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Background: Asthma attacks are a common problem for people with asthma and are responsible for significant healthcare costs. There is interest in a precision medicine approach to treatment. However, the choice of trial outcome measures for asthma attack treatment is hampered by the absence of a consensus on suitability. We carried out a systematic review to understand the characteristics of outcome measures used in randomised controlled trials of asthma attack treatment. Have randomised controlled trials of asthma attack treatment measured outcomes that are useful to patients and healthcare providers?, Methods: The protocol was registered on PROSPERO (CRD42022311479). We searched for randomised controlled trials comparing treatments for adults with asthma attacks, published in English between 1972 and 2022 on MEDLINE, Embase and Cochrane Library databases. We recorded the outcome measures and study characteristics., Results: We identified 208 eligible randomised controlled trials from 35 countries. Trials ranged from 12 to 1109 participants, with a median of 60. The most common settings were the emergency department (n=165) and hospital admission (n=33). Only 128 studies had primary and secondary outcomes defined clearly. In those that did, 73% of primary outcomes measured change in lung function or other physiological parameters over a short period (usually <24 h). Patient-reported and healthcare utilisation outcomes were the primary outcome in 27%., Conclusions: Outcomes in randomised controlled trials of asthma attack treatment focus on short-term changes in lung function and may not capture patient-centred and economically important longer-term measures. More work is needed to investigate patient and other stakeholder preferences on core outcome sets., Competing Interests: Conflicts of interest: I. Howell reports conference travel support from GSK. Conflicts of interest: A. Howell reports conference travel support from GSK. Conflicts of interest: S. Ramakrishnan reports research funding from the National Institute of Health and Care Research and the Australian Government Research Training Program; S. Ramakrishnan’s institution has received unrestricted grant funding from AstraZeneca which was used to fund a research project; and S. Ramakrishnan has received personal speaker fees and conference travel support from AstraZeneca. Conflicts of interest: M. Bafadhel reports grants from AstraZeneca, and personal fees from AstraZeneca, Chiesi, GSK, Albus Health and ProAxsis. Conflicts of interest: I. Pavord reports having, over the last 5 years, received speaker’s honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini and GSK, as well as payments for organising educational events from AstraZeneca, GSK, Sanofi/Regeneron and Teva; and has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi and Knopp, as well as payments to support US Food and Drug Aministration approval meetings from GSK; receiving sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva and Chiesi; and has received a grant from Chiesi to support a phase 2 clinical trial in Oxford., (Copyright ©The authors 2024.)

The treatable traits approach represents a strategy for patient management. It is based on the identification of characteristics susceptible to treatments or predictive of treatment response in each individual patient. With the objective of accelerating progress in research and clinical practice relating to such a treatable traits approach, the Portraits event was convened in Barcelona, Spain, in November 2022. Here, while reporting the key concepts that emerged from the discussions during the meeting, we review the current state of the art related to treatable traits and chronic respiratory diseases management, and we describe the possible actions that clinicians can take in clinical practice to implement the treatable traits framework. Furthermore, we explore the new concept of GETomics and the new models of research in the field of COPD., Competing Interests: Conflicts of interest: A Papi reports honoraria from AstraZeneca, Chiesi Farmaceutici, Boehringer Ingelheim, GlaxoSmithKline, Gentili, Pfizer, Novartis, Mundipharma, Novartis, TEVA and Zambon; research grants from AstraZeneca, Chiesi Farmaceutici, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Fondazione Maugeri and Fondazione Chiesi; participation in a company sponsored bureau with AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Edmondpharma, GlaxoSmithKline, Mundipharma, Novartis, Sanofi/Regeneron, TEVA and Zambon. R. Faner reports honoraria from AstraZeneca and Chiesi, and research grants from GSK, AstraZeneca and Menarini. I. Pavord reports honoraria from AstraZeneca, Boehringer Ingelheim, Aerocrine, Chiesi, Novartis, Sanofi, Regeneron and GSK; research grants from Boehringer Ingelheim, GSK, AstraZeneca, Chiesi and Napp; participation in a company sponsored bureau with Almirall, AstraZeneca, Boehringer Ingelheim, GSK, MSD, Schering-Plough, Novartis, Dey, Napp, Sanofi and Regeneron. F. Baraldi reports no conflicts. V.M. McDonald reports honoraria from GSK and AstraZeneca; research grants from NHMRC and the Medical Reseach Futures Fund; other support or other potential conflict of interest: committee member for the COPD X guideline committee. M. Thomas reports honoraria from GSK, Boehringer Ingelheim and Chiesi. M. Miravitlles reports honoraria from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Inhibrx, Laboratorios Esteve, Ferrer, Menarini, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols; research grants from Grifols; participation in a company sponsored bureau with AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Kamada, Takeda, Sandoz, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis. N. Roche reports honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Zambon, Novartis, Pfizer, Sanofi, Teva, MSD and Austral; research grants from GSK, Novartis, Pfizer and Boehringer Ingelheim; other support or other potential conflict of interest: GOLD science committee, Respiratory Effectiveness Group, European Respiratory Society. A. Agustí reports honoraria from AstraZeneca, Chiesi, GSK, Menarini, MSD, Sanofi and Zambon; and research grants from AstraZeneca, GSK and Menarini., (Copyright ©The authors 2024.)

