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Airway Clearance, Mucoactive Therapies and Pulmonary Rehabilitation in Bronchiectasis

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Airway Clearance, Mucoactive Therapies and Pulmonary Rehabilitation in Bronchiectasis INVITED REVIEW SERIES: PAEDIATRIC AND ADULT BRONCHIECTASIS SERIES EDITORS: ADAM T. HILL AND ANNE B. CHANG Airway clearance, mucoactive therapies and pulmonary rehabilitation in bronchiectasis 1 2 1 KATHERINE O’NEILL, ANNE E. O’DONNELL AND JUDY M. BRADLEY 1The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast, UK; 2Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Hospital, Washington, DC, USA ABSTRACT the main clinical manifestations reported in patients 1–3 This paper aims to provide physiological rationale for with bronchiectasis. These symptoms worsen during airway clearance, mucoactive therapy and pulmonary exacerbations and impact negatively on health-related 4 rehabilitation (PR) (or exercise interventions) in bronchi- quality of life (HRQoL). This paper summarizes the ectasis. There is increasing emphasis on the role of airway physiological rationale for airway clearance including clearance techniques (ACT) in the management of bron- mucoactive therapy as well as pulmonary rehabilitation chiectasis. No single ACT has currently shown superior (PR) (or exercise interventions) in bronchiectasis. effect over another. Given the large range of different tech- niques available, consideration of the physiological effects underpinning a technique including expiratory flow, venti- AIRWAY CLEARANCE IN lation and oscillation, is essential to effectively personalize BRONCHIECTASIS ACT. Key clinical trials of mucoactives in bronchiectasis areunderwayandwillprovideclarityontheroleofthese Airway clearance techniques (ACT) are non- agents in the management of patients with bronchiectasis. pharmacological strategies to improve symptoms and Prescription of mucoactive therapies should be done in HRQoL and reduce exacerbation frequency.5,6 Short- conjunction with ACT and therefore the mechanism of term goals are to provide more effective sputum clear- action of mucoactive drugs and their timing with ACT ance that improves ventilation and reduces cough should be taken into consideration. PR and/or exercise impact and breathlessness. Longer term goals are training are recommended in all current bronchiectasis reducing further airway damage by halting the vicious guidelines. There is a clear physiological rationale that fl muscle weakness and physical inactivity may play a role in cycle of bacterial colonization and subsequent in am- mation, reducing the number of pulmonary exacerba- disease progression as well as impacting health-related 7–9 quality of life, frequency of pulmonary exacerbations and tions and hospitalizations and improving HRQoL. ability to mobilize sputum. However, there are residual Published guidelines agree that ACT are a key com- unanswered questions surrounding the delivery and acces- ponent in the management of bronchiectasis and that sibility to PR. This review summarizes the physiological all patients with bronchiectasis should be taught ACT principles and supporting evidence for airway clearance, by a respiratory physiotherapist. ACT which can be mucoactive medication and PR, which are key components performed independently are recommended in these in the management of bronchiectasis. guidelines.7,9 Patients with a chronic productive cough or difficulty expectorating sputum may benefit from regular twice daily ACT as recommended in current Key words: airway clearance, bronchiectasis, mucoactives, guidelines.9 In addition, the physiotherapist can discuss pulmonary rehabilitation. step up and step down ACT in managing exacerba- tions.9 In practice, ACT remain significantly underuti- INTRODUCTION lized. Data from the European Bronchiectasis Data Registry (EMBARC) report that only 45% of data regis- Chronic cough, sputum production as well as trants perform an ACT regularly.10 Furthermore, airway decreased exercise capacity and inactivity are some of clearance has very low rates of adherence.11 ACT rely on two overriding physiological principles. First, a mechanism to allow air to move behind the Correspondence: Katherine O’Neill, The Wellcome-Wolfson obstruction and ventilate the regions distally and second, Institute for Experimental Medicine, School of Medicine, modulation of expiratory airflow to propel secretions prox- Dentistry and Biomedical Science, Queen’s University Belfast, fl Lisburn Road, Belfast BT9 7BL, UK. Email: [email protected] imally up the airways. in vitro ow models suggest two Received 02 July 2018; invited to revise 26 July 2018; revised conditions that improve airway clearance: (i) the peak 15 October 2018; accepted 27 November 2018. expiratory flow rate should be greater than the peak © 2019 Asian Pacific Society