Lung Clearance Index (LCI) measurements are reproducible and associated with airway physiological changes in steroid naive asthmatic (SNA) adults

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Introduction: LCI measures ventilation inhomogeneity which may arise from small airway dysfunction. LCI can be used to detect airway dysfunction not observed by spirometry. The use of LCI in adult asthma has not been extensively studied. We investigated the relationships between LCI and measurements of asthma pathophysiology in SNA adults and evaluated LCI reproducibility. Methods: 24 SNA were recruited. At Visit 1, symptoms were assessed using the Asthma Control Questionnaire. FeNO, spirometry and LCI (multiple breath nitrogen washout) measurements were done. Reversibility following 400mcg of inhaled salbutamol was measured. Blood eosinophil counts were measured. Induced sputum was processed and cytospin prepared for differential cell counts. At Visit 2 patients underwent a methacholine challenge. Patients came for a reproducibility visit within 1 month. Statistical analysis was done using Graphpad v6.0 and SPSS v22. Results: LCI measurements correlated with FEV1 (r = -0.60, p=0.002), FEV1/FVC (r = 0.59, p=0.003) and reversibility (r=0.46, p=0.02). There was no significant association with ACQ, PC20, FeNO or blood/sputum eosinophil and neutrophil counts. Bland Altman plots and intraclass correlation coefficient (Ri = 0.94) for LCI measurements between two visits show very good agreement. Conclusions: LCI correlates well with airflow limitation and reversibility in patients with mild asthma. LCI measurements also showed a high degree of reproducibility. The lack of association to symptom control may be related to sample size. Larger studies are needed to evaluate the utility of LCI to monitor asthma, particularly as a tool in clinical trials.