Background: The stepwise approach to long-term asthma management, which traditionally incorporates short-acting β 2 -agonist reliever therapy, has been a core feature of asthma guidelines for over 30 years. There have been no studies, however, directly investigating the use of an entire guideline-recommended track. Recently, inhaled corticosteroid-formoterol has been recommended as the preferred reliever therapy in adult asthma, in accordance with a stepwise "Anti-Inflammatory Reliever" (AIR) treatment track., Objective: The aim of this study was to evaluate the AIR stepwise approach recommended by the New Zealand adolescent and adult asthma guidelines, in combination with a novel algorithm for transitioning between treatment steps., Methods: This 52-week, open-label, single-group study will recruit 100 adults aged 18 to 75 years with mild, moderate and moderate-severe asthma (ACTRN12620001010987). Participants will be allocated to budesonide-formoterol 200/6 µg, one actuation as needed (Step 1), one actuation twice daily and as needed (Step 2), or two actuations twice daily and one as needed (Step 3). Treatment steps will be adjusted throughout the study, in response to reliever use and asthma attacks, according to a stepwise AIR algorithm. Following a 26-week period of investigator-led transitions, participants will adjust their own treatment step. The primary outcome is participant satisfaction as measured by the Global Satisfaction score of the Treatment Satisfaction Questionnaire for Medication. Secondary outcomes will assess efficacy and safety, and describe patterns of medication use and participant flow through the treatment steps., Conclusion: This is the first trial to assess the AIR treatment track and algorithm. The results will provide knowledge to guide the clinical use of this approach., Competing Interests: Conflict of interest: M. Holliday reports support for the present manuscript from AstraZeneca (to the Medical Research Institute of New Zealand) for inhaler monitor devices and associated costs and study drugs provided free of charge. Conflict of interest: A. Semprini reports grants or contracts from the Health Research Council of New Zealand, and NZ Pharmacy Education and Research Foundation, outside the submitted work. Conflict of interest: I. Pavord reports support for manuscript writing from GSK and Fishawack Health, outside the submitted work; grants or contracts from Chiesi, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini and GSK; payment for expert testimony from AstraZeneca and Teva; support for attending meetings and/or travel from GSK, Boehringer Ingelheim, AstraZeneca, Teva and Chiesi, outside the submitted work; patents planned, issued or pending for Merck Co. (patent holder of right to Leicester Cough Questionnaire), Bayer and Insmed, outside the submitted work; and participation on a data safety monitoring board or advisory board for Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia and Chiesi, outside the submitted work. Conflict of interest: T. Harrison is an employee of AstraZeneca and owns stock. Conflict of interest: A. Papi reports grants or contracts from Chiesi, AstraZeneca, GSK, Sanofi and Agenzia Italiana del Farmaco, outside the submitted work; consulting fees from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Avillion and Elpen Pharmaceutica, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chiesi, AstraZeneca, GSK, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion and Elpen Pharmaceuticals, outside the submitted work; and participation on advisory boards for Chiesi, AstraZeneca, GSK, MSD, Novartis, Sanofi, Iqvia, Avillion and Elpen Pharmaceuticals, outside the submitted work. Conflict of interest: R. Horne reports royalties or licences from GSK, AstraZeneca, TEVA, Novartis, UCB, Eli Lilly, Sanofi, Pfizer and Gilead, outside the submitted work; consulting fees from AstraZeneca, UCB, Daiichi, Sciencus, Esai and Vertex, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AbbVie, Abbott, Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Biogen, Gilead Sciences, GlaxoSmithKline, Janssen, Merck Sharp Dohme, Merck, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi, Shire, TEVA and UCB, outside the submitted work; participation on advisory boards for AstraZeneca, UCB, Abbott and Novartis, outside the submitted work; and stock or stock options as Founding Director of a UCL-Business company (Spoonful of Sugar Ltd) providing consultancy on treatment engagement and patient support programmes to healthcare policy makers, providers and pharmaceutical industry. Conflict of interest: R. Beasley reports support for the present manuscript form AstraZeneca and the Health Research Council of New Zealand; grants or contracts from AstraZeneca, Genentech and the Health Research Council New Zealand Cure Kids (NZ), outside the submitted work; consulting fees from AstraZeneca, Cipla, Avillion, the Health Research Council New Zealand, CSL Seqirus and Teva Pharmaceuticals, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Cipla, Avillion, the Health Research Council New Zealand, CSL Seqirus and Teva Pharmaceuticals, outside the submitted work; support for attending meetings and/or travel from AstraZeneca, Cipla, Avillion, the Health Research Council New Zealand, CSL Seqirus and Teva Pharmaceuticals, outside the submitted work; participation on a data safety monitoring board or advisory board for AstraZeneca, Cipla, Avillion, the Health Research Council New Zealand, CSL Seqirus and Teva Pharmaceuticals, outside the submitted work; and is Chair for Asthma and Respiratory Foundation NZ adolescent and adult asthma guidelines, a Member of the GOLD Board, and a Consultant for GINA. All other authors have no conflicts to declare., (Copyright ©The authors 2023.)

