Related Experiment Videos
Evolution of airway hyperresponsiveness in infants with severe congenital diaphragmatic hernia
S R Boas1, G Kurland, P G Greally
1Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Insights
Infants with congenital diaphragmatic hernia (DH) show pulmonary hypoplasia and airway hyperresponsiveness early in life. Lung function improves over the first four months, but lower airway obstruction develops.
Area of Science:
- Pediatric Pulmonology
- Neonatal Medicine
- Thoracic Surgery
Background:
- Congenital diaphragmatic hernia (DH) characteristically leads to pulmonary hypoplasia in neonates.
- Airway hyperresponsiveness is common in the first month of life for infants with DH.
- Early postnatal lung development in severe DH cases requires further characterization.
Purpose of the Study:
- To investigate early postnatal lung growth and pulmonary function in infants with congenital diaphragmatic hernia (DH).
- To compare lung function between infants with DH and healthy controls at different early life stages.
Main Methods:
- Utilized the forced deflation method to assess pulmonary function in 18 infants with DH and 13 control infants.
- Divided infants into early (<=7 days) and late (>=29 days) groups for analysis.
- Measured weight-corrected forced vital capacity (FVC) and the MEF25/FVC rate constant.
Main Results:
- Infants with early DH (EDH) exhibited significantly reduced FVC (13.9 ml/kg) compared to early controls (44.4 ml/kg), indicating pulmonary hypoplasia.
- FVC increased significantly in late DH (LDH) infants (24.5 ml/kg) compared to EDH infants over four months.
- EDH subjects showed elevated MEF25/FVC (1.87/sec), suggesting increased lower airway caliber, while LDH subjects showed reduced rate constants (0.36/sec), indicating obstruction.
Conclusions:
- Infants with congenital DH present with pulmonary hypoplasia and lung restriction.
- These infants demonstrate rapid postnatal lung growth and the development of lower airway obstruction and hyperresponsiveness within the first four months of life.
- Findings suggest a progression from lung restriction to obstructive airway disease in the early postnatal period for DH patients.
Abstract:
Infants born with severe congenital diaphragmatic hernia (DH) characteristically have pulmonary hypoplasia. Airway hyperresponsiveness during the first 4 weeks of life can be demonstrated in most of these neonates. Early postnatal pulmonary development in infants with severe DH has not been well characterized. We examined lung growth in patients with congenital DH by using the forced deflation method to study pulmonary function in 18 infants on mechanical ventilation who survived neonatal repair of their congenital DH. Thirteen infants without primary pulmonary pathology who required general anesthesia for other surgery served as controls. Infants were further divided according to age at the time of testing into early (age < or = 7 days at time of testing) and late (age > or = 29 days) groups, yielding four groups of subjects: early diaphragmatic hernia (EDH): n = 9; mean age, 4.2 days; range, 1-7 days; early controls (EC): n = 8; mean age, 3.1 days; range, 1-6 days; late diaphragmatic hernia (LDH): n = 11; mean age, 57.7 days, range, 28-120 days; and late controls (LC); n = 5; mean age, 52.2 days; range 32-90 days. All infants were studied once, with the exception of two infants with DH who were studied on two occasions at EDH and LDH stages. A marked reduction in weight-corrected forced vital capacity (FVC) was seen in the EDH group (13.9 +/- 3.9 ml/kg) as compared to the EC group (44.4 +/- 4.9 ml/kg). During the ensuing 4 months of life, FVC in patients with LDH (24.5 +/- 1.9 ml/kg) was much higher than FVC in patients with EDH (P < 0.05). These findings demonstrate the presence of pulmonary hypoplasia in the EDH group and suggest subsequent rapid postnatal lung growth. An index of rate constant, MEF25/FVC, as compared with control groups was abnormally elevated in EDH subjects (1.87 +/- 0.30/second vs 1.16 +/- 0.32/ second, P < 0.05), indicating significantly increased lower airway caliber relative to lung volume. The severe reduction of the rate constant in the LDH group (0.36 +/- 0.05/second vs 0.73 +/- 0.07/second, P < 0.05) suggests the development of lower airway obstruction. After the administration of a nebulized bronchodilator (BD), an increase in MEF25 (32.9%) in the EDH group was not significant, but an increase of 134.7% in the LDH group was significant (P < 0.05). Although the study utilized a cross-sectional design with most of the infants in either the early or late group, present findings suggest that infants with EDH have lung restriction reflecting pulmonary hypoplasia. These infants developed lower airway obstruction and airway hyperresponsiveness with only mild fixed obstruction over the first 4 months of life.