perform pulmonary function tests FEV1 ≥ 30% predicted18. Additional inclusion criteria for sub-sample undergoing antibiotic therapy: Above criteria Admitted to hospital for i.v. antibiotic therapy Exclusion Criteria: Acute respiratory distress or hypoxia (oxygen saturation <92% at room air) New onset of wheezing Previous history of intolerance of inhalation of HS

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 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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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Hypertonic Saline<br>* After each subject has performed post-bronchodilator spirometry, he/she will inhale increasing concentrations of 3, 4, and 5% of hypertonic saline for 7 minutes each for 3 cycles until expectorating a sufficient sputum sample.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional positive bacterial culture yield post IS technique for known and emerging CF pathogens over conventional methods of bacterial culturing (ES and TS). |  | 60 minutes; for subgroup, this will be repeated a second time after 14 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory profile as measured by relative neutrophil count and IL-8 concentration in the IS |  | 60 minutes; for subgroup, this will be repeated a second time after 14 days. | 
| Bacterial colony counts |  | 60 minutes; for subgroup, this will be repeated a second time after 14 days. | 
| Frequency of change in clinical management based on results from IS |  | 60 minutes; for subgroup, this will be repeated a second time after 14 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatrics, Cystic Fibrosis, Hypertonic Saline, Induced Sputum, Expectorated Sputum