
==== Front
Eur Respir J
Eur Respir J
ERJ
erj
The European Respiratory Journal
0903-1936
1399-3003
European Respiratory Society

38609097
10.1183/13993003.01689-2023
ERJ-01689-2023
Version of Record
Original Research Articles
Bronchiectasis
3
Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)
Airway clearance management in bronchiectasis
https://orcid.org/0000-0002-3442-4739
Spinou Arietta 1254
Hererro-Cortina Beatriz 34554
https://orcid.org/0000-0002-0090-4531
Aliberti Stefano 67
Goeminne Pieter C. 8
Polverino Eva 9
Dimakou Katerina 10
Haworth Charles S. 11
Loebinger Michael R. 12
https://orcid.org/0000-0002-8566-0344
De Soyza Anthony 13
Vendrell Montserrat 14
https://orcid.org/0000-0003-0903-9828
Burgel Pierre Regis 1516
https://orcid.org/0000-0002-5721-5710
McDonnell Melissa 17
Sutharsan Sivagurunathan 18
Škrgat Sabina 192021
Maiz-Carro Luiz 22
Sibila Oriol 2324
Stolz Daiana 2526
Kauppi Paula 27
https://orcid.org/0000-0002-0494-2690
Bossios Apostolos 2829
Hill Adam T. 30
Clifton Ian 31
Crichton Megan L. 32
Walker Paul 33
Menendez Rosario 34
Borekci Sermin 35
Obradovic Dusanka 3637
Nowinski Adam 38
Amorim Adelina 3940
https://orcid.org/0000-0002-8643-2167
Torres Antoni 41
https://orcid.org/0000-0002-2653-5885
Lorent Natalie 42
https://orcid.org/0000-0002-9947-7356
Welte Tobias 434445
Blasi Francesco 4647
https://orcid.org/0000-0002-0171-764X
Jankovic Makek Mateja 4849
https://orcid.org/0000-0002-0432-3398
Shteinberg Michal 5051
Boersma Wim 52
Elborn J. Stuart 53
Chalmers James D. 32
https://orcid.org/0000-0001-9084-4968
Ringshausen Felix C. 434445
on behalf of the EMBARC Registry Collaborators
1 Population Health Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
2 King's Centre for Lung Health, King's College London, London, UK
3 Universidad San Jorge, Zaragoza, Spain
4 Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
5 Instituto de Investigación Sanitaria (IIS) de Aragón, Zaragoza, Spain
6 IRCCS Humanitas Research Hospital, Respiratory Unit, Milan, Italy
7 Department of Biomedical Sciences, Humanitas University, Milan, Italy
8 Department of Respiratory Disease, AZ Nikolaas, Sint-Niklaas, Belgium
9 Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBERES, Barcelona, Spain
10 5th Respiratory Department and Bronchiectasis Unit, “SOTIRIA” General Hospital of Chest Diseases Medical Practice, Athens, Greece
11 Cambridge Centre for Lung Infection, Royal Papworth Hospital and University of Cambridge, Cambridge, UK
12 Royal Brompton and Harefield Hospitals and National Heart and Lung Institute, Imperial College London, London, UK
13 Population and Health Science Institute, Newcastle University and NIHR Biomedical Research Centre for Ageing, Freeman Hospital, Newcastle, UK
14 Department of Pulmonology, Dr Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), University of Girona, Girona, Spain
15 Department of Respiratory Medicine and French Cystic Fibrosis National Reference Center, Hôpital Cochin, AP-HP, Paris, France
16 Université Paris Cité, Inserm U1016, Institut Cochin, Paris, France
17 Department of Respiratory Medicine, Galway University Hospital, Galway, Ireland
18 Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Adult Cystic Fibrosis Center, University of Duisburg-Essen, Essen, Germany
19 University Medical Centre Ljubljana, Department of Pulmonary Diseases and Allergy, Ljubljana, Slovenia
20 Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
21 University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia
22 Chronic Bronchial Infection Unit, Pneumology Service, Ramón y Cajal Hospital, Alcalá de Henares University, Madrid, Spain
23 Servicio de Neumología, Instituto Clínico de Respiratorio, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain
24 CIBER de Enfermedades Respiratorias, ISCIII, Madrid, Spain
25 Department of Pneumology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
26 Clinic of Respiratory Medicine and Pulmonary Cell Research, University of Basel, Basel, Switzerland
27 Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
28 Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
29 Division of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
30 Royal Infirmary of Edinburgh, Department of Respiratory Medicine, Edinburgh, UK
31 Leeds Teaching Hospitals NHS Trust, Leeds, UK
32 Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
33 Liverpool University Hospitals Foundation NHS Trust, Liverpool, UK
34 Pneumology Department, Hospital Universitario y Politécnico La Fe–Instituto de Investigación Sanitaria La Fe, Valencia, Spain
35 Istanbul University – Cerrahpasa, Cerrahpasa Medical Faculty, Department of Pulmonology Diseases, Istanbul, Turkey
36 Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
37 Institute for Pulmonary Diseases, University of Novi Sad, Sremska Kamenica, Serbia
38 Department of Epidemiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
39 Pulmonology Department, Centro Hospitalar Universitário S. João, Porto, Portugal
40 Faculty of Medicine, University of Porto, Porto, Portugal
41 Department of Pulmonology Hospital Clinic of Barcelona, Spain University of Barcelona, CIBERES, IDIBAPS, ICREA Barcelona, Barcelona, Spain
42 Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium
43 Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany
44 Biomedical Research in End-Stage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany
45 European Reference Network on Rare and Complex Respiratory Diseases, Frankfurt, Germany
46 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
47 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
48 University of Zagreb School of Medicine and University Hospital Centre Zagreb, Zagreb, Croatia
49 Clinic for Pulmonary Diseases, University Hospital Centre Zagreb, Zagreb, Croatia
50 Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel
51 The Technion, Israel Institute of Technology, The B. Rappaport Faculty of Medicine, Haifa, Israel
52 Department of Pulmonary Diseases, Northwest Clinics, Alkmaar, The Netherlands
53 Faculty of Medicine, Health and Life Sciences, Queen's University, Belfast, UK
54 A. Spinou and B. Herrero-Cortina contributed equally to this paper
Corresponding author: James D. Chalmers (j.chalmers@dundee.ac.uk)
6 2024
06 6 2024
63 6 230168903 10 2023
03 3 2024
Copyright ©The authors 2024.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org
Graphical Abstract

