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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 BMI25 kg/mThis 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.75 participants were recruited; 57 accelerometer readings were valid and included in analysis. Inactive time was significantly higher (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.

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). Methods: We did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed. Findings: Patients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n=240) or to the control group(n=61). 28·4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18·5% of patients in the control group (adjusted odds ratio [aOR] 1·71 [95% CI 0·80–3·63]; p=0·17). In the per-protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30·7% of patients) compared with the control group (5·0% of patients; aOR 11·48 [95% CI 1·35–97·83]; p=0·026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose. Interpretation: Biomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low.

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.\ud \ud 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 analysed overall, and by asthma severity, T2-status and BMI tertile.\ud \ud Results: Increasing BMI was associated with reduction in FeNO when stratified by BMI tertile (25ppb lowest tertile, 18ppb 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 (β= -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).\ud \ud 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.

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 randomised, controlled, single-blind (study participant), multi-centre, parallel group 48-week clinical study comparing biomarker directed treatment adjustment to standard care in severe asthma.Results: of 1572 treatment advisories (301 participants), instructions were followed in 1377 cases (87.6%). Patients were more likely to follow advice to remain on treatment (96.7%) than to either reduce (70.3%) or increase (67.1%) their treatment, with 64% of patients following all treatment advice. Multivariate analysis associated belonging to an ethnic minority group (OR: 3.10; 95% CI: 1.68, 5.73) and prior study medication changes (≥2 OR: 2.77, 95% CI: 1.51, 5.10) with failure to follow treatment advice. In contrast, emergency room attendance in the prior year (OR: 0.54, 95% CI: 0.32, 0.92) was associated with following treatment advice. The largest effect was seen with transition onto or off oral corticosteroids (OR: 29.28; 95% CI: 16.07, 53.36) when compared to those requested to maintain treatment. Centre was also an important determinant regarding the likelihood of patients to follow treatment advice.Conclusions: belonging to an ethnic minority group and multiple prior treatment adjustments were associated with not following HCP treatment advice. Patients also responded differently to HCP advice across UK specialist centres. These findings have implications for generalisability for models of care in severe asthma and require further focussed studies.

Introduction: Increasing corticosteroids (CS) to control asthma symptoms and exacerbations has potential for inappropriately high and difficult to down-titrate CS doses. Aims and Objectives: We tested whether a T2 biomarker-based strategy (BS) to guide CS reduction (factoring fractional exhaled nitric oxide (FeNO), blood eosinophils, serum periostin) vs. a symptom-based control would see fewer exacerbations and better asthma control and lung function. Methods: In this randomised (4:1/BS:control), single-blind parallel group trial, patients (pts) with severe asthma and FeNO Results: In the intention-to-treat population (240 BS vs. 61 control pts), the proportion of BS pts on lower CS dose at Wk48 was 28.4% vs. 18.5% in the controls (adjusted OR: 1.71; 95%CI 0.80, 3.63; p=0.165). In the per protocol (PP) population (n=121), significantly more pts had lower CS doses at Wk48 in the BS vs. the control group (30.7% vs. 5.0% (OR: 11.48; 95%CI 1.35, 97.83; p=0.026). Failure to follow treatment advice was the main reason for ITT and PP population differences. There was no difference in secondary outcomes between study arms. Conclusion: Biomarker based CS adjustment did not result in a greater proportion of pts reducing CS vs. control, probably because many pts did not follow treatment advice. The biomarker strategy seemed beneficial in pts where symptoms and T2 biomarker profile were discordant.

