(157) A Randomized Controlled Trial to Determine the Most Sensitive Outcome Measure of Airway Clearance in Cystic Fibrosis

Background: The best outcome measure (OM) for airway clearance (AC) in cystic fibrosis (CF) is unknown. Our NIHR-funded randomized controlled trial compared five primary OMs - sputum weight, FEV₁, end expiratory lung impedance (ΔEELI) from electronic impedance tomography (EIT), lung clearance index (LCI) from multiple breath washout (MBW) & R5-R20 from impulse oscillometry (IOS)) - to determine the most sensitive measure of a single session of AC.

Methods: Subjects completed OMs of MBW, IOS & spirometry then were randomized to either a single session of supervised AC or rest for 30 minutes. MBW, IOS & spirometry were repeated straight afterwards. EIT & sputum were collected during rest/AC period. At a subsequent visit the OMs were completed with the other intervention. Primary endpoint was difference in change in OMs pre-& post- AC/rest. Secondary endpoints included within group treatment effect & other physiological parameters. Target sample size was 64 to allow subgroup analysis of 2 groups stratified by FEV₁ percent predicted (pp) (FEV₁ >pp60 & FEV₁ ≤pp60). Changes reported as median (IQR).

Results: 68 participants completed: 42male; mean age 41yrs (SD 14.2); mean ppFEV₁ 64.5 (SD 23.9).

Primary OMs - sputum weight significantly differed after AC v. rest, change 4.4g (1.4-8.4) & 0g change (0-0.75), respectively (p< 0.05). No other significant differences for primary OMs were observed (table). In subgroup analysis there were no additional differences in the change in primary OMs after ACT v. rest by FEV₁ severity (table).

Conclusions: This study aimed to determine the most sensitive OM for a single session of AC. Our results show that of the 5 primary OMs (R5-R20, LCI 2.5, FEV₁, ΔEELI & sputum weight) only sputum weight significantly changed after ACT compared to rest, with minimal or no change in other OMs. Analysis of primary & secondary endpoints, & their potential clinical significance with subgroup stratification are ongoing.



Our results suggest that for adults with CF, FEV₁, LCI 2.5, R5-R20 & ΔEELI may not be suitable OMs to assess the efficacy of a single AC session. While sputum weight did show a significant change, this measure is limited in use to those who are productive of sputum. Further work is required to identify alternative OMs which are sensitive for both short & long-term assessment of AC for the whole adult CF cohort.

Acknowledgements: Funding statement - this work was supported by an HEE/NIHR clinical doctoral fellowship grant for G. Stanford (CDRF-2014-05-055).



Acknowledgements – RBH physiotherapy dept; C. Short; C. Saunders; M. Biddescombe; S. Meah; W. Banya.



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