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Rationale: The past 25 years have seen huge progress in understanding of the pathobiology of type-2 (T2) asthma, identification of measurable biomarkers, and the emergence of novel monoclonal antibody treatments. Although present in a minority of patients with severe asthma, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. Objectives: The objective of this study was to explore the differences between study exacerbators and nonexacerbators, to describe physiological changes at exacerbation in those who are T2 HIGH and T2 LOW at the time of exacerbation, and to evaluate the stability of inflammatory phenotypes when stable and at exacerbation. Methods: Exacerbation assessment was a prespecified secondary analysis of data from a 48-week, multicenter, randomized controlled clinical study comparing the use of biomarkers and symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2 LOW (fractional exhaled nitric oxide < 20 ppb and blood eosinophil count < 150 cells/ml) or T2 HIGH (fractional exhaled nitric oxide. 20 or blood eosinophil count. 150) at study enrollment and at each exacerbation. Here, we report the findings of the exacerbation analyses, including comparison of exacerbators and nonexacerbators, the physiological changes at exacerbation in those who had evidence of T2 biology at exacerbation versus those that did not, and the stability of inflammatory phenotypes when stable and at exacerbation.Measurements and Main Results: Of the 301 participants, 60.8% (183) had one or more self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher body mass index, and have more exacerbations requiring oral corticosteroid and unscheduled primary care attendances for exacerbations. At enrollment, 23.6% (71) were T2 LOW and 76.4% (230) T2 HIGH. The T2 LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU (high dependency unit)/ICU and to be receiving maintenance oral corticosteroids. At exacerbation, the T2 LOW events were indistinguishable from T2 HIGH exacerbations in terms of lung function (mean fall in T2 LOW FEV 1, 200 [400] ml vs. T2 HIGH 200 [300] ml; P = 0.93) and symptom increase (ACQ5: T2 LOW, 1.4 [0.8] vs. T2 HIGH, 1.3 [0.8]; P = 0.72), with no increase in T2 biomarkers from stable to exacerbation state in the T2 LOW exacerbations. The inflammatory phenotype within individual patients was dynamic; inflammatory phenotype at study entry did not have a significant association with exacerbation phenotype. Conclusions: Asthma exacerbations demonstrating a T2 LOW phenotype were physiologically and symptomatically similar to T2 HIGH exacerbations. T2 LOW asthma was an unstable phenotype, suggesting that exacerbation phenotyping should occur at the time of exacerbation. The clinically significant exacerbations in participants without evidence of T2 biology at the time of exacerbation highlight the unmet and pressing need to further understand the mechanisms at play in non-T2 asthma.

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.

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.

Although once considered a single disease entity, asthma is now known to be a complex inflammatory disease engaging a range of causal pathways. The most frequent forms of asthma are identified by sputum/blood eosinophilia and activation of type 2 inflammatory pathways involving interleukins-3, -4, -5, and granulocyte-macrophage colony-stimulating factor. The use of diagnostics that identify T2 engagement linked to the selective use of highly targeted biologics has opened up a new way of managing severe disease. Novel technologies, such as wearables and intelligent inhalers, enable real-time remote monitoring of asthma, creating a unique opportunity for personalized health care.

International audience; In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system for integrated care with organizational health literacy. MASK (Mobile Airways Sentinel NetworK) (1), a new development of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health) (2), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life integrated care pathways (ICPs) (3)-centred around the patient with rhinitis and using mHealth monitoring of environmental exposure (4).An expert meeting took place at the Pasteur Institute in Paris, December 3, 2018. The aim was to discuss next-generation care pathways: (I) Patient participation, health literacy and self-care through technology-assisted “patient activation”; (II) Implementation of care pathways by pharmacists and (III) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) assessed by mobile technology.The EU (5) and global political agendas are of great importance in supporting health care transformation. MASK has been recognized by DG Santé as a Good Practice (6) in the field of digitally-enabled, integrated, person-centred care.The one-day meeting objectives were clear (Figure 1). The meeting was followed by a workshop. The present paper reports the background of the two-day meeting.

