Congenital Diaphragmatic Hernia
Conditions
Keywords
Congenital Diaphragmatic Hernia, Airway Inflammation, Asthma, Hypersaline, Pediatrics
Brief summary
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.
Interventions
DRUGHypersaline
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.
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.
Sponsors
The Hospital for Sick Children
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Elevated Sputum Eosinophils | post sputum induction | Number of participants with sputum eosinophils greater than 3% percent of cells in the sputum |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant With Elevated Sputum Neutrophils | Baseline, +30 minutes | Elevation is defined as sputum neutrophils \> or = 61% neutrophils = neutrophilic inflammation |
| Number of Participant With Elevated Exhaled Nitric Oxide (NO) Level | 30 min | 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 |
| Number of Participant With Bronchodilator Response | life time of child (age 6 to present age) | defined as a = or \> 12% change in FEV1 post bronchodilator |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 to obtain cells for analysis. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Hypersaline and Bronchodilator Response | — |
|---|---|---|
| Age, Categorical <=18 years | 21 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 7 Participants | — |
| Sex: Female, Male Male | 14 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Number of Participants With Elevated Sputum Eosinophils
Number of participants with sputum eosinophils greater than 3% percent of cells in the sputum
Time frame: post sputum induction
Population: 15 gave reasonable sputum for analysis, none had elevated sputum eosinophils
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypersaline and Bronchodilator Response | Number of Participants With Elevated Sputum Eosinophils | 0 participants |
Secondary
Number of Participant With Bronchodilator Response
defined as a = or \> 12% change in FEV1 post bronchodilator
Time frame: life time of child (age 6 to present age)
Population: all subjects performed PFTs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypersaline and Bronchodilator Response | Number of Participant With Bronchodilator Response | 15 participants |
Secondary
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
Time frame: 30 min
Population: only 12 performed eNO
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypersaline and Bronchodilator Response | Number of Participant With Elevated Exhaled Nitric Oxide (NO) Level | 2 Participants |
Secondary
Number of Participant With Elevated Sputum Neutrophils
Elevation is defined as sputum neutrophils \> or = 61% neutrophils = neutrophilic inflammation
Time frame: Baseline, +30 minutes
Population: 15 gave reasonable sputum
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypersaline and Bronchodilator Response | Number of Participant With Elevated Sputum Neutrophils | 0 participants |