Summary of the study. EMBARC: European Multicentre Bronchiectasis Audit and Research Collaboration; BSI: bronchiectasis severity index; QoL-B-Resp: Quality of Life Questionnaire–Bronchiectasis Respiratory symptoms; ACT: airway clearance technique; y/n: yes/no; ACBT: active cycle of breathing technique; ELTGOL: slow expiration with glottis opened in lateral position; PEP: positive expiratory pressure; HFCWO: high-frequency chest wall oscillation; HS+HA: hypertonic saline and hyaluronic acid.

Background

International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use.

Methods

This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs.

Results

16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57–74 years, range 18–100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51–53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe.

Conclusions

Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

Shareable abstract

Only around a half of patients with bronchiectasis in Europe perform regular airway clearance. Techniques and use of airway clearance management is heterogeneous, suggesting the need for clearer guidelines and stronger evidence. https://bit.ly/3v2CFGy

European Respiratory Society 10.13039/100008593
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pmcIntroduction

Impaired mucociliary clearance is one of the defining features of the clinical syndrome of bronchiectasis [1, 2]. The most frequent symptoms that impact upon patients’ quality of life are cough and sputum production, commonly characterised by secretions with high viscoelasticity [3–5]. Chronic inflammation and infection in bronchiectasis result in excess mucus production through hyperplasia and metaplasia of goblets cells, reduced hydration of the airway surface liquid and impaired cilia beating [3, 6, 7]. Failure of mucociliary transport leads to progressive lung damage, bacterial infection and an increased risk of exacerbations [8].

Improving clearance of mucus from the airways is therefore recognised by international and national guidelines for bronchiectasis as a central component of management [9–11]. Airway clearance is, however, not supported by high-quality evidence [5, 12, 13]. The European Respiratory Society (ERS) guidelines in 2017 recommended using airway clearance management in symptomatic adult patients as a weak recommendation with a low quality of evidence due to a paucity of randomised studies [9]. The limited research into airway clearance techniques (ACTs), as well as the heterogeneity in the patient population, leads to diverse practice [5]. Access to healthcare is variable across Europe and worldwide, and therefore access to specialist respiratory physiotherapists and airway clearance management is also variable between different countries and within countries [5, 14, 15].

To date there have been no large studies describing the use of airway clearance management, including ACTs, devices and mucoactive drug treatments, in people with bronchiectasis in Europe. The objective of this study was to describe the proportion of people using regular airway clearance management; to describe the most commonly used techniques, devices and mucoactive drugs; and to evaluate the characteristics of patients receiving these treatments using the large prospective European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) registry.

Methods

The EMBARC registry is a prospective observational study of patients with clinically and computed tomography-confirmed bronchiectasis conducted across 28 countries in Europe and Israel [16]. The study was approved by the ethics committee in the host country (UK) and by institutional review boards or ethics committees in all countries in which the study is conducted. A detailed protocol of the study has been previously published and baseline characteristics reported in detail [15, 16].

Data collection

Patient enrolment commenced in January 2015 and recruitment is open-ended and ongoing. For the present analysis, patients enrolled up to April 2022 were included. Patient data were collected annually using a standardised case report form. Comprehensive clinical data incorporating demographics, comorbidities, medications, aetiological testing, microbiology, radiology, lung function and disease history were recorded. Aetiology was recorded by the attending physician/medical team and the aetiology in the opinion of the investigator is reported. Data on aetiological testing supporting the investigator decision is recorded. Data on clinically indicated sputum samples, sent during clinical stability and exacerbation, were collected and patients classified according to whether they had isolated specific bacteria in any sample in the previous 12 months. Data on microbiology and frequency of exacerbations were collected for 12 months prior to date of consent into the EMBARC registry. Radiological severity was evaluated in the patients’ most recent computed tomography scan using the modified Reiff score, as previously described [17]. Disease severity was evaluated using the bronchiectasis severity index (BSI) [18]. Data on medication use at the time of enrolment and during follow-up were collected through patient history and clinical records. Exacerbations were defined as use of antibiotics for acute respiratory symptoms and were recorded from a combination of patient history, hospital and prescription records [19]. Breathlessness was evaluated using the modified Medical Research Council dyspnoea scale. Symptoms were evaluated using the Quality of Life Questionnaire–Bronchiectasis (QoL-B) version 3.1 using validated translations into native languages [20, 21].

Airway clearance management

To standardise data collection, a number of airway clearance management options were prespecified within the electronic EMBARC case report form (CRF). The CRF included the question, “does the patient practice regular chest physiotherapy”. For participants replying yes, a series of additional options were provided. Regular chest physiotherapy could include manual ACT, devices or both. The list of options was developed by the EMBARC steering committee and a specialist working group, including physiotherapists with special interest in bronchiectasis and/or cystic fibrosis. For self-administered and manual ACTs, the options were active cycle of breathing technique (ACBT), autogenic drainage, postural drainage, assisted cough, manual vibration, manual percussion, slow expiration with glottis opened in lateral position (ELTGOL), regular exercise, other and none. It is acknowledged that exercise is not strictly an ACT [22], but based on patient feedback that this is widely used to aid airway clearance, it was included in the CRF. Data are presented with and without regular exercise as an ACT.

The ERS bronchiectasis guidelines and national guidelines recommend regular ACT for all patients with bronchiectasis, including those with regular expectoration and those with difficulty expectorating who do not expectorate daily. Therefore, the primary analysis used all participants as the denominator. We also report the proportion using ACT when limited only to those with daily expectoration of sputum.

For airway clearance devices the options were positive expiratory pressure (PEP) device, Flutter, Acapella, Cornet, mechanical vibration, intrapulmonary percussive ventilation, high-frequency chest wall oscillation (HFCWO), other and none.

For mucoactive drugs the options were nebulised normal saline, nebulised hypertonic saline, nebulised hypertonic saline with the addition of hyaluronic acid, inhaled mannitol, inhaled Dornase alfa (recombinant human deoxyribonuclease), N-acetylcysteine/carbocistine (oral mucoactive drugs), other and none.

The CRF recorded data on “regular use” of these ACTs, devices and mucoactive treatments to differentiate from situations where these interventions may be used only during exacerbations or otherwise intermittently. To meet the registry's definition of regular use, the CRF required that participants use the technique/device/drug most days while clinically stable. The CRF did not record data on frequency or duration of ACT use.

Participants who did not practice airway clearance management were requested to provide the reasons for this and the options provided were non-adherence due to lack of time, non-adherence due to lack of motivation or perception of benefit, doctor or other healthcare professional indicated that it was not needed, and physical inability to perform ACT.

At 12 months follow-up and annually thereafter, the data collection tool included a question asking if the patient had seen a specialist respiratory physiotherapist in the previous 12 months. This was designed to account for new patients, so that patients have had at least 1 year before it is reasonable to expect they have seen a physiotherapist. At follow-up, data were again collected on the use of ACTs, devices and mucoactive drugs.

Statistical analysis

Summary data are presented as median with interquartile range (IQR). Comparisons between two groups used the Mann–Whitney U test. To identify if the differences in practice between countries were independent of disease severity and other clinical variables, we performed logistic regression analysis. Airway clearance management was used as the dependent variable and country as the independent variable, with the model adjusted for multiple confounders known from the literature as being associated with severity, prognosis or practice [18, 23–25]. Results are expressed as adjusted odds ratios with 95% CIs. The UK was used as the reference country for analysis as the country with the largest group of patients in the registry [15]. All analyses used SPSS version 27 (IBM, Chicago, IL, USA) or GraphPad Prism version 9 (GraphPad Software, La Jolla, CA, USA).

Results

Population

Data were collected from 16 963 patients. 240 patients were excluded due to missing or incomplete data on ACT use. Therefore, the analysis included 16 723 adults with bronchiectasis from 28 countries. The overall demographics, patient characteristics and countries contributing to the EMBARC registry population have been previously described [15]. The flow of patients through the study is shown in figure 1.

FIGURE 1 Flow chart of participants in the study. EMBARC: European Multicentre Bronchiectasis Audit and Research Collaboration.

The median (IQR) age of participants was 67 years (57–74 years) and 10 182 participants (60.9%) were female. The cohort was evenly distributed into participants with mild (n=4857, 29.0%), moderate (n=5968, 35.7%) and severe (n=5898, 35.3%) bronchiectasis according to the BSI (figure 1). Most patients reported daily expectoration of sputum (n=11 971, 71.6%). Median (IQR) daily sputum volume was 6 mL (0–20 mL) across the whole population, including patients without daily expectoration.

Use of airway clearance management

8739 participants (52.2%, 95% CI 51–53%) reported using regular airway clearance management at baseline. Rates by region varied from 58.9% of patients in the UK to 33.0% in Central and Eastern Europe (table 1). In 570 participants (3.4%), the only method of airway clearance management reported was regular exercise. Excluding these patients, 8169 (48.8%) reported regular airway clearance management. Table 1 shows the baseline characteristics of participants who did and did not use airway clearance management at baseline. Participants performing airway clearance were more likely to be female, nonsmokers and without co-existing COPD. Participants who used airway clearance management had more severe bronchiectasis, reflected by worse lung function and higher radiological severity using the Reiff score, as well as a higher proportion presenting with daily sputum production and a higher daily sputum volume. Consistent with the greater disease severity, participants who used airway clearance management were more likely to receive macrolides, oral antibiotics, inhaled antibiotics and inhaled corticosteroids (table 1). The results were similar when considering participants who expectorated on a daily basis, with 6387 participants (53.4%) performing regular airway clearance. Subsequent analyses are performed on the overall population.