Exposure to air pollution is a major contributor to the pathogenesis of COPD worldwide. Indeed, most recent estimates suggest that 50% of the total attributable risk of COPD may be related to air pollution. In response, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Scientific Committee performed a comprehensive review on this topic, qualitatively synthesised the evidence to date and proffered recommendations to mitigate the risk. The review found that both gaseous and particulate components of air pollution are likely contributors to COPD. There are no absolutely safe levels of ambient air pollution and the relationship between air pollution levels and respiratory events is supra-linear. Wildfires and extreme weather events such as heat waves, which are becoming more common owing to climate change, are major threats to COPD patients and acutely increase their risk of morbidity and mortality. Exposure to air pollution also impairs lung growth in children and as such may lead to developmental COPD. GOLD recommends strong public health policies around the world to reduce ambient air pollution and for implementation of public warning systems and advisories, including where possible the use of personalised apps, to alert patients when ambient air pollution levels exceed acceptable minimal thresholds. When household particulate content exceeds acceptable thresholds, patients should consider using air cleaners and filters where feasible. Air pollution is a major health threat to patients living with COPD and actions are urgently required to reduce the morbidity and mortality related to poor air quality around the world., Competing Interests: Conflict of interest: There was no external funding for the submitted work. D.D. Sin reports receipt of honorarium from AstraZeneca, GlaxoSmithKline and Boehringer Ingelheim for giving talks on COPD, and participation on an advisory board for an NHLBI-sponsored trial. A. Agusti reports grants from AstraZeneca, GlaxoSmithKline, Menarini, Sanofi and Chiesi, and receipt of consulting fees and honoraria for presentations from AstraZeneca, GlaxoSmithKline, Chiesi, Menarini, Sanofi and Zambon. F.J. Martinez reports grants from AstraZeneca, Chiesi, GlaxoSmithKline and Sanofi/Regeneron, receipt of consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Bering, GlaxoSmithKline, Novartis, Polarean, Pulmonx, Sanofi, Regeneron, Sunovion, Teva, Theravance and UptoDate, honoraria for presentations from AstraZeneca and GlaxoSmithKline, and advisory board participation with MedTronic and GlaxoSmithKline. A. Anzueto reports receipt of consulting fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Viatix/Theravance. B.R. Celli reports receipt of consulting fees from GlaxoSmithKline, AstraZeneca, Axios, Menarini and Sanofi, honoraria for presentations from GlaxoSmithKline, AstraZeneca, Menarini, Chiesi and Regeneron, travel support from GlaxoSmithKline and Sanofi, and advisory board participation for AstraZeneca Therapeutics, Sanofi Aventis and Vertx. D. Halpin reports receipt of honoraria for presentations from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, Sanofi, Berlin-Chemie and Menarini, travel support from Menarini, and advisory board participation with Chiesi, GlaxoSmithKline and Inogen. M.K. Han reports grants from the NIH, Sanofi, Novartis, Nuvaira, Sunovion, Gala Therapeutics, COPD Foundation, AstraZeneca, American Lung Association, Boehringer Ingelheim and Biodesix, consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pulmonox, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, United Therapeutics, Regeneron, Altesa Biopharma and Amgen, honoraria for presentations from Cipla, Chiesi, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Medscape, Integrity and NACE, royalties from UptoDate, Norton Publishing and Penguin Random House, advisory board membership for Novartis and Medtronic, leadership roles with the COPD Foundation (board), COPD Foundation (scientific advisory committee), ALA (advisory committee), American Thoracic Society (journal editor), ALA (volunteer spokesperson), GOLD (scientific committee) and Emerson School Board, Ann Arbor, MI, stock or stock options from Meissa Vaccines and Altesa BioPharma, writing support from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca and Novartis, and other personal fees from Medscape and Integrity. A. Papi reports grants from Chiesi, AstraZeneca, GlaxoSmithKline, Sanofi and Agenzia Italiana del Farmaco (AIFA), receipt of consulting fees from Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Avillion and Elpen Pharmaceuticals, honoraria for presentations from Chiesi, AstraZeneca, GlaxoSmithKline, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion and Elpen Pharmaceuticals, and advisory board participation for Chiesi, AstraZeneca, GlaxoSmithKline, MSD, Novartis, Sanofi, Iqvia, Avillion and Elpen Pharmaceuticals. I. Pavord reports grants from Chiesi, receipt of consulting fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Regeneron, Sanofi, Teva, Circassia, Dey Pharma, Genentech, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, RespiVert and Schering-Plough, and honoraria for presentations from Aerocrine BB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva. N. Roche reports grants from Boehringer Ingelheim, Novartis, GlaxoSmithKline and Pfizer, receipt of consulting fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva and Bayer, and honoraria for presentations from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva, Zambon and MSD. D. Singh reports receipt of consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Bering, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance and Verona, outside of the submitted work. R. Stockley reports receipt of consulting fees from Vertex, CSL Bering and Mereo Biopharma, and data safety monitoring board participation with Syneos. J. Wedzicha reports grants from AstraZeneca, Boehringer, Chiesi, GlaxoSmithKline, Novartis, Genentech and 37Clinical, receipt of consulting fees from AstraZeneca, Epiendo, GlaxoSmithKline, Gilead, Novartis, Pieris and Pulmatrix, honoraria for presentations from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Recipharm and Novartis, and data safety monitoring board participation with Virtus. C. Vogelmeier reports grants from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Grifols and, Novartis, and personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Grifols, Menarini, Novartis, Nuvaira, MedUpdate, Aerogen, Roche, Sanofi and Insmed, outside of the submitted work. J. Bourbeau reports grants from the Canadian Institute of Heath Research (CIHR), Réseau en santé respiratoire du FRQS, McGill University, McGill University Health Centre Foundation, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Grifols, Novartis, Sanofi and Trudell Canada Ltd, and receipt of honoraria from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Trudell and COVIS Pharma for presentations, outside of the submitted work. The remaining authors disclose no potential conflicts of interest., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Competing Interests: Conflict of interest: A. Agustí is Chair of the Board of Directors of GOLD (no payment received), and reports grants or contracts from AZ, GSK, Chiesi and Menarini, consultancy fees from AZ, GSK, Chiesi, Menarini, Zambon, MSD and Sanofi, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AZ, GSK, Chiesi, Menarini and Zambon, outside the submitted work. B.R. Celli reports support for the present work from Chiesi Farmaceutici; grants or contracts from GlaxoSmithKline, AstraZeneca, Menarini, Sanofi Aventis and Axios, consultancy fees from GlaxoSmithKline, AstraZeneca and Sanofi Aventis, payment or honoraria for lectures, presentations, manuscript writing or educational events from GlaxoSmithKline, AstraZeneca, Menarini, Chiesi and Regeneron, support for attending meetings and/or travel from GlaxoSmithKline and Sanofi Aventis, and participation on a data safety monitoring board or advisory board for AZ Therapeutics, Sanofi Aventis and Vertex, outside the submitted work. G.J. Criner reports support for the present work from GlaxoSmithKline; grants or contracts from ALung Technologies Inc., American College of Radiology, American Lung Association, AstraZeneca, BioScale Inc., Boehringer Ingelheim, BREATH Therapeutics Inc., COPD Foundation, Coridea/ZIDAN, Corvus, Dr Karen Burns of St Michael's Hospital, Fisher & Paykel Healthcare Ltd, Galapagos NV, GlaxoSmithKline, Kinevent, Lungpacer Medical Inc., National Heart, Lung, and Blood Institute, Nurvaira Inc., Patient-Centered Outcomes Research Institute, Pulmonary Fibrosis Foundation, PulmonX, Respironics Inc., Respivant Sciences, Spiration Inc., Steward St Elizabeth's Medical Center of Boston Inc. and Veracyte Inc., and personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Broncus Medical, CSA Medical, EOLO Medical, Gala Therapeutics, GlaxoSmithKline, Helios Medical, Ion, Merck, Medtronic, Mereo BioPharma, NGM Biopharmaceuticals, Novartis, Olympus, PulmonX, Respironics Inc., Respivant Sciences, The Implementation Group and Verona Pharma, outside the submitted work. D. Halpin reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Pfizer, Sanofi and Menarini, support for attending meetings and/or travel from Menarini, and participation on a data safety monitoring board or advisory board with Chiesi, outside the submitted work. A. Anzueto reports consultancy fees from GlaxoSmithKline, AstraZeneca and Boehringer Ingelheim, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Viatrix Pharma, outside the submitted work. P. Barnes reports grants or contracts from AstraZeneca and Boehringer Ingelheim, consultancy fees from AstraZeneca, Boehringer Ingelheim, Novartis, Teva and Epi-Endo, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Novartis and Teva, outside the submitted work. J. Bourbeau reports grants or contracts from Canadian Institute of Heath Research (CIHR), Réseau en santé respiratoire du FRQS, McGill University, McGill University Health Centre Foundation, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Grifols, Novartis, Sanofi and Trudell Canada Ltd, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca Canada Ltd, COVIS Pharma Canada Ltd, GlaxoSmithKline Canada Ltd, Pfizer Canada Ltd and Trudell Canada Ltd, outside the submitted work. M.K. Han reports grants or contracts from NIH, Sanofi, Novartis, Nuvaira, Sunovion, Gala Therapeutics, COPD Foundation, AstraZeneca, American Lung Association, Boehringer Ingelheim and Biodesix, royalties or licences from Uptodate, Norton Publishing and Penguin Random House, consultancy fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, United Therapeutics, Regeneron, Altesa BioPharma and Amgen, payment or honoraria for lectures, presentations, manuscript writing or educational events from Cipla, Chiesi, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Medscape, Integrity and NACE, participation on a data safety monitoring board or advisory board with Novartis and Medtronic, leadership or fiduciary roles with COPD Foundation, COPD Foundation Scientific Advisory Committee, ALA advisory committee, American Thoracic Society (journal editor), ALA (volunteer spokesperson), GOLD scientific committee and Emerson School Board, stock or stock options with Meissa Vaccines and Altesa BioPharma, receipt of equipment, materials, drugs, medical writing, gifts or other services from GSK, Boehringer Ingelheim, AstraZeneca and Novartis, and personal fees from Medscape and Integrity, outside the submitted work. F.J. Martinez reports grants or contracts from AstraZeneca, Chiesi, GSK and Sanofi/Regeneron, consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Novartis, Polarean, Pulmonx, Sanofi/Regeneron, Sunovion, Teva, Theravance/Viatris and UpToDate, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and AstraZeneca, and participation on a data safety monitoring board or advisory board for MedTronic and GSK, outside the submitted work. M. Montes de Oca reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GlaxoSmithKline and AstraZeneca, outside the submitted work. K. Mortimer has contributed to advisory boards for AstraZeneca and GlaxoSmithKline, outside the submitted work. A. Papi reports grants or contracts from Chiesi, AstraZeneca, GSK, Sanofi and Agenzia Italiana del Farmaco (AIFA), consultancy fees from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Avillion and Elpen Pharmaceuticals, payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi, AstraZeneca, GSK, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion and Elpen Pharmaceuticals, and participation on a data safety monitoring board or advisory board for Chiesi, AstraZeneca, GSK, MSD, Novartis, Sanofi, Iqvia, Avillion and Elpen Pharmaceuticals, outside the submitted work. I. Pavord reports speaker fees from Aerocrine AB, speaker and consultancy fees from Almirall and Novartis, speaker fees, payments for organization of educational events, consultancy fees and international scientific meeting sponsorship from AstraZeneca, GSK, Regeneron Pharmaceuticals, Inc., Sanofi and Teva, speaker fees, consultancy fees and international scientific meeting sponsorship from Boehringer Ingelheim, speaker fees, consultancy fees, research grants and international scientific meeting sponsorship from Chiesi, consultancy fees from Circassia, Dey Pharma, Genentech, Knopp Biosciences, Merck, MSD, RespiVert and Schering-Plough, and consultancy fees and international scientific meeting sponsorship from Napp Pharmaceuticals, outside the submitted work. N. Roche reports grants or contracts from Boehringer Ingelheim, Novartis, GSK and Pfizer, consultancy fees from Boehringer Ingelheim, GSK, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva and Bayer, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, GSK, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva, Zambon and MSD, outside the submitted work. D.D. Sin reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim and GSK, outside the submitted work. D. Singh reports consultancy fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance and Verona, outside the submitted work. R. Stockley reports consultancy fees from CSL Behring and Mereo Biopharma, and participation on a data safety monitoring board or advisory board for Kamada and Syneos, outside the submitted work. J.A. Wedzicha reports grants or contracts from AstraZeneca, Boehringer, Chiesi, GSK, Novartis, Genentech and 37Clinical, consultancy fees from AstraZeneca, Epiendo, GSK, Gilead, Novartis, Pieris and Pulmatrix, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GSK, Boehringer, Recipharm and Novartis, and participation on a data safety monitoring board or advisory board for Virtus, outside the submitted work. C.F. Vogelmeier reports grants or contracts from German Ministry of Education and Science (BMBF), AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols and Novartis, consultancy fees from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini, Novartis and Nuvaira, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini, Novartis, Roche and Sanofi, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose.

