Search

Background: In asthma, clinical response is characterized by disease improvement with treatment, whereas clinical remission is characterized by long-term disease stabilization with or without ongoing treatment. The proportion of patients receiving tezepelumab who responded to treatment and those who achieved on-treatment clinical remission was assessed in the NAVIGATOR (NCT03347279) and DESTINATION (NCT03706079) studies of severe, uncontrolled asthma., Methods: NAVIGATOR and DESTINATION were phase 3, randomized, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR. Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV 1 ) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physicians' assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV 1 >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed., Results: Higher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0-52 (46% versus 24%; OR: 2.83 [95% CI: 2.10-3.82]), and on-treatment clinical remission over weeks 0-52 (28.5% versus 21.9%; OR: 1.44 [95% CI: 0.95-2.19]) and weeks >52-104 (33.5% versus 26.7%; OR: 1.44 [95% CI: 0.97-2.14]). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarkers at baseline, and fewer exacerbations in the 12 months before the study., Conclusions: Among patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes but may be driven by different patient characteristics., (Copyright ©The authors 2024.)

Background: Pivotal phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection., Methods: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps)., Results: Out of 1002 patients analysed, 380 were biologic-experienced. At week 48, 71.3% were exacerbation-free ( versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130 out of 274) eliminated their use by week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed., Conclusion: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice., Competing Interests: Conflict of interest: D.J. Jackson has received consultancy fees and speakers’ fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Sanofi Regeneron, and research grants from AstraZeneca. G. Pelaia has received lecture fees and advisory board fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Guidotti, Insmed, Lusofarmaco, Menarini, Neopharmed Gentili, Novartis, Sanofi and Zambon. B. Emmanuel, T.N. Tran, D. Cohen, V.H. Shih, A. Shavit, M. Watt, S. Kayaniyil, M. Pardal, D. Arbetter and A.P.J. Rabe are employees of, and own stock in, AstraZeneca. S. Boarino and J. Nuevo are employees of AstraZeneca. R. Katial (currently of National Jewish Health and University of Colorado Denver, Denver, CO, USA) and E. Garcia-Gil (currently of Almirall, Barcelona, Spain) were employees of AstraZeneca at the time the study was conducted. C. Chaves Loureiro has received consultancy fees and speakers’ fees from AstraZeneca, Chiesi, GlaxoSmithKline, Sanofi Regeneron and Teva, and research grants from GlaxoSmithKline. A. Padilla-Galo reports grants, personal fees and non-financial support from AstraZeneca and Sanofi, personal fees, and non-financial support from Chiesi, GlaxoSmithKline, Novartis and Teva, and personal fees from ALK, Bial and FAES, outside the submitted work. P. Nair reports that in the past two years, his institution received grant support from AstraZeneca, Cyclomedica, Equillium, Foresee, Genentech, Sanofi and Teva; he has also received honoraria from Arrowhead, AstraZeneca, CSL Behring, GlaxoSmithKline and Sanofi., (Copyright ©The authors 2024.)

Background: Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort., Methods: This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline., Results: 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria., Conclusions: 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required., Competing Interests: Conflict of interest: The UK Severe Asthma Registry (UKSAR) does not receive any monetary benefits or benefits-in-kind from any pharmaceutical entity; UKSAR does make limited data contributions to the International Severe Asthma Registry (ISAR) and the European Respiratory Society Clinical Research Collaborative (SHARP), which do receive pharmaceutical funding. P.J. McDowell reports speaker fees from GlaxoSmithKline and scientific meeting support from Chiesi. R. McDowell and M. Patel have no conflicts of interest to declare. M.C. Eastwood reports support to attend meetings from GlaxoSmithKline. J. Busby reports grants from AstraZeneca and personal fees from Nuvoair. P.H. Patel received advisory board fees and lecture fees from AstraZeneca, GlaxoSmithKline, Novartis and Sanofi. D.J. Jackson has received speaker fees and consultancy fees from AstraZeneca, GlaxoSmithKline and Sanofi Regeneron. A. Mansur declares personal and to institution payment for talks, advisory board meetings and sponsorship to attend conferences from AstraZeneca, GlaxoSmithKline, Teva, Sanofi, Novartis and Boehringer Ingelheim; he also declares research grants from GlaxoSmithKline. H. Burhan reports fees for advisory board meetings from AstraZeneca and Novartis, honoraria for lectures from AstraZeneca, Chiesi, GSK and Sanofi, and support for attending conferences from AstraZeneca, Chiesi and GSK. S. Doe has participated on advisory boards for Vertex, Gilead and Novartis, and has received support for travel to meetings from GlaxoSmithKline, AstraZeneca, Gilead, Teva; Sanofi, Chiesi and Forest, and fees for lectures from GlaxoSmithKline, AstraZeneca and Sanofi. R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis, honoraria for advisory board meetings from GlaxoSmithKline and AstraZeneca, sponsorship to attend international scientific meetings from Chiesi, Sanofi and GlaxoSmithKline, and a research grant (paid to institute) from AstraZeneca for a UK multicentre study. R. Gore has received fees for lecturing from AstraZeneca, Novartis, Sanofi and GlaxoSmithKline. J.W. Dodd declares he has received honoraria for participating in advisory boards and given lectures at meetings supported by GlaxoSmithKline, Boehringer Ingelheim, Chiesi, AstraZeneca, Fisher & Paykel and Aerogen; he has received sponsorship for attending international scientific meetings from Chiesi; he has also taken part in asthma clinical trials sponsored by Sanofi, AstraZeneca and Chiesi, for which his institution received remuneration; his institution has received funding for research from the MRC, NIHR, SBRI, NHSx, Templeton Foundation and Southmead Hospital research charity. T. Brown has received fees as an external expert from AstraZeneca, speaker fees from AstraZeneca, GlaxoSmithKline, Sanofi, Teva, Novartis and Chiesi, honoraria for advisory board attendance from AstraZeneca, Sanofi and Teva, and sponsorship to attend international scientific meetings from Sanofi, GlaxoSmithKline, Teva, Chiesi and Napp Pharmaceuticals. D. Subramanian is part of the AstraZeneca Precision National Working group and has received speaker fees from Chiesi. L.G. Heaney is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with a number of pharmaceutical companies., (Copyright ©The authors 2023.)