BackgroundAsthma exacerbations affect the quality of life of patients with asthma and have a major effect on the overall costs of asthma care. An asthma self-management plan that advises the temporary quadrupling of inhaled corticosteroid dose may prevent asthma exacerbations, but this needs to be confirmed before being adopted widely.ObjectivesTo compare the clinical effectiveness and cost-effectiveness of an asthma self-management plan that advises patients to temporarily quadruple the dose of inhaled corticosteroid when asthma control starts to deteriorate with a standard self-management plan.DesignA multicentre, parallel-group, pragmatic randomised trial, with follow-up for 12 months.SettingPrimary and secondary care across 207 sites in the UK.ParticipantsAsthma patients aged ≥ 16 years treated with an inhaled corticosteroid who had experienced at least one exacerbation in the previous 12 months.InterventionsParticipants were randomised (1 : 1) to a usual-care self-management plan or to a modified self-management plan that advised a temporary quadrupling of the inhaled corticosteroid at the point of asthma deterioration, both of which were actively implemented and supported by local research staff.Primary outcomeThe primary outcome of ‘time to first asthma exacerbation’ was defined as the need for systemic corticosteroids (for at least 3 consecutive days) and/or unscheduled health-care consultations for asthma (i.e. reaching zone 3 or 4 of the Asthma UK self-management plan).ResultsA total of 1922 participants were randomised: the primary analysis included 938 participants (97%) in the usual-care group and 933 participants (97%) in the modified self-management group. The number of participants having at least one exacerbation of asthma in the year after randomisation was 484 (51.6%) in the usual-care group and 420 (45.0%) in the modified self-management group [adjusted hazard ratio 0.81, 95% confidence interval (CI) 0.71 to 0.92;p = 0.002]. There were fewer serious adverse events reported in the modified self-management group than in the usual-care group (11 vs. 32, respectively). Eight and six events of pneumonia, lower respiratory tract infections or influenza were reported in the usual-care group and the modified self-management group, respectively. Health-care-related costs were lower in the modified self-management group. The modified self-management group was £24 (bootstrapped 95% CI –£122 to £71) less costly than usual care, with a greater quality-adjusted life-year gain of 0.02 (bootstrapped 95% CI –0.005 to 0.04). Therefore, the modified self-management group was ‘dominant’, with a 94–95% probability of being cost-effective at the £20,000–30,000 threshold.LimitationsAs the Fourfold Asthma STudy (FAST) was an open-label pragmatic trial, the possibility of treatment bias that may have affected the participants in the modified self-management group cannot be ruled out. Poorer than expected completion of participant diary cards, particularly within the usual-care self-management group, could have led to a null bias, underestimating the true effect of the intervention.ConclusionsAn asthma self-management plan that advises patients to temporarily quadruple their dose of inhaled corticosteroid at the point of asthma symptoms worsening does reduce clinically important asthma exacerbations. In addition, the plan is cost-effective compared with the usual-care self-management plan.Future workTo effectively implement asthma self-management plans that advise a temporary quadrupling of inhaled steroid at asthma deterioration into routine practice.Trial registrationCurrent Controlled Trials ISRCTN15441965.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 70. See the NIHR Journals Library website for further project information.

Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airways diseases. Both are complex and heterogeneous. Traditionally, clinical guidelines have advocated a stepwise approach to pharmacotherapy of asthma and COPD, but there is increasing realization that both require a more personalized and precise management approach. To this end, a management strategy based on the so-called Treatable Traits has been proposed. Emerging evidence suggests that this model improves relevant outcomes in patients with chronic airway diseases but further research is needed to guide implementation. This review discusses the challenges, opportunities, and hurdles that its implementation will have to face.

BackgroundThere is no published algorithm predicting asthma crisis events (accident and emergency [A&E] attendance, hospitalisation, or death) using routinely available electronic health record (EHR) data.AimTo develop an algorithm to identify individuals at high risk of an asthma crisis event.Design and settingDatabase analysis from primary care EHRs of people with asthma across England and Scotland.MethodMultivariable logistic regression was applied to a dataset of 61 861 people with asthma from England and Scotland using the Clinical Practice Research Datalink. External validation was performed using the Secure Anonymised Information Linkage Databank of 174 240 patients from Wales. Outcomes were ≥1 hospitalisation (development dataset) and asthma-related hospitalisation, A&E attendance, or death (validation dataset) within a 12-month period.ResultsRisk factors for asthma-related crisis events included previous hospitalisation, older age, underweight, smoking, and blood eosinophilia. The prediction algorithm had acceptable predictive ability with a receiver operating characteristic of 0.71 (95% confidence interval [CI] = 0.70 to 0.72) in the validation dataset. Using a cut-point based on the 7% of the population at greatest risk results in a positive predictive value of 5.7% (95% CI = 5.3% to 6.1%) and a negative predictive value of 98.9% (95% CI = 98.9% to 99.0%), with sensitivity of 28.5% (95% CI = 26.7% to 30.3%) and specificity of 93.3% (95% CI = 93.2% to 93.4%); those individuals had an event risk of 6.0% compared with 1.1% for the remaining population. In total, 18 people would need to be followed to identify one admission.ConclusionThis externally validated algorithm has acceptable predictive ability for identifying patients at high risk of asthma-related crisis events and excluding those not at high risk.

Background: People aged 18-29 receive the lowest level (33%) of basic asthma care for any age group in the UK[1]. This group has lower levels of health literacy, but high levels of digital engagement. Asthma UK provides a nurse-led telephone service, and piloted a WhatsApp instant messaging service to provide advice and support to address this unmet need. Objectives: To evaluate the feasibility and acceptability of delivering a personalised WhatsApp service as part of Asthma UK’s suite of support services, and to gain preliminary data on whether the service improves self-reported confidence in asthma self-management. Method: Users message a nurse on WhatsApp, via mobile device or desktop, and receive advice, links, video content and infographics on their query. Users completed a post-chat online survey on their experience of the service and confidence in managing their asthma. The survey gained 669 responses between January 2019 and January 2020. Results: 93.6% of respondents said that the asthma nurse was able to answer all their questions, and 91.5% were very satisfied with the service. 98.4% found the advice easy to understand. 63.3% (and 65.9% of the 18-33 age group) felt more confident managing their asthma post-chat. 36.7% had not heard of Asthma UK before using the service and 67.1% of this unengaged group said the service improved their confidence. Conclusions: Users responded positively, with improved confidence in managing their asthma. This work has implications for future care delivery, with virtual consultations for asthma advice proving a popular and effective way to reach an unengaged younger audience. [1] Asthma UK. The reality of asthma care in the UK, 2018

BACKGROUND: \ud Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.\ud \ud METHODS: \ud We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.\ud \ud RESULTS: \ud A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.\ud \ud CONCLUSIONS: \ud In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965 .).

