Introduction We previously reported improved Asthma Control Questionnaire (ACQ6) and Asthma Quality of Life Questionnaire (AQLQ) scores with weight-loss after 16 weeks of the Counterweight-Plus weight management programme (CWP) compared to usual care (UC) in a single-centre, randomised, controlled trial in patients with difficult-to-treat asthma and obesity.1 Here we report one-year asthma outcomes from this trial. Methods We randomised (1:1 CWP:UC) adults with difficult-to-treat asthma and body mass index (BMI) ≥30 kg/m2. CWP with dietitian support: 12-week total diet replacement phase (850kcal/day low-energy formula); stepwise food reintroduction and weight loss maintenance up to week 52. Study visits occurred at baseline, 16-weeks and 52-weeks. Outcomes measured include ACQ6, AQLQ and healthcare usage. Minimal clinically important difference (MCID) in ACQ6 is –0.5 and in AQLQ 0.5. Results Of 36 recruited, 29 attended at 52-weeks for intention-to-treat analysis: 13 CWP, 16 UC. CWP resulted in greater weight change (median –14 kg [IQR –15, –9]) compared to UC (2 kg [-7, 8]; p=0.015) at 52-weeks. 53% in CWP achieved MCID in ACQ6 at 16-weeks (vs 19% UC [p=0.041]) and these 53% sustained improvement at 52-weeks (vs 25% UC [p=0.101]). Over 52-weeks a greater proportion of participants achieved MCID with CWP vs UC in AQLQ (71% vs 6% respectively; p<0.001), including AQLQ symptom domain (71% vs 31%; p=0.024), activity domain (53% vs 19%; p=0.041) and environmental domain (65% vs 19%; p=0.008), figure 1. Median annualised prednisolone courses reduced with CWP from 4 (IQR 2, 5) at baseline to 0 (0, 2) at 52-weeks (χ²Friedman[2]=14.8, p<0.001, Kendall's W=0.44). Conclusion Weight-loss, with a structured low-energy formula diet replacement programme, results in sustained weight-loss and improvements in asthma quality of life and frequency of exacerbations compared to usual care over one year. The Counterweight-Plus weight management programme is a non-pharmacological option for the challenging phenotype of difficult-to-treat asthma and obesity. Further study is needed to assess effects on spirometry and inflammation. Reference Sharma, et al, CHEST, May 2023, doi: https://doi.org/10.1016/j.chest.2023.01.015 Please refer to page A290 for declarations of interest related to this abstract.

Introduction and aims: Asthma associated with elevated body mass index (BMI) is challenging, with limited treatment options. Benefits of pulmonary rehabilitation (PR) in this population are unclear, but our previous randomised controlled trial (NCT03630432) showed some improved outcomes at 8 weeks. In the current study, we aimed to evaluate short- and longer-term effects of tailored PR in participants with difficult-to-control asthma and BMI ≥25 kg/m2. Methods: In this prospective observational study, participants with difficult-to-control asthma and elevated BMI who completed an 8-week asthma-tailored PR course were assessed at 8 (V2) and 52 weeks (V3), and asthma-related outcomes compared to those at baseline (V1), using repeated measures ANOVA. Results: 96 participants were consented, and 56 entered the study. Significant differences were seen for asthma control questionnaire (ACQ6) (mean (95% CI) at V1 2.5 (2.1-2.9), V2 2.2 (1.8-2.5) and V3 2.3 (1.9-2.7), p<0.003), Borg breathlessness at completion of 6-minute walk test (median (IQR) at V1 2 (0.5-3), V2 1 (0-2) and V3 1 (0.5-2), p<0.035), and annualised exacerbations requiring prednisolone (median (IQR) at V1 3 (2-5), V2 0 (0-4.7) and V3 1.5 (0-4.2), p<0.003). Participants with higher ACQ6 scores at baseline were more likely to respond to PR (defined as ≥0.5 point improvement in ACQ6). At V2: mean (SD) baseline ACQ6 2.9 (1.3) in responders vs 2.0 (1.3) in non-responders, p=0.015; and at V3: mean (SD) baseline ACQ6 3.1 (1.3) in responders vs 2.1 (1.3) in non-responders, p=0.013. Conclusions: PR can improve asthma control and reduce exacerbation rates in this population.

