Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia - Full Text View

Purpose

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.

Condition	Intervention
Cystic Fibrosis Primary Ciliary Dyskinesia	Procedure: Sputum Collection Procedure: Pulmonary Function Testing Procedure: Exhaled Nitric Oxide

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis primary ciliary dyskinesia

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Nitric oxide

U.S. FDA Resources

Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:

Change in sputum bacterial colony count [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
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 [ Time Frame: Up to 100 days ] [ Designated as safety issue: Yes ]
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. [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
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 [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
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)).

Estimated Enrollment:	52
Study Start Date:	January 2010
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Primary Ciliary Dyskinesia (PCD) Patients	Procedure: Sputum 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. Procedure: Pulmonary Function Testing Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines. Procedure: Exhaled 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.
Experimental: Cystic Fibrosis (CF) Patients	Procedure: Sputum 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. Procedure: Pulmonary Function Testing Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines. Procedure: Exhaled 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.

Arms

Assigned Interventions

Experimental: Primary Ciliary Dyskinesia (PCD) Patients

Procedure: Sputum 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.

Procedure: Pulmonary Function Testing

Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines.

Procedure: Exhaled 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.

Experimental: Cystic Fibrosis (CF) Patients

Procedure: Sputum 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.

Procedure: Pulmonary Function Testing

Participants will perform spirometry at each visit according to the American Thoracic Society and European Respiratory Society guidelines.

Procedure: Exhaled 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.

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

Ages Eligible for Study:	6 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01155115

Contacts

Contact: Felix Ratjen, MD

416-813-6167

felix.ratjen@sickkids.ca

Locations

Canada, Ontario
The Hospital for Sick Children	Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Felix Ratjen, MD 416 813 6167 felix.ratjen@sickkids.ca
Principal Investigator: Felix Ratjen, MD
Sub-Investigator: Timothy Leahy, MB
Sub-Investigator: Valerie Waters, MD
Sub-Investigator: Yvonne Yau, MD
Sub-Investigator: Sharon Dell, MD
Sub-Investigator: Hartmut Grasemann, MD

Sponsors and Collaborators

The Hospital for Sick Children

Investigators

Principal Investigator:

Felix Ratjen, MD

The Hospital for Sick Children, Toronto Canada

More Information

No publications provided

Responsible Party:	Felix Ratjen / Principal Investigator, Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT01155115 History of Changes
Other Study ID Numbers:	1000013966
Study First Received:	June 29, 2010
Last Updated:	June 29, 2010
Health Authority:	Canada: Health Canada

Keywords provided by The Hospital for Sick Children:

pediatrics
CF
PCD

exacerbation
inflammatory markers
induced sputum

Additional relevant MeSH terms:

Ciliary Motility Disorders
Kartagener Syndrome
Cystic Fibrosis
Dyskinesias
Fibrosis
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Bronchiectasis
Bronchial Diseases
Respiratory System Abnormalities
Dextrocardia
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases

Congenital Abnormalities
Situs Inversus
Genetic Diseases, Inborn
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Infant, Newborn, Diseases
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes
Nitric Oxide
Bronchodilator Agents

ClinicalTrials.gov processed this record on May 19, 2013