International Journal of Cardiology Congenital Heart Disease (May 2021)
Abnormal spirometry in adults with 22q11.2 microdeletion and congenital heart disease
Abstract
Background: In adults with congenital heart disease (CHD), pulmonary dysfunction is prevalent and associated with poor outcomes; however, underlying genetic contributors remain unexamined. We investigated whether the 22q11.2 microdeletion, an important genetic cause of CHD, was associated with abnormal spirometry in adults with CHD. Methods: We conducted a retrospective case-control study of 207 adults with CHD (predominantly tetralogy of Fallot), and spirometry data available from cardiopulmonary exercise testing, matching 58 with a confirmed 22q11.2 microdeletion to 149 controls on age (median 26.4, 28.2 years, respectively), sex, ethnicity, and CHD severity (37.9%, 29.5% complex, respectively). We examined forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), their % predicted values, and FEV1/FVC ratio. Results: All respiratory parameters assessed were significantly worse in those with 22q11.2 deletion syndrome (22q11.2DS-CHD) as compared to CHD-controls. Linear regression models indicated that the 22q11.2 microdeletion was associated with worse spirometry values even when accounting for complex CHD (FVC% predicted, p < 0.0001), scoliosis (FVC% predicted, p = 0.0007), and asthma (FEV1/FVC, p < 0.0001). The 22q11.2 microdeletion effect appeared mixed: associated with both FVC% predicted ≤70%, suggestive of a restrictive defect (OR 3.82, p = 0.0020), and FEV1/FVC <70%, suggestive of an obstructive defect (OR 2.80, p = 0.015). Intellectual disability did not affect the 22q11.2DS-CHD spirometry results. Conclusions: The findings indicate that adults with CHD and a 22q11.2 microdeletion are disproportionately represented amongst those with abnormal spirometry, supporting the potential value of early pulmonary function testing in those with 22q11.2DS and enhanced genetic testing for the 22q11.2 microdeletion in CHD.
