Clinical trial NCT01155115: 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
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Primary Ciliary Dyskinesia
Keywords: pediatrics
CF
PCD
exacerbation
inflammatory markers
induced sputum
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2010-07-01
Enrollment: 46
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in sputum bacterial colony count
timeFrame: Up to 100 days
measure: Airway Inflammatory Profile
timeFrame: Up to 100 days
Secondary outcomes:
measure: Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples
timeFrame: Up to 100 days
measure: Tolerability and need for sputum induction in Cystic Fibrosis (CF) patients in comparison to Primary Ciliary Dyskinesia (PCD) patients
timeFrame: Up to 100 days
measure: Change in forced expiratory volume in 1 second (FEV1) in response to a treatment course of antibiotics for pulmonary exacerbation.
timeFrame: Up to 100 days
measure: Other markers of airway inflammation
timeFrame: Up to 100 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Felix Ratjen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.