Background: In the UK a national investigation of asthma deaths in 2014 (National Review of Asthma Deaths, NRAD) led to the recommendation that patients should be referred to specialist care after commencing high-dose inhaled corticosteroids (HD-ICS) or ≥3 courses of oral corticosteroids (OCS). We sought to assess the prevalence and temporal change in referral to specialist care so that we can identify unmet need and develop better referral pathways. Methods: Representative English primary care electronic healthcare data, linked to hospital respiratory clinic attendances, were used to identify asthma patients (aged 18-55 years), their prescriptions, and any respiratory clinic attendances, 2006 to 2015. Referrals within 6 months of incident HD-ICS or third annual OCS were measured Results: 261,051 eligible asthma patients were identified; median follow-up was 3.2 years (IQR=1.5-6.4). During follow-up 7.6% had ≥1 HD-ICS prescription, and 2.7% had ≥3 OCS in 12-months. Referrals have increased over time in all patients but were highest in patients after prescription of ≥3 OCS or ≥1 HD-ICS (Figure 1). In 2016, 18.2% of patients prescribed ≥1 HD-ICS, and 23.4% of patients prescribed ≥3 OCS, were referred within 6-months. Conclusion: Although referrals from primary care to specialist care increased after NRAD and the consequent changes to guidelines, they occurred in under a quarter of considered high risk patients.

Severe asthma affects a small proportion of asthma patients (~ 3-5%) and reflects a failure of conventional asthma medications to provide adequate control. Severe asthma is a disease of significant clinical heterogeneity, likely caused by different pathobiological mechanisms, frequently referred to as endotypes. In the last decade, multiple monoclonal therapies have been developed to target airway type-2 eosinophilic and/or allergic severe asthma. However, the underlying mechanisms of both type 2 immunity and eosinophilia (blood and airway) remain incompletely understood and offer a potential for novel therapies that target eosinophil maturation in the bone marrow and specific kinases expressed in type 2 cells, such as JAK-STAT inhibitors. Furthermore, some patients do not consistently demonstrate a type 2 disease clinical profile and display other inflammatory phenotypes at a given point in time. Targeting airway smooth muscle dysfunction, airway mucous, type-17 immunity and airway dysbiosis, may represent novel therapeutic approaches for severe asthma in the future. Unfortunately, the biomarkers for these subtypes of severe asthma are underdeveloped, rendering it difficult to conduct effective clinical trials. There are also barriers regarding the efficiency of standard clinical trials. Moving beyond these barriers will require innovation in trial design, effective partnerships with patient groups and effective multi-national trials consortia. There are current transatlantic opportunities to conduct clinical trials that could facilitate the development of common trial platforms to maximize overall efficiency and move the field of severe asthma forward.

Although once considered a single disease entity, asthma is now known to be a complex inflammatory disease engaging a range of causal pathways. The most frequent forms of asthma are identified by sputum/blood eosinophilia and activation of type 2 inflammatory pathways involving interleukins-3, -4, -5, and granulocyte-macrophage colony-stimulating factor. The use of diagnostics that identify T2 engagement linked to the selective use of highly targeted biologics has opened up a new way of managing severe disease. Novel technologies, such as wearables and intelligent inhalers, enable real-time remote monitoring of asthma, creating a unique opportunity for personalized health care.

Background The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. MASK (Mobile Airways Sentinel NetworK) (1), a new development of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative (2), and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health) (3), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs—centred around the patient with rhinitis and using mHealth monitoring of environmental exposure. An expert meeting took place at the Pasteur Institute in Paris, December 3, 2018. The aim was to discuss nextgeneration care pathways following an ongoing political agenda (4,5): (I) patient participation, health literacy and self-care through technology-assisted “patient activation”; (II) implementation of care pathways by pharmacists and (III) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) assessed by mobile technology. The present document reviews the workshop report and follows on from Part 1.

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:145 issue:1 pages:70-+ ispartof: location:United States status: published

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients. This article is protected by copyright. All rights reserved.

The toxic side effects of oral corticosteroids (OCS) have long been recognised. The need to show effectiveness of new, expensive, potentially steroid-sparing biological therapies for severe asthma requires objective measurement of steroid-induced complications. Existing questionnaires do not capture the myriad adverse effects on quality of life of corticosteroids such as agitation or poor sleep. To inform the development of a new OCS side effects questionnaire, we sought the views of people with asthma who had taken OCS. An online survey hosted on SurveyMonkey was shared with Asthma UK’s patient network through Facebook (>70k), Twitter (>39k) and the supporter mailing list (>80k). The survey asked people to report their experience of any of 29 symptoms collated from clinical and patient experience, and to report other side-effects not listed. 1,210 people with self-reported asthma responded, 92.5% of whom were on a daily dose of OCS or had had ≥2 asthma attacks requiring OCS in the previous year. The table below shows the 10 most frequently selected side effects and the percentage of respondents who selected each. These findings illustrate the impact of OCS on people with asthma. Results have been used to inform the development of a new side effects questionnaire for use in severe asthma services. It is important that patient-reported side effects are incorporated to fully evaluate clinical effectiveness.

This review presents seven national asthma programmes to support the European Asthma Research and Innovation Partnership in developing strategies to reduce asthma mortality and morbidity across Europe. From published data it appears that in order to influence asthma care, national/regional asthma programmes are more effective than conventional treatment guidelines. An asthma programme should start with the universal commitments of stakeholders at all levels and the programme has to be endorsed by political and governmental bodies. When the national problems have been identified, the goals of the programme have to be clearly defined with measures to evaluate progress. An action plan has to be developed, including defined re-allocation of patients and existing resources, if necessary, between primary care and specialised healthcare units or hospital centres. Patients should be involved in guided self-management education and structured follow-up in relation to disease severity. The three evaluated programmes show that, thanks to rigorous efforts, it is possible to improve patients' quality of life and reduce hospitalisation, asthma mortality, sick leave and disability pensions. The direct and indirect costs, both for the individual patient and for society, can be significantly reduced. The results can form the basis for development of further programme activities in Europe.

