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

NCT ID: NCT01155115

Last Updated: 2015-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2014-12-31

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.

Conditions

Cystic Fibrosis; Primary Ciliary Dyskinesia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Primary Ciliary Dyskinesia (PCD) Patients

Group Type: EXPERIMENTAL

Sputum Collection

Intervention Type: 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

Intervention Type: PROCEDURE

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

Exhaled Nitric Oxide

Intervention Type: 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

Group Type: EXPERIMENTAL

Sputum Collection

Intervention Type: 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

Intervention Type: PROCEDURE

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

Exhaled Nitric Oxide

Intervention Type: 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.

Interventions

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.

Intervention Type: PROCEDURE

Pulmonary Function Testing

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

Intervention Type: 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.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Felix Ratjen

Division Head, Respiratory Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Felix Ratjen, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto Canada

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 35120987 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26585432 (View on PubMed)

Other Identifiers

1000013966

Identifier Type: -

Identifier Source: org_study_id