Short- and medium-term effect of inhaled corticosteroids on exhaled breath biomarkers in severe asthma.

Inhaled corticosteroids (ICS) are the mainstay of therapy in asthma, but benefits vary due to disease heterogeneity. Steroid insensitivity is a particular problem in severe asthma, where patients may require systemic corticosteroids and/or biologics. Biomarkers sensitive to ICS over a short period of time could inform earlier and more personalised treatment choices. To investigate how exhaled breath biomarkers change over two-hours and one-week following monitored ICS dosing in severe asthma patients with evidence of uncontrolled airway inflammation. Patients with severe asthma and elevated fractional exhaled nitric oxide (FeNO) (⩾45 ppb, indicative of active airway inflammation) were recruited. Exhaled breath biomarkers were evaluated using (FeNO), exhaled breath temperature (EBT), particles in exhaled air (PExA) and volatile organic compounds (VOCs). Samples were collected over 2 h following observed inhalation of 1000 mcg fluticasone propionate, and at a second visit 1 week after taking the same dose daily via an inhaler monitoring device that recorded correct actuation and inhalation. Changes in parameters over 2 h were analysed by the Friedman test and 1 week by Wilcoxon's test (p-value for significance set at 0.05; for VOCs false discovery rateqof 0.1 by Benjamini-Hochberg method applied). 17 participants (9 male) were recruited, but three could not complete PExA and two FeNO testing, as they were unable to comply with the necessary technique; complete datasets were available from 12 (9 male) with median (interquartile range) age 45 (36-59) yrs. EBT (p< 0.05) and levels of six VOCs (q< 0.1) fell over the 2 h after high dose ICS; there were no changes in FeNO or PExA. After one week of using high dose ICS, there were falls in FeNO, EBT and two VOCs (p< 0.05), but no changes in PExA. Reduction in EBT over the short and medium term after high dose ICS may reflect airway vascular changes, and this, together with the observed changes in exhaled VOCs, merits further investigation as potential markers of ICS use and effectiveness.

Ethnic Differences in Severe Asthma Clinical Care and Outcomes: An Analysis of United Kingdom Primary and Specialist Care.

BACKGROUND: Understanding the effects of ethnicity in severe asthma is important for optimal personalized patient care. OBJECTIVE: To assess ethnic differences in disease control, exacerbations, biological phenotype, and treatment in severe asthma in the United Kingdom. METHODS: We compared demographics, type 2 biomarkers, lung function, asthma control, medications, and health care use between White and underrepresented ethnic group patients in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD). RESULTS: A total of 3637 patients (665 from the underrepresented ethnic group) were included from UKSAR and 10,549 (577 from the underrepresented ethnic group) from OPCRD. Patients in the underrepresented ethnic group had higher levels of uncontrolled disease when measurements were made using the asthma control questionnaire in UKSAR (odds ratio [OR] = 1.47; 95% confidence interval [CI], 1.12-1.93) and the Royal College of Physicians 3 Questions in OPCRD (OR = 1.82; 95% CI, 1.27-2.60). Although exacerbation rates were similar, patients in the underrepresented ethnic group were more likely to have recently attended the emergency department (OR = 1.55; 95% CI, 1.26-1.92) or to have been hospitalized (OR = 1.31; 95% CI, 1.07-1.59) owing to asthma. Inflammatory biomarkers were consistently higher in the underrepresented ethnic group, including blood eosinophils in OPCRD (ratio = 1.12; 95% CI, 1.05-1.20) and in UKSAR blood eosinophils (ratio = 1.16; 95% CI, 1.06-1.27), FeNO (ratio = 1.14; 95% CI, 1.04-1.26), and IgE (ratio = 1.70; 95% CI, 1.47-1.97). Patients in the underrepresented ethnic group were more likely to be atopic in the UKSAR (OR = 1.32; 95% CI, 1.07-1.63) and OPCRD (OR = 1.67; 95% CI, 1.26-2.21), and less likely to be using maintenance oral corticosteroids at referral (OR = 0.75; 95% CI, 0.61-0.92). CONCLUSIONS: Severe asthma patients from underrepresented ethnic groups presented with a higher disease burden and were more likely to attend the emergency department. They had a distinct phenotypic presentation and differences in medicine use, with higher levels of type 2 biomarkers.

Assessment of adherence to corticosteroids in asthma by drug monitoring or fractional exhaled nitric oxide: A literature review.

BACKGROUND: Although the efficacy of corticosteroid treatment in controlling asthma is widely accepted, its effectiveness is undermined by poor adherence. However, the optimal method for measuring adherence to asthma therapy remains unclear. OBJECTIVE: To perform a review of the literature reporting biological, objective methods for assessing adherence to inhaled or oral corticosteroids in asthma; we included studies reporting direct measurement of exogenous corticosteroids in blood, or the effect of adherence on exhaled nitric oxide. DESIGN: We searched three databases MEDLINE (using both PubMed and Ovid), the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Web of Science for articles published between January 1975 and July 2020. Quality of the studies was assessed using the National Institute of Health checklist. RESULTS: From 2850 screened articles, 26 fulfilled the inclusion criteria. Measurement of blood prednisolone with or without cortisol was used in eight studies as a measure of oral corticosteroid adherence, and fractional exhaled nitric oxide (FeNO) in 17 studies for inhaled corticosteroid adherence. Inhaled corticosteroids were measured directly in the blood in one study. By direct measurement of drug levels in the blood, adherence rates to oral corticosteroids ranged from 47% to 92%, although the performance and timing of the test were often not known, making interpretation of findings and serum prednisolone concentrations difficult. FeNO is generally lower in adherent than non-adherent patients, but no absolute cut-off can be proposed based on the available data. However, a fall in FeNO following supervised inhaled corticosteroid dosing could indicate previous poor adherence. CONCLUSIONS AND CLINICAL RELEVANCE: Despite prednisolone and cortisol levels commonly being used as adherence markers in clinical practice, further work is required to assess the influence of the dose and timing on blood levels. The promising findings of FeNO suppression testing should be explored in further prospective studies.

Using prednisolone and cortisol assays to assess adherence in oral corticosteroid dependant asthma: An analysis of test-retest repeatability.

BACKGROUND AND OBJECTIVE: Non-adherence is an important issue within severe asthma. Prednisolone and cortisol assays have been proposed as an inexpensive, objective measure of adherence for oral corticosteroid (OCS)-dependent asthmatics, however, little is known about the reliability of these tests. METHODS: 41 severe OCS-dependent asthmatics had their prednisolone and cortisol measured during six study visits over a three month time period. Subjects were classed as non-adherent/variably-adherent if they had undetectable prednisolone and/or cortisol >100 nmol/L. Intraclass correlation coefficients (ICCs) were used to assess the test-retest reliability of prednisolone and cortisol, and Gwets AC1 kappa was used to assess the reliability of the adherence classification. Mean change in blood eosinophils for adherent and variably/non-adherent visits were calculated and linear regression with cluster-robust standard errors was used to test for differences. RESULTS: 30 subjects were included in the analysis. Reliability was poor for prednisolone (ICC: 0.43; 95% CI: 0.27, 0.59), and moderate for cortisol (ICC: 0.60; 95% CI: 0.44, 0.74). Using the combined rule, subjects were classified as adherent during 141 (88%) visits, with 21 subjects (70%) adherent during all study visits. The adherence classification had almost perfect reliability (Kappa: 0.84; 95% CI: 0.74, 0.95). Blood eosinophils were decreased by 47 cells/µl (95% CI: 11, 84) during adherent visits but increased by 65 cells/µl (95% CI: 4, 134; Pdifference = 0.03) during variably/non-adherent visits. CONCLUSIONS: Assessing adherence to maintenance OCS using a simple rule based on prednisolone and cortisol assays is highly reliable and correlated with blood eosinophil changes. Clinicians should have confidence in the results of this rule.

Achalasia with massive oesophageal dilation causing tracheomalacia and asthma symptoms.

Achalasia is an uncommon oesophageal motor disorder characterized by failure of relaxation of the lower oesophageal sphincter and muscle hypertrophy, resulting in a loss of peristalsis and a dilated oesophagus. Gastrointestinal symptoms are invariably present in all cases of achalasia observed in adults. We report a case of a 34 year-old female patient with long standing history of asthma-like symptoms, labelled as uncontrolled and steroid resistant asthma with no gastrointestinal manifestations. Thoracic CT scan revealed a massive oesophagus due to achalasia, which caused severe tracheomalacia as a result of tracheal compression. Her symptoms regressed completely after a laparoscopic Heller myotomy surgery intervention.

Corticosteroid treatment is associated with increased filamentous fungal burden in allergic fungal disease.

BACKGROUND: Allergic diseases caused by fungi are common. The best understood conditions are allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Our knowledge of the fungal microbiome (mycobiome) is limited to a few studies involving healthy individuals, asthmatics, and smokers. No study has yet examined the mycobiome in fungal lung disease. OBJECTIVES: The main aim of this study was to determine the mycobiome in lungs of individuals with well-characterized fungal disease. A secondary objective was to determine possible effects of treatment on the mycobiome. METHODS: After bronchoscopy, ribosomal internal transcribed spacer region 1 DNA was amplified and sequenced and fungal load determined by real-time PCR. Clinical and treatment variables were correlated with the main species identified. Bronchopulmonary aspergillosis (n = 16), severe asthma with fungal sensitization (n = 16), severe asthma not sensitized to fungi (n = 9), mild asthma patients (n = 7), and 10 healthy control subjects were studied. RESULTS: The mycobiome was highly varied with severe asthmatics carrying higher loads of fungus. Healthy individuals had low fungal loads, mostly poorly characterized Malasezziales. The most common fungus in asthmatics was Aspergillus fumigatus complex and this taxon accounted for the increased burden of fungus in the high-level samples. Corticosteroid treatment was significantly associated with increased fungal load (P < .01). CONCLUSIONS: The mycobiome is highly variable. Highest loads of fungus are observed in severe asthmatics and the most common fungus is Aspergillus fumigatus complex. Individuals receiving steroid therapy had significantly higher levels of Aspergillus and total fungus in their bronchoalveolar lavage.

Successful long-term terbinafine therapy in an asthmatic patient with Aspergillus sensitization and bronchiectasis.

Severe asthma with fungal sensitization (SAFS) is estimated to affect ~25% of patients with poorly controlled asthma. Tri-azole therapy is effective in only 60-80% and side effects are common. We report a 25 years-old woman with severe asthma, Aspergillus sensitization and marked bronchiectasis that developed a rare Achilles-tendinopathy with both itraconazole and voriconazole. She started a trial with terbinafine as salvage therapy that led to a striking improvement and long-term control of her respiratory disease.

A randomised controlled feasibility trial of Group Cognitive Behavioural Therapy for people with severe asthma.

OBJECTIVES: Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma. METHOD: This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression - Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS. RESULTS: 51 patients were randomised: 36% (51 out of 140) consent rate and attrition at week 16 was 12. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants. CONCLUSIONS: This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration.

Dysfunctional breathing: a review of the literature and proposal for classification.