The enduring view of eosinophils, as immune effector cells whose primary function is host defence against infection by helminths and other microbial pathogens, sets the stage for a fundamental question regarding the safety of therapeutic eosinophil depletion. If eosinophils are significantly reduced or altogether depleted in an effort to alleviate the negative effects of tissue eosinophilia and eosinophilic inflammation in conditions such as asthma, COPD, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome, would these patients become susceptible to infection or another illness? Development of mouse models in which the eosinophil lineage has been ablated, observations in patients naturally lacking eosinophils and data from studies of eosinophil-depleting medical therapies indicate that the absence of eosinophils is not detrimental to health. The evidence available to date, as presented in this review, supports the conclusion that even if certain homeostatic roles for the eosinophil may be demonstrable in controlled animal models and human in vitro settings, the evolution of the human species appears to have provided sufficient immune redundancy such that one may be hale and hearty without eosinophils., Competing Interests: Conflict of interest: D.J. Jackson reports advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, Chiesi Pharmaceuticals, Boehringer Ingelheim and GSK. I.D. Pavord reports honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine AB, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini and GSK; payments for organising educational events from AstraZeneca, GSK, Sanofi/Regeneron and Teva; honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi and Knopp; payments to support FDA approval meetings from GSK; and sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva and Chiesi., (Copyright ©The authors 2023.)

