Pulmonary Rehabilitation for Uncontrolled Asthma Associated With Elevated BMI (PRODA01)

A Pragmatic, Randomised, Controlled, Trial of the Effect of a Tailored Pulmonary Rehabilitation Package in Uncontrolled Asthma Associated With Elevated Body Mass Index

Aim to evaluate the impact of a pulmonary rehabilitation (rehab) programme tailored and delivered to overweight and obese patients with difficult asthma on:

1. Asthma related quality of life (primary outcome) and asthma control (secondary outcome)
2. Treatment burden and healthcare usage (secondary outcomes)
3. Physical activity level, exercise tolerance, lung function and inflammation (secondary outcome)
4. Anxiety and depression (secondary outcome)

Study Overview

• Status: Unknown
• Conditions: Asthma
• Intervention / Treatment: Other: Usual Care; Behavioral: Pulmonary rehabilitation

Detailed Description

Eligible individuals will be identified through Difficult Asthma Clinics or ward admissions. Those wishing to participate will receive an information sheet and be invited to provide written informed consent prior to commencing the study.

Baseline Visit

Measurements taken at the baseline visit will include:

Demographics - age, gender, smoking history (current, ex, none, years since stopped, pack years), age at asthma diagnosis, duration of asthma, atopy, co-morbidities (allergic/perennial rhinitis, nasal polyps, nasal surgery, eczema, gastro-oesophageal reflux disease (GORD), diabetes, hypertension, cardiac disease, osteopenia/osteoporosis etc), medications (inhaled/nebulised short acting beta2-agonists (SABA), inhaled and oral corticosteroids (OCS) etc), healthcare usage (oral corticosteroid boosts, unscheduled general practice (GP) or accident and emergency (A+E) attendances, hospital and intensive care unit (ICU) admissions in preceding year), weight, height and body mass index (BMI).

Questionnaires - Medical Research Council (MRC) dyspnoea scale, Asthma Control Questionnaire (ACQ6), Asthma Quality of Life Questionnaire (AQLQ), and Hospital Anxiety and Depression Scale (HAD).

Inflammatory - Blood eosinophils, Fraction of exhaled nitric oxide (FENO).

Lung Function - peak expiratory flow (PEF) (best of 3), Spirometry (pre- and post-bronchodilator).

Exercise tolerance - 6 minute walk test (6MWT) (practice test and repeat test), Modified Borg Dyspnoea Scale, pulse oximetry.

Physical Activity - actigraphy

Participants will be provided with a Personalized Asthma Management Plan, and Symptoms Diary that includes SABA use and other healthcare usage (OCS) boosts, unscheduled GP or A+E attendances, hospital and ICU admissions); inhaler technique will be corrected if necessary.

Participants will be randomized 1:1 to Group A and Group B. Group A will enter the 8 week pulmonary rehabilitation arm of the study immediately while Group B will enter the 8 week usual care arm. Group A will return for Visit 2 and Group B for Visit 1(2) at 8 weeks.

Measurements taken at Visits 1(2), 2. and 3 will include:

Demographics - medications (inhaled/nebulised short acting beta2-agonists (SABA), inhaled and oral corticosteroids etc), healthcare usage (OCS) boosts, unscheduled GP or A+E attendances, hospital and ICU admissions since last visit), weight, height, and BMI.

Questionnaires - MRC dyspnoea scale, Asthma Control Questionnaire (ACQ6), Asthma Quality of Life Questionnaire (AQLQ), and Hospital Anxiety and Depression Scale (HAD).

Inflammatory - Blood eosinophils, Fraction of exhaled nitric oxide (FENO).

Lung Function - PEF (best of 3), Spirometry (pre- and post-bronchodilator).

Exercise tolerance - 6 minute walk test, Modified Borg Dyspnoea Scale, pulse oximetry.

Physical Activity - actigraphy

After Visit 2, Group A will discontinue pulmonary rehabilitation; Group A will return for Visit 3 (48 weeks). Group B will enter the 8 week pulmonary rehabilitation arm and return for Visit 2 at 16 weeks; Group B will return for Visit 3 (56 weeks). Visits will be postponed by 4 weeks in the event of exacerbation or respiratory infection. Throughout the study period changes to asthma medications will be allowed as clinically indicated.

