A Total Diet Replacement Weight Management Program for Difficult-to-Treat Asthma Associated With Obesity

Abstract

BackgroundObesity often is associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes, but with heterogenous asthma populations studied and unclear consensus on the optimal method of weight management. The Counterweight-Plus Programme (CWP) for weight management is an evidence-based, dietitian-led total diet replacement (TDR) program.Research QuestionCan use of the CWP compared with usual care (UC) improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity?Study Design and MethodsWe conducted a 1:1 (CWP to UC) randomized, controlled single-center trial in adults with difficult-to-treat asthma and BMI of ≥ 30 kg/m2. The CWP was a 12-week TDR phase (800 kcal/d low-energy formula) with stepwise food reintroduction and weight loss maintenance for up to 1 year. The primary outcome was the change in Asthma Control Questionnaire 6 (ACQ6) score over 16 weeks. The secondary outcome was change in Asthma Quality of Life Questionnaire (AQLQ) score.ResultsThirty-five participants were randomized (36 screened) and 33 attended the 16-week follow-up (n = 17 in the CWP group, n = 16 in the UC group). Overall, mean ACQ6 score at baseline was 2.8 (95% CI, 2.4-3.1). Weight loss was greater in the CWP than UC group (mean difference, –12.1 kg; 95% CI, –16.9 to –7.4; P < .001). ACQ6 score improved more in the CWP than UC group (mean difference, –0.69; 95% CI, –1.37 to –0.01; P = .048). A larger proportion of participants achieved the minimal clinically important difference in ACQ6 score with CWP than with UC (53% vs 19%; P = .041; NNT, 3 [95% CI, 1.5-26.9]). AQLQ score improvement was greater in the CWP than UC group (mean difference, 0.76; 95% CI, 0.18-1.34; P = .013).InterpretationUsing a structured weight management program results in clinically important improvements in asthma control and quality of life over 16 weeks compared with UC in adults with difficult-to-treat asthma and obesity. This generalizable program is easy to deliver for this challenging phenotype. Longer-term outcomes continue to be studied.Trial RegistryClinicalTrials.gov; No.: NCT03858608; URL: www.clinicaltrials.gov Obesity often is associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes, but with heterogenous asthma populations studied and unclear consensus on the optimal method of weight management. The Counterweight-Plus Programme (CWP) for weight management is an evidence-based, dietitian-led total diet replacement (TDR) program. Can use of the CWP compared with usual care (UC) improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity? We conducted a 1:1 (CWP to UC) randomized, controlled single-center trial in adults with difficult-to-treat asthma and BMI of ≥ 30 kg/m2. The CWP was a 12-week TDR phase (800 kcal/d low-energy formula) with stepwise food reintroduction and weight loss maintenance for up to 1 year. The primary outcome was the change in Asthma Control Questionnaire 6 (ACQ6) score over 16 weeks. The secondary outcome was change in Asthma Quality of Life Questionnaire (AQLQ) score. Thirty-five participants were randomized (36 screened) and 33 attended the 16-week follow-up (n = 17 in the CWP group, n = 16 in the UC group). Overall, mean ACQ6 score at baseline was 2.8 (95% CI, 2.4-3.1). Weight loss was greater in the CWP than UC group (mean difference, –12.1 kg; 95% CI, –16.9 to –7.4; P < .001). ACQ6 score improved more in the CWP than UC group (mean difference, –0.69; 95% CI, –1.37 to –0.01; P = .048). A larger proportion of participants achieved the minimal clinically important difference in ACQ6 score with CWP than with UC (53% vs 19%; P = .041; NNT, 3 [95% CI, 1.5-26.9]). AQLQ score improvement was greater in the CWP than UC group (mean difference, 0.76; 95% CI, 0.18-1.34; P = .013). Using a structured weight management program results in clinically important improvements in asthma control and quality of life over 16 weeks compared with UC in adults with difficult-to-treat asthma and obesity. This generalizable program is easy to deliver for this challenging phenotype. Longer-term outcomes continue to be studied. ClinicalTrials.gov; No.: NCT03858608; URL: www.clinicaltrials.gov Take-home PointsStudy Question: Can use of the Counterweight-Plus Programme (CWP) for weight management improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity, compared with those receiving usual care (UC)?Results: Over 16 weeks, the CWP resulted in clinically relevant improvements in both asthma control and quality-of-life indexes, with substantial weight loss, as compared with UC.Interpretation: Initial results using the CWP are encouraging, and adherence to the program was better than expected, although longer-term outcomes are awaited to assess sustainability of the benefits seen. Study Question: Can use of the Counterweight-Plus Programme (CWP) for weight management improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity, compared with those receiving usual care (UC)? Results: Over 16 weeks, the CWP resulted in clinically relevant improvements in both asthma control and quality-of-life indexes, with substantial weight loss, as compared with UC. Interpretation: Initial results using the CWP are encouraging, and adherence to the program was better than expected, although longer-term outcomes are awaited to assess sustainability of the benefits seen. Approximately 17% of people living with asthma have difficult-to-treat disease because of factors including poor inhaler technique, treatment nonadherence, and comorbidities such as obesity.1Global Initiative for AsthmaDiagnosis and management of difficult-to-treat and severe asthma. 2021. 23/05/2022. Global Initiative for Asthma website.www.ginasthma.org/severeasthmaGoogle Scholar,2Global Burden of Disease 2015 Chronic Respiratory Disease CollaboratorsGlobal, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet Respir Med. 2017; 5: 691-706Abstract Full Text Full Text PDF PubMed Scopus (1361) Google Scholar Asthma associated with obesity is less steroid responsive; is linked with poorer control, quality of life, and increased morbidity and mortality; and has limited treatment options.3Sutherland E.R. Goleva E. Strand M. et al.Body mass and glucocorticoid response in asthma.Am J Respir Crit Care Med. 2008; 178: 682-687Crossref PubMed Scopus (254) Google Scholar,4Taylor B. Mannino D. Brown C. et al.Body mass index and asthma severity in the National Asthma Survey.Thorax. 2008; 63: 14-20Crossref PubMed Scopus (236) Google Scholar The pathophysiologic effects of obesity on asthma are multifactorial. Weight excess has direct effects on thoracic wall mechanics,5Jones R.L. Nzekwu M.M. The effects of body mass index on lung volumes.Chest. 2006; 130: 827-833Abstract Full Text Full Text PDF PubMed Scopus (646) Google Scholar as well as increased airway closure,6Kaminsky D.A. Chapman D.G. Holbrook J.T. et al.Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma.Respirology. 2019; 24: 638-645Crossref PubMed Scopus (14) Google Scholar,7Peters U. Subramanian M. Chapman D.G. et al.BMI but not central obesity predisposes to airway closure during bronchoconstriction.Respirology. 2019; 24: 543-550Crossref PubMed Scopus (21) Google Scholar airway hyperresponsiveness,8Orfanos S. Jude J. Deeney B.T. et al.Obesity increases airway smooth muscle responses to contractile agonists.Am J Physiol Lung Cell Mol Physiol. 2018; 315: L673-L681Crossref Scopus (34) Google Scholar,9Pampuch A. Milewski R. Rogowska A. et al.Predictors of airway hyperreactivity in house dust mite allergic patients.Adv Respir Med. 2019; 87: 152-158Crossref Scopus (3) Google Scholar and airway inflammation.10Kwon H. Pessin J.E. Adipokines mediate inflammation and insulin resistance.Front Endocrinol (Lausanne). 2013; 4: 71Crossref PubMed Scopus (402) Google Scholar, 11Pereira S A.-L.J. Adipokines: biological functions and metabolically healthy obese profile. J.Receptor Ligand Channel Res. 2014; 7: 15-25Crossref Scopus (17) Google Scholar, 12White S.R. Laxman B. Naureckas E.T. et al.Evidence for an IL-6-high asthma phenotype in asthmatic patients of African ancestry.J Allergy Clin Immunol. 2019; 144: 304-306.e4Abstract Full Text Full Text PDF Google Scholar A Cochrane review13Adeniyi F.B. Young T. Weight loss interventions for chronic asthma.Cochrane Database Syst Rev. 2012; 7: Cd009339PubMed Google Scholar of four studies (N = 197) suggested that weight loss may improve asthma control, but the quality of the evidence was poor and further well-constructed randomized controlled trials were recommended. In the United Kingdom, the Counterweight-Plus Programme (CWP) for weight management is a commercially available dietitian-supported regimen of total diet replacement (TDR), stepwise food reintroduction, and weight loss maintenance. It has shown efficacy in obesity (mean weight loss, 10 kg; approximately one-third achieving loss of ≥ 15 kg) and type 2 diabetes mellitus (remission in 46% of patients).14Lean M. Brosnahan N. McLoone P. et al.Feasibility and indicative results from a 12-month low-energy liquid diet treatment and maintenance programme for severe obesity.Br J Gen Pract. 