Weight Loss for Uncontrolled Asthma Associated With Elevated BMI
Weight Loss for Uncontrolled Asthma Associated With Elevated BMI
Weight loss for uncontrolled asthma associated with elevated BMI. Asthma is a common
 condition with different types recognised that have variable responses to current treatments.
 It is often poorly controlled and there is a need to discover new treatments. Obesity is
 common in asthma and is associated with increase in symptoms, poorer asthma control and
 quality of life, and increased healthcare utilisation and treatment burden. The Counterweight
 Plus programme is a safe, evidence-based non-surgical intervention that is associated with
 sustained weight losses of up to 15% in obese individuals but its effects in asthma have not
 been tested. Our study aims to evaluate the impact of this intervention in individuals with
 difficult asthma associated with obesity.

 The Counterweight Plus programme includes a total diet replacement (TDR) phase (12 weeks)
 followed by structured food reintroduction (6 weeks) and long term weight loss maintenance
 (34 weeks) and will be provided by Dieticians trained in the delivery of this intervention.
 Participants will attend fortnightly clinic reviews with Dieticians during the first 18 weeks
 and then monthly clinic reviews during the weight loss maintenance period.

 Participants will be randomised to Counterweight Plus programme or usual care (control) and
 followed for 1 year with study visits at baseline, 4 months and 1 year. During study visits
 participants will be invited to complete questionnaires, provide a blood sample, perform
 breathing tests and a walking test, and wear an activity monitor for one week.

 If the Counterweight Plus programme is proven to be of benefit in this patient group, this
 may lead to service development so that this intervention may be made available to similar
 patients in the future within the clinical setting.
This study will be a unblinded, pragmatic, pilot, randomised, controlled trial of the
 Counterweight Plus programme versus usual care in individuals with difficult asthma
 associated with obesity. 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, diabetes, hypertension, cardiac disease, osteopenia/osteoporosis etc), medications
 (inhaled/nebulised short acting beta2-agonists (SABA), inhaled and oral corticosteroids etc),
 healthcare usage (oral corticosteroid (OCS) boosts, unscheduled General Practitioner (GP) or
 Accident + Emergency (A+E) attendances, hospital and Intensive Care Unit (ICU) admissions in
 preceding year), weight, height and 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).

 Venepuncture - full blood count, urea and electrolytes, liver function tests, magnesium, bone
 profile, insulin, glucose, HbA1c, lipids, C-reactive Protein (CRP), Interleukin-6 (IL-6),
 leptin and adiponectin Lung Function/inflammometry - peak expiratory flow (PEF) (best of 3),
 Spirometry (pre- and post-bronchodilator), Fraction of exhaled nitric oxide (FENO) Exercise
 tolerance - 6 minute walk test (practice test and repeat test)[29], Modified Borg Dyspnoea
 Scale, pulse oximetry.

 Physical Activity - actigraphy. Participants will be given the Actigraph device and asked to
 wear it continuously for 7 days on their non-dominant wrist, then hand it back.

 Participants will be provided with a Personalized Asthma Management Plan, and Symptoms Diary
 that includes SABA use and other healthcare usage (oral corticosteroid (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
 Counterweight Plus programme and Group B will enter the usual care arm.

 Participants will return for Visit 2 at 16 weeks and Visit 3 at 52 weeks.

 Measurements taken at Visits 2 and 3 will include:

 Demographics - medications (inhaled/nebulised short acting beta2-agonists (SABA), inhaled and
 oral corticosteroids etc), healthcare usage (oral corticosteroid (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).

 Venepuncture - full blood count, urea and electrolytes, liver function tests, magnesium, bone
 profile, insulin, glucose, HbA1c, lipids, CRP, IL-6, leptin and adiponectin Lung
 Function/inflammometry - PEF (best of 3), Spirometry (pre- and post-bronchodilator), Fraction
 of exhaled nitric oxide (FENO) Exercise tolerance - 6 minute walk test, Modified Borg
 Dyspnoea Scale, pulse oximetry.

 Physical Activity - actigraphy 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.

 Rescue Package for weight regain or re-emergence of diabetes Some patients find weight
 maintenance difficult, some relapse temporarily and gain weight rapidly. Others may tend to
 let things slip more gradually. Pilot studies showed the value of a sympathetic, but firm
 approach to relapse/regain management. If weight regains occurs in TDR randomised
 participants, or if diabetes is found to have returned (HbA1c risen above 6.5%) at any time
 during the 18 month weight loss maintenance stage, 'rescue plans' for weight gain prevention
 will be offered.

 1. Weight regain of >2kg: offer the use of TDR to replace one main-meal per day for 4
 weeks, and offer orlistat 120 mg tid, with each meal.

 2. Weight gain of >4kg, or to <15kg below starting weight or if diabetes recurs: offer 4
 weeks TDR with fortnightly weekly practice nurse/dietitian review and then a 2-4 week
 food re-introduction (adding 1 meal/week as before). Lowfat dietary advice and physical
 activity will be reinforced for weight maintenance and orlistat treatment will be
 offered.

 This package can be repeated as required in each year of the maintenance phase.
Inclusion Criteria:

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

 • Reversible airflow limitation - 12% and 200ml increase in forced expiratory volume
 (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. Provocation concentration
 (PC20) methacholine or histamine <8mg/ml ii. Provocative dose (PD15) mannitol <635mg

 2. 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

 3. BMI ≥ 30 kg/m2

 Exclusion Criteria:

 1. ICU admission +/- mechanical ventilation in the previous 6 months 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. Recent (within the preceding 6 months) commencement of antifungal, biologic
 (omalizumab, lebrikizumab, mepolizumab) or "Airsonett" device; eligible if on
 treatment for > 6months or discontinued

 7. Current insulin use

 8. Current treatment with anti-obesity drugs