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Meta-Analysis
. 2023 Apr 12;4(4):CD001401.
doi: 10.1002/14651858.CD001401.pub4.

Airway clearance techniques compared to no airway clearance techniques for cystic fibrosis

Louise Warnock  1 , Alison Gates  1
Affiliations
Meta-Analysis

Airway clearance techniques compared to no airway clearance techniques for cystic fibrosis

Louise Warnock et al. Cochrane Database Syst Rev. .

Abstract

Background: Cystic fibrosis (CF) is an inherited progressive life-limiting disease characterised by the build-up of abnormally thick, sticky mucus affecting mostly the lungs, pancreas, and digestive system. Airway clearance techniques (ACTs), traditionally referred to as chest physiotherapy, are recommended as part of a complex treatment programme for people with CF. The aim of an ACTs is to enhance mucociliary clearance and remove viscous secretions from the airways within the lung to prevent distal airway obstruction. This reduces the infective burden and associated inflammatory effects on the airway epithelia. There are a number of recognised ACTs, none of which have shown superiority in improving short-term outcomes related to mucus transport. This systematic review, which has been updated regularly since it was first published in 2000, considers the efficacy of ACTs compared to not performing any ACT in adults and children with CF. It is important to continue to review this evidence, particularly the long-term outcomes, given the recent introduction of highly effective modulator therapies and the improved health outcomes and potential changes to CF management associated with these drugs.

Objectives: To determine the effectiveness and acceptability of airway clearance techniques compared to no airway clearance techniques or cough alone in people with cystic fibrosis.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings, to 17 October 2022. We searched ongoing trials registers (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) to 7 November 2022.

Selection criteria: We included randomised or quasi-randomised studies that compared airway clearance techniques (chest physiotherapy) with no airway clearance techniques or spontaneous cough alone in people with CF.

Data collection and analysis: Both review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of the included studies. We used GRADE methodology to assess the certainty of the evidence.

Main results: We included 11 cross-over studies (153 participants) and one parallel study (41 participants). There were differences between studies in how the interventions were delivered, with several intervention groups combining more than one ACT. One study used autogenic drainage; five used conventional chest physiotherapy; nine used positive expiratory pressure (PEP), with one study varying the water pressure between arms; three studies used oscillating PEP; two used exercise; and two used high-frequency chest wall oscillation (HFCWO). Of the 12 included studies, 10 were single-treatment studies, and two delivered the intervention over two consecutive days (once daily in one study, twice daily in the second). This substantial heterogeneity in the treatment interventions precluded pooling of data for meta-analysis. Blinding of participants, caregivers, and clinicians is impossible in airway clearance studies; we therefore judged all studies at unclear risk of performance bias. Lack of information in eight studies made assessment of risk of bias unclear for most other domains. We rated the certainty of evidence as low or very low due to the short-term cross-over trial design, small numbers of participants, and uncertain risk of bias across most or all domains. Six studies (84 participants) reported no effect on pulmonary function variables following intervention; but one study (14 participants) reported an improvement in pulmonary function following the intervention in some of the treatment groups. Two studies reported lung clearance index: one (41 participants) found a variable response to treatment with HFCWO, whilst another (15 participants) found no effect on lung clearance index with PEP therapy (low-certainty evidence). Five studies (55 participants) reported that ACTs, including coughing, increased radioactive tracer clearance compared to control, while a further study (eight participants) reported no improvement in radioactive tracer clearance when comparing PEP to control, although coughing was discouraged during the PEP intervention. We rated the certainty of evidence on the effect of ACTs on radioactive tracer clearance as very low. Four studies (46 participants) investigated the weight of mucus cleared from the lungs and reported greater secretions during chest physiotherapy compared to a control. One study (18 participants) reported no differences in sputum weight (very low-certainty evidence).

Authors' conclusions: The evidence from this review shows that ACTs may have short-term effects on increasing mucus transport in people with CF. All included studies had short-term follow-up; consequently, we were unable to draw any conclusions on the long-term effects of ACTs compared to no ACTs in people with CF. The evidence in this review represents the use of airway clearance techniques in a CF population before widespread use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Further research is needed to determine the effectiveness and acceptability of airway clearance in those treated with highly effective CFTR modulators.

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Conflict of interest statement

AG declares no known conflicts of interest. LW declares no known conflicts of interest.

Figures

1
1
Study selection process for 2023 update.
2
2
1.1
1.1. Analysis
Comparison 1: Airway clearance techniques (ACTs) versus no ACTs, Outcome 1: FEV1 (L) – change from baseline
1.2
1.2. Analysis
Comparison 1: Airway clearance techniques (ACTs) versus no ACTs, Outcome 2: FVC (L) – change from baseline
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Falk 1988 {published data only}
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Gaskin 1998 {published data only}
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Giles 1995 {published data only}
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Gondor 1999 {published data only}
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Gotz 1995 {published data only}
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Hansen 1990 {published data only}
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Hare 2002 {published data only}
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Hartsell 1978 {published data only}
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Helper 2020 {published data only}
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Hofmeyr 1986 {published data only}
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Holland 2003 {published data only}
    1. Holland A, Denehy L, Ntoumenopoulos G, McMeeken J, Wilson J. Non-invasive ventilation prevents inspiratory muscle fatigue and oxygen desaturation during airway clearance in adults with acute exacerbations of cystic fibrosis. In: Thoracic Society of Australia & New Zealand Annual Scientific Meeting; 2003 April 4-9; Adelaide, Australia. 2003:Abstract no: P140. [CENTRAL: 460951] [CFGD REGISTER: PE143d]
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    1. Holland A, Denehy L, Ntoumenopoulos G, Naughton M, et al. Non-invasive ventilation preserves inspiratory muscle strength and prevents oxygen desaturation during airway clearance in adults with exacerbations of cystic fibrosis. Australian Journal of Physiotherapy 2004;50(3):A6. [CFGD REGISTER: PE143e]
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Homnick 1995 {published data only}
    1. Homnick D, Spillers C, White F. The intrapulmonary percussive ventilator compared to standard aerosol therapy and chest physiotherapy in the treatment of patients with cystic fibrosis [abstract]. Pediatric Pulmonology 1994;18 Suppl 10:312. [CFGD REGISTER: PE27a]
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Homnick 1998 {published data only}
    1. Homnick DN, Anderson K, Marks JH. Comparison of the Flutter device to standard chest physiotherapy in hospitalized patients with cystic fibrosis: a pilot study. Chest 1998;114(4):993-7. [CFGD REGISTER: PE72b] - PubMed
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Horsley 2007 {published data only}
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Hristara‐Papadopoulou 2007 {published data only}
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Kerrebijn 1982 {published data only}
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Kluft 1996 {published data only}
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Kofler 1994 {published data only}
    1. Kofler AM, Belluscio M, Bressan T, Carlesi A, Leone P, Lucidi V, et al. PEP-mask and active cycle of breathing techniques. What is better in children with cystic fibrosis. In: 19th European Cystic Fibrosis Conference; 1994. 1994:O66. [CFGD REGISTER: PE50]
Kofler 1998 {published data only}
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Konstan 1994 {published data only}
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Lagerkvist 2006 {published data only}
    1. Lagerkvist AL, Sten G, Lindblad A, Redfors S. Chest physiotherapy with positive expiratory pressure (PEP) and oscillating positive expiratory pressure (Flutter) in patients with cystic fibrosis-a comparative study. In: 21st European Cystic Fibrosis Conference; 1997; Davos, Switzerland. 1997:132. [CFGD REGISTER: PE87a]
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Lannefors 1992 {published data only}
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Leemans 2020 {published data only}
    1. Leemans G, Belmans D, Van Holsbeke C, Becker B, Vissers D, Ides K, et al. The effectiveness of a mobile high-frequency chest wall oscillation (HFCWO) device for airway clearance. Pediatric Pulmonology 2020;55(8):1984-92. Online supporting information. [CFGD REGISTER: PE259d] - PMC - PubMed
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Lyons 1992 {published data only}
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Majaesic 1996 {published data only}
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Marks 1999 {published data only}
    1. Marks JH, Hare KL, Homnick D. The PercussiveTech HF device compared to standard chest physiotherapy in patients with cystic fibrosis. In: XIII Cystic Fibrosis Congress; 2000 June 4-8; Stockholm, Sweden. 2000:151. [CFGD REGISTER: PE109b]
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Maxwell 1979 {published data only}
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McCarren 2006 {published data only}
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McIlwaine 2001 {published data only}
    1. Davidson AG, McIlwaine PM, Wong LT, Peacock D. "Flutter versus PEP": a long-term comparative trial of positive expiratory pressure (PEP) versus oscillating positive expiratory pressure (Flutter) physiotherapy techniques. In: 22nd European Cystic Fibrosis Conference; 1998 June 13-18; Berlin. 1998:71. [CFGD REGISTER: PE89b]
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McIlwaine 2010 {published data only}
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McIlwaine 2013 {published data only}
    1. Alarie N, Agnew JL, McIlwaine M, Ratjen F, Davidson G, Lands LC. Canadian National Airway Clearance Study: how physically active are CF patients? [abstract]. Pediatric Pulmonology 2012;47 Suppl 35:367, Abstract no:398. [CFGD REGISTER: PE187e]
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McIlwaine 2014 {published data only}
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Miller 1995 {published data only}
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Morris 1982 {published data only}
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Murphy 1983 {published data only}
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NCT01266473 {published data only}
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NCT03655249 {published data only}
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NCT04010253 {published data only}
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Oberwaldner 1991 {published data only}
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Osman 2010 {published data only}
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Patel 2013 {published data only}
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Phillips 2004 {published data only}
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Placidi 2006 {published data only}
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Prasad 2005 {published data only}
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Pryor 1979a {published data only}
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Pryor 1990 {published data only}
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Pryor 1994 {published data only}
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Pryor 2010 {published data only}
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Rodriguez 2013 {published data only}
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    1. Sanchez Riera H, Dapena Fernandez FJ, Gomez Dominguez F, Ortega Ruiz F, Elias Hernandez T, Montemayor Rubio T, et al. Comparative study of the efficacy of 2 respiratory physiotherapy protocols for patients with cystic fibrosis [Estudio comparativo de la eficacia de dos protocolos de fisioterapia respiratoria en pacientes con fibrosis quística]. Archivos de Bronconeumología 1999;35(6):275-9. [CFGD REGISTER: PE106a] - PubMed
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San Miguel Pagola 2020 {published data only}
    1. Herrero Cortina B, San Miguel Pagola M, Cebria i Ranzo MA, Gomez Romero M, Diaz Gutierrez F, Reychler G. Short-term effects of hypertonic saline nebulization combined with oscillatory positive expiratory pressure in cystic fibrosis: randomised crossover trial. Journal of Cystic Fibrosis 2016;15 Suppl 1:S33. [ABSTRACT NO.: WS21.3] [CFGD REGISTER: BD229a] - PubMed
    1. NCT02303808. Positive expiratory pressure during inhalation of hypertonic saline in patients with cystic fibrosis. clinicaltrials.gov/show/nct02303808 (first received 1 December 2014). [CFGD REGISTER: BD229c]
    1. San Miguel Pagola M, Herrero Cortina B, Cebria i Iranzo MA, Gomez Romero M, Diaz Gutierrez F, Reychler G. Hypertonic saline nebulization combined with oscillatory positive expiratory pressure accelerate sputum clearance in cystic fibrosis: a randomised crossover trial. European Respiratory Journal 2016;48 Suppl 60:PA1369. [CFGD REGISTER: BD229b] - PubMed
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Stanford 2019a {published data only}
    1. NCT01885650. The addition of non-invasive ventilation to airway clearance techniques in adults with cystic fibrosis. clinicaltrials.gov/show/nct01885650 (first received 25 June 2013). [CFGD REGISTER: OV25a]
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Steven 1992 {published data only}
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van Asperen 1987 {published data only}
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References to ongoing studies