Background: Many patients with asthma experience loss of lung function over time, and in certain patients this can lead to progressive obstructive patterns similar to COPD. Patients with severe asthma may experience accelerated lung function decline (LFD). However, characteristics and risk factors for LFD in asthma have not been well described. Dupilumab may prevent or slow the rate of LFD in patients with uncontrolled, moderate-to-severe asthma. ATLAS trial is designed to evaluate the role of dupilumab in preventing/slowing LFD over a period of 3 years versus standard-of-care therapy., Methods: ATLAS (clinicaltrials.gov identifier NCT05097287) is a randomised, double-blind, placebo-controlled, multicentre study that will include adult patients with uncontrolled moderate-to-severe asthma. ∼1828 patients will be randomised (2:1) to dupilumab 300 mg or placebo in combination with maintenance therapy every 2 weeks for 3 years. The primary objective is to assess the effect of dupilumab on preventing or slowing LFD by year 1 in the exhaled nitric oxide fraction ( F eNO ) population (patients with F eNO ≥35 ppb). The effect of dupilumab in slowing the rate of LFD by year 2 and year 3 in both F eNO and total populations, exacerbations, asthma control, quality of life, biomarker changes and utility of F eNO as a biomarker of LFD will also be evaluated., Discussion: ATLAS is the first trial assessing the effect of a biologic on LFD, designed to establish the role of dupilumab in prevention of long-term loss of lung function and its potential effect on disease modification, which may provide unique insights into asthma pathophysiology, including predictive and prognostic factors of LFD., Competing Interests: Conflict of interest: L. De Prado Gomez, M. Zhang, J. Xing, J.A. Jacob-Nara and P.J. Rowe are employees of Sanofi, and may hold stock and/or stock options in the company. I. Pavord has received speaker fees from Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Sanofi/Regeneron and Teva; payments for organising educational events from AstraZeneca, GSK, Sanofi/Regeneron and Teva; consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Genentech, GSK, Knopp Biosciences, Merck, Novartis, Sanofi/Regeneron and Teva; international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Teva; a research grant from Chiesi; and payments to support Food and Drug Administration approval meetings from GSK; payments for use of the Leicester Cough Questionnaire (of which he is a co-patent holder of the rights) in clinical trials from Bayer, Insmed and Merck. He served as an expert witness for a patent dispute involving AstraZeneca and Teva. W. Busse has received consultancy and speaker fees from GlaxoSmithKline, Novartis, Sanofi and Teva. C.E. Brightling has received grants and consultancy fees from GSK, AstraZeneca, Novartis, Chiesi, BI, Genentech, Roche, Sanofi, Regeneron, Mologic and 4DPharma, paid to his institution. M.E. Wechsler has received consulting fees and honoraria from AstraZeneca, Amgen, GlaxoSmithKline, Sanofi, Regeneron, Boehringer Ingelheim, Novartis, Genentech, Pulmatrix, Teva, Equillium, Cytoreason, Restorbio, Cohero Health, Cerecor, Incyte, Sound Biologics and Kinaset. K.F. Rabe has received consultancy and speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Sanofi and Teva., (Copyright ©The authors 2023.)