2013; 63: e115-e124Crossref Scopus (57) Google Scholar,15Lean M.E. Leslie W.S. Barnes A.C. et al.Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial.Lancet. 2018; 391: 541-551Abstract Full Text Full Text PDF PubMed Scopus (868) Google Scholar Its effects on asthma have not been evaluated, and we hypothesized that use of the CWP would result in improvements in asthma control and asthma-related quality of life. To test this hypothesis, we performed a randomized, controlled, proof-of-concept feasibility trial of CWP in patients with obesity and difficult-to-treat asthma. Herein, we report the primary outcome results for the first 16 weeks of treatment after completion of the first phase of the intervention program. In this randomized, controlled, open-label, parallel study of a TDR weight loss program compared with usual care (UC) in individuals with difficult-to-treat asthma and obesity, participants were randomized 1:1 using a password-protected, online, third-party randomization service to CWP or UC.16Sealed Envelope. Simple randomisation service. 2021. Sealed Envelope website.https://www.sealedenvelope.com/simple-randomiser/v1/Google Scholar Study visits were scheduled at baseline and 16 weeks, with further visits planned for the 1-year and 2-year follow-up. The trial was approved by the West of Scotland Regional Ethics Committee (Identifier: 18/WS/0216), was sponsored and funded by an NHS Greater Glasgow and Clyde Endowment Fund, and is registered at ClinicalTrials.gov (Identifier: NCT03858608), where trial protocol is described.17National Institutes of Health Clinical CenterWeight loss for uncontrolled asthma associated with elevated BMI. NCT03858608. National Institutes of Health; 2022. 23/05/2022.https://ClinicalTrials.gov/show/NCT03858608Google Scholar The funder and contributors to the fund had no input in study design or the trial outcomes. Because of the COVID-19 pandemic, face-to-face follow-up study visits were substituted for telephone consultations where necessary to optimize and randomization was by the Study visits and were performed by the and at the Glasgow Clinical participants to years of age with BMI of ≥ a of asthma to Global Initiative for Asthma Initiative for for asthma management and 23/05/2022. Global Initiative for Asthma Scholar and difficult-to-treat disease to and on the management of asthma. A national 23/05/2022. Scholar were from secondary and asthma and NHS Greater Glasgow and Clyde Asthma and asthma patients to the for after a of the program. Asthma were of in the trial were to but were not in study or participants were with and were to the Glasgow Clinical where was randomization and baseline were and randomized by the asthma and and were at the Asthma Control Questionnaire 6 (ACQ6) and Asthma Quality of Life Questionnaire (AQLQ) were The ACQ6 is a asthma control score et and of a to asthma Respir J. PubMed Scopus Google Scholar a score of ≥ poor disease control, and with a minimal clinically important difference of The AQLQ is a score and quality of life in A. et a minimal important change in a Quality of Life Clin Full Text PDF PubMed Scopus Google Scholar A score better quality of life and the is as Respiratory J. et of Respir J. PubMed Scopus Google Scholar to et of for J Respir Crit Care Med. PubMed Scopus Google Scholar test to Respiratory T. et Respiratory in chronic Respir J. 2014; PubMed Scopus Google Scholar and The CWP of TDR food reintroduction and weight loss maintenance and was by with CWP The TDR phase a low-energy liquid diet of to kcal/d and of and in a of up with by the The participants at 1 and To for or this phase was to weeks participants not 15 by a BMI to < food reintroduction was The food reintroduction phase a diet and stepwise reintroduction of of 2 to weeks were for this phase on with weight loss management. In the weight loss maintenance for weight and to weight with program were by change W.S. N. et Clinical (DiRECT): protocol for a Pract. Scopus Google Brosnahan N. H. et the intervention service of an weight management programme for severe and 2019; PubMed Scopus Google Scholar to weight were N. 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