Background The prevalence of asthma in children with congenital heart disease is unknown. During surgical correction of pulmonary atresia and ventricular septal defect (PA-VSD), significant perioperative bronchospasm has been observed; particularly when the PA-VSD was part of the Velo-Cardio-Facial Syndrome (VCFS). VCFS comprises multiple anomalies; cleft palate, heart malformations, stereotypical facies, and learning disabilities. VCFS is associated with a chromosome 22 microdeletion. We hypothesized that PA-VSD and/or VCFS secondary to microdeletion at chromosome 22q 11.2 may predispose children to asthma.

Methodology Prospective enrollment, cross-sectional study of children (> 5 years) with PA-VSD seen in pediatric cardiology at the Mayo Clinic between 6/96 - 11/97. The clinical diagnoses of VCFS and asthma were made utilizing strict criteria. Then, all patients were evaluated for chromosome 22 microdeletion by fluorescent in situ hybridization. In addition, patients with non-syndromic PA-VSD underwent pulmonary function testing with methacholine provocation to measure airway hyperresponsiveness. We were not able to successfully perform methacholine challenge testing in all patients with VCFS.

Results 25 children with PA-VSD were enrolled prospectively. Nine of the 10 children with suspected VCFS were haploinsufficient at chromosome 22. No patient (n=15) with non-syndromic PA-VSD had evidence of chromosome 22 microdeletion. Overall, 18 of 25 patients (72%) had asthma clinically; 7/9 in the VCFS/microdeletion positive group and 11/16 in the non-syndromic PA-VSD group. Interestingly, methacholine challenge testing fully corroborated the presence of significant, reversible airway hyperreactivity in the non-syndromic PA-VSD group.

Conclusions A remarkably high association (72%) between PA-VSD and asthma was revealed in this prospective study. To our surprise, the presence of VCFS or chromosome 22 microdeletion did not influence this association. Given this marked association, bronchospasm should be anticipated and aggressively managed in the perioperative setting for children with PA-VSD. Moreover, asthma should be considered strongly in the evaluation of a child with PA-VSD. These findings offer new insights into the management of children with PA-VSD as well as to the fundamental relationship between heart, lung vessel, and lung airway development. Results of this study have initiated a large prospective clinical study evaluating airway hyperreactivity by methacholine challenge in children with other types of congenital heart defects.