Coronavirus Disease 19 (COVID-19) can present as an Adult Respiratory Distress Syndrome (ARDS)-like pneumonia Continuous Positive Airway Pressure (CPAP) for ARDS is usually delivered in Intensive Care Units (ICU) Pressure for ICU beds led to Glasgow Royal Infirmary developing a COVID-19 High Dependency Unit (C-HDU) where domiciliary non-invasive ventilators (NIV) (Lumis 150, Resmed) with supplementary oxygen delivered CPAP for respiratory failure due to COVID-19 pneumonia We review the feasibility and efficacy of delivering CPAP outside the ICU setting Method: Retrospective analysis of data from patients receiving CPAP in C-HDU (25th March to 8th May 2020) Results: 58 patients received CPAP in total 46/58 received CPAP only 18/46 improved and were discharged by day 30 12/46 died by day 30 12/46 required mechanical ventilation - of these 6/12 successfully extubated and well at day 30, 3/12 remain in ICU and 3/12 died 4/46 failed CPAP but survived with simple oxygen therapy 12/58 did not tolerate CPAP and were switched to nasal high flow oxygen - of these 8/12 are well at day 30 Conclusions: It is feasible to deliver CPAP using domiciliary NIV machines with supplementary oxygen for COVID-19 pneumonia outwith ICU CPAP has potential to improve patient outcomes, prevent ICU admissions and deliver tangible service efficiencies C-HDU established a multi-disciplinary approach to patient care, incorporating acute medical and respiratory physicians with respiratory physiology support and developed protocols using an iterative learning approach Trials for CPAP in COVID-19 pneumonia are ongoing, but our experience supports its role and the practicality of delivering CPAP using domiciliary NIV equipment

Asthma is heterogeneous with different endotypes/phenotypes. Response to corticosteroids is variable and novel biological therapies are proving useful. Biomarkers allow individualization of treatment. This review provides an update on available data regarding asthma biomarkers with focus on their utility for prediction of response to steroidal and new biological therapies.Blood eosinophils are a biomarker with acceptable accuracy as a surrogate for sputum eosinophilia, are associated with relevant outcomes, and are more readily measureable. New evidence supports fraction of exhaled nitric oxide (FENO)-based treatment algorithms for cost-effective maintenance of asthma control/quality of life. Serum and sputum-derived periostin are biomarkers of lung function decline and associated with eosinophilic airway inflammation. Transcriptomics show promise for endotyping; their role in management remains to be determined. Biomarker panels may improve predictive value as shown for the combination of FENO/urinary bromotyrosine in prediction of steroid responsiveness. Novel biological therapies are proving effective in biomarker-selected populations.Biomarkers including blood eosinophils and FENO are proving to have utility for the effective administration of steroidal and novel biological therapies in asthma, allowing individualized treatment. Transcriptomics can discriminate subtypes of asthma and may have a role in delivery of individualized therapy.

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. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT (n=18) and MCT/CPA3 (mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.

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.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.Exercise programmes and pulmonary rehabilitation, weight loss programmes targeting 5-10% weight loss and bariatric surgery are effective treatments for the obese asthma phenotype.

Background: Exacerbations are an important cause of morbidity in asthma, particularly in severe disease. Previous studies have identified variables associated with exacerbations, although little is known about risk factors in real-life populations of severe asthma. Methods: We determined the influence of demographics, disease characteristics and biomarkers of inflammation on the frequency of severe exacerbations in 872 adults with refractory asthma recruited to the British Thoracic Society Severe Asthma Registry. Results: 717 (82%) of subjects gave a history of ≥2 severe exacerbations in the last year and almost two-thirds had ≥4. Frequent exacerbations were significantly associated with younger age, higher BMI, higher ACQ score, worse asthma quality-of-life score, higher anxiety and depression score, history of GORD, increased unscheduled GP/emergency visits and hospital admissions in the last year and higher exhaled nitric oxide (FeNO). Preliminary analyses revealed independent variables associated with an increased risk of exacerbations were ACQ score, unscheduled GP/emergency visits in the last year, number of hospital admissions in the last year and FeNO in the total population and blood eosinophils in those not on maintenance oral steroids. Conclusion: Over 80% of a real-life population of adults with severe refractory asthma gave a history of frequent (≥2) severe exacerbations in the last year. Clinical outcomes and inflammatory variables were independent risk factors for severe exacerbations in this population. Further analysis will examine whether combining the independent risk factors in a scoring system can identify those at greatest risk of severe exacerbations.

