Lung Clearance Index May Detect Early Peripheral Lung Disease in Sickle Cell Anemia

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 (S_acin), and conductive ventilation inhomogeneity (S_cond) 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 6 SD age, 16.4 6 3.5 yr) and 31 control subjects (48% boys; 16.2 6 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), S_acin (mean difference, 0.014 units; 95% CI, 0.001 to 0.026; P = 0.04), forced expiratory volume in 1 second (FEV₁) (mean difference, 20.79 z-scores; 95% CI, 21.28 to 20.30; P = 0.002), forced vital capacity (FVC) (mean difference, 20.80 z-scores; 95% CI, 21.28 to 20.31, P = 0.002), and total lung capacity (mean difference, 20.76 z-scores; 95% CI, 21.25 to 20.29, P = 0.002), but not in S_cond 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 S_acin but not in S_cond and FEV₁to-FVC ratio suggest that the lung function changes were most likely owing to patchy peripheral lung disease.