TABLE 1 Demographics, clinical characteristics and differences between patients who use airway clearance management versus those who do not use airway clearance management

Variables	Regular airway clearance management	No regular airway clearance management	p-value	
Participants (n)	8739	7984		
Demographics	
 Age (years)	67 (58–74)	67 (57–74)	0.74	
 Female	5513 (63.1)	4669 (58.5)	<0.0001	
 BMI (kg·m−2)	24.7 (21.6–28.6)	25.1 (21.9–28.7)	<0.0001	
 Never-smoker	4952 (56.7)	4001 (50.1)		
 Ex-smoker	3454 (39.5)	3237 (40.5)		
 Current smoker	333 (3.8)	746 (9.3)	<0.0001	
Comorbidities	
 Cardiovascular disorders	2711 (31.0)	2752 (34.5)	<0.0001	
 Stroke	315 (3.6)	273 (3.4)	0.52	
 Diabetes	845 (9.7)	863 (10.8)	0.015	
 Liver disease	46 (0.5)	49 (0.6)	0.45	
 Chronic renal failure	341 (3.9)	317 (4.0)	0.82	
 COPD	2072 (23.7)	2201 (27.6)	<0.0001	
 Asthma	3002 (34.4)	2207 (27.6)	<0.0001	
 Osteoporosis	1263 (14.5)	947 (11.9)	<0.0001	
 Depression	1298 (14.9)	1066 (13.4)	0.0054	
 Solid tumour	950 (10.9)	893 (11.2)	0.52	
Aetiology	
 Idiopathic	3416 (39.1)	3009 (37.7)		
 Post-infective	1862 (21.3)	1728 (21.6)		
 COPD	573 (6.6)	776 (9.7)		
 Asthma	592 (6.8)	546 (6.8)		
 Tuberculosis	302 (3.5)	523 (6.6)		
 Immunodeficiency	364 (4.2)	330 (4.1)		
 ABPA	285 (3.3)	179 (2.2)		
 Rheumatoid arthritis	250 (2.9)	202 (2.5)		
 Other	1095 (12.5)	691 (8.7)	<0.0001	
Clinical status				
 FEV1 (L)	1.73 (1.24–2.31)	1.84 (1.24–2.31)	<0.0001	
 FEV1 (% predicted)	75.1 (54.4–95.2)	78.6 (57.7–98.1)	<0.0001	
 FVC (L)	2.61 (2.03–3.30)	2.68 (2.05–3.40)	0.55	
 FVC (% predicted)	90.9 (73.3–107.2)	91.7 (73.7–107.8)	0.38	
 Reiff score	4 (2–6)	3 (2–6)	<0.0001	
 Sputum volume (mL·day−1)	10 (2–25)	5 (0–15)	<0.0001	
 QoL-B-Resp score	59.3 (40.7–74.1)¶	66.7 (45.8–81.5)+	<0.0001	
 Does not produce daily sputum	1767 (20.2)	2985 (37.4)	<0.0001	
 mMRC score	
  0	2165 (24.8)	2214 (27.7)		
  1	2940 (33.6)	2531 (31.7)		
  2	1923 (22.0)	1659 (20.8)		
  3	1125 (12.9)	1043 (13.1)		
  4	507 (5.8)	383 (4.8)		
  Missing	79 (0.9)	154 (1.9)	<0.0001	
Treatment	
 Long-term macrolide treatment	1878 (21.5)	975 (12.2)	<0.0001	
 Other long-term non-macrolide oral antibiotics treatment	496 (5.7)	298 (3.7)	<0.0001	
 Inhaled/nebulised antibiotic treatment	958 (11.0)	343 (4.3)	<0.0001	
 Inhaled corticosteroids	4927 (56.4)	3660 (45.8)	<0.0001	
Region #	
 UK	4807 (55.0)	3356 (42.0)		
 Western and Northern Europe	1830 (20.9)	1374 (17.2)		
 Southern Europe	1752 (20.0)	2543 (31.9)		
 Central and Eastern Europe	350 (4.0)	711 (8.9)	<0.0001	
Data are presented as median (interquartile range) or n (%), unless otherwise indicated. BMI: body mass index; ABPA: allergic bronchopulmonary aspergillosis; QoL-B-Resp: Quality of Life Questionnaire–Bronchiectasis Respiratory symptoms; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; mMRC: modified Medical Research Council. #: data show the proportion of patients using and not using airway clearance management; ¶: n=6354 patients with available baseline data; +: n=4798 patients with available baseline data.

Participants who used airway clearance management versus those who did not use it had a higher median (IQR) BSI score (7 points (5–11 points) versus 6 points (4–10 points), p<0.0001), were more frequently infected with Pseudomonas aeruginosa (22.7% versus 13.2%, p<0.0001) and had more frequent exacerbations (≥3 exacerbations) in the past year (44.5% versus 32.3%, p<0.0001). Participants receiving airway clearance management also had worse median (IQR) score on the respiratory domain of QoL-B (59.3 points (40.7–74.1 points) versus 66.7 points (45.8–81.5 points), p<0.0001). Disease severity is shown in supplementary table S1. Supplementary table S2 shows that the types of ACTs and devices used were similar across the majority of different bronchiectasis aetiologies.

