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).

Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.

Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma.

Efficacy and safety of bronchial thermoplasty in clinical practice: a prospective, longitudinal, cohort study using evidence from the UK Severe Asthma Registry.

Objectives: Use data from the UK Severe Asthma Registry (UKSAR) to assess the efficacy and safety of bronchial thermoplasty (BT) in routine UK clinical practice and to identify characteristics of 'responders'.

Design: Prospective, longitudinal, cohort, multicentre registry study.

Setting: All (11) UK centres performing BT.

An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness.

It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A hydrolase (LTAH) mediates opposing proinflammatory and anti-inflammatory activities, through the generation of leukotriene B (LTB) and degradation of proneutrophilic matrikine Pro-Gly-Pro (PGP), respectively. We show that abrogation of LTB signaling ameliorated inflammation and airway hyperresponsiveness (AHR) in a murine asthma model, yet global loss of LTAH exacerbated AHR, despite the absence of LTB This exacerbated AHR was attributable to a neutrophil-independent capacity of PGP to promote pathological airway epithelial remodeling.

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.

Indirect comparison of bronchial thermoplasty versus omalizumab for uncontrolled severe asthma.

Objective: Bronchial thermoplasty (BT) as an add-on therapy for uncontrolled severe asthma is an alternative to biologic therapies like omalizumab (OM). We conducted an indirect treatment comparison (ITC) to appraise comparative effectiveness of BT and OM.

Methods: A systematic literature review identified relevant randomized controlled trials.

Procedural and short-term safety of bronchial thermoplasty in clinical practice: evidence from a national registry and Hospital Episode Statistics.

Objective: Bronchial thermoplasty (BT) is a novel treatment for severe asthma. Its mode of action and ideal target patient group remain poorly defined, though clinical trials provided some evidence on efficacy and safety. This study presents procedural and short-term safety evidence from routine UK clinical practice.

Impact of omalizumab on treatment of severe allergic asthma in UK clinical practice: a UK multicentre observational study (the APEX II study).

Objective: To describe the impact of omalizumab on asthma management in patients treated as part of normal clinical practice in the UK National Health Service (NHS).

Design: A non-interventional, mixed methodology study, combining retrospective and prospective data collection for 12 months pre-omalizumab and post-omalizumab initiation, respectively.

Setting: Data were collected in 22 UK NHS centres, including specialist centres and district general hospitals in the UK.

T1-weighted Dynamic Contrast-enhanced MR Imaging of the Lung in Asthma: Semiquantitative Analysis for the Assessment of Contrast Agent Kinetic Characteristics.

Purpose: To evaluate the contrast agent kinetics of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging in healthy lungs and asthmatic lungs by using non-model-based semiquantitative parameters and to explore the relationships with pulmonary function testing and eosinophil level.

Materials And Methods: The study was approved by the National Research Ethical Committee (reference no. 11/NW/0387), and written informed consent was obtained from all individuals.

Immunoglobulin E in irritable bowel syndrome: another target for treatment? A case report and literature review.

Irritable bowel syndrome (IBS) is notoriously difficult to treat and this situation is unlikely to change until the pathophysiology is better understood. There is no doubt that IBS is a multifactorial condition but it is likely that the relative contribution of the various factors involved varies from patient to patient. Consequently, in some individuals one mechanism may have such a strong effect that its elimination may lead to a substantial improvement in symptoms.

Dynamic oxygen-enhanced magnetic resonance imaging of the lung in asthma -- initial experience.

Objectives: To prospectively estimate the feasibility and reproducibility of dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) in the assessment of regional oxygen delivery, uptake and washout in asthmatic lungs.

Materials And Methods: The study was approved by the National Research Ethics Committee and written informed consent was obtained. Dynamic OE-MRI was performed twice at one month apart on four mild asthmatic patients (23±5 years old, FEV1=96±3% of predicted value) and six severe asthmatic patients (41±12 years old, FEV1=60±14% of predicted value) on a 1.

Efficacy and safety of nebulised amphotericin B (NAB) in severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA).

Background And Rationale: Antifungal therapy for severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. We assessed the efficacy and safety of NAB as second and third line therapy in SAFS and ABPA.

Methods: 21 adult asthmatics with SAFS (n = 11) and ABPA (n = 10) who had either failed itraconazole (n = 8), voriconazole proceeded by itraconazole (n = 5) or developed adverse events (AEs) to either agent (n = 7) were treated with 10mg of NAB (Fungizone) twice daily.

Safety of bronchial thermoplasty in patients with severe refractory asthma.

Background: Patients with severe refractory asthma treated with bronchial thermoplasty (BT), a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle, were followed up for 5 years to evaluate long-term safety of this procedure.

Objectives: To assess long-term safety of BT for 5 years.

Methods: Patients with asthma aged 18 to 65 years requiring high-dose inhaled corticosteroids (ICSs) (>750 μg/d of fluticasone propionate or equivalent) and long-acting β2-agonists (LABAs) (at least 100 μg/d of salmeterol or equivalent), with or without oral prednisone (≤30 mg/d), leukotriene modifiers, theophylline, or other asthma controller medications were enrolled in the Research in Severe Asthma (RISA) Trial.

Does BCG vaccination protect against childhood asthma? Final results from the Manchester Community Asthma Study retrospective cohort study and updated systematic review and meta-analysis.

Background: The Manchester Community Asthma Study (MANCAS) found a protective effect against the risk of wheeze at age 6 to 11 years for children given neonatal BCG vaccination. Our subsequent systematic review and meta-analysis suggested that BCG vaccination did not protect against allergic sensitization but might have exerted a protective effect against nonatopic asthma.

Objectives: We sought to assess whether the protective effect of BCG vaccination on wheeze observed in the MANCAS cohort was maintained at age 13 to 17 years and to incorporate the findings from this final MANCAS analysis into an updated systematic review and meta-analysis.

Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma.

Background: Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma.

Objective: We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy.

Methods: BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.

Clinical outcomes and inflammatory biomarkers in current smokers and exsmokers with severe asthma.

Background: Clinical outcomes are worse in current smokers and exsmokers with mild-to-moderate asthma compared with never smokers, but little is known about the influence of smoking status in patients with severe asthma.

Objectives: We sought to examine the association of current or previous cigarette smoking with clinical and inflammatory variables in patients with severe asthma.

Methods: We compared patients' demographics, disease characteristics, and biomarkers of inflammation in current smokers (n=69 [9%]), exsmokers (n=210 [28%]), and never smokers (n=461 [62%]) with severe asthma (n=760) recruited to the British Thoracic Society Severe Asthma Registry.

Prevalence of respiratory symptoms at two time points in a population of children in Manchester--a cohort study.

Objective: Although the prevalence of asthma and atopy has been noted to have increased in recent decades, patterns of asthma prevalence have, traditionally, been difficult to track. Most reports on trends in childhood asthma have been cross-sectional measuring the prevalence in cohorts of similar aged children at different time points. The aim of this paper is to report on the prevalence of symptoms in the same cohort at two separate time points.

Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization.

Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal lung diseases whose effective treatment remains to be established. Current treatment with itraconazole is associated with a 40% failure rate and adverse events (AEs).

Fungi and allergic lower respiratory tract diseases.

Asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the United States.

Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial.

Background: Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure.

Methods: Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal.