Cystic Fibrosis, Primary Ciliary Dyskinesia
Conditions
Keywords
pediatrics, CF, PCD, exacerbation, inflammatory markers, induced sputum
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.
Interventions
PROCEDURESputum Collection
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.
PROCEDUREPulmonary Function Testing
Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines.
PROCEDUREExhaled Nitric Oxide
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.
Sponsors
The Hospital for Sick Children
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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)). |
Countries
Canada
Outcome results
None listed