A reason for not performing airway clearance was recorded in 4361 participants (55% of those not using regular airway clearance management). The most common reason in 3115 participants (71.4%) was “clinician decision that it was not needed”, while 839 participants (19.2%) reported lack of motivation, 240 participants (5.5%) were physically unable to perform airway clearance management and just 167 participants (3.8%) reported the lack of time as the main reason. Characteristics of these participants are shown in supplementary table S3. Participants physically unable to perform airway clearance management were markedly older and had higher disease severity and a higher frequency of comorbidities, including COPD and cardiovascular disease, than other participants. Participants who were judged to not require airway clearance management by their clinician had slightly milder disease than the other groups. However, 58.3% of the patients in this group reported daily sputum production, 11.4% were receiving long-term macrolide treatment and 3.2% were receiving inhaled antibiotics.

Airway clearance management showed marked geographic variability

The most frequently used ACTs were ACBT (n=4751, 28.4%), regular exercise (n=1550, 9.3%), postural drainage (n=1332, 8.0%), autogenic drainage (n=1081, 6.5%) and assisted cough (n=577, 3.5%). Patients were able to report using more than one method of airway clearance management. There was marked geographical variability in the use of specific techniques as shown in figure 2 and in supplementary table S4.

FIGURE 2 Heatmap illustrating differences in airway clearance techniques (ACTs) between different countries. Heat colour represents the percentage of patients who reported using each ACT. y/n: yes/no; ACBT: active cycle of breathing technique; ELTGOL: slow expiration with glottis opened in lateral posture.

The highest use of airway clearance management was in Ukraine (92.0%), Denmark (91.7%), Finland (89.6%) and Sweden (72.0%). The lowest use of airway clearance management was in Central and Eastern European countries, particularly in Bulgaria (2.9%), Romania (3.1%), Moldova (6.7%), Switzerland (11.8%) and Turkey (14.9%).

Remarkable differences were also observed in the use of specific ACTs. The highest use of ACBT was reported in Ukraine, UK, Sweden, Slovenia, Ireland and Portugal. In contrast, ACBT was used by only 8.1% of the participants in Italy and 8.0% of the participants in Israel; these countries had relatively high use of airway clearance management but a preference for other techniques. Autogenic drainage was particularly favoured in Belgium and Israel, and postural drainage was most popular in Ukraine, Poland, Portugal, Ireland and France. Percussion and manual vibrations were infrequently used. Participants in Finland were largely using exercise for airway clearance. ELTGOL was almost exclusively used in Belgium, Spain, Italy and France (figure 2).

Airway clearance devices and mucoactive drugs

Among those receiving airway clearance management, airway clearance devices were used by 2748 participants (16.4%). Similar to ACTs, there was substantial variation between countries as shown in figure 3. Denmark, Finland and Sweden showed the highest use of airway clearance devices, followed by Israel, Italy and Germany. Full details are shown in supplementary table S5.

FIGURE 3 Heatmap illustrating the differences in airway clearance device use between different countries. Heat colour represents the percentage of patients who reported using each airway clearance device. y/n: yes/no; PEP: positive expiratory pressure; HFCWO: high-frequency chest wall oscillation.

Mucoactive drugs were used by 4680 participants (28.0%). The most commonly used were carbocisteine/n-acetylcysteine, which were used by 2907 participants (17.4%), and hypertonic saline, which was used by 1454 participants (8.7%). Other mucoactive drugs were less commonly used. Figure 4 shows the geographical variation in the use of mucoactive drugs, illustrating that Austria, Germany, Ireland, Israel, Portugal and Sweden had among the highest use. Portugal, UK and Ireland had the highest use of cysteine derivatives (carbocisteine/N-acetylcysteine), while hypertonic saline was more commonly used in other countries. Supplementary table S6 shows full details of the differences between countries.

FIGURE 4 Heatmap illustrating differences in mucoactive drug use between different countries. Heat colour represents percentage of patients who reported using each mucoactive drug treatment. y/n: yes/no; HS+HA: hypertonic saline and hyaluronic acid; DNase: deoxyribonuclease.

Combination treatments

Of 8739 participants (52.2%) reporting using regular airway clearance management at baseline, 3285 participants (37.5% of those using any airway clearance management) used a single airway clearance modality, 2956 (33.8%) used two modalities, 1582 (18.1%) used three modalities and 916 (10.5%) used four or more (maximum 12 per person). ACTs were most frequently combined with devices; 1889 participants (21.6%) used one or more ACT with one or more device. 2826 participants (32.3%) used ACT plus one or more mucoactive drug. 786 participants (9.0%) used ACTs, devices and mucoactive drugs. The most common combinations were ACBT plus cysteine derivatives (n=1316, 15.1%), ABCT plus Flutter (n=661, 7.6%), ABT plus Acapella (n=541, 6.2%), ACBT plus hypertonic saline (n=488, 5.6%) and ACBT plus PEP (n=400, 4.6%).