Background Asthma is one of the commonest chronic diseases in the UK. Acute exacerbations of asthma are unpredictable, disruptive and frightening. They cause considerable morbidity and account for a large component of the health service costs of asthma. The widespread use of an asthma self-management plan, designed to encourage disease monitoring and timely intervention, can reduce exacerbations and is, therefore, recommended for all patients with asthma. Unfortunately, the majority of patients are not provided with such a plan. There are a variety of reasons for this but uncertainty about what to include in the plan when asthma control is deteriorating, but before the need for orally administered corticosteroids, is a contributing factor. The aim of this trial is to determine whether an asthma self-management plan, which includes a temporary quadrupling of the dose of inhaled corticosteroid when asthma control starts to deteriorate, reduces asthma exacerbations requiring orally administered corticosteroids or unscheduled health care consultation for asthma. Methods A multicentre, pragmatic, randomised trial in adults aged over 16 years with a clinical diagnosis of asthma, treated with a licensed dose of inhaled corticosteroid and at least one exacerbation in the previous 12 months requiring treatment with systemic corticosteroids. Participants will be randomised to either a self-management plan, which includes a temporary (maximum of 14 days) fourfold increase in inhaled corticosteroid or the same plan without an increase in inhaled corticosteroid. Participants will be followed up at 6 and 12 months and will attend the clinic for an additional visit if their asthma control deteriorates. The primary outcome is time to first asthma exacerbation, defined as the need for systemic corticosteroids and/or unscheduled health care consultation for asthma. The estimated sample size is 1800 participants. Discussion The FAST trial is an independent study that has been prioritised and commissioned by the National Institute for Health Research (NIHR) in the United Kingdom. It will provide high-quality evidence to inform clinical decision-making on the role of an asthma self-management plan, which includes a temporary fourfold increase of inhaled corticosteroid, when asthma control starts to deteriorate. The first participant was randomised on 17th May 2013 and recruitment will close on 31 January 2016 with the last patient last visit taking place in January 2017. Trial registration ISRCTN: 15441965, registered on 25 April 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1608-6) contains supplementary material, which is available to authorized users.

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control. Therapeutic advances have been slow despite greater understanding of basic mechanisms and the lack of satisfactory preventative and disease modifying management for asthma constitutes a significant unmet clinical need. Preventing, treating and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which has taken a co-ordinated and integrated approach to analysing the future of asthma research and development. This report aims to identify the mechanistic areas in which investment is required to bring about significant improvements in asthma outcomes.

BACKGROUND: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalised management approach can be provided.OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinico-physiological parameters and performed an -omics analysis of sputum.METHODS: Partition-around-medoid clustering was applied to a training set of 266 asthma participants from the European U-BIOPRED adult cohort using 8 pre-specified clinic-physiological variables. This was repeated in a separate validation set of 152 asthmatics. The clusters were compared based on sputum proteomic and transcriptomic data.RESULTS: Four reproducible and stable clusters of asthmatics were identified. The training set cluster T1 consists of well-controlled moderate-to-severe asthmatics, while cluster T2 is a group of late-onset severe asthmatics with history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of non-smokers. Cluster T4 is predominantly composed of obese female uncontrolled severe asthmatics with increased exacerbations, but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters, T2, T3 and T4, had higher sputum eosinophilia than T1 with no differences in sputum neutrophil counts, exhaled nitric oxide and serum IgE levels.CONCLUSION: Clustering based on clinico-physiological parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.CLINICAL IMPLICATIONS: The definition of four distinct clusters of asthma linked to different pathobiological pathways provides a better template for the phenotyping and personalised treatment of severe asthma, where high unmet needs remain.CAPSULE SUMMARY: Unsupervised clustering of asthma on clinical features alone has led to the definition of four phenotypes. Sputum 'omics' analysis has revealed different biological pathways pointing towards potential new treatments.

A coordinated European multi-stakeholder approach to asthma research Asthma is highly prevalent and associated with high morbidity and mortality. It affects 30-50 million people in Europe, often starting in infancy and persisting throughout life. Asthma is a major global health challenge, affecting more than 300 million people worldwide and at least 10% of all Europeans [1]. People with asthma live at risk of life-threatening asthma attacks, leading to over 500 000 hospitalisations each year. Approximately 5-10% of asthma cases are so severe that current treatments do not work. The Framework Programme 7-funded European Asthma Research and Innovation Partnership (EARIP; www.EARIP.eu) was established in 2013 to harmonise efforts to reduce mortality and morbidity from asthma by agreeing the most important research priorities across relevant stakeholders in Europe. This is essential to address the significant impact of asthma on the individual, healthcare systems and national and European economies, outlined in the accompanying editorial in this issue of the European Respiratory Journal [2]. EARIP produced an evidence- and consensus-based list of the research priorities (a "roadmap") and investment needed to reduce asthma deaths and hospitalisations. By identifying the priorities, a coordinated effort can be made to fast-track change to better manage, prevent and cure asthma [3]. The roadmap will be the foundation on which future EU, national and international research funding programmes can transform asthma outcomes throughout Europe. The roadmap is the product of a comprehensive multi-stage process, led by the European Lung Foundation and Asthma UK (figure 1) [4]. Multiple stakeholder groups informed the roadmap process to ensure scientific accuracy, clinical relevance and outcomes that reflect the priorities of patients and caregivers, with an overarching steering board. A final consensus workshop brought together 28 experts from 15 European countries comprising: patients, patient organisations, primary healthcare professionals (HCPs), secondary HCPs, researchers, industry representatives and policy influencers. A full list of the roadmap contributors is available at www.EARIP.eu/roadmap. The rest of this article describes its development and outcomes.

Asthma is highly prevalent, often starting in infancy and persisting throughout life, and is associated with high morbidity and burden. It is a major global health challenge with growing impact, affecting more than 300 million people worldwide and at least 10% of all Europeans [1]. Furthermore, it is the most prevalent long-term condition in children [2]. Approximately 5–10% of asthma cases are so severe that current treatments do not work, and over five million people in the European Union (EU) fall into this category. People with asthma live at risk of life-threatening asthma attacks, leading to at least 500 000 hospitalisations worldwide each year [3]. A European study estimated that unscheduled care and rescue medication accounted for 47% of the total cost-per-patient in infants, 45% in children and 56% in adults [4]. This results in high socio-economic impact, estimated at more than €70 billion annually [1]. This includes the costs of direct primary and hospital healthcare (estimated to be close to €20 billion per annum), costs due to lost productivity (€14 billion) [1], and the monetised value of disability-adjusted life-years (DALYs) lost (over €38 billion) [1]. Close to 1 million DALYs are lost due to asthma in Europe every year [5]. Despite the fact that the direct and indirect costs of asthma are substantial and continue to rise, asthma remains under-prioritised in the EU research agenda. Only 0.5% of the Seventh Framework Programme (FP7) health research budget was devoted to asthma and chronic obstructive pulmonary disease (COPD) (€30 million) [5]. In comparison, some 5.4 times this amount (over €163 million) was spent on cardiovascular conditions and some 20.6 times (over €618 million) on brain research. Asthma, with its high global prevalence and an associated multi-billion global market for treatments, plus its historical underfunding and the demand for new treatments and diagnostics, represents an enormous opportunity to drive substantial economic growth. This paper sets out how the EU may capitalise on this via investment in research with high commercial potential that can radically improve the EUs research agenda and public health.

Background : To realise the P4 vision of predictive, preventive, personalised and participatory medicine in asthma there is an urgent need for improved sub-phenotyping of asthma. Aim: To identify the strategies required to fill knowledge gaps and unmet research needs concerning clinical and translational research on asthma phenotyping. Methods : An expert working group comprising scientists, clinicians, pharma-leaders and people with asthma contributed to a focused review of the field with strategic recommendations as a primary outcome. Results : The review identified a number of shortcomings which prevent the translation of research observations and hypotheses into clinical management strategies: 1) Most studies are cross-sectional and the long-term stability of the proposed phenotypes remains unknown. 2) There are few controlled and long-term interventional trials underpinning proposed pathobiological hypotheses. 3) Most studies of biomarkers focus on narrow panels. 4) There is a lack of phenotyping studies performed in a community setting where the majority of asthmatics are seen. Conclusions : Substantial investment into large-team science is needed where patients, academia, industry and regulatory authorities can meet and address these deficiencies. Longitudinal studies, standardised outcome measures, increased bio-banking, application of basic science discoveries, and systems biology approaches to integrate data are key factors which could lead to the development of simple biomarkers that can be used at the point-of-care. Funding: EU Grant agreement number 602077.

Asthma guidelines focus on day-to-day control of symptoms. However, asthma attacks remain common. They continue to cause mortality and considerable morbidity, and are a major financial burden to the UK National Health Service (NHS) and the wider community. Asthma attacks have chronic consequences, being associated with loss of lung function and significant psychological morbidity. In this article we argue that addressing daily symptom control is only one aspect of asthma treatment, and that there should be a more explicit focus on reducing the risk of asthma attacks. Management of future risk by general practitioners is already central to other conditions such as ischaemic heart disease and chronic renal impairment. We therefore propose a revised approach that separately considers the related domains of daily control and future risk of asthma attack. We believe this approach will have advantages over the current 'stepwise' approach to asthma management. It should encourage individualised treatment, including non-pharmacological measures, and thus may lead to more efficacious and less harmful management strategies. We speculate that this type of approach has the potential to reduce morbidity and healthcare costs related to asthma attacks. © 2013 Primary Care Respiratory Society UK. All rights reserved.

Although the ultimate goal of asthma treatment is to improve asthma-specific Health-Related Quality-Of-Life (HRQOL), in the UK population this is insufficiently studied. National asthma-specific HRQOL data is needed to inform strategies to address this condition.To benchmark asthma-specific HRQOL in a national survey of adults with asthma, and explore differences in this measure within subsections of the population.We analysed answers to the Marks Asthma Quality-of-Life Questionnaire (AQLQ-M) from a representative sample of 658 adults with asthma. Respondents answered asthma-specific questions to assess control, previous hospital admissions, asthma attacks and an indicator of severity. Higher scores indicate poorer HRQOL (maximum = 60). The highest quintile formed a subgroup 'Poor HRQOL'. Data were weighted to correct for any biases caused by differential non-response. Chi-square analyses were used to determine differences between good and poor quality of life and regression analyses performed to determine what factors are associated with poor HRQOL.The response rate was 49%. AQLQ-M median (IQR) scores were 5 (2-13) for the total sample (poor HRQOL = 21, good HRQOL = 3). Significant differences between good and poor HRQOL were observed in smoking status, SES, employment status and co-morbidities, but no differences were found between age groups. Those with poorly controlled asthma were significantly more likely to have poor HRQOL, ≥1 breathing related hospital admission or ≥1 asthma attack.This article provides benchmarking data on asthma-specific HRQOL. Improved strategies are needed to target interventions towards people experiencing poor HRQOL.

