Longitudinal Decline in Lung Volume in a Population of Children with Sickle Cell Disease

Rationale: Sickle cell disease (SCD) results in significant morbidity and mortality attributable to pulmonary complications. The pattern of lung function change across childhood in SCD is not well delineated. Objectives: To determine if the pattern of lung function in SCD differs from race-matched, predicted values across childhood, to describe that pattern of change, and to examine the effect of clinical covariates on lung function. Methods: Lung function measurements for children with SCID, aged 8-18 years, from a single center were examined for inclusion. Mixed-model analysis was used to retrospectively review lung function in these children in comparison with those predicted by race-matched reference equations. The contribution of age, sex, Hb level, and P-globin genotype on longitudinal changes in lung function was examined. Measurements and Main Results: Children with SCID show significant decline in spirometric lung volumes across childhood that are concordant with the pattern of change in other measures of lung volume. The average decline for FEV1 and total lung capacity is 2.93 and 2.15% predicted/year for males and 2.95 and 2.43% predicted/year for females. beta-Globin genotypes known to be associated with more severe disease showed a faster decline in lung function, whereas sex showed an inconsistent effect on lung function. Conclusions: Lung volumes in children with SCD decline with age. The pattern of decline begins in childhood, and supports a predominately restrictive defect.