Adjustment for severity and clinical characteristics

The above differences between countries may reflect genuine differences in clinical practice but could also reflect differences in patient characteristics between different countries, such as enrolment of patients with more severe disease, with different aetiologies or with comorbid conditions. To account for this, we performed a logistic regression analysis adjusting for multiple confounders. This confirmed statistically significant differences between countries, using the largest enrolling country (the UK) as a reference (figure 5).

FIGURE 5 Forest plot showing the adjusted odds ratios and 95% confidence intervals for the relationship between country and the use of different airway clearance management modalities. Logistic regression models were adjusted for age, sex, exacerbation frequency, infection status, cardiovascular disease, neoplastic disease, diabetes, forced expiratory volume in 1 s, asthma, COPD, smoking history, aetiology, radiological severity, inhaled antibiotic use, macrolide use and inhaled corticosteroid use.

Supplementary tables S7–S9 show the logistic regression models for ACTs, devices and mucoactive drugs, respectively. In addition to the geographical variation, these models show that multiple markers of severity including lung function, radiology, infection with P. aeruginosa and use of oral and inhaled antibiotics were associated with airway clearance management, confirming that airway clearance is more frequently used in patients with more severe disease.

Out of 10 817 follow-up visits at 12 months, 2455 participants (22.7%) had seen a specialist respiratory physiotherapist. The countries with the highest proportion of participants seen by respiratory physiotherapy were Belgium (45.7%), Ireland (37.5%), Italy (37.4%) and France (30.2%). The countries with the lowest proportion were Romania (0%), Bulgaria (0%) and Moldova (3.0%). The distribution of countries is shown in figure 6, and overall shows low access to respiratory physiotherapy in Central and Eastern Europe with higher levels of access in Northern and Western Europe as well as Southern Europe.

FIGURE 6 Access to specialist respiratory physiotherapy for airway clearance management across Europe. n=10 817 patients with a minimum of 12 months observation included. Created with mapchart.net.

Discussion

This study represents the largest and most detailed description on the use of airway clearance management in bronchiectasis to date. Using the EMBARC registry, which has prospectively collected data from across European bronchiectasis centres, we show that nearly a half of European people with bronchiectasis do not regularly practice airway clearance management. The proportion performing airway clearance was similar when analysis was limited to patients reporting daily sputum expectoration. This is despite recommendations from all the major bronchiectasis guidelines to teach airway clearance management to people with bronchiectasis and for patients to practice these techniques regularly. Although our data show that people with more severe bronchiectasis are more likely to receive airway clearance management, we found that large numbers of people with severe bronchiectasis, including people chronically infected with P. aeruginosa and people receiving long-term antibiotic treatments, are not regularly practicing airway clearance management.

Most guidelines recommend that airway clearance is best implemented by specialist respiratory physiotherapy, but we show that after at least 1 year of follow-up less than a quarter of people with bronchiectasis had received training from a respiratory physiotherapist. This suggests widespread lack of implementation of airway clearance management as an intervention for people with bronchiectasis.

There is a lack of high-quality evidence for the benefits of airway clearance management in bronchiectasis but available trial data show substantial benefits. For example, a 12-month trial by Muñoz et al. [26] found a significant reduction in exacerbations and there is a marked improvement in quality of life in patients with productive cough when ELTGOL technique is used twice daily [27]. Increased use of airway clearance management, particularly in people with severe bronchiectasis, could potentially reduce the burden of disease seen in Europe [23, 28]. Barriers to implementation of airway clearance management include the lack of access to specialist physiotherapists, lack of access to airway clearance devices and mucoactive drugs, lack of knowledge and experience among healthcare professionals and lack of motivation from patients [29–31]. Nevertheless, the ERS guidelines for bronchiectasis were only able to make a weak recommendation for ACTs in bronchiectasis owing to the low quality of evidence. This low quality of evidence and lack of large-scale randomised trials demonstrating benefit may be one of the key reasons for the inconsistent uptake observed in our study [9, 11].

The large sample size of the EMBARC registry allowed us to explore differences between countries in terms of the use of airway clearance management. We observed marked differences, with higher use of ACTs in Northern European and some Western European countries in particular, and low use in many Eastern European countries. Interestingly, however, even within Western and Southern European countries we observed great differences in the use of interventions such as ACBT, autogenic drainage and the use of airway clearance devices. The scale of these differences suggests that the lack of evidence in this field leads to decisions based on local preference and clinical experience rather than evidence, given that differences between countries persisted even after adjustment for patient characteristics and disease severity. Our data are similar to those reported in a study of 905 patients by Basavaraj et al. [32], who found that 59% of US patients used ACTs at baseline. Although it had a small sample size, the US study found that 44% of patients used PEP devices and 10% used HFCWO at baseline, in contrast to our European data where only 16% used devices and HFCWO was not used in most European countries, and the country with the highest use only had a frequency of 1.9%. These data emphasise global variation in practice, likely reflecting differences in reimbursement practices as well as lack of availability of specialist chest physiotherapists in many countries [24, 32]. It should be noted that, while we had a large sample size overall, the numbers in individual countries varied. Some estimates for countries where low number of patients were enrolled may not be fully representative.

