Accelerometer-derived sleep metrics in mild and difficult-to-treat asthma.

INTRODUCTION: Poor sleep health is associated with increased asthma morbidity and mortality. Accelerometers have been validated to assess sleep parameters though studies using this method in patients with asthma are sparse and none have compared mild to difficult-to-treat asthma populations. METHODS: We performed a retrospective analysis from two recent in-house trials comparing sleep metrics between patients with mild and difficult-to-treat asthma. Participants wore accelerometers for 24-hours/day for seven days. RESULTS: Of 124 participants (44 mild, 80 difficult-to-treat), no between-group differences were observed in sleep-window, sleep-time, sleep efficiency or wake time. Sleep-onset time was ~ 40 min later in the difficult-to-treat group (p = 0.019). DISCUSSION: Broadly, we observed no difference in accelerometer-derived sleep-metrics between mild and difficult-to-treat asthma. This is the largest analysis of accelerometer-derived sleep parameters in asthma and the first comparing groups by asthma severity. Sleep-onset initiation may be delayed in difficult-to-treat asthma but a dedicated study is needed to confirm.

A Total Diet Replacement Weight Management Program for Difficult-to-Treat Asthma Associated With Obesity: A Randomized Controlled Feasibility Trial.

BACKGROUND: Obesity is often 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 QUESTION: 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? STUDY DESIGN AND METHODS: 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) followed by 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. RESULTS: 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; Number needed to treat, 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). INTERPRETATION: 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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03858608; URL: www. CLINICALTRIALS: gov.

Physical activity levels in asthma: relationship with disease severity, body mass index and novel accelerometer-derived metrics.

OBJECTIVES: Patients with asthma may feel limited in physical activity (PA). Reduced PA has been demonstrated in asthmatics versus healthy controls, and increasing PA associated with improved asthma outcomes. Obesity is commonly found with difficult-to-control asthma and worsens outcomes. We compared PA levels in participants with difficult-to-control asthma and elevated body mass index (BMI) (DOW group) and two mild-moderate asthma groups: one with BMI <25 kg/m2 (MHW) and one with BMI ≥25 (MOW). METHODS: This cross-sectional study used 7-day recordings from wrist-worn accelerometers to compare PA between groups. Inactive time, light (LPA), moderate-vigorous PA (MVPA) were measured, along with two novel metrics: intensity gradient (IG) reflecting PA intensity, and average acceleration (AA) reflecting PA volume. PA parameters were compared using ANOVA or Kruskall-Wallis testing. Correlation and linear regression analyses explored associations between PA parameters and asthma outcomes. As AA was the PA parameter correlated most closely with asthma-related outcomes, an exploratory analysis compared outcomes in highest and lowest AA quartiles. RESULTS: 75 participants were recruited; 57 accelerometer readings were valid and included in analysis. 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 versus MHW and MOW groups, even after adjusting for age and BMI. Quartiles based on AA had significantly different asthma profiles. CONCLUSIONS: Overweight/obese participants with difficult-to-control asthma performed less PA, and activity of reduced intensity and volume. Increased AA is associated with improvement in several asthma-related outcomes. Increased PA should be recommended to relevant patients.

Obesity affects type 2 biomarker levels in asthma.

OBJECTIVE: Type 2 (T2) inflammation offers a therapeutic target for biologics. Previous trials suggest obesity influences T2-biomarker levels in asthma, though have not accounted for key variables, e.g. inhaled (ICS)/oral corticosteroid (OCS) use. We hypothesized that body mass index (BMI) would affect T2-biomarker levels, after adjusting for covariates. METHODS: A retrospective analysis of data from two recent local trials of 153 participants with asthma (102 difficult-to-treat, 51 mild). Measurements included BMI, fractional exhaled nitric oxide (FeNO) and eosinophils. Correlation and regression analysis were performed for each biomarker to describe their relationship with BMI. Data was analyzed overall, and by asthma severity, T2-status and BMI tertile. RESULTS: Increasing BMI was associated with reduction in FeNO when stratified by BMI tertile (25 ppb lowest tertile, 18 ppb highest tertile; p = 0.014). Spearmans rank showed a negative correlation between BMI and FeNO in difficult-to-treat asthma (ρ= -0.309, p = 0.002). Linear regression adjusting for sex, age, smoking, atopy, allergic/perennial rhinitis, ICS and OCS confirmed BMI as a predictor of FeNO overall (ß= -2.848, p = 0.019). Eosinophils were reduced in the highest BMI tertile versus lowest in difficult-to-treat asthma (0.2x109/L, 0.3x109/L respectively; p = 0.02). CONCLUSIONS: Increasing BMI is associated with lower FeNO in asthma when adjusted for relevant covariates, including steroid use. There also appears to be an effect on eosinophil levels. Obesity, therefore, affects T2 biomarker levels with implications for disease endotyping and determination of eligibility for biologic therapy. Whether this is due to masking of underlying T2-high status or development of a truly T2-low endotype requires further research.

A pragmatic randomised controlled trial of tailored pulmonary rehabilitation in participants with difficult-to-control asthma and elevated body mass index.

BACKGROUND: Difficult-to-control asthma associated with elevated body mass index (BMI) is challenging with limited treatment options. The effects of pulmonary rehabilitation (PR) in this population are uncertain. METHODS: This is a randomised controlled trial of an eight-week asthma-tailored PR programme versus usual care (UC) in participants with difficult-to-control asthma and BMI ≥ 25 kg/m2. PR comprised two hours of education and supervised exercise per week, with encouragement for two individual exercise sessions. Primary outcome was difference in change in Asthma Quality of Life Questionnaire (AQLQ) in PR versus UC groups between visits. Secondary outcomes included difference in change in Asthma Control Questionnaire-6 (ACQ6), and a responder analysis comparing proportion reaching minimum clinically important difference for AQLQ and ACQ6. RESULTS: 95 participants were randomised 1:1 to PR or UC. Median age was 54 years, 60% were female and median BMI was 33.8 kg/m2. Mean  (SD) AQLQ was 3.9 (+/-1.2) and median (IQR) ACQ6 2.8(1.8-3.6). 77 participants attended a second visit and had results analysed. 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. 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, but below minimum clinically important difference. In ACQ6 responder analysis, minimum clinically important difference was reached by 18 PR participants (54.5%) versus 10 UC (22.7%), p = 0.009. Dropout rate was 31% between visits in PR group, and time to completion was significantly prolonged in PR group at 94 (70-107) days versus 63 (56-73) in UC, p < 0.001. CONCLUSIONS: PR improved asthma control and reduced perceived breathlessness in participants with difficult-to-control asthma and elevated BMI. However, this format appears to be suboptimal for this population with high drop-out rates and prolonged time to completion. Trial registration Clinicaltrials.gov. ID NCT03630432. Retrospectively registered, submitted May 26th 2017, posted August 14th 2018.