Recommendations following a modified UK-Delphi consensus study on best practice for referral and management of severe asthma

IntroductionSevere asthma affects an estimated 3%–5% of people with asthma and is associated with frequent exacerbations, poor symptom control and significant morbidity from the disease itself, as well as high dose of inhaled and systemic steroids used to treat it. The introduction of specialist asthma services across the UK has attempted to improve quality of care and ensure that patients undergo a full systematic assessment prior to initiation of advanced biological therapies. However, improvements are required in the patient pathway to minimise avoidable harm.ObjectivesTo define standards of care in areas where the evidence base is lacking through patient and healthcare professional (HCP) consensus.MethodsThe precision UK National Working Group of asthma experts identified 42 statements formed from 7 key themes. An online four-point Likert scale questionnaire was sent to HCPs working in asthma throughout the UK to assess agreement (consensus) with these statements; a subset of the statements formed a patient questionnaire. Consensus was defined as high if ≥75% and very high if ≥90% of respondents agreed with a statement.ResultsA total of 117/197 responses (59.3% response rate) were received from severe asthma patients (n=15) and HCPs (n=102) including respiratory physicians, respiratory nurse specialists, respiratory pharmacists, specialist physiotherapists and general practitioners. Consensus was very high in 25 (60%) statements, high in 12 (29%) statements and was not achieved in 5 (12%) statements. Based on the consensus scores, the precision UK National Working Group derived 10 key recommendations. These focus on referrals from primary and secondary care, accessing specialist asthma services, homecare provision for severe asthma patients and outcome measures.ConclusionsImplementation of these 10 recommendations across the severe asthma pathway in the UK has the potential to improve outcomes for patients by reducing delays to assessment and initiation of advanced phenotype-specific therapies.

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Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era

Thorax ◽

10.1136/thoraxjnl-2020-215168 ◽

2020 ◽

pp. thoraxjnl-2020-215168

Author(s):

David J Jackson ◽

John Busby ◽

Paul E Pfeffer ◽

Andrew Menzies-Gow ◽

Thomas Brown ◽

...

Keyword(s):

Asthma Control ◽

Severe Asthma ◽

Symptom Control ◽

Unmet Need ◽

High Dose ◽

Blood Eosinophil ◽

Biologic Therapies ◽

Exacerbation Rate ◽

The Uk ◽

Blood Eosinophils

BackgroundThe UK Severe Asthma Registry (UKSAR) is the world’s largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids.MethodsDemographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL).ResultsAge (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)).ConclusionsThe UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure.

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Diagnosis and Management of Severe Asthma

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0037-1607391 ◽

2018 ◽

Vol 39 (01) ◽

pp. 091-099 ◽

Cited By ~ 5

Author(s):

Kian Fan Chung

Keyword(s):

Severe Asthma ◽

Inhaled Corticosteroids ◽

Immunoglobulin E ◽

High Dose ◽

Blood Eosinophil ◽

Exhaled Breath ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Asthma Patients ◽

Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

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Late Breaking Abstract - Characteristics of T2-biomarker low severe asthma patients in the UK Severe Asthma Registry (UKSAR)

10.1183/13993003.congress-2019.pa2788 ◽

2019 ◽

Author(s):

John Busby ◽

Paul E Pfeffer ◽

David J Jackson ◽

Adel H Mansur ◽

Andrew Menzies-Gow ◽

...

Keyword(s):

Severe Asthma ◽

Asthma Patients ◽

The Uk

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Typical Antipsychotics Increase Risk of Severe Exacerbation in Asthma Patients– A Nationwide Population-Based Cohort Study

10.21203/rs.3.rs-778754/v1 ◽

2021 ◽

Author(s):

Chin-Wei Kuo ◽

Szu-Chun Yang ◽

Yu-Fen Shih ◽

Xin-Min Liao ◽

Sheng-Hsiang Lin

Keyword(s):

