Search

There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide (T LCO); however, it is not always clear which reference set should be used in clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for T LCOData from 19 centres in 14 countries were collected to define T LCO reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R.12 660 T LCO measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5-85 years were derived for T LCO, transfer coefficient of the lung for carbon monoxide and alveolar volume.This is the largest collection of normative T LCO data, and the first global reference values available for T LCO.

The objective of this study was to investigate the reliability, feasibility and analytical impact of home-based measurement of forced vital capacity (FVC) and dyspnoea as clinical endpoints in idiopathic pulmonary fibrosis (IPF).Patients with IPF performed weekly home-based assessment of FVC and dyspnoea using a mobile hand-held spirometer and self-administered dyspnoea questionnaires. Weekly variability in FVC and dyspnoea was estimated, and sample sizes were simulated for a hypothetical 24-week clinical trial using either traditional office-based interval measurement or mobile weekly assessment.In total, 25 patients were enrolled. Mean adherence to weekly assessments over 24 weeks was greater than 90%. Compared with change assessment using baseline and 24-week measurements only, weekly assessment of FVC resulted in enhanced precision and power. For example, a hypothetical 24-week clinical trial with FVC as the primary endpoint would require 951 patients using weekly home spirometry compared with 3840 patients using office spirometry measures at weeks 1 and 24 only. The ability of repeated measures to reduce clinical trial sample size was influenced by the correlation structure of the data.Home monitoring can improve the precision of endpoint assessments, allowing for greater efficiency in clinical trials of therapeutics for IPF.

Background: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood., Methods: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV 1 ) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status., Results: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV 1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL -1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV 1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used., Conclusions: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease., Competing Interests: Conflict of interest: D. Singh reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Menarini, Mundipharma, Novartis, Peptinnovate, Pfizer, Pulmatrix, Theravance and Verona, outside the submitted work. The remaining authors declare no competing interests., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

This document updates the 2005 European Respiratory Society (ERS) and American Thoracic Society (ATS) technical standard for the measurement of lung volumes. The 2005 document integrated the recommendations of an ATS/ERS task force with those from an earlier National Heart, Lung, and Blood Institute workshop that led to the publication of background papers between 1995 and 1999 and a consensus workshop report with more in-depth descriptions and discussion. Advancements in hardware and software, new research and emerging approaches have necessitated an update to the 2005 technical standard to guide laboratory directors, physiologists, operators, pulmonologists and manufacturers. Key updates include standardisation of linked spirometry, new equipment quality control and validation recommendations, generalisation of the multiple breath washout concept beyond nitrogen, a new acceptability and grading system with addition of example tracings, and a brief review of imaging and other new techniques to measure lung volumes. Future directions and key research questions are also noted., Competing Interests: Conflict of interest: D.A. Kaminsky and K. McCarthy report speaker fees from MGC Diagnostics. C.G. Irvin is a member of a scientific advisory board for MGC Diagnostics. C. Mottram is a paid consultant to Vitalograph Ltd, receives royalties from Elsevier for a book on pulmonary function testing, and honoraria from MGC Diagnostics. F. Burgos is on the scientific advisory board of MGC Diagnostics. K. Sylvester reports consulting payments from Aseptika and honoraria from Chiesi, NDD, and Royal Brompton and Harefield NHS Trust. A.L. Coates reports honoraria from the Ontario Lung Association for teaching courses. B. Borg reports royalties from Wiley-Blackwell Publishing for authorship of a book on interpreting lung function, and member of the executive branch of the Thoracic Society of Australia and New Zealand. G. Skloot is employed by Chiesi. All of the preceding potential conflicts are outside the submitted work. E.R. Swenson, M. McCormack, F. García-Río, I. Steenbruggen, B.G. Cooper, K.A. Ramsey, J. Kivastik, A. McGowan, S.L. Knight and N.R. Bhakta have no potential conflicts of interest to report., (The content of this work is not subject to copyright. Design and branding are copyright ©ERS 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: Small airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of the Small Airways Dysfunction Tool (SADT) questionnaire, basic patient characteristics and respiratory tests available depending on the clinical setting to predict SAD in asthma., Methods: This study was based on the data of the multinational ATLANTIS (Assessment of Small Airways Involvement in Asthma) study including the earlier developed SADT questionnaire. Key SADT items together with clinical information were now used to build logistic regression models to predict SAD group (less likely or more likely to have SAD). Diagnostic ability of the models was expressed as area under the receiver operating characteristic curve (AUC) and positive likelihood ratio (LR+)., Results: SADT item 8, "I sometimes wheeze when I am sitting or lying quietly", and the patient characteristics age, age at asthma diagnosis and body mass index could reasonably well detect SAD (AUC 0.74, LR+ 2.3). The diagnostic ability increased by adding spirometry (percentage predicted forced expiratory volume in 1 s: AUC 0.87, LR+ 5.0) and oscillometry (resistance difference between 5 and 20 Hz and reactance area: AUC 0.96, LR+ 12.8)., Conclusions: If access to respiratory tests is limited ( e.g. primary care in many countries), patients with SAD could reasonably well be identified by asking about wheezing at rest and a few patient characteristics. In (advanced) hospital settings patients with SAD could be identified with considerably higher accuracy using spirometry and oscillometry., Competing Interests: Conflict of interest: J. Kocks reports grants, personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, grants and personal fees from Chiesi and Teva, nonfinancial support from Mundi Pharma, personal fees from MSD and COVIS Pharma, grants from Valneva, outside the submitted work; holds <5% shares of Lothar Medtec GmbH and 72.5% of shares in the General Practitioners Research Institute. T. van der Molen reports personal fees and nonfinancial support from Chiesi, GlaxoSmithKline and AstraZeneca. J. Voorham reports no conflict of interest. S. Baldi reports no conflict of interest. M. van den Berge reports research grants paid to institution from Chiesi, Novartis, Genentech, Roche, AstraZeneca and GlaxoSmithKline. C. Brightling reports support for the present manuscript from Chiesi and NIHR BRC; grants and consulting fees from AstraZeneca, GlaxoSmithKline, Chiesi, Sanofi, Roche, Genentech, Mologic and 4DPharma, outside the submitted work. L.M. Fabbri reports grants, personal fees, and nonfinancial support from AstraZeneca, Chiesi, GlaxoSmithKline, Alfasigma, Lusofarma and Novartis. M. Kraft reports grants (paid to institution) for research from the National Institutes of Health, American Lung Association and Chiesi (for support of this study), AstraZeneca and Sanofi Regeneron; personal fees for consultancies from Chiesi, Genentech (Roche), GlaxoSmithKline, Sanofi Regeneron and AstraZeneca, speaker fees from Chiesi; personal fees from participation on data safety and monitoring boards from AstraZeneca and ALung; and leadership of the American Thoracic Society. G. Nicolini is an employee of Chiesi, the company who sponsored the ATLANTIS study generating the data analysed in the current manuscript. A. Papi reports grants from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Teva and Sanofi; consulting fees, honoraria for lectures or advisory boards from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Sanofi, IQVIA, Avillon, Elpen Pharmaceuticals, Menarini, Zambon and Mundipharma. K.F. Rabe reports grants, personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim, Chiesi, DevPro and Sanofi Regeneron. Klaus F. Rabe is co-founder of rnatics and receives federal grants from the BMBF, Germany for the German Center for Lung Research. S. Siddiqui reports grants, personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Boehringer Ingelheim, Novartis, ERT Medical, Knopp Biosciences and Thorasys Ltd. D. Singh has received personal 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. J. Vonk reports no conflict of interest. M. Leving and B. Flokstra-de Blok were employed by General Practitioners Research Institute (GPRI) at the time of the study. In the past 3 years (2019–2021), GPRI conducted investigator- and sponsor-initiated research funded by noncommercial organisations, academic institutes, and pharmaceutical companies (including AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Novartis and Teva)., (Copyright ©The authors 2023.)

