Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
Primary Purpose
Cystic Fibrosis, Primary Ciliary Dyskinesia
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Sputum Collection
Pulmonary Function Testing
Exhaled Nitric Oxide
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring pediatrics, CF, PCD, exacerbation, inflammatory markers, induced sputum
Eligibility Criteria
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
Sites / Locations
- The Hospital for Sick Children
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Primary Ciliary Dyskinesia (PCD) Patients
Cystic Fibrosis (CF) Patients
Arm Description
Outcomes
Primary Outcome Measures
Change in sputum bacterial colony count
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
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
Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples
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
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.
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
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)).
Full Information
NCT ID
NCT01155115
First Posted
June 29, 2010
Last Updated
May 21, 2015
Sponsor
The Hospital for Sick Children
1. Study Identification
Unique Protocol Identification Number
NCT01155115
Brief Title
Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
Official Title
Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis, Primary Ciliary Dyskinesia
Keywords
pediatrics, CF, PCD, exacerbation, inflammatory markers, induced sputum
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Primary Ciliary Dyskinesia (PCD) Patients
Arm Type
Experimental
Arm Title
Cystic Fibrosis (CF) Patients
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
Sputum Collection
Intervention Description
Each study participant will be invited to expectorate sputum for culture, sensitivity, cytology and analysis of cytokine levels. Culture and sensitivity will be performed routinely at the beginning of a pulmonary exacerbation, as per standard of care, and will only be performed at subsequent visits if there is clinical indication. A volume of 5ml of sputum will be required at each visit for analysis. If the participant is unable to expectorate this volume of sputum, he/she will be invited to induce sputum instead as per standard protocols.
Intervention Type
Procedure
Intervention Name(s)
Pulmonary Function Testing
Intervention Description
Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines.
Intervention Type
Procedure
Intervention Name(s)
Exhaled Nitric Oxide
Intervention Description
The investigators will measure exhaled Nitric Oxide (eNO) at each visit according to the American Thoracic Society and European Respiratory Society guidelines using a chemiluminescence analyzer. Briefly, single breath exhalation are performed in triplicate at flows of 30, 50, 100, 150, 200 and 250 ml/s and eNO is measured at the end of the exhalation. The higher the flow rate the more peripheral the airways that are being sampled.
Primary Outcome Measure Information:
Title
Change in sputum bacterial colony count
Description
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.
Time Frame
Up to 100 days
Title
Airway Inflammatory Profile
Description
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)).
Time Frame
Up to 100 days
Secondary Outcome Measure Information:
Title
Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples
Description
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.
Time Frame
Up to 100 days
Title
Tolerability and need for sputum induction in Cystic Fibrosis (CF) patients in comparison to Primary Ciliary Dyskinesia (PCD) patients
Description
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)).
Time Frame
Up to 100 days
Title
Change in forced expiratory volume in 1 second (FEV1) in response to a treatment course of antibiotics for pulmonary exacerbation.
Description
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.
Time Frame
Up to 100 days
Title
Other markers of airway inflammation
Description
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)).
Time Frame
Up to 100 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felix Ratjen, MD
Organizational Affiliation
The Hospital for Sick Children, Toronto Canada
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
35120987
Citation
Grasemann H, McDonald N, Yuan XZ, Dell S, Waters V, Ratjen F. Lower Airway Nitrogen Oxide Levels in Children with Primary Ciliary Dyskinesia Is Linked to Neutrophilic Inflammation. J Pediatr. 2022 May;244:230-233. doi: 10.1016/j.jpeds.2022.01.040. Epub 2022 Feb 2.
Results Reference
derived
PubMed Identifier
26585432
Citation
Ratjen F, Waters V, Klingel M, McDonald N, Dell S, Leahy TR, Yau Y, Grasemann H. Changes in airway inflammation during pulmonary exacerbations in patients with cystic fibrosis and primary ciliary dyskinesia. Eur Respir J. 2016 Mar;47(3):829-36. doi: 10.1183/13993003.01390-2015. Epub 2015 Nov 19.
Results Reference
derived
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Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
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