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NCT Number: NCT01155115

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

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.

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Key information

Conditions

Cystic Fibrosis Abnormalities, Multiple Ciliary Motility Disorders Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Otorhinolaryngologic Diseases Pancreatic Diseases Primary Ciliary Dyskinesia Respiratory Tract Diseases

Age range

6 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sputum Collection

Procedure

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.

Pulmonary Function Testing

Procedure

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

Exhaled Nitric Oxide

Procedure

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 outcomes

  1. Change in sputum bacterial colony count

    Time frame: 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.

  2. Airway Inflammatory Profile

    Time frame: 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 outcomes

  1. Culture, identification, and antibiotic susceptibility pattern of respiratory pathogens from sputum samples

    Time frame: 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.

  2. 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

    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)).

  3. 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

    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.

  4. Other markers of airway inflammation

    Time frame: 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)).

Sponsors and collaborators

Lead sponsor

The Hospital for Sick Children

Other

Registry information

Official study title

Inflammatory and Microbiologic Markers in Sputum in Response to Pulmonary Exacerbation: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Jul 1, 2010
Registry last updated
May 22, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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