ObjectiveTo determine the acceptability of using data on medicines dispensed in primary care to inform out-patient treatment of patients with difficult-to-treat asthma. ApproachConsultant respiratory physicians’ access to a summary of all relevant medicines dispensed by community pharmacists to patients with difficult to treat asthma was piloted in 2015 (therapy review (TR)). Dispensed medicine data were collected using the patient’s unique NHS identifier. This information was aggregated monthly for the year before the patient attended their clinic appointment. Patients gave consent and the summary data were used to assess concordance with therapy and inform a discussion about future management. Semi-structured interviews were conducted with eight patients who had received TR and eight respiratory physicians: two with access to the summary. The interviews aimed to highlight the experiences of patients and physicians on the utility of therapy reviews the views of physicians without access to summaries on the prospective use of therapy reviews. With the participant’s consent, interviews were recorded and transcribed. Thematic analysis of grouped responses was conducted using NVivo software. ResultsAll physicians agreed that poor compliance remains a significant concern when treating patients with difficult asthma and supported the use of TR. Physicians with experience of TR identified reliability over current methods of assessing compliance; ability to inform future treatment; and assistance in the discussion of concordance as advantages. The lag of three months in available dispensed data was a disadvantage. Physicians without experience of TR raised concern that use may lead to confrontation: reflected in the experience of one patient who expressed that TR discouraged them from improving compliance. Additional interventions are needed to improve compliance. Opinions from other patients were positive and supported the inclusion of TR as part of a consultation. Physicians with experience of TR found the summary accessible, if access to computers containing specific software to view TR was available. This limitation was considered potentially problematic and physicians without access to TR expressed a preference to accessing TR via NHS Portal - a secure online platform permitting registered users access to patient-level information. ConclusionThis demonstrates the positive impact of using data about primary care dispensed medicine in secondary care to assess medicine concordance and inform individual patient’s ongoing treatment. This supplements other data collected from clinical tests and patient-physician discussion. Development of a more efficient system to access the summary data is required before it is more widely used.

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.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 aged65 years (n = 896) versus ≥65 years (n = 146) and onset at age18 years (n = 430) versus ≥18 years (n = 526).Severe asthma patients aged ≥65 years had improved symptom control, better asthma quality of life and in the last year, less emergency visits and rescue oral steroid courses [3 (1-6) versus 5 (2-7), p 0.001] than severe asthmatics aged65 years. Blood eosinophils were lower in the elderly group. Patients with severe adult-onset asthma had similar symptom control, lung function and health-care utilization compared to severe childhood-onset asthma. Adult-onset asthmatics had higher blood eosinophils and were less atopic.Patients with severe refractory asthma aged ≥65 years exhibit better clinical and health care outcomes and have lower blood eosinophils compared to those aged65 years. Severe refractory adult-onset asthma is associated with similar levels of asthma control, higher blood eosinophils and less atopy than severe refractory childhood-onset asthma.

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies.

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. Methods: Clinically stable, non-smoking, asthmatic adults were enrolled in one of two studies. In study one, induced sputum cell counts from 28 subjects were analysed after 4 weeks without corticosteroid treatment and after 6 week treatments with placebo, regular inhaled beta-agonist, inhaled corticosteroid, and combined beta-agonist and corticosteroid. In study two, sputum from 26 subjects with non-eosinophilic asthma was analysed after 12 weeks of placebo and after four 2-week corticosteroid washouts. Sputum with

Published information on the effectiveness of bronchial thermoplasty (BT) for severe asthma in ‘real life’ patients is limited. We compared safety and efficacy outcomes 12 months post procedure in 10 clinic patients and 15 patients recruited to clinical trials of BT at the same centre. Baseline asthma severity was greater in the clinic group. Adverse events were similar. Clinical improvements occurred in 50% of the clinic patients compared with 73% of the research patients.

Background and objective: Exercise-induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (FENO) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies.We assessed: the efficacy of cromoglycate, formoterol and montelukast in patients with EIW and low FENO ( 35 ppb) group. Methods: Patients had EIW and airway hyperresponsiveness (AHR) to mannitol and/or exercise.Those with low FENO (n = 19) received cromoglycate (20 mg inh. bd + before challenge tests), formoterol (12 mg inh. bd + before challenge tests) and montelukast (10 mg p.o. od), each for 2 weeks. Those with high FENO (n = 20) took inhaled fluticasone (500 mg) daily for 4 weeks. Primary end-points were: 50% reduction in maximumFEV1%fall(clinicalprotection)anddecrease in AHR to mannitol. Results: In patients with low FENO,cromoglycate,formoterol and montelukast significantly decreased AHR to mannitol in 63%, 61% and 47% of patients, respectively.In this group,the magnitude of exercise-induced bronchoconstriction (EIB) was significantly reduced with montelukast and formoterol; between-treatment differences were not significant. Of 6/19 with low FENO and EIB, protection occurred in 67% (cromoglycate), 83% (formoterol) and 50% (montelukast),respectively. In the high FENO group, AHR to mannitol and EIB decreased significantly with fluticasone (P < 0.001, P = 0.005,respectively),and protection occurred in 7/8 (88%) with EIB. Conclusions: In patients with EIW and low FENO, the number of ‘responders’ to cromoglycate, formoterol