Our data should serve as a call to action on two fronts: first, to improve the global uptake of airway clearance management in bronchiectasis, with the goal of reducing exacerbations, potentially avoidable antibiotic exposures and improving symptom burden and quality of life; and second, to generate additional evidence to determine which ACTs and devices are most effective for specific patient groups and to strengthen the guidelines on which healthcare professionals and healthcare commissioners rely [11, 33]. Airway clearance management in bronchiectasis has been described as a neglected aspect of a neglected disease and our data support calls for further research [11]. The lack of evidence in this field extends to mucoactive drug treatments, such as hypertonic saline, for which large-scale trials are also lacking.

Limitations of our analysis should be acknowledged. We prespecified several ACTs and devices, which may bias responses towards these. Participation in the registry is voluntary and so the patients enrolled may not be representative of the countries described here. No data were collected in the registry on the dose or frequency of airway clearance management and associated treatments. We also did not collect data on the professionals who taught airway clearance to patients and their professional background and experience. Terminology in airway clearance management across Europe is not standardised and this may confound data on the use of specific techniques. We are unable to capture data regarding patient adherence in the registry. Most importantly, the poor evidence base for ACT in bronchiectasis means that while our data show a generally low uptake of ACT compared to guideline recommendations, it is not possible to definitively state which patient subgroups would benefit most from manual ACT, devices or mucoactive treatments. In some cases, ACT may provide little benefit, while in others it may be highly beneficial. Bronchiectasis is a heterogeneous disease and mucus properties are highly heterogeneous between individuals. It is important that future studies generate a more robust evidence base for ACT in addition to identifying appropriate precision medicine approaches [3, 24, 33–35].

In summary, our data show that airway clearance management is underused in people with bronchiectasis in Europe. It is also reserved for patients with severe disease, suggesting a reactive rather than proactive approach to preventing disease progression. The choice of ACT, airway clearance device and mucoactive drug is determined primarily through local practice rather than evidence. Thus, efforts to increase the use and standardisation of airway clearance management in Europe are needed.

Supplementary material

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Supplementary material ERJ-01689-2023.Supplement

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This article has been revised according to the correction published in the July 2024 issue of the European Respiratory Journal.

Ethics statement: The study was approved by the ethics committee in the host country (UK) and by institutional review boards or ethics committees in all countries and regions in which the study was conducted.

This article has an editorial commentary: https://doi.org/10.1183/13993003.00687-2023