Pulmonary rehabilitation arm

The pulmonary rehabilitation course will be provided on a rolling basis and for each individual will be of 8 weeks duration including once weekly, 1.5 hour hospital sessions and encouragement to perform twice weekly home exercise sessions. Hospital sessions will include 1 hour of supervised exercise and 30 minutes education. Hospital sessions will run in Glasgow Royal Infirmary every Thursday morning with education (11:15-11:45) and exercise (12:00-13:00). Sessions will run with minimum 6 participants and aiming for 12-16.

Exercise Component: This will include a combination of aerobic, resistance and flexibility training. Participants will be screened prior to commencing exercise to confirm stability of asthma. Pre-exercise administration of bronchodilators (participant's own salbutamol inhaler) will occur and there will a gradual warm-up with stretches for 7 to 8 minutes. The prescribed training intensity will be defined by the exercise capacity during baseline 6MWT with progressive increase in repetitions. Nebulised salbutamol will be available in the venue. Individuals will then rotate through the following exercises:

12 leg extensions alternating right/left (R/L) +/- weights 12 arm weights (R/L together) 12 step ups Bike 12 Sit to stands 12 pole raises 12 knee lifts (alternating R/L) Walk

Educational Component: This will include the following topics:

What is asthma - and relation to physical activity Medications in asthma Recognizing warning signs, self management and personalized asthma action plans Inhaler technique and PEF recording Co-morbidities and asthma Dysfunctional breathing and breathing control exercises Anxiety management Relaxation Chest clearance Health promotion - smoking cessation, healthy eating etc Benefits of exercise and maintenance

On completion of the formal pulmonary rehabilitation course, participants will be encouraged to continue regular exercise sessions by accessing community based "Vitality Classes".

Usual care arm

During this 8 week period, individuals will be asked not to alter their physical activity level from baseline, and to continue their pre-study asthma management.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Scotland
    • Glasgow, Scotland, United Kingdom, G31 2ER
      • Recruiting
      • Glasgow Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults aged 18-80 year (smokers, ex-smokers and non-smokers)

2. Confirmed asthma as per Global Initiative for Asthma (GINA) guidelines 2015[4] with characteristic symptoms and at least one of the following:

   • Airflow limitation - FEV1/FVC < 70% (at any time in the past) and 12% and 200ml increase in FEV1 in the preceding 5 years either:

     i. After inhaled/nebulised bronchodilator or 4+ weeks of anti- inflammatory treatment ii. Between visits

   • Positive bronchial challenge in the preceding 5 years:

   I. Histamine or methacholine provocation concentration causing a 20% drop in FEV1 (PC20) <8mg/ml ii. Provoking dose of mannitol required to cause a drop in FEV1 of 15% (PD15) mannitol <635mg

3. Difficult asthma defined as per Scottish Intercollegiate Guidelines Network(SIGN)/British Thoracic Society(BTS) guideline 2014 as persistent symptoms and/or frequent asthma attacks despite treatment at step 4 or step 5 with either:

   • ACQ6>1.5
   • ≥2 systemic corticosteroid boosts in previous year
   • ≥1 hospitalization in previous year
4. BMI≥25 kg/m2
5. MRC dyspnoea scale ≥3/5

Exclusion Criteria:

1. ICU admission +/- mechanical ventilation in the previous year for asthma exacerbation
2. Respiratory tract infection requiring antibiotics or asthma exacerbation requiring corticosteroid boost in preceding 4 weeks
3. Significant respiratory or other co-morbidity likely to influence the conduct of the study
4. Pregnancy and breast feeding
5. Severe and/or unstable cardiac disease
6. Impaired mobility that impacts on ability to participate in physical training
7. Recent (within the preceding 6 months) commencement of antifungal, biologic (omalizumab, lebrikizumab, mepolizumab) or Airsonett device; eligible if on treatment for >6months or discontinued >6 months ago.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; Immediate 8 week course of pulmonary rehabilitation	Behavioral: Pulmonary rehabilitation; The pulmonary rehabilitation course will be provided on a rolling basis and for each individual will be of 8 weeks duration including once weekly, 1.5 hour hospital sessions and encouragement to perform twice weekly home exercise sessions. Hospital sessions will include 1 hour of supervised exercise and 30 minutes education. Exercise Component: This will include a combination of aerobic, resistance and flexibility training. Educational Component will cover many topics including what is asthma, treatments and inhaler technique, self-management, importance of exercise and health promotion. On completion of the formal pulmonary rehabilitation course, participants will be encouraged to continue regular exercise sessions by accessing community based "Vitality Classes".
Placebo Comparator: Group B; Initial 8 weeks of usual care	Other: Usual Care; Usual Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AQLQ- Asthma quality of life questionnaire	change from week 0 to week 8 for pulmonary rehab vs usual care control group. AQLQ consists of 32 questions related to quality of life scored out of 7, and then averaged. Total score is out of 7 with 1 being the worst and 7 the best. There is also a score between 1 and 7 for 4 subscales which cover areas of symptoms, activity limitation, emotional function and environmental stimuli. These subscales are also averaged over a number of questions with 1 being worst and 7 best.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AQLQ- asthma quality of life questionnaire	percentage with more than or equal to 0.5 point improvement from beginning to end of pulmonary rehab programme versus percentage in usual care control group. AQLQ consists of 32 questions related to quality of life scored out of 7, and then averaged. Total score is out of 7 with 1 being the worst and 7 the best. There is also a score between 1 and 7 for 4 subscales which cover areas of symptoms, activity limitation, emotional function and environmental stimuli. These subscales are also averaged over a number of questions with 1 being worst and 7 best.	8 weeks
ACQ6- asthma control questionnaire 6	Change from week 0 to week 8 for pulmonary rehab vs usual care control group. ACQ6 comprises 6 questions scored out of 6 then averaged, value will range from 0-6, with 0 reflecting excellent asthma control and 6 very poor control.	8 weeks
ACQ6- asthma control questionnaire 6	percentage with more than or equal to 0.5 point improvement from beginning to end of pulmonary rehab programme versus percentage in usual care control group. ACQ6 comprises 6 questions scored out of 6 then averaged, value will range from 0-6, with 0 reflecting excellent asthma control and 6 very poor control.	8 weeks
ACQ6- asthma control questionnaire 6	Change from baseline to end of study period. ACQ6 comprises 6 questions scored out of 6 then averaged, value will range from 0-6, with 0 reflecting excellent asthma control and 6 very poor control.	48 (or 56) weeks depending on group
AQLQ	Change from baseline to end of study period. AQLQ consists of 32 questions related to quality of life scored out of 7, and then averaged. Total score is out of 7 with 1 being the worst and 7 the best. There is also a score between 1 and 7 for 4 subscales which cover areas of symptoms, activity limitation, emotional function and environmental stimuli. These subscales are also averaged over a number of questions with 1 being worst and 7 best.	48 (or 56) weeks depending on group
Change in treatment burden	Has there been a change in short acting beta agonist use, inhaled corticosteroid dose, maintenance prednisolone dose, frequency of prednisolone boosts; i.e. is the patient requiring any more or less treatment for asthma control than at baseline. This will be assessed by asking the patient and completing an asthma medication use treatment chart	48 or 56 weeks
Change in healthcare usage	Number of episodes of in scheduled care, including GP or A&E attendances, hospital and ICU admission. This will be compared to pre-trial episodes of the same.	48/56 weeks
Medical Research Council (MRC) dyspnoea score	Change in score on MRC dyspnoea scale. This is a score from 1-5 used to grade degree of breathlessness, 1 is the best result, 5 is the worst (most breathless)	48/56 weeks
Body mass index	Change in body mass index over study period, calculated using height in metres and weight in kilograms to give BMI in kg/m2	48/56 weeks
Inflammation	Changes in Blood eosinophils and FENO	48/56 weeks
Lung function	Change in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC); lowest O2 saturation	48/56 weeks
Exercise tolerance	Change in 6MWT distance, modified Borg dyspnoea scale and lowest O2 saturation;	48/56 weeks
Physical activity	Change in actigraphy data	48/56 weeks
Hospital anxiety and depression scale	Change in score on HAD. This is a scale comprised of 14 questions where responses are graded from 0-3, with the responses then being totalled. A lower score is better, i.e. a higher score is indicative of more significant symptoms of anxiety and depression.	48/56 weeks

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde

Publications and helpful links

General Publications

• Ricketts HC, Sharma V, Steffensen F, Goodfellow A, Mackay E, MacDonald G, Buchan DS, Chaudhuri R, Cowan DC. A pragmatic randomised controlled trial of tailored pulmonary rehabilitation in participants with difficult-to-control asthma and elevated body mass index. BMC Pulm Med. 2022 Sep 24;22(1):363. doi: 10.1186/s12890-022-02152-2.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2017
• Primary Completion (Anticipated): May 10, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Severe; Difficult; Overweight and obese
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: GN16RM503

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No