Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia

Not Applicable

Completed

• Conditions: Primary Ciliary Dyskinesia; Cystic Fibrosis
• Interventions: Procedure: Sputum Collection; Procedure: Pulmonary Function Testing; Procedure: Exhaled Nitric Oxide

• Registration Number: NCT01155115
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

The objective of this study is to compare the lower airways inflammatory response to infection/pulmonary exacerbation among children known to have Primary Ciliary Dyskinesia (PCD) with children known to have Cystic Fibrosis (CF) as measured by the presence of inflammatory mediators in expectorated/induced sputum.

Detailed Description

The inflammatory response to infection and pulmonary exacerbation in CF is well documented, as is the response to intravenous antibiotic treatment. On the other hand, the inflammatory response to infection and treatment in PCD has not been well characterized. Given differences in disease progression, we hypothesize that children with CF respond to infection with a more exaggerated and prolonged inflammatory response than those with PCD.

Study Timeline

• Study Start: 2010-01
• Study First Submitted: 2010-06-29
• Study First Submitted QC: 2010-06-29
• Study First Posted: 2010-07-01
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2015-05
• Last Update Submitted: 2015-05-21
• Last Update Posted: 2015-05-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Diagnosis of Cystic Fibrosis (CF) as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease-causing mutations or a diagnosis of Primary Ciliary Dyskinesia (PCD) as follows: definite PCD (compatible phenotype, diagnostic abnormality of ciliary ultrastructure and/or two disease-causing gene mutations) or "probable" PCD (compatible phenotype, ciliary biopsy not diagnostic but low nasal NO (<100nl/min) with negative investigation screen for both CF and immunodeficiency
• Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
• 6-18 years of age at enrolment and able to perform reproducible spirometry
• Clinically stable at enrolment (FEV > 30%, oxyhaemoglobin sats > 93%)
• Ability to comply with study visits and study procedures

Exclusion Criteria

• Respiratory culture positive for non-tuberculous mycobacteria (NTM), Stenotrophomonas maltophilia, Aspergillus fumigatus, Burkholderia cepacia complex, or Pseudomonas aeruginosa within past year.
• Use of intravenous antibiotics or oral quinolones within previous 14 days
• Use of inhaled antibiotics within the previous 28 days
• Pneumothorax or haemoptysis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Primary Ciliary Dyskinesia (PCD) Patients	Exhaled Nitric Oxide	-
Primary Ciliary Dyskinesia (PCD) Patients	Sputum Collection	-
Primary Ciliary Dyskinesia (PCD) Patients	Pulmonary Function Testing	-
Cystic Fibrosis (CF) Patients	Sputum Collection	-
Cystic Fibrosis (CF) Patients	Pulmonary Function Testing	-
Cystic Fibrosis (CF) Patients	Exhaled Nitric Oxide	-

Primary Outcome Measures

Name	Time	Method
Change in sputum bacterial colony count	Up to 100 days	For the following organisms (Staphylococcus aureus, Haemophilus influenza) in response to a prescribed treatment course of oral antibiotics.; Colony count will be done at three time points: * during respiratory exacerbation (Visit 1 - Day 0),; * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),; * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).during the study.
Airway Inflammatory Profile	Up to 100 days	As measured by sputum interleukin 8 (IL-8) at three time points: * during respiratory exacerbation (Visit 1 - Day 0),; * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),; * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).

Secondary Outcome Measures

Name	Time	Method
Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples	Up to 100 days	Will be done at three time points: * during respiratory exacerbation (Visit 1 - Day 0),; * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),; * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).during the study.
Tolerability and need for sputum induction in Cystic Fibrosis (CF) patients in comparison to Primary Ciliary Dyskinesia (PCD) patients	Up to 100 days	Sputum will be collected at three time points: * during respiratory exacerbation (Visit 1 - Day 0),; * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),; * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).
Change in forced expiratory volume in 1 second (FEV1) in response to a treatment course of antibiotics for pulmonary exacerbation.	Up to 100 days	FEV1 will be measured at three time points: * during respiratory exacerbation (Visit 1 - Day 0),; * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),; * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).during the study.
Other markers of airway inflammation	Up to 100 days	Measurement of sputum white cell and neutrophil count (absolute and relative values), neutrophil elastase, nitric oxide (NO), NO metabolites and arginase levels at three time points: * during respiratory exacerbation (Visit 1 - Day 0),; * post-antibiotic treatment of exacerbation (Visit 2 - Day 21-42),; * and on return to clinical baseline (Visit 3 - Day 42-100 (End of Study)).

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada