In a proof-of-concept feasibility study among adults with difficult-to-treat asthma and body mass index ≥ 30kg/m2, an evidence-based, dietitian-led program resulted in clinically important improvements in asthma control and quality of life over 16 weeks compared to usual care.
The Counterweight-Plus weight management program (CWP) used in the study includes 12 weeks of total diet replacement (TDR), stepwise food reintroduction in weeks 13-18, and weight loss maintenance up to 1 year, according to a report by Varun Sharma, MBChB, and fellow researchers at University of Glasgow.
Difficult-to-treat asthma, found among about 17% of asthma-affected patients, may be attributed to factors such as poor inhaler technique, treatment nonadherence, and comorbidities such as obesity. Obesity is frequently associated with difficult-to-treat, uncontrolled asthma and increased morbidity and mortality. Among multifactorial effects of obesity on asthma are direct ones on thoracic wall mechanics, increased airway closure, airway hyper-responsiveness and airway inflammation. Prior research showing that weight loss may improve asthma outcomes has been conducted among heterogeneous asthma populations, with no clear consensus regarding optimal methods of weight management, according to the authors.
They tested whether use of the CWP compared to usual care (1:1) would improve asthma control and quality of life in this population of patients with obesity. The TDR phase comprised a low-energy liquid diet consisting of 825-853 kcal/day (approximately 59% carbohydrate, 13% fat, 26% protein, 2% fiber), with meals supplied dried in sachets by the dietitian team and reconstituted with water by the participants. A review by the dietitian team at 1 week was followed by reviews every other week.
The primary outcome was difference in change in Asthma Control Questionnaire (ACQ6) from baseline (visit 1) to 16 weeks (visit 2), between CWP and usual care.
The single-center trial included 33 evaluable adult patients (75 years or younger; mean age 53 years; 63% women) with asthma (as per Global Initiative for Asthma guidelines) that was difficult to treat (as per Scottish Intercollegiate Guidelines Network/British Thoracic Society guidelines). The study population consisted of patients with frequent exacerbations with uncontrolled disease as reflected by the median interquartile range (IQR) for oral corticosteroid courses in the previous 12 months of 3 (2 to 5) and mean ACQ6 of 2.8 (2.4 to 3.1). Mean overall Asthma Quality of Life Questionnaire (AQLQ) was 3.8 (3.4 to 4.2). Median weight was 101.7 (91.4 to 118.7) kg, with a median BMI of 37.5 (35.0 to 42.3) kg/m2. Recruitment was discontinued before the target of 40 patients because the CWP dropout rate (n = 2) was lower than expected.
The researchers reported that the mean change in ACQ6 over 16 weeks was –0.45 for CWP and 0.23 for usual care with a mean difference of –0.69 (P = .048) between groups. The secondary outcome of mean change in overall AQLQ was 0.81 for CWP and 0.08 for usual care with a mean difference of 0.76 (P = .013) between groups.
No unexpected serious adverse events or intervention-related adverse events were observed during the trial.
“In this pragmatic open label, randomized, controlled trial we showed that delivery of a supported low-calorie total diet replacement program (Counterweight-Plus) to patients with difficult-to treat asthma and obesity, was safe and led to significant improvements in asthma control and quality of life compared to usual care over 16 weeks,” the authors wrote.
“Findings from the study are a welcome addition to this field of study,” Diego J. Maselli, MD, associate professor of medicine and interim chief, division of pulmonary diseases and critical care, UT Health at San Antonio, said in an interview. “ Obesity is an important comorbid condition because, although by itself it may have an effect on asthma patients, it is also associated with other comorbidities such as gastroesophageal reflux disease, obstructive sleep apnea, anxiety, depression, and others that in turn can affect asthmatics. Also, obesity may influence pulmonary physiology and it’s considered a proinflammatory state by many, and this can favor uncontrolled disease.”
While underscoring the clinically relevant weight loss and improvements in ACQ6 and AQLQ, Dr. Maselli said that the study did not follow the patients long enough to determine if weight loss was associated with a reduction in exacerbations and other long-term outcomes in asthma such as resource utilization and changes in maintenance medications, which may be explored in future studies.
“It remains to be seen if the weight loss of these types of programs can be sustained over longer periods of time, given the considerable caloric restriction in the initial stages of the weight reduction program. Interestingly, the majority of the patients in the study did not exhibit features of type 2 inflammation and had low-T2 endotype with low eosinophil count and low FeNO [fractional exhaled nitric oxide],” Dr. Maselli added. “Although obesity has been linked to this phenotype, the vast majority of [people with asthma], about 80%, have high T2 phenotype. Future studies are still need with larger and more representative samples and with longer follow-up times to determine the effects of weight loss on asthma outcomes, especially in severe asthma,” he concluded.
The trial was funded by an NHS Greater Glasgow and Clyde Endowment Fund grant. Several of the authors reported having received travel awards to attend conferences and funding from Cambridge Weight Plan and one author is an employee of and another a medical adviser for Counterweight Ltd., the developer of the program used. Other authors reported receiving funding from a variety of pharmaceutical companies. Dr. Maselli reported no relevant conflicts.