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). OBJECTIVES To assess the inflammatory cell phenotypes in asthma after eliminating potentially confounding effects; to compare steroid response in EA versus NEA; and to investigate changes in sputum cells with inhaled corticosteroid (ICS). METHODS Subjects undertook ICS withdrawal until loss of control or 28 days. Those with airway hyper-responsiveness (AHR) took inhaled fluticasone 1000 microg daily for 28+ days. Cut-off points wereor = or2% for sputum eosinophils andor = or61% for neutrophils. RESULTS After steroid withdrawal (n=94), 67% of subjects were eosinophilic, 31% paucigranulocytic and 2% mixed; there were no neutrophilic subjects. With ICS (n=88), 39% were eosinophilic, 46% paucigranulocytic, 3% mixed and 5% neutrophilic. Sputum neutrophils increased from 19.3% to 27.7% (p=0.024). The treatment response was greater in EA for symptoms (p0.001), quality of life (p=0.012), AHR (p=0.036) and exhaled nitric oxide (p=0.007). Lesser but significant changes occurred in NEA (ie, paucigranulocytic asthma). Exhaled nitric oxide was the best predictor of steroid response in NEA for AHR (area under the curve 0.810), with an optimum cut-off point of 33 ppb. CONCLUSIONS After eliminating the effects of ICS and smoking, a neutrophilic phenotype could be identified in patients with moderate stable asthma. ICS use led to phenotype misclassification. Steroid responsiveness was greater in EA, but the absence of eosinophilia did not indicate the absence of a steroid response. In NEA this was best predicted by baseline exhaled nitric oxide.

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.\ud \ud Setting North Glasgow Sleep Service (a tertiary referral centre).\ud \ud Participants 129 consecutive patients, aged ≥16 years, referred to the sleep clinic for assessment of possible obstructive sleep apnoea.\ud \ud Interventions We selected cut-points of apnoea hypopnoea index (AHI) of ≥5 and ≥15/h from their home polygraphy and determined associations of these with individual symptoms, questionnaire scores and other results. Receiver operating characteristic analysis and univariate and multivariate logistic regression were used to explore these.\ud \ud Primary and secondary outcomes measures Primary: The utility of STOP, STOP-BANG and Berlin Questionnaires for prediction of SDB. Secondary: The utility of other measures for prediction of SDB.\ud \ud Results AHI was ≥5 in 97 patients and ≥15 in 56 patients. STOP and STOP-BANG scores were associated with both AHI cut-points but results with ESS and Berlin Questionnaire scores were negative. STOP-BANG had a negative predictive value 1.00 (0.77–1.00) for an AHI ≥15 with a score ≥3 predicting AHI ≥5 with sensitivity 0.93 (95% CI 0.84 to 0.98) and accuracy 79%, while a score ≥6 predicted AHI ≥15 with specificity 0.78 (0.65 to 0.88) and accuracy 72%. Neck circumference ≥17 inch and presence of witnessed apnoeas were independent predictors of SDB.\ud \ud Conclusions STOP and STOP-BANG Questionnaires have utility for the prediction of SDB in the sleep clinic population. Modification of the STOP-BANG Questionnaire merits further study in this and other patient groups.

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. Behavioural therapy programs that focus on aspects such as dietary intervention, exercise prescription patients and general lifestyle counselling have been tested. Bariatric surgery is an option in the severely obese when nonsurgical measures have failed, and laparoscopic adjustable gastric banding and Roux-en-Y gastric bypass are the most commonly employed techniques in the United Kingdom. Most evidence for efficacy of surgery comes from cohort studies. The role of sibutramine in OSA in the obese patients has been investigated, however, there are concerns regarding associated cardiovascular risk. In this paper the links between obesity and OSA are discussed, and the recent studies evaluating the behavioural, pharmacological and surgical approaches to weight loss in OSA are reviewed.

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.Clinically stable, non-smoking, asthmatic adults were enrolled in one of two studies. In study one, induced sputum cell counts from 28 subjects were analysed after 4 weeks without corticosteroid treatment and after 6 week treatments with placebo, regular inhaled beta-agonist, inhaled corticosteroid, and combined beta-agonist and corticosteroid. In study two, sputum from 26 subjects with non-eosinophilic asthma was analysed after 12 weeks of placebo and after four 2-week corticosteroid washouts. Sputum with2% eosinophils was classified as non-eosinophilic.Sputum classification changed frequently in both studies. In study one, only one of eight participants with non-eosinophilic sputum after placebo treatment remained non-eosinophilic throughout. In study two, all of participants had at least one eosinophilic sputum sample, despite the fact that all had been non-eosinophilic at recruitment. Neutrophilic asthma was uncommon in both studies and was also inconsistent.The phenotypic classification of asthma changes frequently. A diagnosis of non-eosinophilic asthma should not be based on a single sputum sample.

Nitric oxide (NO) is a potent vasodilator that regulates pulmonary vascular tone. During ascent to high altitude, pulmonary vascular tone increases leading to pulmonary hypertension. To explore the mechanisms underpinning this effect, we investigated the relationship between exhaled NO ( P E NO ; nmHg) and pulmonary artery systolic pressure (PASP; mmHg) in 11 healthy adults during hypoxic challenge at sea level [with oxygen saturations ( S P O 2 ) of 80% and 90%] and at intervals during graded ascent to 5050 m. During normobaric hypoxia, PASP progressively increased from 22.7 mmHg to 33.5 mmHg (p = 0.006), whilst P E NO remained unchanged. In contrast, during ascent to high altitude, PASP increased progressively from 22.7 mmHg to 39.1 mmHg (p P E NO decreased from 18.8 nmHg to 9.0 nmHg (p P E NO had no significant effect on PASP at altitude (p = 0.309). These findings indicate that although exhaled NO decreases with altitude, it does not appear to be a major contributor to hypoxic pulmonary vasoconstriction.

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. We assessed: the efficacy of cromoglycate, formoterol and montelukast in patients with EIW and low F(E)NO (35 ppb) in a randomized cross-over trial, and the efficacy of inhaled corticosteroid in a high F(E)NO (35 ppb) group.Patients had EIW and airway hyperresponsiveness (AHR) to mannitol and/or exercise. Those with low F(E)NO (n = 19) received cromoglycate (20 mg inh. bd + before challenge tests), formoterol (12 microg inh. bd + before challenge tests) and montelukast (10 mg p.o. od), each for 2 weeks. Those with high F(E)NO (n = 20) took inhaled fluticasone (500 microg) daily for 4 weeks. Primary end-points were: 50% reduction in maximum FEV(1) %fall (clinical protection) and decrease in AHR to mannitol.In patients with low F(E)NO, cromoglycate, formoterol and montelukast significantly decreased AHR to mannitol in 63%, 61% and 47% of patients, respectively. In this group, the magnitude of exercise-induced bronchoconstriction (EIB) was significantly reduced with montelukast and formoterol; between-treatment differences were not significant. Of 6/19 with low F(E)NO and EIB, protection occurred in 67% (cromoglycate), 83% (formoterol) and 50% (montelukast), respectively. In the high F(E)NO group, AHR to mannitol and EIB decreased significantly with fluticasone (P0.001, P = 0.005, respectively), and protection occurred in 7/8 (88%) with EIB.In patients with EIW and low F(E)NO, the number of 'responders' to cromoglycate, formoterol and montelukast was similar. In a high F(E)NO population the response to inhaled corticosteroid was highly significant and comparable to previous studies.

BackgroundAsthma 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.ObjectiveWe 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.MethodsThe original study from which this analysis originates comprised 2 phases: a steroid-naive phase 1 and a 28-day trial of ICSs (phase 2) during which Feno values, sputum eosinophil counts, and urinary BrTyr levels were measured. The response to ICSs was based on clinical improvements, including a 12% or greater increase in FEV1, a 0.5-point or greater decrease in Asthma Control Questionnaire score, and 2 doubling dose or greater increase in provocative concentration of adenosine 5′-monophosphate causing a 20% decrease in FEV1 (PC20AMP). Healthy control subjects were also evaluated in this study for comparison of biomarkers with those seen in asthmatic patients.ResultsAsthmatic patients had higher than normal Feno values, sputum eosinophil counts, and urinary BrTyr levels during the steroid-naive phase and after ICS therapy. After 28-day trial of ICSs, Feno values decreased in 82% of asthmatic patients, sputum eosinophil counts decreased in 60%, and urinary BrTyr levels decreased in 58%. Each of the biomarkers at the steroid-naive phase had utility for predicting steroid responsiveness, but the combination of high Feno values and high urinary BrTyr levels had the best power (13.3-fold, P < .01) to predict a favorable response to ICS therapy. However, the magnitude of the decrease in biomarker levels was unrelated to the magnitude of clinical response to ICS therapy.ConclusionA noninvasive panel of biomarkers in steroid-naive asthmatic patients predicts clinical responsiveness to ICS therapy.

