Correlation between change in lung density and lung function parameters in treated alpha-1 protease inhibitor (A1-PI) deficiency

Abstract

Introduction: Lung function parameters are less sensitive for monitoring emphysema progression than computed tomography (CT). In patients with A 1 -PI deficiency the most sensitive measure to assess efficacy of intravenous A 1 -PI therapy is 15 th percentile lung density (PD15). The RAPID trial (NCT00261833) demonstrated a significant reduction in lung tissue loss in patients receiving A 1 -PI (Zemaira ® /Respreeza ® ; n=93) vs. placebo (n=85). Aim: To assess the correlation between changes in PD15 and clinical parameters in patients with A 1 -PI deficiency. Methods: In RAPID, 180 patients with A 1 -PI deficiency were randomized to receive placebo or A 1 -PI for 2 years. Subsequently, 140 patients completed a 2-year open-label extension trial (NCT00670007). Assessments included CT densitometry, spirometry and quality-of-life questionnaire (SGRQ). Change in adjusted PD15 over 4 years was correlated with changes in these parameters using Pearson9s correlation coefficients. Results: Significant weak-to-moderate positive correlations were observed between the change in PD15 and forced expiratory volume in 1s (FEV 1 ; r=0.286), FEV 1 % predicted (r=0.338) and forced vital capacity (FVC; r=0.296), all p≤0.002. Changes in total SGRQ and activity, symptom and impact scores were not correlated with changes in lung density. Conclusion: This study is the first to assess changes in lung density and clinical parameters in A 1 -PI-deficient patients over 4 years in a multicentrecontrolled trial. Consistent positive correlations were found between changes in PD15 and spirometric parameters, confirming that changes in lung density are paralleled by changes in lung function.