Breathing Exercises in Asthma Targeting Dysfunctional Breathing (BEAT_DB)

BEAT DB-study; Breathing Exercises in Asthma Targeting Dysfunctional Breathing-a Randomised Controlled Trial

Zealand University Hospital, Hvidovre University Hospital, Aalborg University Hospital, Bispebjerg Hospital, TrygFonden, Denmark, Slagelse Hospital, Region Zealand, Association of Danish Physiotherapists, Allergi og Lungeklinikken Helsingør, Regionshospitalet Silkeborg, Odense University Hospital

Dyspnoe can disable patients with asthma. Dysfunctional breathing (DB), resulting in dyspnoe, can mimic or exaggerate asthma. Around every forth patient with asthma have DB. Breathing exercises (BrEX) can improve asthma-related quality of live (QOL) in less severe asthma. No study has investigated the effect of BrEX on QOL neither on level of physical activity in severe asthma. A randomised controlled multicentre trial will include 190 adults with poor asthma control (Asthma Control Questionnaire (ACQ6)-score≥0.8) from seven outpatient departments and one specialized private clinic. Patients will be allocated to either usual care (no intervention) or breathing exercises (BrEX)-treatment consisting of 12-week intervention including three physiotherapist-sessions focusing on breathing pattern modification (Papworth Method; Buteyko technique) in rest and activity and 10 minutes home-exercise twice daily. Primary outcome is change in Mini Asthma Quality of Life Questionnaire (MiniAQLQ) at six-months follow-up.

In Denmark around 300,000 suffer from asthma. Dyspnoe can disable patients with asthma. Dysfunctional breathing (DB), resulting in dyspnoe, can mimic or exaggerate asthma. Around 20-29% of asthmatic patients have DB. Breathing exercises (BrEX) can improve asthma-related quality of life (QOL) and control of asthma symptoms in less severe asthma. No study has investigated the effect of BrEX on QOL neither on level of physical activity in severe asthma. A randomised controlled multicentre trial will include 190 adults with poor asthma control (Asthma Control Questionnaire (ACQ6)-score≥0.8) from seven outpatient departments and one specialized private clinic. After optimizing of inhalation technique, patients will be allocated to either usual care (no intervention) or BrEX-treatment consisting of 12-week intervention including three physiotherapist-sessions focusing on breathing pattern modification (Papworth Method; Buteyko technique) in rest and activity and 10 minutes home-exercise twice daily. Primary outcome is change in Mini Asthma Quality of Life Questionnaire (MiniAQLQ) at six-months follow-up. Secondary outcomes are changes in ACQ6, Nijmegen Hyperventilation Questionnaire (NQ), Hospital Anxiety and Depression Scale (HAD), accelerometry (physical activity level, number of steps), 6 minutes walk distance, and forced expiratory volume in first second (FEV1), besides response of Global perceived effect rate (GPE) in asthma-related QOL and asthma control.

Three assessors (physiotherapists) will perform the objective assessment of capacity and lung parameters. Nurses in the outpatient departments will obtain data from medical records. The assessors and the nurses will be blinded for the allocation. The primary invenstigator will have no access to the data during the period of datacollection. Primary and most of the secondary outcomes will be patient-reported.

Individual instruction from a nurse at baseline aimed at knowledge on pharmacological treatment and optimized inhalation techniques. The participants will be encouraged to use online video instruction. Three physiotherapist-sessions of Breathing Exercises (BrEX) with duration of 60 minutes (the initial) and 30 minutes (other sessions) at week 1, 4, and 9. The participant is expected to do 10 minutes of home exercise twice daily. The entire intervention combines elements of the Papworth method, and the Buteyko technique.

Individual instruction from a nurse at baseline aimed at knowledge on pharmacological treatment and optimized inhalation techniques. The participants will be encouraged to use online video instruction. Besides the individual instruction described above, patients will receive only short information given initially at recruitment. They are allowed to receive instruction in positive expiratory pressure-treatment and physiotherapy targeting other problems than dysfunctional breathing (DB).

Key points in the intervention are Reduction (or normalising) of the respiration rate; use of rhythmic, nasal inspiration, diaphragmatic breathing; reduction of depth of breath, longer expiration; breath-holding at functional residual capacity. Relaxation, especially the neck, jaw, tongue, and shoulders. Emphasizing the impact of gravity to the body. Inclusion of the breathing modification into walking and other physical activities. Daily home exercise of BrEX.

Participants will receive only short information given initially at recruitment. No instruction or booklet will be distributed in the Usual care-Group.

MiniAQLQ is a disease-specific patient-reported outcome on experiences during the previous two weeks. The original version of AQLQ (32 items) is recommended for clinical use, whereas this shortened version is suggested for research. In moderate to severe asthma cohorts, MiniAQLQ has good reliability (ICC 0.83-0.86) and strong validity (criteria validity to AQLQ, r≥0.80; construct validity against ACQ, r=0.69). MiniAQLQ has 15 items in four domains (symptoms, activity limitation, emotions, environment), which are answered using a 7-point Likert scale (1=maximum impairment; 7=no impairment).

