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+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), 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, -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.