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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Hypertonic Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Children diagnosed with CF (by sweat chloride ≥60 and/or genetic testing)
2. Children ages between 6-18 years
3. Ability to perform pulmonary function tests
4. FEV1 ≥ 30% predicted18.

Additional inclusion criteria for sub-sample undergoing antibiotic therapy:

1. Above criteria
2. Admitted to hospital for i.v. antibiotic therapy

Exclusion Criteria:

1. Acute respiratory distress or hypoxia (oxygen saturation <92% at room air)
2. New onset of wheezing
3. Previous history of intolerance of inhalation of HS

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Hypertonic Saline; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Felix Ratjen, MD, The Hospital for Sick Children, Toronto Canada

Publications and helpful links

General Publications

• Al-Saleh S, Dell SD, Grasemann H, Yau YC, Waters V, Martin S, Ratjen F. Sputum induction in routine clinical care of children with cystic fibrosis. J Pediatr. 2010 Dec;157(6):1006-1011.e1. doi: 10.1016/j.jpeds.2010.06.001. Epub 2010 Jul 14.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: July 21, 2008
• First Submitted That Met QC Criteria: July 21, 2008
• First Posted (Estimate): July 23, 2008

Study Record Updates

• Last Update Posted (Estimate): September 2, 2013
• Last Update Submitted That Met QC Criteria: August 30, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Pediatrics; Hypertonic Saline; Induced Sputum; Expectorated Sputum
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Inflammation; Cystic Fibrosis
• Other Study ID Numbers: 1000009154

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No