Timing of hypertonic saline and airway clearance techniques in adults with cystic fibrosis during pulmonary exacerbation: pilot data from a randomised crossover study

Katherine O'Neill, Fidelma Moran, Michael M Tunney, J Stuart Elborn, Ian Bradbury, Damian G Downey, Jackie Rendall, Judy M Bradley, Katherine O'Neill, Fidelma Moran, Michael M Tunney, J Stuart Elborn, Ian Bradbury, Damian G Downey, Jackie Rendall, Judy M Bradley

Abstract

Background: Streamlining the timing of treatments in cystic fibrosis (CF) is important to optimise adherence while ensuring efficacy. The optimal timing of treatment with hypertonic saline (HTS) and airway clearance techniques (ACT) is unknown.

Objectives: This study hypothesised that HTS before ACT would be more effective than HTS during ACT as measured by Lung Clearance Index (LCI).

Methods: Adults with CF providing written informed consent were randomised to a crossover trial of HTS before ACT or HTS during ACT on consecutive days. ACT treatment consisted of Acapella Duet. Patients completed LCI and spirometry at baseline and 90 min post treatment. Mean difference (MD) and 95% CIs were reported.

Results: 13 subjects completed the study (mean (SD) age 33 (12) years, forced expiratory volume in 1second % (FEV1%) predicted 51% (22), LCI (no. turnovers) 14 (4)). Comparing the two treatments (HTS before ACT vs HTS during ACT), the change from baseline to 90 min post treatment in LCI (MD (95% CI) -0.02 (-0.63 to 0.59)) and FEV1% predicted (MD (95% CI) -0.25 (-2.50 to 1.99)) was not significant. There was no difference in sputum weight (MD (95% CI) -3.0 (-14.9 to 8.9)), patient perceived ease of clearance (MD (95% CI) 0.4 (-0.6 to 1.3) or satisfaction (MD (95% CI) 0.4 (-0.6 to 1.5)). The time taken for HTS during ACT was significantly shorter (MD (95% CI) 14.7 (9.8 to 19.6)).

Conclusions: In this pilot study, HTS before ACT was no more effective than HTS during ACT as measured by LCI.

Trial registration number: NCT01753869; Pre-results.

Keywords: Cystic Fibrosis; Respiratory Measurement.

Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
Flow chart of recruitment.
Figure 2
Figure 2
Change in LCI with (A) HTS before ACT and (B) HTS during ACT (mean and 95% CIs). ACT, airway clearance treatment; HTS, hypertonic saline; LCI, Lung Clearance Index.

References

    1. Warnock L, Gates A. Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis. Cochrane Database Syst Rev 2015(12):CD001401
    1. Morrison L, Agnew J. Oscillating devices for airway clearance in people with cystic fibrosis. Cochrane Database Syst Rev 2014;(7):CD006842
    1. Main E, Prasad A, Schans C. Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis. Cochrane Database Syst Rev 2005;(1):CD002011
    1. van der Schans C, Prasad A, Main E. Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis. Cochrane Database Syst Rev 2000;(2):CD001401
    1. McIlwaine M, Button B, Dwan K. Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis. Cochrane Database Syst Rev 2015;(6):CD003147
    1. Main E, Grillo L, Rand S. Airway clearance strategies in cystic fibrosis and non-cystic fibrosis bronchiectasis. Semin Respir Crit Care Med 2015;36:251–66.
    1. Bradley JM, Moran FM, Elborn JS. Evidence for physical therapies (airway clearance and physical training) in cystic fibrosis: an overview of five Cochrane systematic reviews. Respir Med 2006;100:191–201.
    1. Rand S, Hill L, Prasad SA. Physiotherapy in cystic fibrosis: optimising techniques to improve outcomes. Paediatr Respir Rev 2013;14:263–9.
    1. Amin R, Stanojevic S, Kane M et al. . A randomized controlled trial to evaluate the lung clearance index as an outcome measure for early phase studies in patients with cystic fibrosis. Respir Med 2016;112:59–64.
    1. Dentice RL, Elkins MR, Middleton PG et al. . A randomised trial of hypertonic saline during hospitalisation for exacerbation of cystic fibrosis. Thorax 2016;71:141–7.
    1. Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev 2009;(2):CD001506
    1. Elkins MR, Bye PT. Inhaled hypertonic saline as a therapy for cystic fibrosis. Curr Opin Pulm Med 2006;12:445–52.
    1. Eng PA, Morton J, Douglass JA et al. . Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis. Pediatr Pulmonol 1996;21:77–83.
    1. Subbarao P, Stanojevic S, Brown M et al. . Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline. Am J Respir Crit Care Med 2013;188:456–60.
    1. Elkins M, Dentice R. Timing of hypertonic saline inhalation for cystic fibrosis. Cochrane Database Syst Rev 2012;(2):CD008816
    1. Dentice RL, Elkins MR, Bye PTP. Adults with cystic fibrosis prefer hypertonic saline before or during airway clearance techniques: a randomised crossover trial. J Physiother 2012;58:33–40.
    1. Stanojevic S, Ratjen F. Physiologic endpoints for clinical studies for cystic fibrosis. J Cyst Fibros 2016;15:416–23.
    1. Robinson PD, Goldman MD, Gustafsson PM. Inert gas washout: theoretical background and clinical utility in respiratory disease. Respiration 2009;78:339–55.
    1. Aurora P, Bush A, Gustafsson P et al. . Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis. Am J Respir Crit Care Med 2005;171:249–56.
    1. O'Neill K, Tunney MM, Johnston E et al. . Lung clearance index in adults and children with cystic fibrosis. Chest 2016;150:1323–32.
    1. Amin R, Subbarao P, Jabar A et al. . Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax 2010;65:379–83.
    1. Amin R, Subbarao P, Lou W et al. . The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis. Eur Respir J 2011;37:806–12.
    1. Rodriguez Hortal MC, Nygren-Bonnier M, Hjelte L. Non-invasive ventilation as airway clearance technique in cystic fibrosis. Physiother Res Int 2016. doi: 10.1002/pri.1667. [Epub ahead of print 29 Feb 2016]
    1. Davies J, Sheridan H, Bell N et al. . Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomised controlled trial. Lancet Respir Med 2013;1:630–8.
    1. Horsley AR, Gustafsson PM, Macleod KA et al. . Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. Thorax 2008;63:135–40.
    1. Miller MR, Hankinson J, Brusasco V et al. . Standardisation of spirometry. Eur Respir J 2005;26:319–38.
    1. Stanojevic S, Wade A, Stocks J et al. . Reference ranges for spirometry across all ages. Am J Respir Crit Care Med 2008;177:253–60.
    1. Main E. What is the best airway clearance technique in cystic fibrosis? Paediatr Respir Rev 2013;14(Suppl 1):10–12.
    1. Fuchs SI, Toussaint S, Edlhaimb B et al. . Short-term effect of physiotherapy on variability of the lung clearance index in children with cystic fibrosis. Pediatr Pulmonol 2010;45:301–6.
    1. Pfleger A, Steinbacher M, Schwantzer G et al. . Short-term effects of physiotherapy on ventilation inhomogeneity in cystic fibrosis patients with a wide range of lung disease severity. J Cyst Fibros 2015;14:627–31.
    1. Sonneveld N, Stanojevic S, Amin R et al. . Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations. Eur Respir J 2015;46:1055–64.
    1. Horsley A. Lung clearance index in the assessment of airways disease. Respir Med 2009;103:793–9.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren