Lung clearance index to detect the efficacy of Aztreonam lysine inhalation in patients with cystic fibrosis and near normal spirometry - A single-centre feasibility study.

Helmut Ellemunter,Gratiana Steinkamp

doi:10.1371/journal.pone.0221673

Helmut Ellemunter, Gratiana Steinkamp

Open Access

https://doi.org/10.1371/journal.pone.0221673

Copy DOI

Abstract

Comparing the efficacy of inhaled antibiotics can be difficult in small groups of patients with cystic fibrosis and mild lung disease. In a feasibility study we compared Aztreonam lysine for inhalation solution (AZLI; Cayston®) to standard inhaled antibiotic therapy in patients with cystic fibrosis and near normal spirometry. To detect treatment responses we used both lung clearance index (LCI) and forced expiratory volume in one second (FEV1). At baseline, median FEV1 was 87% pred. and median LCI was 8.6 (upper limit of normal: 7.0). After 4 weeks, LCI improved by -0.36 after AZLI and deteriorated by +0.12 after tobramycin treatment (p = 0.039). No significant differences between treatments (p = 0.195) were observed using FEV1. These results suggest that lung clearance index can be used to detect treatment induced changes in subjects with mild lung disease.

Highlights

Inhaled antibiotics are important for the suppression of chronic P. aeruginosa (PA) infection in patients with cystic fibrosis (CF)
In a small group of patients with cystic fibrosis and mild lung disease, greater improvements in lung clearance index and respiratory symptoms were observed after a 4-week course of Aztreonam lysine for inhalation solution (AZLI) compared to the standard inhaled antibiotic tobramycin
FEV1 did not show significant differences between the two treatment periods. The results of this small feasibility study are in agreement with previous findings that using FEV1 as an outcome measure requires larger groups of patients with predominantly moderate to severe lung disease and a greater potential for improvement [15,16,17,18]

Summary

Introduction

Inhaled antibiotics are important for the suppression of chronic P. aeruginosa (PA) infection in patients with cystic fibrosis (CF). Aztreonam lysine (AZLI, Cayston1) for inhalation solution was licensed in Europe in 2009 for the suppressive therapy of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with CF aged 6 years and older. With small patient cohorts of up to 20 patients, it is difficult to detect changes after treatment using FEV1 as an endpoint [5,6]. This is relevant if two active compounds are to be compared or if the inhaled antibiotic is switched from a conventional to a new drug. At the CF Centre Innsbruck, we have been using the multiple breath washout (MBW)

Methods

Results

Conclusion