Introduction: Objective cough frequency is a key clinical end-point but existing wearable monitors are limited to 24-h recordings. Albus Home uses contactless motion, acoustic and environmental sensors to monitor multiple metrics, including respiratory rate and cough without encroaching on patient lifestyle. The aim of this study was to evaluate measurement characteristics of nocturnal cough monitoring by Albus Home compared to manual counts., Methods: Adults with respiratory conditions underwent overnight monitoring using Albus Home in their usual bedroom environments. Participants set-up the plug-and-play device themselves. For reference counts, each audio recording was counted by two annotators, and cough defined as explosive phases audio-visually labelled by both. In parallel, recordings were processed by a proprietary Albus system, comprising a deep-learning algorithm with a human screening step for verifying or excluding occasional events that mimic cough. Performance of the Albus system in detecting individual cough events and reporting hourly cough counts was compared against reference counts., Results: 30 nights from 10 subjects comprised 375 hours of recording. Mean±sd coughs per night were 90±76. Coughs per hour ranged from 0 to 129. Albus counts were accurate across hours with high and low cough frequencies, with median sensitivity, specificity, positive predictive value and negative predictive values of 94.8, 100.0, 99.1 and 100.0%, respectively. Agreement between Albus and reference was strong (intra-class correlation coefficient (ICC) 0.99; 95% CI 0.99-0.99; p<0.001) and equivalent to agreement between observers and reference counts (ICC 0.98 and 0.99, respectively)., Conclusions: Albus Home provides a unique, contactless and accurate system for cough monitoring, enabling collection of high-quality and potentially clinically relevant longitudinal data., Competing Interests: Conflict of interest: W. Do is a co-founding shareholder and director of Albus Health. R. Russell is a scientific advisor and minority shareholder of Albus Health; and reports grants from AstraZeneca, and personal fees from Boehringer Ingelheim, Chiesi UK and GlaxoSmithKline, outside the submitted work. C. Wheeler, H. Javed, C. Dogan, G. Cunningham and V. Khanna were employees of Albus Health during the conduct of the study. M. De Vos reports consulting fees and minority shareholding from Albus Health; and reports grants from J&J/Janssen and public government outside the submitted work. I. Satia reports grants from Merck, GSK, Bellus and Bayer, personal speaker and consulting fees from GSK, AstraZeneca, Merck, Genentech and Respiplus outside the submitted work, and is an associate editor of this journal. M. Bafadhel is a scientific advisor and minority shareholder of Albus Health, reports grants from AstraZeneca, personal fees from AstraZeneca, Chiesi, and GlaxoSmithKline, and is a scientific advisor of ProAxsis, outside of submitted work. I. Pavord has received speaker's honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine AB, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini and GSK, and payments for organising educational events from AstraZeneca, GSK, Sanofi/Regeneron, and Teva; has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi and Knopp, and payments to support FDA approval meetings from GSK; has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva and Chiesi; has received grants from Chiesi and Sanofi Genzyme; and is co-patent holder of the rights to the Leicester Cough Questionnaire and has received payments for its use in clinical trials from Merck, Bayer and Insmed, outside the submitted work., (Copyright ©The authors or their employers 2022.)

Inhaled corticosteroids (ICS) combined with bronchodilators can reduce the frequency of exacerbations in some patients with chronic obstructive pulmonary disease (COPD). There is evidence, however, that ICS are frequently used in patients where their benefit has not been established. Therefore, there is a need for a personalised approach to the use of ICS in COPD and to consider withdrawal of ICS in patients without a clear indication. This document reports European Respiratory Society recommendations regarding ICS withdrawal in patients with COPD.Comprehensive evidence synthesis was performed to summarise all available evidence relevant to the question: should ICS be withdrawn in patients with COPD? The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence synthesis was discussed and recommendations formulated by a committee with expertise in COPD and guideline methodology.After considering the balance of desirable and undesirable consequences, quality of evidence, and feasibility and acceptability of interventions, the guideline panel made: 1) conditional recommendation for the withdrawal of ICS in patients with COPD without a history of frequent exacerbations, 2) strong recommendation not to withdraw ICS in patients with blood eosinophil counts ≥300 eosinophils·µL -1 and 3) strong recommendation to treat with one or two long-acting bronchodilators if ICS are withdrawn.A conditional recommendation indicates that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention., Competing Interests: Conflict of interest: J.D. Chalmers has received speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Insmed; consultancy fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Insmed and Zambon; and holds research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences Grifols and Novartis. Conflict of interest: I.F. Laska has nothing to disclose. Conflict of interest: F.M.E. Franssen reports research grants from AstraZeneca and Novartis and fees for consultancy from Boehringer Ingelheim, Chiesi, GSK and Teva. Conflict of interest: W. Janssens reports grants, speakers’ and consultancy fees from Chiesi, AstraZeneca, Boehringer and GSK, outside the submitted work. Conflict of interest: I. Pavord reports fees for consultancy from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, GSK, Genentech, Regeneron, Teva, Chiesi, Sanofi, Cricassia, and Knopp, grants from the National Institute for Health Research. Conflict of interest: D. Rigau is methodologist of the European Respiratory Society. Conflict of interest: M.J. McDonnell reports personal fees from Boehringer Ingelheim and Menarini, grants from Health Research Board Ireland, outside the submitted work. Conflict of interest: N. Roche reports grants and personal fees from Boehringer Ingelheim, Novartis and Pfizer, and personal fees from Teva, GSK, AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, 3M, Trudell and Zambon. Conflict of interest: D.D. Sin has received research funding from AstraZeneca and Merck, has received honoraria for speaking engagements from Novartis, Boehringer Ingelheim and AstraZeneca, and fees for advisory board work from Sanofi-Aventis and Regeneron. Conflict of interest: D. Stolz reports research grants from AstraZeneca, Curetis and Boston Scientific, and fees for consultancy from AstraZeneca, Novartis, GSK, Roche, Zambon, Pfizer and Schwabe Pharma. Conflict of interest: S. Suissa reports grants and personal fees from Novartis and Boehringer Ingelheim, and personal fees from AstraZeneca, outside the submitted work. Conflict of interest: J. Wedzicha has received research grants from GlaxoSmithKline, Boehringer Ingelheim, Novartis, AstraZeneca, Chiesi and Johnson & Johnson. D. Stolz reports research grants from AstraZeneca, Curetis and Boston Scientific, and fees for consultancy from AstraZeneca, Novartis, GSK, Roche, Zambon, Pfizer and Schwabe Pharma. Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Teva, pH Pharma, Novartis, Sanofi and Grifols, and research grants from GlaxoSmithKline and Grifols., (Copyright ©ERS 2020.)

