A One-Year Weight Management Program for Difficult-to-Treat Asthma With Obesity: A Randomized Controlled Study.

Background: Obesity-associated asthma results in increased morbidity and mortality. We report 1-year asthma outcomes with a weight management regimen, the Counterweight-Plus Programme (CWP), compared with usual care (UC) in a single-center, randomized controlled trial in patients with difficult-to-treat asthma and obesity.

Research Question: Can use of the CWP result in improved asthma control and quality of life compared with UC at 1 year in patients with difficult-to-treat asthma and obesity?

Study Design And Methods: Adults with difficult-to-treat asthma and BMI ≥ 30 kg/m were randomized (1:1 CWP:UC) to treatment.

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.

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.

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/m.

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.

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.

Obesity, Inflammation, and Severe Asthma: an Update.

Purpose Of Review: Obesity-associated difficult asthma continues to be a substantial problem and, despite a move to address treatable traits affecting asthma morbidity and mortality, it remains poorly understood with limited phenotype-specific treatments. The complex association between asthma, obesity, and inflammation is highlighted and recent advances in treatment options explored.

Recent Findings: Obesity negatively impacts asthma outcomes and has a causal link in the pathogenesis of adult-onset asthma.

Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma.

Background: Understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management.

Methods: We reviewed patient choice to follow HCP advice to adjust asthma treatment in a UK-based randomised, controlled, single-blind (study participant), multicentre, parallel group 48-week clinical study comparing biomarker-directed treatment adjustment with standard care in severe asthma.

Results: Of 1572 treatment advisories (291 participants), instructions were followed in 1377 cases (87.

Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial.

Background: Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom-risk-based algorithm (control).

Asthma, obesity and targeted interventions: an update.

Purpose Of Review: Obese asthma is now widely recognized as a phenotype of difficult asthma that is common and less responsive to traditional asthma treatments, so identifying specific treatments is increasingly important.

Recent Findings: Obesity can lead to asthma through a complex relationship of causes including mechanical, inflammatory, metabolic and genetic factors. Exercise programmes including pulmonary rehabilitation, weight loss via dietary restriction, exercise and bariatric surgery, or combinations of all of these can improve quality of life, symptoms, and exercise capacity, with reductions in medication use and exacerbations, and represent tailored treatment for this phenotype of severe difficult to treat asthmatic patients.

A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial.

Background: Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy.

Effects of older age and age of asthma onset on clinical and inflammatory variables in severe refractory asthma.

Background: Asthma in the elderly as well as asthma of adult-onset has been associated with increased morbidity, but little is known specifically about the effects of age on clinical and inflammatory outcomes in severe refractory asthma. The aims of the study were to examine the effects of age [<65 versus ≥65 years] and age of onset of asthma [childhood-onset, <18 versus adult-onset, ≥18 years] on clinical and inflammatory variables in patients with severe asthma.

Methods: In 1042 subjects with refractory asthma recruited to the British Thoracic Society Severe Asthma Registry, we compared patient demographics, disease characteristics and biomarkers of inflammation in patients aged <65 years (n = 896) versus ≥65 years (n = 146) and onset at age <18 years (n = 430) versus ≥18 years (n = 526).

Biomarkers and asthma management: an update.

Purpose Of Review: Asthma is heterogeneous with different endotypes/phenotypes. Response to corticosteroids is variable and novel biological therapies are proving useful. Biomarkers allow individualization of treatment.

Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma.

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed.

Biomarker-based asthma phenotypes of corticosteroid response.

Background: Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable.

Objective: We hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.

Predicting sleep disordered breathing in outpatients with suspected OSA.

Objective: To validate the utilities of Berlin, STOP and STOP-BANG Questionnaires, other patient characteristics, comorbidities, Epworth Sleepiness Scale (ESS), fractional exhaled nitric oxide (FENO) and blood markers for the prediction of sleep disordered breathing (SDB) on limited polygraphy.

Setting: North Glasgow Sleep Service (a tertiary referral centre).

Participants: 129 consecutive patients, aged ≥16 years, referred to the sleep clinic for assessment of possible obstructive sleep apnoea.

Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes.

Background: Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms.

Objective: This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes.

Methods: An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients.

Obstructive sleep apnoea syndrome and weight loss: review.

Obstructive sleep apnoea (OSA) syndrome is common, and obesity is a major risk factor. Increased peripharyngeal and central adiposity result in increased pharyngeal collapsibility, through increased mechanical loading around the upper airway, reduced tracheal traction on the pharynx, and reduced neuromuscular activity, particularly during sleep. Significant and sustained weight loss, if achieved, is likely to be a useful therapeutic option in the management of OSA and may be attempted by behavioural, pharmacological, and surgical approaches.

Asthma phenotypes: consistency of classification using induced sputum.

Background And Objective: Asthma can be classified as eosinophilic or non-eosinophilic based on the cell profile of induced sputum. This classification can help determine whether corticosteroid treatment is indicated. We assessed the stability of these phenotypes over time and with different treatment regimens.

Simvastatin in the treatment of asthma: lack of steroid-sparing effect.

Background: Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma. Small trials have failed to show a significant benefit, but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out.

Methods: A randomised, placebo-controlled, crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred, followed by an increase until regain of control ('minimum' dose required) in 51 patients with asthma and sputum eosinophils (steroid-free) ≥ 2%.

Exercise-induced wheeze: Fraction of exhaled nitric oxide-directed management.

Background And Objective: Exercise-induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (F(E)NO) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies.

Effects of steroid therapy on inflammatory cell subtypes in asthma.

RATIONALE Airway inflammation in asthma is heterogeneous with different phenotypes. The inflammatory cell phenotype is modified by corticosteroids and smoking. Steroid therapy is beneficial in eosinophilic asthma (EA), but evidence is conflicting regarding non-eosinophilic asthma (NEA).