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.

Objective The Paediatric Asthma Quality of Life Questionnaire (PAQLQ) is a validated tool developed to assess the impact of symptoms on quality of life. Here we assess the validity, reliability and responsiveness of two new simpler versions of this questionnaire: the Standardised PAQLQ and the MiniPAQLQ. Study Design and Setting Participants included 42 children with asthma, who completed the PAQLQ, PAQLQ(S), MiniPAQLQ, Asthma Control Questionnaire, and Health Utilities Index at baseline, one, five and nine weeks. Concordance between questionnaires was examined using intraclass correlation coefficients (ICC), bias by paired Student's t -tests and closeness of association by Pearson correlation coefficients. Results Correlation coefficients for each of the corresponding domains of the PAQLQ with the PAQLQ(S) were strong ( r >0.97), and moderate to strong ( r =0.50–0.94) with the MiniPAQLQ. Reliability was strong for both the PAQLQ(S) (ICC>0.89) and MiniPAQLQ (ICC>0.91). The responsiveness index values for the PAQLQ(S) (0.96) and the MiniPAQLQ (1.05) were both higher than that of the original PAQLQ (0.90). Cross sectional and longitudinal correlation coefficients were similar for all three instruments. Conclusion The PAQLQ(S) and the MiniPAQLQ are valid, reliable and responsive to change. They can be used with confidence for long-term monitoring in clinical trials.

Allergic rhinitis (AR) affects more than 20% of the population in the United Kingdom and western Europe and represents a major cause of morbidity that includes interference with usual daily activities and impairment of sleep quality. This guidance prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) is for the management of AR in patients that have failed to achieve adequate relief of symptoms despite treatment with intranasal corticosteroids and/or antihistamines. The guideline is based on evidence and is for use by both adult physicians and paediatricians practising allergy. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are indications and contraindications for immunotherapy, criteria for patient selection, the evidence for short- and long-term efficacy of subcutaneous and sublingual immunotherapy, and discussion on safety and the different modes of immunotherapy including, pre-seasonal and co-seasonal treatments. There are sections on children, allergen standardization, vaccines used in the United Kingdom, oral allergy syndrome, cost effectiveness of immunotherapy and practical considerations of undertaking immunotherapy including recommendations on who should undertake immunotherapy and dosing schedules. Finally, there is discussion on potential biomarkers of response to immunotherapy, the use of component-resolved diagnostics, novel approaches, alternative routes and potential areas for future research.

Background Although patients with asthma would like more involvement in the decision-making process, and UK government policy concerning chronic conditions supports shared decision making, it is not widely used in practice. Objective To investigate how nurses approach decision making in relation to inhaler choice and long-term inhaler use within a routine asthma consultation and to better understand the barriers and facilitators to shared decision making in practice. Setting and participants Semi-structured interviews were conducted with post-registration, qualified nurses who routinely undertook asthma consultations and were registered on a respiratory course. Interviews were recorded, transcribed and analysed using the Framework approach. Results Twenty participants were interviewed. Despite holding positive views about shared decision making, limited shared decision making was reported. Opportunities for patients to share decisions were only offered in relation to inhaler device, which were based on the nurses pre-selected recommendations. Giving patients this choice was seen as key to improving adherence. Discussion There is a discrepancy between nurses understanding of shared decision making and the depictions of shared decision making presented in the academic literature and NHS policy. In this study, shared decision making was used as a tool to support the nurses agenda, rather than as a natural expression of equality between the nurse and patient.

Rhinitis is a common problem in primary care which is often managed sub-optimally. It causes considerable morbidity and has been shown to have a detrimental impact on people's ability to concentrate at school and at work. Rhinitis and asthma often present together, and symptomatic rhinitis can be associated with poor asthma control and increased risk of exacerbations. There is therefore a clear need to recognise and treat rhinitis according to guideline recommendations. This article is a primary care summary of the British Society for Allergy & Clinical Immunology (BSACI) Standards of Care Committee guideline on the management of rhinitis, written by a multi-disciplinary group of clinicians. It takes into account the time restrictions on assessment and the tests and equipment available in primary care, as well as the need for practical, clear and intuitive strategies for investigation and management. It recommends a stepwise approach to treatment, and highlights the relevance of less frequently prescribed treatments, including nasal douching leukotriene receptor antagonists and anticholinergics. Red flag symptoms are identified, together with indicators for referral. As with many other long term conditions, good communication between primary and secondary care in terms of timely and appropriate referral is a key factor for success.

This guidance for the management of patients with allergic and non-allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co-morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.

OBJECTIVES: To describe nurse-led UK general practice asthma and chronic obstructive pulmonary disease (COPD) care, and the training undertaken to support it. METHODS: Questionnaires were sent to 500 randomly-selected UK asthma and COPD practice nurses. RESULTS: 382 nurses (76%) completed the practice characteristics section, 389 (78%) described their asthma roles and training, and 368 (74%) described their COPD roles and training. 96 practices (25%; 95%CI 21–29%) ran designated asthma clinics, 87 (23%; 95%CI 19–27%) ran designated COPD clinics, and 170 (45%; 95%CI 40–49%) did not run designated respiratory clinics. Of the 255 nurses with an advanced asthma role, 51 (20%; 95%CI 15–25%) did not have accredited asthma training. Of the 215 nurses with an advanced COPD role, 111 (52%; 95%CI 45–58%) did not have accredited COPD training. CONCLUSION: Patients are increasingly being seen outside of designated asthma or COPD clinics, often by nurses with an advanced role. It is important that nurses have the training to fulfil this role.