Dysfunctional breathing is a term describing breathing disorders where chronic changes in breathing pattern result in dyspnoea and other symptoms in the absence or in excess of the magnitude of physiological respiratory or cardiac disease. We reviewed the literature and propose a classification system for the common dysfunctional breathing patterns described. The literature was searched using the terms: dysfunctional breathing, hyperventilation, Nijmegen questionnaire and thoraco-abdominal asynchrony. We have summarised the presentation, assessment and treatment of dysfunctional breathing, and propose that the following system be used for classification. 1) Hyperventilation syndrome: associated with symptoms both related to respiratory alkalosis and independent of hypocapnia. 2) Periodic deep sighing: frequent sighing with an irregular breathing pattern. 3) Thoracic dominant breathing: can often manifest in somatic disease, if occurring without disease it may be considered dysfunctional and results in dyspnoea. 4) Forced abdominal expiration: these patients utilise inappropriate and excessive abdominal muscle contraction to aid expiration. 5) Thoraco-abdominal asynchrony: where there is delay between rib cage and abdominal contraction resulting in ineffective breathing mechanics.This review highlights the common abnormalities, current diagnostic methods and therapeutic implications in dysfunctional breathing. Future work should aim to further investigate the prevalence, clinical associations and treatment of these presentations.

Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry.

OBJECTIVE: To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma. DESIGN: Cross-sectional observational study. SETTING: The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry. PARTICIPANTS: Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)-severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control). MAIN OUTCOME MEASURES: Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group. RESULTS: 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified. CONCLUSIONS: Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.

Respiratory symptoms and cross-shift lung function in relation to cotton dust and endotoxin exposure in textile workers in Nepal: a cross-sectional study.

OBJECTIVES: Inhalation of a cotton-based particulates has previously been associated with respiratory symptoms and impaired lung function. This study investigates the respiratory health of Nepalese textile workers in relation to dust and endotoxin exposure. METHODS: A total of 938 individuals from four sectors (garment, carpet, weaving and recycling) of the textile industry in Kathmandu, Nepal completed a health questionnaire and performed spirometry. A subset (n=384) performed cross-shift spirometry. Personal exposure to inhalable dust and airborne endotoxin was measured during a full shift for 114 workers. RESULTS: The overall prevalence of persistent cough, persistent phlegm, wheeze ever, breathlessness ever and chest tightness ever was 8.5%, 12.5%, 3.2%, 6.5% and 12.3%, respectively. Symptoms were most common among recyclers and least common among garment workers. Exposure to inhalable dust significantly predicted persistent cough and chest tightness. Exposure to endotoxin did not have any independent predictive effect. Significant cross-shift reduction in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were found (p<0.001 for both) being largest for FEV1 in the recyclers (-143 mL), and least in the garment workers (-38 mL; p=0.012). Exposure to inhalable dust predicted a cross-shift reduction in FEV1. CONCLUSIONS: This study is the first to investigate the respiratory health of Nepalese cotton workers. The measured association between inhalable dust exposure and reporting of respiratory symptoms and across-shift decrement in FEV1 and FVC indicates that improved dust control measures should be instituted, particularly in the recycling and carpet sectors. The possible role of other biologically active agents of cotton dust beyond endotoxin should be further explored.

Indications for the use of bronchial thermoplasty in severe asthma.

Approximately 5% of the ~3 million asthmatics in South Africa have severe asthma that is associated with substantial morbidity, cost, absenteeism, preventable mortality, and the requirement for costly chronic medication that may be associated with significant adverse events. There is an unmet need for alternative safer and more effective interventions for severe asthma. A recently introduced option, bronchial thermoplasty (BT), imparts radiofrequency-generated heat energy to the airways to cause regression of airway smooth muscle. The effectiveness of this technique has been confirmed in randomised control trials and is now endorsed by several international guidelines, including the Global Initiative for Asthma (GINA) guideline, the British Asthma Guideline, and the UK National Institute of Clinical Excellence (NICE) guideline. We recommend BT as a potential therapeutic intervention for severe uncontrolled asthma, provided that it is performed by an experienced pulmonologist at an accredited centre and done within the broader context of appropriate management of the disease by doctors experienced in treating difficult-to-control asthma.

Recommendations for the use of bronchial thermoplasty in the management of severe asthma.

