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

NCT01155115 | Completed DMC

• 1 other identifier: 1000013966
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis; Primary Ciliary Dyskinesia

Keywords

pediatrics; CF; PCD; exacerbation; inflammatory markers; induced sputum

Outcome Measures

Primary Outcomes (2)

• Change in sputum bacterial colony count

  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.

  Up to 100 days

• Airway Inflammatory Profile

  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)).

  Up to 100 days

Secondary Outcomes (4)

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

  Up to 100 days

• Tolerability and need for sputum induction in Cystic Fibrosis (CF) patients in comparison to Primary Ciliary Dyskinesia (PCD) patients

  Up to 100 days

• Change in forced expiratory volume in 1 second (FEV1) in response to a treatment course of antibiotics for pulmonary exacerbation.

  Up to 100 days

• Other markers of airway inflammation

  Up to 100 days

Study Arms (2)

Primary Ciliary Dyskinesia (PCD) Patients

EXPERIMENTAL

Procedure: Sputum Collection; Procedure: Pulmonary Function Testing; Procedure: Exhaled Nitric Oxide

Cystic Fibrosis (CF) Patients

EXPERIMENTAL

Procedure: Sputum Collection; Procedure: Pulmonary Function Testing; Procedure: Exhaled Nitric Oxide

Interventions

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.

Cystic Fibrosis (CF) Patients; Primary Ciliary Dyskinesia (PCD) Patients

Pulmonary Function Testing PROCEDURE

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

Cystic Fibrosis (CF) Patients; Primary Ciliary Dyskinesia (PCD) Patients

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.

Cystic Fibrosis (CF) Patients; Primary Ciliary Dyskinesia (PCD) Patients

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (2)

• 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.

  PMID: 35120987 DERIVED

• 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.

  PMID: 26585432 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Ciliary Motility Disorders

Interventions

Respiratory Physiological Phenomena

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Otorhinolaryngologic Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities

Intervention Hierarchy (Ancestors)

Circulatory and Respiratory Physiological Phenomena

Study Officials

• Felix Ratjen, MD

  The Hospital for Sick Children, Toronto Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Head, Respiratory Medicine

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: July 1, 2010
• Study Start: January 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 22, 2015

Record last verified: 2015-05

Locations

CA (1)