Introduction: Uncontrolled asthma can cause sleep disruption. Accelerometer devices have been validated against polysomnography to measure sleep parameters. No studies have used accelerometers to compare sleep outcomes between asthma severity groups. Aim: We hypothesised that sleep parameters may vary between mild asthma (MA) and difficult-to-treat asthma (DTA) and performed a post-hoc analysis from two recent in-house trials (ID NCT03630432, NCT03858608). Methods: 7-day data from 133 participants with MA and DTA were collected using ActiGraph GT3X+ (ActiGraph, Pensacola, Florida, USA) devices. Sleep variables extracted include mean sleep window time (SWT), sleep time (ST), sleep efficiency (SE), sleep onset time (SOT) and wake onset time (WOT). Significance was set at p≤0.05 for comparisons between MA and DTA groups. Data reported as hours:minutes/24-hour clock where appropriate. Results: 9/133 patients were excluded (lack of data) leaving 124 datasets: 44 MA, 80 DTA. Median SWT was 07:49 (06:29 to 08:56); median ST was 06:35 (5:02 to 7:45); median SE was 85%. Median SOT was 00:08 (23:02 to 01:23) and WOT 07:54 (06:48 to 09:22). No differences were seen between MA and DTA in SWT, ST, SE and WOT. There was a difference in SOT between MA and DTA (23:41 [22:52 to 00:45] vs 00:24 [23:16 to 02:02] respectively, p = 0.019). Discussion: Accelerometery has shown no clinically relevant differences in sleep parameters between MA and DTA. Results are comparable to general population results previously reported [Plekhanova, T. et al. Journal for the Measurement of Physical Behaviour, 2020;3(4):294-303]. Prospective studies with associated sleep quality questionnaires are needed to confirm our findings.

Introduction: Obesity is linked with uncontrolled, severe asthma. The Counterweight-Plus weight management programme (CWP) is an evidence-based, dietician-led, structured diet programme. Aim: To evaluate the effects of CWP versus usual care (UC) on asthma-related outcomes in a randomised, controlled trial in uncontrolled asthma associated with obesity. Methods: We randomised (1:1 CWP:UC) adults with uncontrolled asthma and body mass index (BMI) ≥30kg/m2. CWP: 12-week total diet replacement phase (800kcal/day low-energy formula); food reintroduction and weight loss maintenance up to week 52. Primary outcome: change in asthma control questionnaire (ACQ6) score over 16 weeks, adjusting for baseline using ANCOVA (intention-to-treat analysis). Secondary outcome: change in asthma quality of life questionnaire (AQLQ) score. Results: Of 36 participants screened, 35 were randomised and 33 attended 16-week follow-up (17 CWP, 16 UC). Mean (SD) ACQ6 at baseline was 2.6 (1.0) in CWP and 2.7 (1.1) in UC. Weight loss was greater with CWP than UC (mean difference -12.3kg; 95%CI -17.1, -7.5; p<0.001). ACQ6 improved more with CWP than UC (mean difference -0.69; 95%CI -1.37, -0.01; p=0.048). A greater proportion of participants had ≥0.5 improvement in ACQ6 (minimal clinically important difference) with CWP than UC (53% vs 19%; p=0.041). AQLQ improved more with CWP than UC (mean difference 0.76; 95%CI 0.18, 1.34; p=0.013). Conclusion: Weight loss, with a structured low-energy formula diet replacement programme, yields significant improvements in asthma control and quality of life over 16 weeks, compared to usual care, in adults with uncontrolled asthma associated with obesity.

Background Difficult-to-control asthma associated with elevated body mass index (BMI) represents a significant challenge, with limited treatment options. The effects of pulmonary rehabilitation (PR) in this population are uncertain. Methods This randomised controlled trial compared an asthma-tailored PR programme to usual care (UC) in participants with uncontrolled asthma and BMI ≥25 kg/m2. PR comprised an hour of education and of exercise each week for eight weeks. Primary outcome was difference in change in Asthma Quality of Life Questionnaire (AQLQ) in PR versus UC groups post intervention. Secondary outcomes included difference in change in other asthma outcomes including asthma control questionnaire-6 (ACQ6), Medical Research Council (MRC) dyspnoea score, six-minute walk distance (6MWD) and post-exercise Borg breathlessness score. Responder analyses compared proportions reaching the minimum clinically important difference (MCID) for AQLQ and ACQ6. Results 95 participants were randomised 1:1 to PR or UC; median age was 54, with 60% female and median BMI 33.8kg/m2. 18 participants withdrew prior to second visit, meaning 77 were included in analysis. Median (IQR) change in AQLQ was not significantly different: 0.3(-0.2 to 0.6) in PR and -0.1(-0.5 to 0.4) in UC, p= 0.139. There was no difference in proportion reaching MCID for improvement in AQLQ: 13(39%) in PR and 10(23%) in UC, p=0.184. Mean change in ACQ6 was significantly different: -0.4(95% CI -0.6 to -0.2) in PR and 0(-0.3 to +0.3) in UC, p=0.015*. In ACQ6 responder analysis, MCID was reached by 18 participants in PR group (54.5%) versus 10 in UC (22.7%), p=0.009*. Changes in MRC dyspnoea score (p=0.022*), 6MWD (p=0.035*) and Borg breathlessness (p=0.015*) were significantly different in favour of PR. A post-hoc analysis of PR group revealed baseline FeNO was significantly lower in ACQ6 responders (median (IQR) 18(8.5–41)) than non-responders (47(17–71)), p=0.020*; and in AQLQ responders (14(8.5–44.5)) compared to non-responders (40(19–71)), p=0.038*. Conclusion Pulmonary rehabilitation improves asthma control and reduces perception of breathlessness in participants with difficult-to-control asthma associated with elevated BMI. It should be considered as additional therapy for this group. Lower FeNO in PR responders suggests it may be of most value in type-2 low phenotype obese asthma.

Background Patients with asthma may find it impacts their ability to be physically active. Physical activity (PA) has been demonstrated to be lower in asthmatics compared to healthy controls. Obesity is commonly linked with difficult-to-control asthma and can worsen outcomes. At least 150 minutes of moderate physical activity (PA) per week is recommended for all adults by the World Health Organisation. We aimed to compare PA levels in patients with difficult-to-control asthma and body mass index (BMI) ≥25 kg/m2 (DOW group) and two control groups with mild-moderate asthma, one with BMI <25 kg/m2 (MHW group) and one with BMI ≥25 kg/m2 (MOW group). Methods This cross-sectional study used 7-day recordings from wrist-worn accelerometers to compare PA between groups. We recorded inactive time, light (LPA) and moderate-vigorous physical activity (MVPA). We also measured novel metrics: intensity gradient (IG) reflecting PA intensity, and average acceleration (AA) reflecting PA volume. Parameters were compared across groups using ANOVA testing for normally distributed data and Kruskall-Wallis for skewed data. Correlation analysis explored associations between PA parameters and asthma measures. As AA was most closely correlated with asthma measures, we compared the highest and lowest AA quartiles using unpaired t and Mann-Whitney U tests, depending on normality. Results 75 participants were recruited, 25 per group. Inactive time was significantly higher (p<0.001), and LPA (p=0.007), MVPA (p<0.001), IG (p<0.001) and AA (p<0.001) all significantly lower in DOW group compared to MHW and MOW groups, even after adjusting for age and BMI. For AA, notable correlations included beclometasone diproprionate-equivalent dose of inhaled corticosteroid (r=-0.591, p<0.001), asthma-related quality of life score (r=0.531, p<0.001) and six-minute walk distance (r=0.719, p<0.001). Highest and lowest AA quartiles revealed significant differences in 14 of 21 asthma outcomes including the above, and pre-bronchodilator forced expiratory volume in 1 second, 6-point asthma control questionnaire and BMI. Conclusions Participants with difficult-to-control asthma who were overweight/obese performed less physical activity, and activity of reduced intensity and volume compared to participants with milder asthma with normal or elevated BMI. Suboptimal physical activity profile is a treatable trait which should be targeted to improve asthma-related outcomes in appropriate patients. Please refer to page A191 for declarations of interest related to this abstract.

Introduction Obesity-associated asthma is a difficult-to-treat phenotype linked with poorer disease control, reduced quality of life and increased morbidity and mortality. This phenotype coupled with type 2 (T2)-high inflammation may respond to currently available biologic treatments. Previous studies have shown reduction in fractional exhaled nitric oxide (FeNO) with increasing body mass index (BMI) however, to our knowledge, no studies have shown this effect when adjusted for confounding variables such as corticosteroid use. We postulate that obesity has an impact on T2 biomarkers independent of confounders. Methods Data from two recent studies (ID NCT03630432, NCT03858608) was analysed retrospectively, including patient demographics, medical and drug history, BMI, eosinophils, FeNO and atopic status; and most recently available total Immunoglobulin E (IgE) was collected for this analysis. The primary outcome of interest was the effect of BMI on T2 biomarkers: blood eosinophil count, FeNO and total IgE. Multiple linear regression was performed to investigate whether BMI could predict FeNO when adjusted for other variables (age, sex, atopic status, smoking status, allergic rhinitis, perennial rhinitis, and inhaled and oral corticosteroid dose). All statistical analysis was performed using IBM SPSS Statistics (version 27.0.1.0) and significance was set at <0.05. Results The dataset included 102 overweight and obese difficult asthma participants, 26 overweight and obese mild asthma participants and 25 healthy-BMI mild asthma participants (n = 153). In multiple linear regression, BMI was a significant predictor of FeNO ( β = -2.848, p = 0.019*); in this model, for every increase in BMI by 1 kg/m2, FeNO decreased by 3 parts per billion (ppb) when adjusted for age, sex, atopy, smoking, rhinitis and corticosteroid dose. The overall model was significant, F(9,18) = 3.20, p =0.017*, with an R2 = 0.62. Conclusions Our data indicates there is a significant negative relationship between BMI and FeNO after adjusting for relevant variables, particularly corticosteroid use. This could have important implications for endotyping in this already hard-to-treat population, and affects subsequent assessment for advanced asthma therapies, such as biologics, that are tailored to T2-high endotypes. Limitations include non-equal weighting between groups and low numbers in this unpowered study.