The European Respiratory Biologics Forum gathered participants from 21 countries in Madrid, Spain, to discuss the management and treatment of severe asthma in the era of biologics. The current insights on the pathophysiology of severe asthma were discussed, as well as the role of respiratory biologics in clinical practice and strategies for eliminating chronic use of oral corticosteroids. The participants also highlighted the key challenges in identifying patients with severe asthma based on phenotypes, biomarkers and treatable traits, and the existing problems in patient referral to specialist care. The monitoring of treatment was debated and the need for a change towards precision medicine and personalised care was emphasised throughout the meeting. This review provides a summary of the discussions and highlights important concerns identified by the participants regarding the current management of severe asthma., Competing Interests: Conflict of interest: I. Pavord reports personal fees (speaker's honoraria, travel expenses and honoraria for attending advisory boards) from AstraZeneca, GSK, Boehringer Ingelheim and Teva, personal fees (speaker fees, fees for advisory boards and travel expenses for attending international meetings) from Chiesi, personal fees for advisory boards from Sanofi/Regeneron, Merck, Novartis, Knopp, Afferent and Roche/Genentech, and personal speaker fees from Circassia and Mundipharma, as well as research grants from Chiesi and Afferent, all outside the submitted work. Conflict of interest: T. Bahmer reports personal fees and other support (including compensation for travel expenses) from Chiesi, AstraZeneca, Roche, GlaxoSmithKline and Novartis, outside the submitted work. Conflict of interest: F. Braido reports personal fees (speaker's honoraria and travel expenses) from AstraZeneca, outside the submitted work. Conflict of interest: B.G. Cosío reports personal fees from AstraZeneca during the conduct of the study; as well as personal fees from AstraZeneca, Teva and Mundipharma, and grants and personal fees from Chiesi, Boehringer Ingelheim, Menarini and Novartis, outside the submitted work. Conflict of interest: M. Humbert reports personal fees from AstraZeneca, GSK, Novartis, Roche, Sanofi and Teva, during the conduct of the study. Conflict of interest: M. Idzko has nothing to disclose. Conflict of interest: L. Adamek is an employee of AstraZeneca., (Copyright ©ERS 2019.)