Severe Asthma ◽

Asthma Exacerbation ◽

High Dose ◽

Severe Exacerbation ◽

Severe Asthma Exacerbation ◽

Increased Risk ◽

Asthma Patients ◽

Ed Visits ◽

Dose Dependent ◽

Typical Antipsychotics

Abstract Background:Severe asthma exacerbation reduces patients’ life quality, results in visits to the emergency department (ED) and hospitalization, and incurs additional medical costs. Antipsychotics block receptors with bronchodilation function; however, the effects of antipsychotics use on severe asthma exacerbation are unknown. This study aimed to investigate the effects of antipsychotics on asthma-related ED visits and hospitalizations.Methods:This study used a case-crossover design. Using the 2003-2017 Taiwan National Health Insurance Reimbursement Database, we established a cohort of 18,657 adults with severe asthma exacerbation leading to ED visits or hospitalization. Univariate and multivariate conditional logistic regressions were conducted to explore the association of antipsychotics use with severe asthma exacerbation. Subgroup analyses of different classes, doses, receptor functions of antipsychotics and schizophrenia were also performed.Results:Antipsychotics use was associated with a higher risk of severe asthma exacerbation (adjusted odds ratio (OR): 1.27; 95% confidence interval (CI): 1.05-1.54; P = 0.013) compared with no use of antipsychotics. Use of typical antipsychotics increased the risk of severe asthma exacerbation (adjusted OR: 1.40, 95% CI: 1.10-1.79, P = 0.007), whereas use of atypical antipsychotics did not. There was a dose-dependent effect of antipsychotics (test for trend: P =0.025). Antipsychotics that block the M2 muscarinic or D2 dopaminergic receptor were associated with an increased risk of severe asthma exacerbation (adjusted OR: 1.39, 95% CI: 1.10-1.76, P = 0.007 and adjusted OR: 1.33, 95% CI: 1.08-1.63, P = 0.008, respectively).Conclusions: Use of typical antipsychotics is associated with a dose-dependent increased risk of severe asthma exacerbation. Physicians should thus weight the risk and benefit of prescribing high-dose typical antipsychotics for asthma patients.

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PRP7 A CROSS-SECTIONAL, OBSERVATIONAL STUDY TO ESTABLISH THE RESOURCES AND COSTS ASSOCIATED WITH CONTROLLED AND POORLY CONTROLLED MODERATE TO SEVERE ASTHMA PATIENTS IN THE UK

Value in Health ◽

10.1016/s1098-3015(10)61982-1 ◽

2003 ◽

Vol 6 (6) ◽

pp. 778

Author(s):

DF Ossa ◽

R Brown ◽

D Price ◽

F Everhard

Keyword(s):

Observational Study ◽

Severe Asthma ◽

Cross Sectional ◽

Asthma Patients ◽

The Uk

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The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK

Primary Care Respiratory Journal ◽

10.3132/pcrj.2007.00002 ◽

2007 ◽

Vol 16 (1) ◽

pp. 22-27 ◽

Cited By ~ 65

Author(s):

Andrew Lloyd ◽

David Price ◽

Ruth Brown

Keyword(s):

Quality Of Life ◽

Severe Asthma ◽

Health Related Quality ◽

Asthma Exacerbations ◽

Asthma Patients ◽

Related Quality ◽

Health Related ◽

The Uk ◽

The Impact

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Real-life effectiveness of omalizumab in difficult-to-treat versus severe asthma: a national cohort study in Belgium

ERJ Open Research ◽

10.1183/23120541.00253-2018 ◽

2019 ◽

Vol 5 (4) ◽

pp. 00253-2018 ◽

Cited By ~ 1

Author(s):

Katia M.C. Verhamme ◽

Catherine Lucet ◽

Alain Van Meerhaeghe ◽

Guy G.O. Brusselle ◽

Marie-Laurence Lambert

Keyword(s):

Severe Asthma ◽

Absolute Risk ◽

Real Life ◽

Absolute Risk Reduction ◽

High Dose ◽

Eligibility Criteria ◽

Systemic Corticosteroids ◽

Asthma Patients ◽

The Cost ◽

Chronic Use

BackgroundGuidelines recommend omalizumab in patients with uncontrolled severe allergic asthma. We investigated real-life use of omalizumab, the proportion of patients fulfilling eligibility criteria, its costs and its effectiveness.MethodIn a cohort of asthma patients initiating treatment with omalizumab in Belgium between 2010 and 2016, we investigated fulfilment of eligibility criteria (chronic use of high-dose inhaled corticosteroids (ICSs) plus long-acting β2-agonists (LABAs) and ≥2 severe asthma exacerbations in previous year), and compared hospitalisations and systemic corticosteroid consumption in the year before and after omalizumab initiation. We computed healthcare costs in the respective time periods and compared the cost per prevented hospitalisation in patients fulfilling eligibility criteria versus those who did not.ResultsBetween 2010 and 2016, omalizumab treatment was initiated in 2068 patients with asthma; only 24% fulfilled the eligibility criteria, mainly due to nonadherence to high-dose ICSs + LABAs. The proportion of patients hospitalised for asthma decreased from 41% to 21% in eligible patients (absolute risk reduction, 20%), whereas the absolute risk reduction was 5% (from 19% to 14%) in noneligible patients. The cost per prevented hospitalisation was €44 238 versus €139 495, respectively. Chronic use of systemic corticosteroids was discontinued in 35% of eligible patients versus 15% of noneligible patients.ConclusionIn Belgium, omalizumab is mostly initiated in uncontrolled asthma patients who are nonadherent to ICSs + LABAs. Omalizumab decreases hospitalisations and the use of systemic corticosteroids, but at a high cost. Careful management of patients with difficult-to-treat asthma should be a priority before prescribing omalizumab.

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P14 Characteristics of T2-biomarker low severe asthma patients in the UK severe asthma registry

10.1136/thorax-2019-btsabstracts2019.157 ◽

2019 ◽

Author(s):

J Busby ◽

PE Pfeffer ◽

DJ Jackson ◽

AH Mansur ◽

A Menzies-Gow ◽

...

Keyword(s):

Severe Asthma ◽

Asthma Patients ◽

The Uk

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Anti-interleukin 5 therapies failure criteria in severe asthma: a Delphi-consensus study

Therapeutic Advances in Respiratory Disease ◽

10.1177/17534666211049735 ◽

2021 ◽

Vol 15 ◽

pp. 175346662110497

Author(s):

Laura Mattei ◽

Carey M. Suehs ◽

Khuder Alagha ◽

Arnaud Bourdin ◽

Christophe Brousse ◽

...

Keyword(s):

Decision Making ◽

Treatment Failure ◽

Severe Asthma ◽

Initial Dosage ◽

Failure Criteria ◽

Delphi Consensus ◽

Interleukin 5 ◽

Therapeutic Class ◽

Asthma Patients ◽

Delphi Exercise

Background: Current practices for assessing response to anti-interleukin 5/R treatment in severe asthma patients are heterogeneous. The objective of this study was to achieve an expert consensus defining failure criteria for anti-interleukin 5/R treatment in severe asthma patients. Methods: Experts were invited to a 5-round Delphi exercise if they were pulmonologists managing ⩾30 patients at a nationally recognized severe asthma expert centre. Following two rounds of statement-generating brainstorming, the expert panel ranked each statement according to a 5-point Likert-type scale during three additional rounds. Positive consensus was considered achieved when ⩾80% of experts agreed with a statement with >50% strong agreement and <15% disagreement. Results: Twenty experts participated in the study. All experts agreed that predefined treatment goals defining effectiveness should be personalized during shared decision making via a patient contract. Treatment failure was defined as (1) absence of a reduction in exacerbation rates by ⩾25% or (2) absence of a reduction in oral corticosteroid therapy by ⩾25% of the initial dosage or (3) occurrence of emergency room visits or hospitalizations after 6 months of treatment. Treatment failure should result in discontinuation. For partial responders, treatment discontinuation was not recommended unless an alternative from another therapeutic class exists and should be discussed in a multidisciplinary consultation. Conclusion: The present study provides objective criteria for anti IL5 or IL5R failure in severe asthma and suggests consensus based guidelines for prescription, evaluation and discontinuation decision-making.

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