There are approximately 3 million asthma suffers in South Africa, and the national death rate is ranked as one of the highest in the world. Approximately 5% have severe asthma (uncontrolled despite being adherent on maximal and optimised therapy). Such uncontrolled asthma is associated with high healthcare expenditure and may require treatment with anti-IgE and/or systemic corticosteroids, in addition to inhaler therapy and oral agents. These treatments may be costly, and those such as oral corticosteroids may have potential serious adverse events. There is therefore a need for more effective, affordable and safe therapies for asthma. A new modality of treatment, bronchial thermoplasty (BT), has recently been developed and approved for the treatment of severe asthma. BT involves delivering radio frequency-generated thermal energy to the airways, with the goal of reducing airway-specific smooth-muscle mass. Several clinical studies have confirmed that BT is effective and safe, that it improves control and quality of life in patients whose asthma remains severe despite optimal medical therapy, and that the beneficial effects are sustained for at least 5 years. We provide recommendations for the management of severe asthma, with an emphasis on the role of BT, and endorse the use of BT in patients with severe persistent asthma who remain uncontrolled despite optimal medical therapy as outlined in steps 4 and 5 of the British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN), UK National Institute of Clinical Excellence (NICE) and Global Initiative for Asthma (GINA) guidelines. We outline the context in which BT should be used, how it works and associated potential adverse events and contraindications, and also review unanswered questions and controversies.

Dedicated severe asthma services improve health-care use and quality of life.

BACKGROUND: Systematic assessment of severe asthma can be used to confirm the diagnosis, identify comorbidities, and address adherence to therapy. However, the prospective usefulness of this approach is yet to be established. The objective of this study was to determine whether the systematic assessment of severe asthma is associated with improved quality of life (QoL) and health-care use and, using prospective data collection, to compare relevant outcomes in patients referred with severe asthma to specialist centers across the United Kingdom. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics, and health-care use between initial assessment and a median follow-up of 286 days. RESULTS: The study population consisted of 346 patients with severe asthma. At follow-up, there were significant reductions in health-care use in terms of primary care or ED visits (66.4% vs 87.8%, P < .0001) and hospital admissions (38% vs 48%, P = .0004). Although no difference was noted in terms of those requiring maintenance oral corticosteroids, there was a reduction in steroid dose (10 mg [8-20 mg] vs 15 mg [10-20 mg], P = .003), and fewer subjects required short-burst steroids (77.4% vs 90.8%, P = .01). Significant improvements were seen in QoL and control using the Asthma Quality of Life Questionnaire and the Asthma Control Questionnaire. CONCLUSIONS: To our knowledge, this is the first time that a prospective study has shown that a systematic assessment at a dedicated severe asthma center is associated with improved QoL and asthma control and a reduction in health-care use and oral steroid burden.

The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry.

Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV1% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.

Refractory asthma - beyond step 5, the role of new and emerging adjuvant therapies.

A small percentage of asthmatics have 'severe refractory asthma', where there is suboptimal response to currently available therapies. A number of novel therapies targeting key biological targets are becoming available. Asthma is a heterogeneous disease, and systematic evaluation of patients is important to target therapies to the underlying inflammatory subtype and clinical features. This review article outlines new and emerging treatments for severe asthma, including monoclonal antibodies targeting eosinophilic disease, anti-neutrophil strategies, novel bronchodilators and bronchial thermoplasty. We highlight the importance of individualized investigation, treatment and management of severe asthmatics.

Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability.

BACKGROUND: Severe refractory asthma is a heterogeneous disease. We sought to determine statistical clusters from the British Thoracic Society Severe refractory Asthma Registry and to examine cluster-specific outcomes and stability. METHODS: Factor analysis and statistical cluster modelling was undertaken to determine the number of clusters and their membership (N = 349). Cluster-specific outcomes were assessed after a median follow-up of 3 years. A classifier was programmed to determine cluster stability and was validated in an independent cohort of new patients recruited to the registry (n = 245). FINDINGS: Five clusters were identified. Cluster 1 (34%) were atopic with early onset disease, cluster 2 (21%) were obese with late onset disease, cluster 3 (15%) had the least severe disease, cluster 4 (15%) were the eosinophilic with late onset disease and cluster 5 (15%) had significant fixed airflow obstruction. At follow-up, the proportion of subjects treated with oral corticosteroids increased in all groups with an increase in body mass index. Exacerbation frequency decreased significantly in clusters 1, 2 and 4 and was associated with a significant fall in the peripheral blood eosinophil count in clusters 2 and 4. Stability of cluster membership at follow-up was 52% for the whole group with stability being best in cluster 2 (71%) and worst in cluster 4 (25%). In an independent validation cohort, the classifier identified the same 5 clusters with similar patient distribution and characteristics. INTERPRETATION: Statistical cluster analysis can identify distinct phenotypes with specific outcomes. Cluster membership can be determined using a classifier, but when treatment is optimised, cluster stability is poor.

Effectiveness of omalizumab in severe allergic asthma: a retrospective UK real-world study.

OBJECTIVE: The aim of this study was to evaluate the "real world" effects of the monoclonal antibody omalizumab (OMB) when used to treat severe persistent allergic asthma in UK clinical practice. METHODS: A 10-center retrospective observational study was carried out to compare oral corticosteroid (OCS) use and exacerbation frequency in 12 months pre- versus post-OMB initiation in 136 patients aged ≥12 years with severe persistent allergic asthma. All patients received ≥1 dose of OMB. Patients who had received OMB in a clinical trial were excluded. Data were obtained from hospital and if necessary general practitioners' (GPs') records on OCS use, lung function, hospital resource use, and routinely used quality of life (QoL) measures at baseline (pre-OMB), 16 weeks, and up to 12 months post-OMB initiation. RESULTS: Mean total quantity of OCS prescribed per year decreased by 34% between the 12 months pre- and post-OMB initiation. During the 12 months post-OMB initiation, 87 patients (64%) stopped/reduced OCS use by 20% or more and 66 (49%) stopped OCS completely. Mean percent predicted forced expiratory volume in one second (FEV(1)) increased from 66.0% at baseline to 75.2% at week 16 of OMB therapy. The number of asthma exacerbations decreased by 53% during the 12 months post-initiation. Accident and emergency visits reduced by 70% and hospitalizations by 61% in the 12 months post-OMB initiation. CONCLUSION: This retrospective analysis showed a reduction in exacerbations and improved QoL as per previous studies with OMB. However, the total reduction in annual steroid burden and improved lung function in this severely ill group of patients taking regular or frequent OCS is greater than that seen in previous trials.

Obesity-associated severe asthma represents a distinct clinical phenotype: analysis of the British Thoracic Society Difficult Asthma Registry Patient cohort according to BMI.

BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airway inflammation. However, the role of obesity in severe asthma remains unclear. Thus, our objective was to explore the association between obesity (defied by BMI) and severe asthma. METHODS: Data from the British Thoracic Society Difficult Asthma Registry were used to compare patient demographics, disease characteristics, and health-care utilization among three BMI categories (normal weight: 18.5-24.99; overweight: 25-29.99; obese: 30) in a well-characterized group of adults with severe asthma. RESULTS: The study population consisted of 666 patients with severe asthma; the group had a median BMI of 29.8 (interquartile range, 22.5-34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% vs 40.4% and 34.5% in the overweight and normal-weight groups, respectively), steroid burst therapy, and short-acting b 2 -agonist use per day. Significant differences were seen with gastroesophageal reflux disease (53.9% vs 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor use. Bone density scores were higher in the obese group, while pulmonary function testing revealed a reduced FVC and elevated carbon monoxide transfer coefficient. Serum IgE levels decreased with increasing BMI and the obese group was more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Patients with severe asthma display particular characteristics according to BMI that support the view that obesity-associated severe asthma may represent a distinct clinical phenotype.