NCT03760120 {published data only}
    1. NCT03760120. Short-term effects of physiotherapy on LCI. clinicaltrials.gov/show/nct03760120 (first received 30 November 2018). [CFGD REGISTER: PE332]
Stanford 2019b {published data only}
    1. ISRCTN11220163. Investigating outcome measures for trials of airway clearance techniques in adults with cystic fibrosis. trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN11220163 (first received 19 September 2016). [CFGD REGISTER: PE281d]
    1. NCT02721498. Improving outcome measures for adult CF ACT trials. clinicaltrials.gov/ct2/show/NCT02721498?term=NCT02721498&rank=1 (first received 29 March 2016). [CFGD REGISTER: PE281b]
    1. Stanford G, Cathcart F, Beverley Z, Short C, Jones M, Bilton D, et al. Investigating outcome measures for physiotherapy trials of airway clearance in adult patients with cystic fibrosis. Journal of Cystic Fibrosis 2019;18 Suppl 1:S3. [CFGD REGISTER: PE281a]
    1. Stanford G, Davies JC, Usmani O, Banya W, Charman S, Jones M, et al. Investigating outcome measures for assessing airway clearance techniques in adults with cystic fibrosis: protocol of a single-centre randomised controlled crossover trial. BMJ Open Respiratory Research 2020;7:e000694. [CFGD REGISTER: PE281c] [DOI: 10.1136/bmjresp-2020-000694] - DOI - PMC - PubMed
    1. Stanford GE, Cathcart F, Beverley Z, Short C, Jones M, Bilton D, et al. Outcome measures for airway clearance in adults with cystic fibrosis (CF): a randomised controlled crossover trial. Thorax 2019;74:A222. [CFGD REGISTER: PE281e]

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