Evolution of airway hyperresponsiveness in infants with severe congenital diaphragmatic hernia.

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.

Interferon-alpha affects the immune response in post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) is associated with Epstein-Barr virus (EBV) and characterized by fever, lymphadenopathy, and graft dysfunction. We describe the clinical course of an EBV seronegative 11-yr-old boy who underwent double lung transplantation and subsequently developed PTLD in the graft. A reduction in immunosuppression and the addition of acyclovir did not result in improvement. Treatment with interferon-alpha (IFN-alpha), however, led to dramatic clinical, radiographic, and histologic improvement. Semiquantitative measurements of cytokine mRNA in his bronchoalveolar lavage cells prior to therapy with IFN-alpha revealed high levels of IL-4 and IL-10 mRNA, which decreased significantly with treatment. We speculate that the beneficial effect of IFN-alpha in the treatment of PTLD is directly related to the inhibition of type 2 helper (Th2-like) T-cells.