Asthma affects 30million people in Europe throughout their education and working lives and puts a heavy cost on EU productivity. Preventing and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which will take a co-ordinated and integrated approach to the future of research and development by creating a roadmap that describes what is needed to reduce asthma9s impact on individuals and healthcare systems in Europe. The first step in this process was to understand the importance people with asthma place on various research topics; this can indicate which topics are likely to achieve the greatest impact. Respondents were asked to indicate the importance of 51 research topics across 5 research themes via an online survey. The survey was open for 4 weeks in July 2014 and promoted in 8 languages to a network of >160 patient organisations in Europe. Data were reported using descriptive statistics, and comparisons by theme and demographics analysed. 1904 surveys from 20 European countries were analysed: >97% of respondents expressed an opinion on each topic, with the majority viewed as important or very important (>90%). Differences could be seen between topics in different research themes, and comparisons between respondent demographics yielded important results. People with asthma view all research areas as important to their care; however some have greater importance. These findings will inform a stakeholder consensus workshop at ERS 2016 and input into the roadmap. This will be used by clinicians, researchers, industry and patient groups to lobby for change and EU investment in asthma.

Background: Non-adherence to corticosteroid treatment has been shown to reduce treatment efficacy, thus compromising asthma control. Aims: To examine the experiences of treatment side effects, treatment concerns and adherence to inhaled (ICS) and oral corticosteroids (OCS) among people with asthma and to identify the degree of concordance between clinician estimates of side effects and the prevalence reported by patients. Methods: Asthma UK members were sent validated questionnaires assessing treatment concerns, experiences of side effects and adherence. Questionnaires measuring clinicians’ estimates of the prevalence of corticosteroid side effects were completed online. Results: Completed questionnaires were returned by 1,524 people taking ICS, 233 taking OCS and 244 clinicians (67% of clinicians were primary care nurses). Among people with asthma, 64% of those taking ICS and 88% of those taking OCS reported ⩾1 side effect. People reporting high adherence to ICS (t=−3.09, Pt=1.86, Pr=0.46, Pr=0.50, Pt=6.90, Pt=1.71; P Conclusions: An unexpectedly large proportion of people with asthma experienced side effects and had strong concerns about their treatment, which compromised adherence. These findings have implications for the design of interventions to optimise asthma control through improved adherence.

The association between the upper and lower airways has been recognised for almost 2000 years. Epidemiological data suggest that most asthma patients also suffer from allergic rhinitis, and that both diseases share similar trigger factors and pathophysiology. This IPCRG Guideline on the management of rhinitis in primary care is fully consistent with the ARIA guidelines. It highlights the treatment goals and the classification of the condition according to symptom frequency (intermittent or persistent) and severity (mild or moderate-severe). It covers the need for allergen avoidance, pharmacologic therapy including immunotherapy, alternative therapies, management of ocular symptoms, the management of co-existing allergic rhinitis and asthma, and the need for follow-up and ongoing care for patients with rhinitis.

Summary Background: There is increasing interest in the possibility that rhinitis and asthma are intricately interlinked. The aim of this baseline audit was to investigate the prevalence and characteristics of rhinitis symptoms in a large-scale UK primary care-based survey of patients with asthma. Methods: A questionnaire about the presence/absence and type of nasal symptoms, seasonal variations, and trigger factors was developed and piloted. This was then distributed among approximately 10,500 patients with clinician-diagnosed asthma via a national database of practice nurses. Results: We achieved a response from 7,129 patients (68%). Of these, 76% ( n = 5,420) had symptoms indicative of rhinitis as shown by the presence of more than one of the following: nasal blockage; runny nose; sneezing; and itchy eyes, ears or palate. 58% reported predominantly seasonal symptoms and 42% predominantly perennial symptoms. Sneezing was reported in a significantly greater proportion of patients with seasonal (66%) than perennial (58%) symptoms, together with itchy eyes/ears/palate (seasonal 60%, perennial 48%) and rhinorrhoea (56%, 51%) (all p ≤ 0.001). Symptoms of nasal blockage were more commonly reported in the group with perennial symptoms (perennial 61%, seasonal 53%) ( p Conclusions: In this large national baseline survey, 76% of patients with asthma reported symptoms indicative of rhinitis. In view of the very high prevalence of rhinitis among people with asthma, we suggest that the diagnosis of rhinitis is considered in all those with asthma.

Allergic rhinitis is defined as a symptomatic disorder of the nose, triggered by allergen exposure via immunoglobulin E (IgE)-mediated inflam-matory mechanisms. Symptoms include rhinorrhoea (runny nose), itching, sneezing and nasal blockage. Allergic rhinitis has a huge impact on the lives of its sufferers and is a global health problem (Bousquet et al, 2001). Its prevalence is increasing and around 15% of adults and 20% of children now suffer from allergic rhinitis, often accompanied by conjunctivitis and asthma (Strachan, 1995).

