Clinical Remission in Severe Asthma : How to Move From Theory to Practice

ACKNOWLEDGMENTS Medical writing support was provided by Dan Jackson, PhD, CMPP, of CiTRUS Health Group, which was in accordance with Good Publication Practice (GPP4) guidelines. AstraZeneca (Cambridge, UK) funded this support. AMG and DBP both conceived and refined the topic for this manuscript. Both authors contributed to the discussion and revision of the content and approved the final version.Peer reviewedPostprin

A Charter to Fundamentally Change the Role of Oral Corticosteroids in the Management of Asthma

Asthma affects 339 million people worldwide, with an estimated 5–10% experiencing severe asthma. In emergency settings, oral corticosteroids (OCS) can be lifesaving, but acute and long-term treatment can produce clinically important adverse outcomes and increase the risk of mortality. Therefore, global guidelines recommend limiting the use of OCS. Despite the risks, research indicates that 40–60% of people with severe asthma are receiving or have received long-term OCS treatment. Although often perceived as a low-cost option, long-term OCS use can result in significant health impairments and costs owing to adverse outcomes and increased utilization of healthcare resources. Alternative treatment methods, such as biologics, may produce cost-saving benefits with a better safety profile. A comprehensive and concerted effort is necessary to tackle the continued reliance on OCS. Accordingly, a threshold for OCS use should be established to help identify patients at risk of OCS-related adverse outcomes. Receiving a total dose of more than 500 mg per year should trigger a review and specialist referral. Changes to national and local policies, following examples from other chronic diseases, will be crucial to achieving this goal. Globally, multiple barriers to change still exist, but specific steps have been identified to help clinicians reduce reliance on OCS. Implementing these changes will result in positive health outcomes for patients and social and economic benefits for societies.</p

Clinical Remission in Oral Corticosteroid (OCS)-dependent Patients with Severe Asthma : An Analysis of the ANDHI-IP and PONENTE Trials

Funding: This study was funded by AstraZeneca (Cambridge, UK).Peer reviewe

Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management

Writing and editing assistance, including preparation of a draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Debra Scates, Ph.D., of JK Associates, Inc., and Michael A. Nissen, E.L.S., of AstraZeneca. This support was funded by AstraZeneca.Peer reviewedPublisher PD

A randomised controlled feasibility study of group cognitive behavioural therapy for people with severe asthma

Objectives: Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma. Method: This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression – Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS. Results: 51 patients were randomised: 36% (51 out of 140) consent rate and 25% (13/51) attrition at week 16. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants. Conclusions: This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration

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

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

Bacteria in sputum of stable severe asthma and increased airway wall thickness

<p>Abstract</p> <p>Background</p> <p>Patients with chronic asthma have thicker intrapulmonary airways measured on high resolution computed tomography (HRCT). We determined whether the presence of lower airway bacteria was associated with increased airway wall thickness.</p> <p>Methods</p> <p>In 56 patients with stable severe asthma, sputum specimens obtained either spontaneously or after induction with hypertonic saline were cultured for bacteria and thoracic HRCT scans obtained. Wall thickness (W_T) and area (W_A) expressed as a ratio of airway diameter (D) and total area, respectively, were measured at five levels.</p> <p>Results</p> <p>Positive bacterial cultures were obtained in 29 patients, with <it>H. influenzae, P. aeruginosa </it>and <it>S. aureus </it>being the commonest strains. Logistic regression analysis showed that this was associated with the duration of asthma and the exacerbations during the past year. In airways > 2 mm, there was no significant difference in W_A(67.5 ± 5.4 vs 66.4 ± 5.4) and W_T/D (21.6 ± 2.7 vs 21.3 ± 2.4) between the culture negative versus positive groups. Similarly, in airways (≤ 2 mm), there were no significant differences in these parameters. The ratio of √wall area to P_iwas negatively correlated with FEV₁% predicted (p < 0.05).</p> <p>Conclusions</p> <p>Bacterial colonization of the lower airways is common in patients with chronic severe asthma and is linked to the duration of asthma and having had exacerbations in the past year, but not with an increase in airway wall thickness.</p

Clinical Remission in Severe Asthma : A Pooled Post hoc Analysis of the Patient Journey with Benralizumab

Funding This study, the Rapid Service Fee, and the Open Access Fee were funded by AstraZeneca (Gaithersburg, MD, USA).Peer reviewedPublisher PD

A Response to : Letter to the Editor Regarding “Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab”

Funding Information: No funding or sponsorship was received for the publication of this article. Medical writing support was provided by Dan Jackson, Ph.D., CMPP (CiTRUS Health Group), and was funded by AstraZeneca (Cambridge, UK) in accordance with Good Publication Practice (GPP3) guidelines. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Andrew Menzies-Gow developed the outline and content of the response letter and commented on previous versions of the manuscript. All authors read and approved the final manuscript. Andrew Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, and Teva; has received speaker fees from AstraZeneca, Novartis, Sanofi, and Teva; has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva; and has had consultancy agreements with AstraZeneca and Sanofi. Flavia L. Hoyte has attended advisory boards for AstraZeneca; has received speaker fees from AstraZeneca and GlaxoSmithKline; and has participated in research sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Teva, Sanofi, and the National Institute of Allergy and Infectious Diseases (NIAID), for which her institution has been remunerated. David B. Price has board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Thermofisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Theravance, and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance, and the UK National Health Service; received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, and Sanofi Genzyme; received payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, and Thermofisher; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; ownership of 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp, which develops adherence monitoring technology; a peer reviewer role for grant committees of the UK Efficacy and Mechanism Evaluation programme and the Health Technology Assessment; and served as an expert witness for GlaxoSmithKline. David Cohen, Peter Barker, James Kreindler, Maria Jison, Chris Brooks, Peggy Papeleu, and Rohit Katial are employees of AstraZeneca. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Data sharing is not applicable to this article as no datasets were generated or analysed for this response letter. Funding Information: Andrew Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, and Teva; has received speaker fees from AstraZeneca, Novartis, Sanofi, and Teva; has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva; and has had consultancy agreements with AstraZeneca and Sanofi. Flavia L. Hoyte has attended advisory boards for AstraZeneca; has received speaker fees from AstraZeneca and GlaxoSmithKline; and has participated in research sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Teva, Sanofi, and the National Institute of Allergy and Infectious Diseases (NIAID), for which her institution has been remunerated. David B. Price has board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Thermofisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Theravance, and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance, and the UK National Health Service; received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, and Sanofi Genzyme; received payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, and Thermofisher; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; ownership of 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp, which develops adherence monitoring technology; a peer reviewer role for grant committees of the UK Efficacy and Mechanism Evaluation programme and the Health Technology Assessment; and served as an expert witness for GlaxoSmithKline. David Cohen, Peter Barker, James Kreindler, Maria Jison, Chris Brooks, Peggy Papeleu, and Rohit Katial are employees of AstraZeneca. Funding Information: Medical writing support was provided by Dan Jackson, Ph.D., CMPP (CiTRUS Health Group), and was funded by AstraZeneca (Cambridge, UK) in accordance with Good Publication Practice (GPP3) guidelines.Peer reviewedPublisher PD