Between-visit variability of small airway obstruction markers in patients with asthma

Abstract

To the Editor: Clinical trials in patients with airway diseases often use forced expiratory volume in 1 s (FEV1) as the sole physiological outcome measure. However, FEV1 is thought to be insensitive to obstruction of the smaller airways, which may be particularly relevant in asthma [1]. Putative markers of small airway obstruction include measures of airway resistance using impulse oscillometry (IOS) [2] and indices of ventilation heterogeneity derived from multiple-breath inert gas washout (MBW) [3]. We recently showed that increased airway resistance at 5 Hz ( R 5) and 20 Hz ( R 20) is associated with worse asthma control and more frequent exacerbations [4], and Farah et al. [5] demonstrated that MBW parameters may be responsive to asthma therapy. In order to conduct clinical trials using these alternative outcome measures, it is necessary to be assured of their repeatability and stability over time. Moreover, an estimate of between-visit variability in the stable state is required so that sample size calculations can be performed. We therefore aimed to determine the between-visit variability of a range of IOS and MBW indices in a group of patients with asthma in the stable state. We investigated between-visit variability over two time intervals, namely 2 weeks and 3 months, in order to encompass the typical lengths of treatment period that are used in clinical trials. We recruited 18 adults (age >18 years) with moderate-to-severe asthma (Global Initiative for Asthma treatment steps 3–5 [6]), diagnosed by a specialist asthma physician in a secondary care setting, according to British Thoracic Society guidelines [ …