Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 46
- Locations
- 2
- Primary Endpoint
- Change in sputum bacterial colony count
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 6 Years to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Change in sputum bacterial colony count
Time Frame: 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
Time Frame: 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 Outcomes
- Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples(Up to 100 days)
- Tolerability and need for sputum induction in Cystic Fibrosis (CF) patients in comparison to Primary Ciliary Dyskinesia (PCD) patients(Up to 100 days)
- Change in forced expiratory volume in 1 second (FEV1) in response to a treatment course of antibiotics for pulmonary exacerbation.(Up to 100 days)
- Other markers of airway inflammation(Up to 100 days)
Investigators
Felix Ratjen
Division Head, Respiratory Medicine
The Hospital for Sick Children