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

The Hospital for Sick Children46 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cystic Fibrosis Primary Ciliary Dyskinesia

Interventions

Sputum CollectionPROCEDURE

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 TestingPROCEDURE

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

Exhaled Nitric OxidePROCEDURE

Eligibility

Sex: ALLMin age: 6 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

The Hospital for Sick Children

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

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.

Time frame: 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)).

Time frame: Up to 100 days

Secondary Outcomes

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

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.

Time frame: Up to 100 days

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

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)).

Time frame: Up to 100 days

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

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.

Data from ClinicalTrials.gov

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