In the first paragraph of most reviews we are reminded that ‘asthma is an inflammatory disease characterised by … ’. This perspective has been influenced by—and, in turn, has driven—a great deal of respiratory research over the last 20 years. In the clinical sphere, studies based on factor analysis inform us that airway inflammation is an independent domain of the asthma syndrome, distinct from airways hyper-responsiveness, abnormal lung function and symptoms.1 2 Established treatments (notably inhaled corticosteroids and antileukotrienes) as well as potential new therapies are directed towards modifying the underlying inflammatory process rather than just providing symptom relief. For all of these reasons, actually measuring airway inflammation ought to be a regular feature in the management of asthma. In that regard, the renowned passion of Professor Freddie Hargreave and colleagues for using induced sputum analysis in the routine assessment of airways disease is entirely logical and is to be applauded.3 The strength of induced sputum analysis is that inflammatory cell characteristics (eosinophil predominance or not) may be used to interpret the aetiology of a patient's symptoms, anticipate the short to medium-term prognosis and, most importantly, the likelihood of response to treatment with corticosteroid.4–6 Unfortunately, 15 years on, for pragmatic reasons, the approach he encouraged is not routine except in a few centres. Against this background, the measurement of nitric oxide as the fraction in exhaled air (FeNO) came on the scene and interest in its clinical applications has grown.7 Chief among these, for reasons we have referred to, has been its role as a surrogate measurement of eosinophilic airway inflammation. This appeared to be very convenient, given the desirability of measuring airway inflammation by a less time-consuming and …

Introduction and Objectives Bronchial thermoplasty involves the delivery of radio frequency energy to the airways during flexible bronchoscopy, and possibly exerts its effect by reduction of airway smooth muscle mass (1). Clinical trials of bronchial thermoplasty have shown benefits in the treatment of patients with moderate or severe asthma. We describe our experience of introducing bronchial thermoplasty into a severe asthma clinical service. Methods Funding was obtained from the Greater Glasgow and Clyde NHS Health Board to evaluate bronchial thermoplasty in the treatment of ten patients with moderate to severe asthma. Patients were assessed at the Difficult Asthma Clinic and selected for the procedure using criteria similar to those employed in clinical trials of bronchial thermoplasty. Patients on all forms of asthma medication were eligible for treatment including omalizumab and oral prednisolone. Procedures were performed by 2 physicians or by 1 physician and a nurse, using conscious sedation with alfentanyl and midazolam. One patient required deeper sedation [remifentanyl and propofol] due to a complicated medical history. Bronchial thermoplasty was administered in three sessions, treating the right lower lobe, the left lower lobe and both upper lobes respectively. Follow up is at 3 monthly intervals for both safety and efficacy outcomes. Results Between 2nd June 2011 and 30th April 2012, ten patients underwent bronchial thermoplasty in Glasgow [7 males, 3 females] (Table 1). Six patients were at Step 5 and four at Step 4 of the British Guideline on the Management of Asthma scale. 4/10 were taking oral prednisolone daily and 2/10 were receiving omalizumab treatment [for 4th year and 3rd year respectively]. Treatment sessions were largely uneventful and adverse effects were similar to those reported in clinical trials. To date, there has been a reduction in some asthma medications: two patients receiving omalizumab have successfully discontinued treatment; those taking oral steroids are being weaned off prednisolone. Conclusion Bronchial thermoplasty can be safely delivered in a clinical setting to patients with severe asthma. References Thomson NC, Bicknell S, Chaudhuri R Bronchial thermoplasty for severe asthma. Curr Opin Allergy Clin Immunol 2012; 12:241–248.