Background: Oral corticosteroid (OCS) dependence among patients with severe eosinophilic asthma can cause adverse outcomes, including adrenal insufficiency. PONENTE's OCS reduction phase showed that, following benralizumab initiation, 91.5% of patients eliminated corticosteroids or achieved a final dosage ≤5 mg·day -1 (median (range) 0.0 (0.0-40.0) mg)., Methods: The maintenance phase assessed the durability of corticosteroid reduction and further adrenal function recovery. For ∼6 months, patients continued benralizumab 30 mg every 8 weeks without corticosteroids or with the final dosage achieved during the reduction phase. Investigators could prescribe corticosteroids for asthma exacerbations or increase daily dosages for asthma control deteriorations. Outcomes included changes in daily OCS dosage, Asthma Control Questionnaire (ACQ)-6 and St George's Respiratory Questionnaire (SGRQ), as well as adrenal status, asthma exacerbations and adverse events., Results: 598 patients entered PONENTE; 563 (94.1%) completed the reduction phase and entered the maintenance phase. From the end of reduction to the end of maintenance, the median (range) OCS dosage was unchanged (0.0 (0.0-40.0) mg), 3.2% (n=18/563) of patients experienced daily dosage increases, the mean ACQ-6 score decreased from 1.26 to 1.18 and 84.5% (n=476/563) of patients were exacerbation free. The mean SGRQ improvement (-19.65 points) from baseline to the end of maintenance indicated substantial quality-of-life improvements. Of patients entering the maintenance phase with adrenal insufficiency, 32.4% (n=104/321) demonstrated an improvement in adrenal function. Adverse events were consistent with previous reports., Conclusions: Most patients successfully maintained maximal OCS reduction while achieving improved asthma control with few exacerbations and maintaining or recovering adrenal function., Competing Interests: Conflict of interest: A. Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi and Teva, and is a steering committee member for the AstraZeneca PONENTE study; received speakers’ fees from AstraZeneca, Novartis, Sanofi and Teva; participated in research with AstraZeneca, for which his institution has been remunerated; attended international conferences with Teva; and made consultancy agreements with AstraZeneca and Sanofi. M. Gurnell is a steering committee member for the AstraZeneca PONENTE study; received travel support from AstraZeneca; and has received speakers’ fees from AstraZeneca, Novartis and Teva. L.G. Heaney is academic lead for the UK MRC Consortium for Stratified Medicine in Severe Asthma; he is industrial partner with Amgen, AstraZeneca, MedImmune, Janssen, Novartis, Roche/Genentech, GlaxoSmithKline and Boehringer Ingelheim; has prior project grant funding from MedImmune, Novartis UK, Roche/Genentech and GlaxoSmithKline; has taken part in advisory boards/lectures supported by AstraZeneca, Chiesi, Novartis, Roche/Genentech, GlaxoSmithKline, Teva, Theravance and Vectura; received travel funding support to attend international respiratory meetings from AstraZeneca, Chiesi, Novartis, Boehringer Ingelheim, Teva and GlaxoSmithKline; and has taken part in asthma clinical trials for GlaxoSmithKline, Schering-Plough, Synairgen, Novartis and Roche/Genentech, for which his institution was remunerated. J. Corren has received grants from AstraZeneca, in addition to grants and personal fees from Genentech, Novartis, Regeneron Pharmaceuticals and Sanofi. E.H. Bel reports grants from GlaxoSmithKline and Teva, which were paid to her institution; serves on the AstraZeneca data safety monitoring board for benralizumab; is a steering committee member for the AstraZeneca PONENTE and NOVELTY studies; serves on the GlaxoSmithKline Nucala Global Steering Committee; and received personal fees from GlaxoSmithKline, AstraZeneca, Chiesi, Sanofi/Regeneron and Teva. J. Maspero has consulted for AstraZeneca, Sanofi and Teva; was a speaker for GlaxoSmithKline, Menarini, Novartis and Uriach; and received research grants from Novartis. T. Harrison reports grants from AstraZeneca and the National Institute for Health Research, UK; personal fees and non-financial support from AstraZeneca; and is a steering committee member for the AstraZeneca PONENTE study, GlaxoSmithKline, Vectura, Boehringer Ingelheim, Chiesi and Synairgen; during the study's completion, he also became an employee of AstraZeneca. D.J. Jackson has received speakers’ honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Teva, and honoraria for attending advisory panels with AstraZeneca, GlaxoSmithKline, Novartis, Chiesi, Sanofi/Regeneron and Teva. D. Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme and Thermo Fisher; 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 SL, 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 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 Thermo Fisher; has stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); has 5% shareholding in Timestamp, which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. N. Lugogo received consulting fees for advisory board participation from Amgen, AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva; honoraria for non-speakers’ bureau presentations from GlaxoSmithKline and AstraZeneca; and travel support from AstraZeneca; her institution received research support from Amgen, AstraZeneca, Avillion, Evidera, Gossamer Bio, Genentech, GlaxoSmithKline, Regeneron, Sanofi, Novartis and Teva. J. Kreindler, A. de Giorgio-Miller, S. Faison and K. Padilla are full-time employees of and stockholders in AstraZeneca. K. Padilla is also a member of the board of advisors for TruLab, Inc., Durham, NC. U.J. Martin was an employee of and stockholder in AstraZeneca at the time of the study. A. Burden was a contract employee of AstraZeneca at the time of the study; her current affiliation is Ardnamhor Consulting Limited, Kilcreggan, UK. E. Garcia Gil was an employee and stockholder of AstraZeneca at the time of the study; her current affiliation is Almirall, Barcelona, Spain., (Copyright ©The authors 2022.)

