Investigating outcome measures for assessing airway clearance techniques in adults with cystic fibrosis: protocol of a single-centre randomised controlled crossover trial

Abstract

IntroductionAirway clearance techniques (ACTs) are a gold standard of cystic fibrosis management; however, the majority of research evidence for their efficacy is of low standard; often attributed to the lack of sensitivity from outcome measures (OMs) used historically. This randomised controlled trial (RCT) investigates these standard OMs (sputum weight, forced expiratory volume in 1 s) and new OMs (electrical impedance tomography (EIT), multiple breath washout (MBW) and impulse oscillometry (IOS)) to determine the most useful measures of ACT.Methods and analysisThis is a single-centre RCT with crossover design. Participants perform MBW, IOS and spirometry, and then are randomised to either rest or supervised ACT lasting 30–60 min. MBW, IOS and spirometry are repeated immediately afterwards. EIT and sputum are collected during rest/ACT. On a separate day, the OMs are performed with the other intervention. Primary endpoint is difference in change in OMs before and after ACT/rest. Sample size was calculated with 80% power and significance of 5% for each OM (target n=64).Ethics and disseminationEthics approval was gained from the London–Chelsea Research Ethics Committee (reference 16/LO/0995, project ID 154635). Dissemination will involve scientific conference presentation and publication in a peer-reviewed journal.Trial registration numbersISRCTN11220163 and NCT02721498.

Clinimetric Analysis of Outcome Measures for Airway Clearance in Adults with Cystic Fibrosis: A Systematic Review

“…Of note, two ongoing studies were identi ed [22,23] but publication of results of these trials is still pending. One of these trials is investigating the use of magnetic-resonance imaging (MRI) scanning compared to spirometry for ACT assessment [23], while the other compares the clinimetric properties of FEV 1 , sputum weight, impulse oscillometry, lung clearance index derived from the multiple breath washout test and electrical impedance tomography when used for ACT assessment [22].…”

“…Of note, two ongoing studies were identi ed [22,23] but publication of results of these trials is still pending. One of these trials is investigating the use of magnetic-resonance imaging (MRI) scanning compared to spirometry for ACT assessment [23], while the other compares the clinimetric properties of FEV 1 , sputum weight, impulse oscillometry, lung clearance index derived from the multiple breath washout test and electrical impedance tomography when used for ACT assessment [22]. We excluded a conference abstract of preliminary results from this group [20] after full text review as it reported upon feasibility and reproducibility of OMS (LCI, IOS, EIT, FEV1) across two different visits, and did not report any pre-versus post-ACT data.…”

“…Reasons for exclusion were being a pilot study not an RCT [24] (one study); having the wrong study design as it investigated the effect of ACT upon LCI rather than if LCI could measure ACT effect [25] (one study); and being a conference abstract lacking detail[26] (one study) or reporting preliminary results only [20] (one study). Of note, the same two ongoing studies were identi ed as per the primary objective [22,23], and one of these was linked to the conference abstract preliminary results report [20] which have been discussed after exclusion following full text review for the primary objective.…”

“…This review identi ed two ongoing studies [22,23], which could suggest that the CF research community is trying to address the lack of robust ACT outcome measures. The results of these trials, which appear to be assessing the clinimetric properties of some of the emerging measures against historical outcomes (spirometry, LCI, plus two forms of MRI [23] and LCI, impulse oscillometry and electrical impedance compared to spirometry and sputum weight [22]) are urgently needed. Randomised controlled trials such as these are essential to enable clinicians and researchers to identify which outcome measures are appropriate to use for airway clearance assessment.…”

Oscillometry of the respiratory system: a translational opportunity not to be missed

“…This disease, as most other lung diseases, starts in the periphery and, as it progresses, it becomes measurable with oscillometry and eventually also with spirometry. Studies are underway to determine how airway clearing techniques impact different measures of lung function, and with the advent of new drugs targeting CF more studies can be expected ( 54 , 147 ). Using oscillometry to monitor children with CF might be a reasonable approach to capture early signs of lung deterioration.…”