Rationale: Chronic lung injury is common in sickle cell anemia (SCA) and worsens outcomes. Sensitive lung function tests might predict reversible disease that might benefit from therapeutic interventions. Objectives: To evaluate whether lung clearance index (LCI) (measuring global ventilation inhomogeneity), intraacinar ventilation inhomogeneity (Sacin), and conductive ventilation inhomogeneity (Scond) are more frequently abnormal than lung volumes in young people with SCA. Methods: Nitrogen multiple-breath washout, spirometry, and body plethysmography were cross-sectionally evaluated at steady state in subjects with SCA (hemoglobin SS) and healthy control subjects aged 8-21 years from London, United Kingdom. Results: Thirty-five patients (51% boys, mean ± SD age, 16.4 ± 3.5 yr) and 31 control subjects (48% boys; 16.2 ± 3.2 yr) were tested. There were significant differences between the study and control groups in mean LCI (mean difference, 0.42 units; 95% confidence interval [CI], 0.22 to 0.63; P = 0.0001), Sacin (mean difference, 0.014 units; 95% CI, 0.001 to 0.026; P = 0.04), forced expiratory volume in 1 second (FEV1) (mean difference, -0.79 z-scores; 95% CI, -1.28 to -0.30; P = 0.002), forced vital capacity (FVC) (mean difference, -0.80 z-scores; 95% CI, -1.28 to -0.31, P = 0.002), and total lung capacity (mean difference, -0.76 z-scores; 95% CI, -1.25 to -0.29, P = 0.002), but not in Scond and FEV1-to-FVC ratio. Whereas 29% (10 of 35) of patients had LCI > 95th percentile of control subjects, 23% (8 of 35) had abnormal FEV1 (<5th percentile of the reference population). Conclusions: LCI detected slightly more abnormalities than lung volumes in young people with SCA. Significant differences from control subjects in LCI and Sacin but not in Scond and FEV1-to-FVC ratio suggest that the lung function changes were most likely owing to patchy peripheral lung disease.
Keywords: children; lung function; multiple-breath washout; sickle cell anemia.