Bronchial reactivity to cigarette smoke (CBR) in a cross-section of 98 smokers has been investigated. All participants were subjects to skin-prick tests to common allergens, lung function measurements and bronchial challenges with methacholine and cigarette smoke. In 38 participants a rechallenge with cigarettes was performed 1 h after the first cigarette challenge. Lung function indices analysed were: forced expiratory volume in one second (FEV1); maximal expiratory flow at 75% of the forced vital capacity (MEF75%); and forced mid-expiratory flow between 25 and 75% of the forced vital capacity (FEF(25-75%)). All participants were tested for asthma and allergy, and were required to provide information regarding respiratory symptoms, first degree relatives with asthma and allergy and smoking habits. A substantial decrease was seen in all lung function indices after 12 cigarette-smoke inhalations, but only FEV1 was related to other variables. The maximal mean percentage fall in FEV1 was 10%, which was directly related to the number of inhalations (p<0.05). In multiple regression analyses the percentage fall in FEV1 was directly related to: FEV1/vital capacity (VC) (p<0.01); to the asthmatic/bronchitic status (p<0.05); and to the accumulated and standardized cigarette consumption (p<0.05). The percentage fall in FEV1 bore no relationship to methacholine bronchial reactivity, sex or age and had a continuous distribution. The repeat challenge showed a smaller fall in FEV1 compared to the first challenge after 12 cigarette smoke inhalations (p<0.05). The percentage fall in FEV1 correlated after the first and the repeat challenge (p<0.05). Repeatability of the challenge could not be determined in this study because of tachyphylaxis. Bronchial reactivity to cigarette smoke is a tobacco smoke-specific bronchial response. All participants responded and the response showed a continuous distribution. Bronchial reactivity to cigarette smoke may be of importance for symptoms and prognosis in chronic bronchitis and chronic obstructive pulmonary disease and should be studied in relation to the degree of accelerated lung function loss in smokers and other cigarette induced lung abnormalities.

Introduction Obesity is often linked with difficult-to-treat asthma and increased morbidity and mortality. Asthma and obesity are on the rise posing a challenge to asthma specialists. The Counterweight-Plus weight management programme (CWP) is a dietitian-supported, structured diet programme with an evidence base in weight management and type 2 diabetes (Lean et al. Lancet, Feb 2018; doi: 10.1016/S0140-6736(17)33102–1). Its effects have not been assessed in patients with asthma and obesity. Objective To evaluate the effects of CWP against usual care (UC) on asthma-related outcomes in a single-centre, randomised, controlled trial in patients with difficult-to-treat asthma and obesity. Methods We randomised (1:1 CWP:UC) adults with difficult-to-treat asthma and body mass index (BMI) ≥30kg/m2. CWP: 12-week total diet replacement phase (850kcal/day low-energy formula); food reintroduction and weight loss maintenance up to week 52. Primary outcome: change in asthma control questionnaire (ACQ6) score over 16 weeks between groups, adjusting for baseline using ANCOVA (intention-to-treat analysis). Secondary outcome: change in asthma quality of life questionnaire (AQLQ) score. Results 35 participants were randomised (36 screened) and 33 attended 16-week follow-up (17 CWP, 16 UC). Mean (95%CI) ACQ6 at baseline was 2.8 (2.2, 3.3) in CWP and 2.7 (2.2, 3.3) in UC. Weight-loss was greater with CWP than UC (mean difference -12.3kg; 95%CI -17.1, -7.5; p<0.001). Over 16 weeks, mean change in ACQ6 was –0.4 (-1.0, 0.1) for CWP and 0.2 (-0.2, 0.6) for UC with a mean difference of –0.69 (-1.37, -0.01; p=0.048) between groups. A greater proportion of participants had ≥0.5 improvement in ACQ6 (minimal clinically important difference) with CWP than UC (53% vs 19%; p=0.041; NNT=3 (95%CI 1.5, 26.9)). AQLQ improved more with CWP than UC (mean difference 0.76; 95%CI 0.18, 1.34; p=0.013), with similar trends observed in AQLQ symptom, activity and environmental domains (see figure 1). Conclusions Weight-loss, with a structured low-energy formula diet replacement programme, yields significant improvements in asthma control and quality of life over 16 weeks, compared to usual care, in adults with difficult-to-treat asthma and obesity. The Counterweight-Plus weight management programme may be a generalisable treatment option for this challenging phenotype. Longer-term outcomes continue to be studied.