BACKGROUND: Patient-reported outcome measures (PROMs) are measures of the outcome of treatment(s) reported directly by the patient or carer. There is increasing international policy interest in using these to assess the impact of clinical care. AIMS: To identify suitably validated PROMs for asthma and examine their potential for use in clinical settings. METHODS: We systematically searched MEDLINE, EMBASE and Web of Science databases from 1990 onwards to identify PROMs for asthma. These were critically appraised, then narratively synthesised. We also identified the generic PROMs commonly used alongside asthma-specific PROMs. RESULTS: We identifi ed 68 PROMs for asthma, 13 of which were selected through screening as being adequately developed to warrant full-quality appraisal: 8 for adults, 4 for children and 1 for a child's caregiver. The PROMs found to be sufficiently well validated to offer promise for use in clinical settings were the Asthma Quality of Life Questionnaire (AQLQ) and mini-AQLQ for adults, and Pediatric Asthma Quality of Life Questionnaire for children. Rhinasthma was considered promising in simultaneously assessing the impact of asthma and rhinitis in those with coexistent disease. We identified 28 generic PROMs commonly used in conjunction with asthma-specific instruments. CONCLUSIONS: We identified asthma PROMs that offer the greatest potential for use in clinical settings. Further work is needed to assess whether these are fit-for-purpose for use in clinical practice with individual patients. In particular, there is a need to ensure these are validated for use in clinical settings, acceptable to patients, caregivers and clinicians, and yield meaningful outcomes. © 2014 Primary Care Respiratory Society/Macmillan Publishers Limited.

Background Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti-IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add-on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE-mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included, as long as they were the same in each arm. Data collection and analysis Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. Main results In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti-IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving background inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab-treated participants compared with those given placebo (weighted mean difference (WMD) -118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI -154 to -84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta2-agonist medication compared with placebo (mean difference (MD) -0.39 puffs per day, 95% CI -0.55 to -0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD -0.58, 95% CI -0.84 to -0.31) and severe (MD -0.30, 95% CI -0.49 to -0.10) asthma subgroups on a background therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a background therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Authors' conclusions Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone-sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research.

The relationship between asthma and the workplace is important to consider in all cases of adult asthma. Early identification of a cause in the workplace offers an opportunity to improve asthma control significantly and reduce the need for long-term medication if further exposures to the cause can be avoided. This typical but fictitious case is designed to give the reader clinical information in the order this would normally be received in clinical practice, with a real-time commentary about management decisions. Pertinent recent guidance is cited to stress the importance of evidence-based practice.

The association of respiratory problems with chemical emissions from common indoor materials has been studied but the specific effect of domestic paint has not been widely investigated. The aim of this review is to provide a comprehensive evaluation of experimental, occupational and epidemiological studies that examine the adverse respiratory effects of exposure to domestic paints.A literature search of PubMed together with consultation with an expert resulted in 997 articles published up to May 2011 of which 3 experimental, 4 occupational and 13 epidemiological studies met selection criteria and were included in the review.The occupational literature suggested that work as a (non-spray) painter increases the risk of asthma, but it provides little insight to the risks of painting in the domestic setting. All epidemiological studies, except one, reported associations with some asthma-like symptoms. In children at least there was evidence that painting was associated with wheezing, but the study designs and the exposure assessment were unsuitable to differentiate between acute and longer terms affects. We found the epidemiological evidence to be weak and certainly insufficient to infer causality.The variable quality of the exposure assignment and heterogeneous study design makes it difficult to draw firm conclusions on whether domestic paint exposures cause or exacerbate asthma in children and/or adults.

Summary: Many factors can impair asthma control. One which is frequently overlooked is rhinitis. Asthma patients with significant rhinitis are over four times more likely to have poorly controlled asthma than those without. Over 80% of patients with asthma have rhinitis, which may be allergic or inflammatory/non-allergic. Both types of rhinitis share pathophysiological similarities with eosinophilic asthma, cause bronchial hyper-reactivity, and are predisposing factors for the subsequent development of asthma. Nasal allergen challenge in allergic rhinitis results in inflammation in the bronchi as well as the nose, and the reverse is also true. This article reviews briefly the evidence for the link between asthma and rhinitis, advocates looking for rhinitis when patients present with poorly controlled asthma, and provides guidance for the diagnosis and treatment of rhinitis.

Background In 2014, the Royal College of Physicians published the National Review of Asthma Deaths. This confidential enquiry into 195 confirmed asthma deaths in the UK highlighted that two thirds of these deaths were associated with potentially modifiable prescription factors including excessive short-acting beta agonist (SABA) use without review and prescription of long acting beta agonists (LABA) without inhaled corticosteroids (ICS), the latter of which have been associated with higher mortality. 1 Aim The aim of this project was to determine how widespread these two modifiable prescription factors are in the treatment of asthma in UK general practice. Methods Primary Care data were obtained from the Optimum Patient Care Research Database (OPCRD). Extraction criteria included patients with a current diagnosis of asthma, at least two years of continuous medical records and at least one asthma prescription in the preceding 12 months. Those who: had a comorbid diagnosis of COPD, had received no treatment for the past 12 months and children Results 94,955 asthma patients met the inclusion criteria, of which 12661 (13%) were children. LABAs with no ICS had been prescribed to 402 patients (0.4%). A total of 5032 patients (5.3%) had been prescribed ≥ 12 SABA inhalers, ranging from 13–136 inhalers of which 1965 (39%) had not had an asthma review. Among these, 117 were children, 0.92% of the total. Conclusion These data, covering a large GP population, suggest evidence of non-guideline recommended prescribing which might contribute to increased risk to asthma patients. Prescribers should consider implementing system alerts to identify and review such prescribing behaviours. Reference 1 Lee C, Corren J. Budesonide/formoterol in the treatment of asthma. Expert Rev Respir Med 2008; 2 :551–64