Background: The benefits of specialist assessment and management have yet to be evaluated within the biologic era of UK severe asthma treatment, and potential disparities have not been considered., Methods: In an uncontrolled before-and-after study, we compared asthma symptoms (Asthma Control Questionnaire-6 (ACQ-6)), exacerbations, unscheduled secondary care use, lung function (forced expiratory volume in 1 s (FEV 1 )) and oral corticosteroid (OCS) dose after 1 year. We compared outcomes by sex, age (18-34, 35-49, 50-64 and ≥65 years), ethnicity (Caucasian versus non-Caucasian) and hospital site after adjusting for demographics and variation in biologic therapy use., Results: 1140 patients were followed-up for 1370 person-years from 12 specialist centres. At annual review, ACQ-6 score was reduced by a median (interquartile range (IQR)) of 0.7 (0.0-1.5), exacerbations by 75% (33-100%) and unscheduled secondary care by 100% (67-100%). FEV 1 increased by a median (IQR) of 20 (-200-340) mL, while OCS dose decreased for 67% of patients. Clinically meaningful improvements occurred across almost all patients, including those not receiving biologic therapy. There was little evidence of differences across demographic groups, although those aged ≥65 years demonstrated larger reductions in exacerbations (69% versus 52%; p<0.001) and unscheduled care use (77% versus 50%; p<0.001) compared with patients aged 18-34 years. There were >2-fold differences between the best and worst performing centres across all study outcomes., Conclusions: Specialist assessment and management is associated with substantially improved patient outcomes, which are broadly consistent across demographic groups and are not restricted to those receiving biologic therapy. Significant variation exists between hospitals, which requires further investigation., Competing Interests: Conflict of interest: C. Redmond and J. Busby declare no competing interests. L.G. Heaney is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with a number of pharmaceutical companies. A. Menzies-Gow has consultancy agreements with AstraZeneca and Sanofi; is participating in research funded by AstraZeneca; has received lecture fees from Teva, AstraZeneca, Novartis and Sanofi; has attended advisory boards for Novartis, Sanofi, GlaxoSmithKline, AstraZeneca and Teva; and has attended international conferences with Teva. D.J. Jackson has received advisory board and speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Napp and Novartis. P. Pfeffer has attended advisory boards for AstraZeneca, GlaxoSmithKline and Sanofi; has given lectures at meetings with/without lecture honoraria supported by AstraZeneca and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, GlaxoSmithKline and Novartis; and is conducting research funded by GlaxoSmithKline for which his institution receives remuneration. R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis; honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Chiesi and Novartis; sponsorship to attend international scientific meetings from Chiesi, Napp, Sanofi and GlaxoSmithKline; and a research grant to her institute from AstraZeneca for a UK multicentre study., (Copyright ©The authors 2022.)

Introduction: Inhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy., Methods: We examined ICS adherence and clinical outcomes in OCS-dependent severe eosinophilic asthma patients who completed 1 year of mepolizumab therapy. The ICS medicines possession ratio (MPR) was calculated (the number of doses of ICS issued on prescription/expected number) for the year before and the year after biologic initiation. Good adherence was defined as MPR >0.75, intermediate 0.74-0.51 and poor <0.5. We examined outcomes after 12 months of biologic therapy, including OCS reduction and annualised exacerbation rate (AER), stratified by adherence to ICS on mepolizumab., Results: Out of 109 patients commencing mepolizumab, 91 who had completed 12 months of treatment were included in the final analysis. While receiving mepolizumab, 68% had good ICS adherence, with 16 (18%) having poor ICS adherence. ICS use within the cohort remained similar before (MPR 0.81±0.32) and during mepolizumab treatment (0.82±0.32; p=0.78). Patients with good adherence had greater reductions in OCS dose (median (interquartile range) OCS reduction 100 (74-100)% versus 60 (27-100)%; p=0.031) and exacerbations (AER change -2.1±3.1 versus 0.3±2.5; p=0.011) than those with poor adherence. Good ICS adherence predicted the likelihood of stopping maintenance OCS (adjusted OR 3.19, 95% CI 1.02-9.94; p=0.045)., Conclusion: ICS nonadherence is common in severe eosinophilic asthma patients receiving mepolizumab, and is associated with a lesser reduction in OCS requirements and AER., Competing Interests: Conflict of interest: G. d'Ancona reports personal fees from GSK, during the conduct of the study; grants and personal fees from AstraZeneca, personal fees from Napp Pharmaceuticals, Chiesi Pharmaceuticals, Boehringer Ingelheim and Teva Pharmaceuticals, outside the submitted work. Conflict of interest: J. Kavanagh has nothing to disclose. Conflict of interest: C. Roxas has nothing to disclose. Conflict of interest: L. Green has nothing to disclose. Conflict of interest: M. Fernandes has nothing to disclose. Conflict of interest: L. Thomson has nothing to disclose. Conflict of interest: J. Dhariwal has nothing to disclose. Conflict of interest: A.M. Nanzer has nothing to disclose. Conflict of interest: D.J. Jackson reports grants and personal fees from AstraZeneca, outside the submitted work. Conflict of interest: B.D. Kent reports personal fees from GSK, during the conduct of the study; personal fees from AstraZeneca, Napp Pharmaceuticals and Chiesi Pharmaceuticals, non-financial support from Boehringer Ingelheim and Teva Pharmaceuticals, outside the submitted work., (Copyright ©ERS 2020.)