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.

After the subject has performed post-bronchodilator spirometry, they will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer.

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.

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

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