Airway Inflammation in Congenital Diaphragmatic Hernia Patients

Investigation of Airway Inflammation in Congenital Diaphragmatic Hernia Patients

We propose to examine Congenital Diaphragmatic Hernia (CDH) patients for evidence of airway inflammation as a first step to characterize the reported bronchodilator responsiveness. Airway biopsy studies are invasive and thus we propose to perform induced sputum studies to document the amount and type of inflammation present. Another ancillary non-invasive measure of airway inflammation that we will use is exhaled nitric oxide (NO). The primary objective of this study is to determine if CDH patients have any evidence of airway inflammation. The hypothesis of this study is that children with CDH do not have evidence of airway inflammation associated with bronchodilator responsiveness. Based on this information, treatment for CDH patients will hopefully be more accurate and appropriate for their specific needs.

Study Overview

• Status: Completed
• Conditions: Congenital Diaphragmatic Hernia
• Intervention / Treatment: Drug: Hypersaline; Drug: Bronchodilator Response

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 6 - 18 years of age at enrolment
• Clinically stable at enrolment
• Attending follow-up in the CDH Clinic at SickKids

Exclusion Criteria:

• Unable to perform pulmonary function testing
• Clinically unstable at enrolment
• Known hypersensitivity to salbutamol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypersaline and Bronchodilator Response; After the subject has performed post-bronchodilator spirometry, they will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer.

Drug: Hypersaline; Subject will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer. Sputum production (with cough) will be attempted post inhalation. A maximum of 3 hypertonic saline inhalations will be attempted if inhalation does not generate a productive cough. If sputum induction is not successful and the FEV1 falls <10%, the concentration of inhaled hypertonic saline will increase from 3 to 4%. If 5 mls of 4% hypertonic saline inhaled for 7 minutes does not produce a productive cough we will proceed to 5%. If 5 mls of 5% hypertonic saline inhaled for 7 minutes does not produce a productive cough the test is complete and the sample is labelled 'no sputum collected'. If FEV1 falls >10%, the previous step will be repeated.; Drug: Bronchodilator Response; A bronchodilator (Salbutamol 200 mcg or 2 puffs inhaled via spacer device) will be administered to all subjects in the pulmonary function laboratory. 15 minutes after administration of the bronchodilator spirometry will be repeated. This is performed routinely in CDH clinic and is not an additional test for this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Elevated Sputum Eosinophils	Number of participants with sputum eosinophils greater than 3% percent of cells in the sputum	post sputum induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participant With Elevated Sputum Neutrophils	Elevation is defined as sputum neutrophils > or = 61% neutrophils = neutrophilic inflammation	Baseline, +30 minutes
Number of Participant With Elevated Exhaled Nitric Oxide (NO) Level	exhaled NO measurements will be performed according to the American Thoracic Society and European Respiratory Society guidelines. These tests are performed routinely as part of the respiratory evaluation of these patients and are not additional tests added for this study. greater than 20 ppb was considered elevated	30 min
Number of Participant With Bronchodilator Response	defined as a = or > 12% change in FEV1 post bronchodilator	life time of child (age 6 to present age)

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Theo Moraes, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: May 21, 2015
• First Submitted That Met QC Criteria: May 21, 2015
• First Posted (Estimate): May 25, 2015

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Asthma; Pediatrics; Airway Inflammation; Congenital Diaphragmatic Hernia; Hypersaline
• Additional Relevant MeSH Terms: Pathologic Processes; Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Inflammation; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Asthmatic Agents; Respiratory System Agents; Bronchodilator Agents
• Other Study ID Numbers: 1000028032