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY aims to recruit real-world patients, unlike clinical studies with restrictive inclusion/exclusion criteria. Data collected at yearly intervals include clinical assessments, spirometry, biospecimens, patient-reported outcomes (PROs) and healthcare utilisation (HCU). PROs and HCU will also be collected 3-monthly via internet/telephone. Data will be used to identify phenotypes and endotypes associated with different trajectories for symptom burden, clinical progression or remission and HCU. Results may allow patient classification across obstructive lung disease by clinical outcomes and biomarker profile, rather than by conventional diagnostic labels and severity categories. NOVELTY will provide a rich data source on obstructive lung disease, to help improve patient outcomes and aid novel drug development., Competing Interests: Conflict of interest: H.K. Reddel reports that this study is funded by AstraZeneca. She received reimbursement from AstraZeneca for time spent working on the study design but not for manuscript preparation. Medical writing support was provided by AstraZeneca, as stated in the support statement. She has served on a data and safety monitoring board (DSMB) and advisory boards, and has received unconditional research grants and honoraria from AstraZeneca and GlaxoSmithKline for providing independent medical education, consulting and studying inhalers. She has served on a DSMB for Merck. She has served on a DSMB and an advisory board for, and received an honorarium from Novartis for providing independent medical education. She has received honoraria from Teva and Mundipharma for providing independent medical education. She has received an honorarium from Boehringer Ingelheim for providing independent medical education from and serving on an advisory board. Conflict of interest: M. Gerhardsson de Verdier is an employee of AstraZeneca. Conflict of interest: A. Agustí reports receiving personal fees from AstraZeneca during the conduct of the study; and grants and personal fees from AstraZeneca and Menarini, and personal fees from Chiesi, Teva and Novartis, outside the submitted work. Conflict of interest: G. Anderson has received honoraria from and serves on an advisory board for Novartis; has received honoraria from, serves on an advisory board for and was employed on a sabbatical basis from 2016 to 2017 by AstraZeneca; and has received honoraria and serves on advisory boards for GlaxoSmithKline, Pieris Pharmaceuticals and Boehringer Ingelheim. Conflict of interest: R. Beasley reports receiving personal fees from Astra Zeneca during the conduct of the study; and grants and personal fees from AstraZeneca, GlaxoSmithKline and the Health Research Council of New Zealand, and grants from Genentech, outside the submitted work. Conflict of interest: E.H. Bel reports receiving grants and personal fees from Novartis, GSK and AstraZeneca, grants from Roche, personal fees from Sanofi Regeneron, Teva, Vectura and Boehringer, outside the submitted work. Conflict of interest: C. Janson reports receiving personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Teva, outside the submitted work. Conflict of interest: Related to the topic of COPD, B. Make reports funding from the NHLBI for the COPDGene study; grants and personal fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and Sunovian; personal fees for DSMB from Spiration and Baxalta; CME personal fees from Consensus Medical Education, Integrity Medical Education, WebMD, National Jewish Health, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, SPIRE Learning, Peer Review Institute, and Medscape; personal fees and other from Mt. Sinai Medical Center; royalties from Up-To-Date; personal fees from Novartis; personal fees from CSL Bering; other from Cleveland Clinic; grants from Pearl (a member of the AstraZeneca Group); and personal fees from Verona, outside the submitted work. Conflict of interest: R.J. Martin reports receiving personal fees from AstraZeneca for service on a steering committee during the conduct of the study; and travel fees from Respiratory Effectiveness Group, consultancy fees from PMD Healthcare, and grants from MedImmune, Chiesi Farmaceutici SpA and NHLBI, outside the submitted work. Conflict of interest: I. Pavord reports receiving speaker fees, advisory board honoraria and sponsorship to attend scientific meetings from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, a speaker fee from Aerocrine, speaker fees and advisory board honoraria from Almirall and Novartis, advisory board honoraria from Genentech, Regeneron, Merck & Co., Schering-Plough and Mylan Speciality (Dey Pharma) and Respivert, advisory board honoraria and sponsorship to attend scientific meetings from Napp Pharmaceuticals, outside the submitted work. Conflict of interest: D. Price reports receiving funding from AstraZeneca for the conduct of this study; and board membership (fees paid to Observational and Pragmatic Research Institute) from Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals, consultancy agreements (fees paid to Observational and Pragmatic Research Institute) with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance, grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute) from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Mylan, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Teva Pharmaceuticals, Theravance, UK National Health Service and Zentiva, lectures/speaking engagements (fees paid to Observational and Pragmatic Research Institute) for Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, CIPLA, GlaxoSmithKline, Kyorin, Mylan, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, and Teva Pharmaceuticals, manuscript preparation (fees paid to Observational and Pragmatic Research Institute) from Mundipharma and Teva Pharmaceuticals, payment for travel/accommodation/meeting expenses (fees paid to Observational and Pragmatic Research Institute) from Aerocrine, AstraZeneca, Boehringer Ingelheim, Mundipharma, Napp, Novartis and Teva Pharmaceuticals, funding for patient enrolment or completion of research (fees paid to Observational and Pragmatic Research Institute) from Chiesi, Novartis, Teva Pharmaceuticals and Zentiva, payment for the development of educational materials (fees paid to Observational and Pragmatic Research Institute) from Mundipharma and Novartis, peer review for grant committees for the Efficacy and Mechanism Evaluation programme and Health Technology Assessment, outside the submitted work; and stock/stock options in AKL Research and Development Ltd, which produces phytopharmaceuticals. He owns 74% of the social enterprise Optimum Patient Care Ltd (Australia, Singapore and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore). Conflict of interest: C. Keen is an employee of AstraZeneca. Conflict of interest: A. Gardev is an employee of AstraZeneca. Conflict of interest: S. Rennard is an employee of AstraZeneca and retains professorship and a part-time appointment at the University of Nebraska Medical Center, Omaha, NE, USA. He reports personal fees from ABIM, Able Associates, Advantage Healthcare, Align2Action, Almirall, APT, ATS, AstraZeneca, Baxter, Boehringer Ingelheim, Cheisi, CIPLA, ClearView Healthcare, the Cleveland Clinic, CME Incite, Complete Medical Group, the COPD Foundation, Cory Paeth, CSA, CSL, CTS Carmel, Dailchi Sankyo, Decision Resources, the Dunn Group, Easton Associates, Elevation Pharma, FirstWord, Forest, the Frankel Group, Gerson, GlaxoSmithKline, Gilead, Grifols, GroupH, Guidepoint Global, Haymarket, HealthStar, Huron Cosulting, Incite, Inthought, IntraMed (Forest), Johnson & Johnson, LEK, McKinsey, Medical Knowledge, MedImmune, the Methodist Health System (Dallas, TX, USA), Navigant, NCI Consulting, Novartis, Nuvis, Pearl (a member of the AstraZeneca Group), Penn Technology, Pfizer, PlanningShop, Prescott, Pro Ed Comm, ProiMed, PSL FirstWord, Pulmatrix, Quadrant, Qwessential, Regeneron, Saatchi and Saatchi, Schlesinger Associates, Strategic North, Synapse, Takeda, Theron, WebMD, NHLBI, the Nebraska DHHS, Otsuka, Pfizer, GlaxoSmithKline, Boehringer Ingelheim, Nycomed, AstraZeneca, Centocor, and Almirall, outside the submitted work. Please note that he has had tobacco industry funding. Specifically, he has received funding from the tobacco industry for studies relating to harm reduction and to the impact of tobacco smoke on stem cells. He has also consulted with R.J. Reynolds, without personal fees, on the topic of harm reduction. He received funding from R.J. Reynolds to evaluate the effect of a harm reduction product in normal smokers (1996) and in subjects with chronic bronchitis (1999) and to assess the effect of smoking cessation on lower respiratory tract inflammation (2000); he participated in a Philip Morris multicentre study to assess biomarkers of smoke exposure (2002); he received funding for a clinical trial from the Institute for Science and Health (2005), which receives support from the tobacco industry, to evaluate biomarkers in exhaled breath associated with smoking cessation and reduction. This study was supplemented with funding from Lorillard and R.J. Reynolds. He has received a grant from the Philip Morris External Research Program (2005) to assess the impact of cigarette smoking on circulating stem cells in the mouse. He has consulted with R.J. Reynolds on the topic of harm reduction until 2007 but did not receive personal remuneration for this. He has no active tobacco industry-funded projects. All ties with tobacco industry companies and entities supported by tobacco companies were terminated in 2007. Conflict of interest: A. Sveréus is an employee of AstraZeneca. Conflict of interest: A.T. Bansal has nothing to disclose. Conflict of interest: L. Brannman is an employee of AstraZeneca. Conflict of interest: N. Karlsson is an employee of AstraZeneca. Conflict of interest: J. Nuevo is an employee of AstraZeneca. Conflict of interest: F. Nyberg is an employee of AstraZeneca. Conflict of interest: S.S. Young is an employee of AstraZeneca. Conflict of interest: J. Vestbo reports receiving an honorarium from AstraZeneca for being a co-principal investigator of the NOVELTY study; and personal fees from GlaxoSmithKline for consultancy for COPD Phase 2 and 3 programme, personal fees from Chiesi Pharmaceuticals, Boeehringer Ingelheim, Novartis and AstraZeneca for consultancy for COPD Phase 2 and 3 programme and payment for lectures including service in speaker bureaus, outside the submitted work.

Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting β2-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10 000 patients from approximately 1070 centres. Eligible patients are aged ≥40 years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12 months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017., (Copyright ©ERS 2016.)

The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults.13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed.Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63-1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43-1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of -0.24 (95% CI -0.56-0.07). No statistically significant differences for health-related quality of life or asthma control were found.FeNO guided management showed no statistically significant benefit in terms of severe exacerbations or inhaled corticosteroid use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most., (Copyright ©ERS 2016.)

This randomised double-blind placebo-controlled parallel-group multicentre phase IIa study evaluated the effect of the CXCR2 antagonist AZD5069 on sputum neutrophil counts in adults with bronchiectasis.Patients were randomised 1:1 to receive AZD5069 80 mg or placebo orally twice daily for 28 days. Assessments included blood cell counts, inflammatory markers in blood, morning spontaneous sputum, lung function, safety and tolerability and patients completed daily BronkoTest diary cards. The primary outcome measure was the change in absolute sputum neutrophil count.Of 52 randomised patients, 45 completed treatment, 20 (76.9%) out of 26 receiving AZD5069 and 25 (96.2%) out of 26 receiving placebo. AZD5069 reduced the absolute neutrophil cell count in morning sputum by 69% versus placebo (p=0.004); percentage sputum neutrophil count was reduced by 36% (p=0.008). The number of infections/exacerbations was similar with AZD5069 and placebo (nine versus eight), but these led to more study discontinuations with AZD5069 (four versus zero). Sputum interleukin (IL)-6 and growth-regulated oncogene (GRO)-α and serum GRO-α, IL-1ß and IL-8 levels increased with AZD5069 versus placebo (all p<0.001), while serum high-sensitivity C-reactive protein levels did not change. AZD5069 was well tolerated.AZD5069 markedly reduced absolute sputum neutrophil counts in bronchiectasis patients, although this was not associated with improvements in clinical outcomes in this exploratory study., (Copyright ©ERS 2015.)

This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR) and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases., (Copyright ©ERS 2015.)

The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence., (Copyright ©ERS 2015.)

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Increased tumour necrosis factor-α levels have been observed in bronchial biopsies and induced sputum from subjects with severe asthma. We investigated etanercept (ETN) as a therapeutic option for treating moderate-to-severe persistent asthma. In this 12-week, randomised, double-blind, placebo-controlled, phase 2 trial, subjects (n=132) with moderate-to-severe persistent asthma received subcutaneous injections of 25 mg ETN or placebo twice weekly, and were evaluated at baseline, and at weeks 2, 4, 8 and 12. The primary end-point was the change from baseline to week 12 in pre-bronchodilator forced expiratory volume in 1 s (FEV1)% predicted. Secondary end-points included morning peak expiratory flow, FEV1% pred, Asthma Control Questionnaire (5-item version), asthma exacerbations, provocative concentration of methacholine causing a 20% decrease in FEV1, and the Asthma Quality of Life Questionnaire. No significant differences were observed between ETN and placebo for any of the efficacy end-points. ETN treatment was well tolerated, with no unexpected safety findings observed during the study. Clinical efficacy of ETN was not shown in subjects with moderate-to-severe persistent asthma over 12 weeks. However, ETN treatment was a well-tolerated therapy. Studies in specific subsets of patients with asthma with longer-term follow-up may be needed to fully evaluate the clinical efficacy of ETN in this population.

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.

Chronic cough is a common condition that presents to both primary and secondary care. Assessment and management are hampered by the absence of well-validated outcome measures. The present study comprises the validation of the Leicester Cough Monitor (LCM), an automated sound-based ambulatory cough monitor. Cough frequency was measured with the LCM and compared with coughs and other sounds counted manually over 2 h of a 6-h recording by two observers in nine patients with chronic cough in order to determine the sensitivity and specificity of the LCM. Automated cough frequency was also compared with manual counts from one observer in 15 patients with chronic cough and eight healthy subjects. All subjects underwent 6-h recordings. A subgroup consisting of six control and five patients with stable chronic cough underwent repeat automated measurements > or = 3 months apart. A further 50 patients with chronic cough underwent 24-h automated cough monitoring. The LCM had a sensitivity and specificity of 91 and 99%, respectively, for detecting cough and a false-positive rate of 2.5 events x h(-1). Mean+/-SEM automated cough counts x patient x h(-1) was 48+/-9 in patients with chronic cough and 2+/-1 in the control group (mean difference 46 counts x patient x h(-1); 95% confidence interval (CI) 20-71). The automated cough counts were repeatable (intra-subject SD 11.4 coughs x patient x h(-1); intra-class correlation coefficient 0.9). The cough frequency in patients undergoing 24-h automated monitoring was 19 coughs x patient x h(-1); daytime (08:00-22:00 h) cough frequency was significantly greater than overnight cough frequency (25 versus 10 coughs x patient x h(-1); mean difference 15 coughs x patient x h(-1), 95% CI 8-22). The Leicester Cough Monitor is a valid and reliable tool that can be used to assess 24-h cough frequency in patients with cough. It should be a useful tool to assess patients with cough in clinical trials and longitudinal studies.

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV(1)) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD. A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed. Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-alpha. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV(1) (% predicted), forced vital capacity (FVC) and FEV(1)/FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed. It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.

Evidence suggests that eosinophilic airway inflammation is important in the pathogenesis of severe chronic obstructive pulmonary disease (COPD) exacerbations. The present authors tested the hypothesis that a management strategy that aims to reduce sputum eosinophil counts is associated with a reduction in exacerbations of COPD. A total of 82 patients with COPD were randomised into two groups. One group was treated according to traditional guidelines (British Thoracic Society (BTS) group) and the other (sputum group) was treated with the additional aim of minimising eosinophilic airway inflammation, assessed using the induced sputum eosinophil count. The primary outcome was exacerbations, which were categorised as mild, moderate or severe. The frequency of severe exacerbations per patient per year was 0.5 and 0.2 in the BTS and sputum groups, respectively (mean reduction 62%). The majority of this benefit was confined to patients with eosinophilic airway inflammation. There was no difference in the frequency of mild and moderate exacerbations. The average daily dose of inhaled or oral corticosteroids during the trial did not differ between the groups. Out of 42 patients in the sputum group, 17 required regular oral corticosteroids to minimise eosinophilic airway inflammation. A management strategy that aims to minimise eosinophilic airway inflammation, as well as symptoms, is associated with a reduction in severe exacerbations of chronic obstructive pulmonary disease.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.

Refractory or difficult-to-control asthma is associated with some clinical and pathological features normally associated with chronic obstructive pulmonary disease (COPD), raising the possibility that there are similarities in their pathogenesis. It is suggested that the coexistence of two or more inflammatory stimuli to the airway (multiple hits) is a key factor leading to the development of more severe airway disease. Airway inflammation in response to chronic inflammatory conditions elsewhere may be a particularly important additional inflammatory stimulus. The "multiple hit" hypothesis for the origins of severe airway disease has important implications for treatment and prevention, since identification and removal of additional inflammatory stimuli may delay progression of the underlying airway disease.

There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (i.e. 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.

Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation. The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration. Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mild-to-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone. In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

Tonsillar enlargement is sometimes seen in patients with otherwise unexplained chronic cough although its significance is unclear. In this study, the authors set out to test the hypothesis that cough symptoms and cough reflex sensitivity will improve after tonsillectomy in patients with otherwise unexplained chronic cough and enlarged tonsils. Eight consecutive patients with unexplained chronic cough and enlarged tonsils were recruited from 236 patients seen in a cough clinic between 2000 and 2001. Six patients with enlarged tonsils and no cough who were undergoing tonsillectomy for other reasons were recruited as a control group. All patients rated cough severity on a cough visual analogue score (0-100 mm) and had capsaicin cough reflex sensitivity measurement twice before and again 3 months after tonsillectomy. Patients with a chronic cough had heightened cough reflex sensitivity compared with the control group at baseline. There was a significant improvement in mean cough visual analogue score 3 months after tonsillectomy in patients with chronic cough (mean difference 30 mm; 95% confidence interval of difference 8-51 mm). The geometric mean concentration of capsaicin required to cause five coughs increased from 4 to 207 micromol L(-1) after tonsillectomy in patients with chronic cough (mean difference from baseline 5.6 doubling concentrations; 95% confidence interval of difference 3.1-8.2). There was no change in cough reflex sensitivity in control patients after tonsillectomy. These preliminary findings suggest for the first time a possible role for tonsillectomy in patients with enlarged tonsils in whom other causes of cough have been ruled out.