Primary endpoint: Change from baseline to 6 months follow up. Secondary endpoints will be 3 and 12 months follow up.

Asthma Control Questionnaire (ACQ6) will be used in the 6 sub-score version omitting FEV1 % of predicted. The outcome-score is the mean of 6 sub-scores (5 questions about symptoms, 1 question in use of reliever medication (beta2-agonist)) using a 7-point Likert scale (0=fully controlled; 6=severely uncontrolled)

A Nijmegen Questionnaire (NQ)-score > 23 suggests symptomatic hyperventilation, but is typically used to define DB.

Hospital Anxiety and Depression Scale (HAD) uses a 0-21 scale; a low score indicates least mental health problems.

Global perceived effect rate (GPE) will be used as a retrospective evaluation of effect in asthma-related QOL as well as in asthma control on a 7-point Likert scale. GPE will only be measured at the follow ups.

Physical activity level (PAL) and numbers of steps will be measured by an accelerometer (BodyMedia SenseWear®) monitoring during 5 days

Spirometry (MedikroPro) will be used to measure forced expiratory volume in first second in liter (FEV1).

6 Minutes Walk Distance (6MWD); 6MWD is the most typically used function-score in pulmonary research.

Average metabolic equivalents (METs) and Total energy expenditure (TEE) will be measured by an accelerometer (BodyMedia SenseWear®) monitoring during 5 days.

Spirometry (MedikroPro) will be used to measure forced vital capacity (FVC), units liter, and peak expiratory flow rate (PEF), units liter/minute.

Adverse events (AE) e.g. emergency room visits will be extracted from medical report and from EasyTrial.Net (research database)

For precise measure extraction of prescriptions on anti-asthmatic medication and comorbid medication on ATC-codes.

Foster Score is used to investigate the number of days during the last seven days the participant took his/her asthma medication as prescribed. The participant is interviewed at the inhalationcheck, and will answer 0 to 7 referring to the number of days. Assessed again at 6 months follow up by questionnaire.

Adherence to the physiotherapist-sessions during the 12 weeks intervention will be investigated though data extracted in the electronically medical records.

The dichotomous Patient Acceptable Symptom State (PASS) evaluates treatment success in the patient's perspective. The PASS will only be measured at the follow ups.

If the participant answers 'no' to Patient Acceptable Symptom State (PASS) he/she will be asked to consider whether the treatment has failed.

Time in seconds when nose is pinched at functional residual capasity until first respiratory muscle movement.

Count Scale (CS) includes the count scale number (starting from 1 counting to as high as possible) and time spent while counting at a constant speed of 2 counts per second during one exhalation from max inspiratory level. CS has lower coefficient of variance at lower exercise level, than Borg Scale.

EuroQual-5Dimension (EQ-5D), a generic QOL tool that has high responsiveness, is translated into Danish and cross-cultural validated. EQ-5D index score of has been derived in the Danish population.

Participants gender, Body Mass Index (e.g., weight and height will be combined to report BMI in kg/m^2), smoking status (smoker/ former smoker/ non-smoker), and age will be self-reported at baseline.

Inclusion Criteria: Referred from GP to a secondary, out-patient respiratory clinic for lack of asthma control Pulmonologist-diagnosed asthma ≥ 2 consultations at a pulmonologist-lead asthma clinic ACQ6 ≥0.8 Able to provide written informed consent. Exclusion Criteria: Trained in breathing exercises by physiotherapist last 6 months Aged <18 Pregnancy Not able to speak, read or understand Danish Any severe disease as judged by the responsible physician Participating in another pulmonary interventional research-project.

University of Southern Denmark, Dep. of Physiotherapy and Occupational Therapy, Neastved-Slagelse-Ringsted Hospitals, Region Zealand, Denmark

Andreasson KH, Skou ST, Ulrik CS, Madsen H, Sidenius K, Jacobsen JS, Assing KD, Rasmussen KB, Porsbjerg C, Thomas M, Bodtger U. Protocol for a multicentre randomised controlled trial to investigate the effect on asthma-related quality of life from breathing retraining in patients with incomplete asthma control attending specialist care in Denmark. BMJ Open. 2019 Dec 31;9(12):e032984. doi: 10.1136/bmjopen-2019-032984.

Andreasson KH, Skou ST, Ulrik CS, Madsen H, Sidenius K, Assing KD, Porsbjerg C, Bloch-Nielsen J, Thomas M, Bodtger U. Breathing Exercises for Patients with Asthma in Specialist Care: A Multicenter Randomized Clinical Trial. Ann Am Thorac Soc. 2022 Sep;19(9):1498-1506. doi: 10.1513/AnnalsATS.202111-1228OC.