Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia

Sponsor

The Hospital for Sick Children (Other)

Overall Status

Completed

CT.gov ID

NCT01155115

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis Primary Ciliary Dyskinesia	Procedure: Sputum Collection Procedure: Pulmonary Function Testing Procedure: Exhaled Nitric Oxide	N/A

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

Actual Enrollment :

46 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)).

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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