of Respirology Respirology (2019) 24, 227–237 doi: 10.1111/resp.13459 228 KO’Neill et al. inspiratory flow rate (at least 10%) for mucus to move Selection of ACT should be targeted according to the proximally; (ii) and a peak expiratory flow rate of 30–60 L/ patient’s individual characteristics, that is personalized min is required to break the adhesive bonds generated to that patient.20,21 McIlwaine et al. highlighted that key between the mucus layer and the airway epithelial sur- to personalizing ACT is considering the physiological face.12 Both are essential for enhancing mucus clearance. principles underpinning the technique. ACT rely on Recommendations and the evidence to support the two main physiological premises: the ability to ventilate use of ACT are based on a limited number of clinical behind obstructed regions of the lung and the capacity trials, many of which are single treatment studies. Two to achieve the minimum expiratory airflow bias neces- Cochrane reviews have summarized data from 16 ran- sary to mobilize secretions. The authors advocate that domized controlled trials (RCT) (13 of which were understanding how each ACT incorporates these pro- crossover design) concluding that airway clearance is posed physiological effects could inform clinical safe and may account for improvements in sputum decision-making and drive personalization of ACT, for expectoration, some measures of lung function, symp- example, use of a forced expiration may need to be toms and HRQoL.5,6 One of the reviews concluded that adapted to a patient with collapsible airways.20 We now positive expiratory pressure (PEP) was as effective as describe how a range of additional techniques utilize other ACT.5 the physiological principles of ventilation and expira- Considering studies with interventions longer than tory airflow (Table 1). These additional techniques single treatments, Patterson et al. demonstrated that have been used in studies of bronchiectasis and/or there was no difference in lung function and sputum reported by the manufacturers to be of benefit in bron- weight with active cycle of breathing techniques chiectasis for airway clearance. Albeit, many of these (ACBT) versus Acapella (Smiths Medical International, techniques have not been subject to clinical trials. Hythe, UK) (oscillating PEP device) over a 10–14 day Table 1 provides a description of the technique and treatment period in 20 stable patients.13 In 17 patients, how they perform considering these key physiological Thompson et al. reported that there was no significant principles (Table 1). difference between ACBT and the Flutter (oscillating For children with bronchiectasis, the principles of PEP device) after a 4-week treatment period, in any of ACT in current practice follow what has been described the outcomes used (HRQoL, lung function and spu- in adults, given the paucity of research which exists.36 tum).14 Over three treatment sessions, the techniques Questions remain around how airway clearance relates of autogenic drainage (AD) and ELTGOL (an active to key clinical outcomes in bronchiectasis in both adults technique where the subject carries out slow expiration and children.6,36 Crucially, there is no strong evidence to with the glottis open in a lateral decubitus position) inform choice, frequency or duration of ACT in bronchi- have been compared to a control group of 31 patients ectasis. Tailoring of ACT to the individual patient is performing temporary PEP in a study by Herrero- recommended across the age range19,37 and physiothera- Cortina et al. Both AD and ELTGOL resulted in signifi- pists must consider how to optimally personalize ACT. cantly greater sputum compared to the control group.15 Tailoring includes physiology, symptoms, evidence base Munoz et al. compared the ELTGOL technique to pla- and patient factors as well as age-related factors when cebo exercises twice daily (b.d.) in 44 patients over a treating children which include levels of understanding, 1-year period and reported fewer exacerbations, maturity and the parent–child relationship, all of which reduced cough impact and improved HRQoL in the may influence adherence to ACT. There are recognized ELTGOL group.16 challenges performing traditional, longer term RCT of In terms of the supporting evidence for oscillating PEP, ACT due to the huge challenge of blinding and random Murray et al.comparedAcapellatonotreatmentin allocation of such treatments as well as the influence of 20 stable adult bronchiectasis patients over a 3-month patient preference. Exploration of different study designs period.17 There was no change in pulmonary exacerba- has been suggested in cystic fibrosis (CF).38 In bronchi- tion frequency or pulmonary function. There was signifi- ectasis, future research using novel designs and long- cant increases in HRQoL, sputum
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