Conflict of interest: B. Hererro-Cortina reports payment or honoraria for lectures, presentations, manuscript writing or educational events from SEPAR (Spanish Respiratory Society), and has a leadership or fiduciary role in SEPAR. S. Aliberti reports grants from Insmed Incorporated, Chiesi, Fisher and Paykel, and GSK; royalties or licences from McGraw Hill; consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Ltd, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MCD Italis Srl, Brahms, Physioassist SAS and GSK SpA; payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK SpA, Thermofisher Scientific, Insmed Italy, Insmed Ireland, Zambon and Fondazione Internazionale Menarini; and participation on a data safety monitoring board or advisory board for Insmed Incorporated, Insmed Italy, AstraZeneca UK Ltd and MSD Italia Srl. P.C. Goeminne reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, GSK and Chiesi; support for attending meetings and/or travel from Chiesi; and participation on a data safety monitoring board or advisory board for Boehringer, GSK and Pfizer. E. Polverino reports grants from Grifols; consulting fees from Insmed, Bayer, Chiesi and Zambon; payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Chiesi, Grifols, GSK, Insmed, Menarini and Zambon; and support for attending meetings and/or travel from Insmed, Pfizer and Moderna. K. Dimakou reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Novartis, Boehringer Ingelheim, GSK, Norma Hellas, Chiesi, AstraZeneca and Zambon; support for attending meetings and/or travel from Novartis, Boehringer Ingelheim, GSK, Norma Hellas, Chiesi, AstraZeneca and Menarini, and participation on a data safety monitoring board or advisory board for Novartis, GSK and Chiesi. C.S. Haworth reports payment or honoraria for lectures, presentations, manuscript writing or educational events from 30 Technology, CSL Behring, Chisi, Insmed, Janssen, LifeArc, Meiji, Mylan, Pneumagen, Shionogi, Vertex and Zambon. M.R. Loebinger reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2 and Boehringer Ingelheim; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed; and is ERS Infection Group Chair. A. De Soyza reports grants from AstraZeneca, Pfizer, GSK and Novartis; consulting fees from AstraZeneca, Insmed, GSK, Boehringer, 30T and Bayer; and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Pfizer, GSK and Novartis. M. Vendrell reports grants from Chiesi; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed and Publi Creation; support for attending meetings and/or travel from Zambon, Chiesi, Novartis, Behring and Gebro; participation on a data safety monitoring board or advisory board for Insmed; and receipt of equipment, materials, drugs, medical writing, gifts or services from Insmed and Novartis. P.R. Burgel reports grants from GSK and Vertex; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, MSD, Vertex, Viatris and Zambon; and support for attending meetings and/or travel from AstraZeneca and Chiesi. S. Sutharsan reports grants from Vertex, Galapagos, Insmed, Proteostasis and Corbus; consulting fees from Insmed, Vertex Pharmaceuticals and Boehringer Ingelheim; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceuticals, Boehringer Ingelheim and Insmed. S. Škrgat reports honoraria for educational events, invited lectures and presentations supported by Sanofi, AstraZeneca, Medis, Berlin-Chemie and Chiesi; and participation on a data safety monitoring board or advisory board for AstraZeneca. D. Stolz reports payment or honoraria for lectures, presentations, manuscript writing or educational events from CSL Behring, Berlin-Chemie, Menarini, Novartis, GSK, AstraZeneca, Vifor, Merck, Chiesi and Sanofi; and participation on a data safety monitoring board or advisory board for GSK and CSL Behring. P. Kauppi reports support for attending meetings and/or travel from Nordic Respiratory Academy; participation on a data safety monitoring board or advisory board for Swedish Orphan Biovitrium; a leadership or fiduciary role for the Finnish Respiratory Society and Finnish Tuberculosis Foundation Grant Committee; and receipt of equipment, materials, drugs, medical writing, gifts or services from Theravance. A. Bossios reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi; and is Secretary of Assembly 5 (Airway diseases, asthma, COPD and chronic cough) of the ERS, Vice-chair of the Nordic Severe Asthma Network (NSAN)-NORDSTAR and a member of the Steering Committee of the ERS CRC for severe asthma (SHARP). I. Clifton reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca and GSK; and participation on a data safety monitoring board or advisory board for AstraZeneca, GSK and Infex Therapeutics. M.L. Crichton reports consulting fees from Boxer Capital LLC. P. Walker is Chair of the British Thoracic Society. D. Obradovic is President of the Serbian Society of Intensive Care Medicine. A. Amorim reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Zambon Group, and support for attending meetings and or/travel from Zambon Group, Boehringer Ingelheim and Novartis Farma. F. Blasi reports grants from AstraZeneca, Chiesi and Insmed; consulting fees from Menarini; and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Chiesi, GSK, Guidotti, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Viatris, Vertex and Zambon. M. Jankovic Makek reports consulting fees from Insmed, Biomerieux and MSD; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, MSD, Pfizer and Teva; and support for attending meetings and/or travel from MSD, Pfizer and Berlin-Chemie. M. Shteinberg reports consulting fees from GSK, Boehringer Ingelheim, Kamada and Zambon; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, Boehringer Ingelheim, GSK, AstraZeneca, Teva, Novartis, Kamada and Sanofi; support for attending meetings and/or travel from Novartis, Actelion, Boehringer Ingelheim, GSK and Rafa; participation on a data safety monitoring board or advisory board for Bonus Therapeutics, Israel; leadership or fiduciary roles for EMBARC Management, Israel Pulmonology Society Board and the Israel Society for TB and Mycobacterial Diseases; receipt of equipment, materials, drugs, medical writing, gifts or services from Trudell Medical Int.; and is and Associate Editor of the American Journal of Respiratory and Critical Care Medicine. J.D. Chalmers reports grants from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GSK, Grifols, Insmed, LifeArc and Novartis; and consulting fees from AstraZeneca, Chiesi, GSK, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon. F.C. Ringshausen reports grants from German Center for Lung Research (DZL), German Center for Infection Research (DZIF), IMI (EU/EFPIA) and iABC Consortium (including Alaxia, Basilea, Novartis and Polyphor), Mukoviszidose Institute, Novartis, Insmed Germany, Grifols, Bayer and InfectoPharm; consulting fees from Parion, Grifols, Zambon, Insmed and Helmholtz-Zentrum für Infektionsforschung; payment or honoraria for lectures, presentations, manuscript writing or educational events from I!DE Werbeagentur GmbH, Interkongress GmbH, AstraZeneca, Insmed, Grifols and Universitätsklinikum Frankfurt am Main; payment for expert testimony from Social Court Cologne; support for attending meetings and/or travel from German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group Mukoviszidose e.V.; participation on a data safety monitoring board or advisory board for Insmed, Grifols and Shionogi; leadership or fiduciary roles as Coordinator of the ERN-LUNG Bronchiectasis Core Network, Chair of the German Bronchiectasis Registry PROGNOSIS, Member of the Steering Committee of the European Bronchiectasis Registry EMBARC, Member of the Steering Committee of the European Nontuberculous Mycobacterial Pulmonary Disease Registry EMBARC-NTM, Co-Speaker of the Medical Advisory Board of the German Kartagener Syndrome and PCD Patient Advocacy Group, Speaker of the Respiratory Infections and TB group of the German Respiratory Society, Speaker of the Cystic Fibrosis group of German Respiratory Society (DGP), principal investigator of the German Center for Lung Research, Member of the Protocol Review Committee of the PCD-CTN and Member of Physician Association of the German Cystic Fibrosis Patient Advocacy Group; and other financial or non-financial interests in AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex and Zambon. The remaining authors have no potential conflicts of interest to disclose.

Support statement: EMBARC3 is funded by the European Respiratory Society through the EMBARC3 clinical research collaboration. EMBARC3 is supported by project partners Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Grifols, Insmed, Janssen, Lifearc and Zambon. Supported by the Innovative Medicines Initiative and The European Federation of Pharmaceutical Industries and Associations companies under the European Commission-funded Horizon 2020 Framework Program and by Inhaled Antibiotic for Bronchiectasis and Cystic Fibrosis (grant 115721). J.D. Chalmers is supported by the GlaxoSmithKline/Asthma and Lung UK Chair of Respiratory Research. Funding information for this article has been deposited with the Crossref Funder Registry.
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