Background: Subjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness (AHR) in association with underlying eosinophilic (type 2 (T2)) inflammation, consistent with undiagnosed asthma. However, the prevalence of undiagnosed asthma in these subjects is unknown., Methods: In this observational study, inhaled corticosteroid-naïve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide ( F ENO ) measurement, methacholine challenge testing and induced sputum analysis. AHR was defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC 20 ) <16 mg·mL -1 and T2 inflammation was defined as sputum eosinophils >2% and/or F ENO >25 ppb., Results: Out of 132 subjects (mean±sd age 57.6±14.2 years, 52% female), 47 (36% (95% CI 28-44%)) showed AHR: 20/132 (15% (95% CI 9-21%)) with PC 20 <4 mg·mL -1 and 27/132 (21% (95% CI 14-28%)) with PC 20 4-15.9 mg·mL -1 . Of 130 participants for whom sputum eosinophils, F ENO or both results were obtained, 45 (35% (95% CI 27-43%)) had T2 inflammation. 14 participants (11% (95% CI 6-16%)) had sputum eosinophils >2% and PC 20 ≥16 mg·mL -1 , suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC 20 <4 mg·mL -1 (12/20 (60%)) than in those with PC 20 4-15.9 mg·mL -1 (8/27 (30%)) or ≥16 mg·mL -1 (25/85 (29%)) (p=0.01)., Conclusions: Asthma, underlying T2 airway inflammation and eosinophilic bronchitis may remain undiagnosed in a high proportion of symptomatic subjects in the community who have normal pre- and post-bronchodilator spirometry., Competing Interests: Conflict of interest: L-P. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi Regeneron for participation in multicentre studies and research projects proposed by the investigator; royalties from UptoDate and Taylor & Francis; lecture fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck and Sanofi; is chair of the Global Initiative for Asthma (GINA) board of directors, president of the Global Asthma Organisation (Interasma), holder of the Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health, and member of the Canadian Thoracic Society Respiratory Guidelines Committee. M-È. Boulay has nothing to disclose. A. Côté reports research grants from GlaxoSmithKline; speaker fees from AstraZeneca, GlaxoSmithKline, Valeo and Sanofi; participation in advisory boards for GlaxoSmithKline, AstraZeneca, Sanofi and Valeo. J.M. FitzGerald has attended advisory boards for GlaxoSmithKline, AstraZeneca, Novartis, Sanofi Regeneron and Theravance; received speaker fees/honoraria from AstraZeneca, GlaxoSmithKline, Sanofi Regeneron and Teva; received research funding from the NIH, Canadian Institute for Health Research, AllerGen National Centre for Excellence, GlaxoSmithKline, AstraZeneca, Sanofi Regeneron, Teva and Novartis, all paid directly to his institution; and was a member of the steering committee for the International Severe Asthma Registry, Principal Investigator for the Canadian Severe Asthma Registry, and member of the GINA Science and Executive Committees. C. Bergeron reports consulting fees from Sanofi, AstraZeneca and Takeda; payments for presentations from Grifols, AstraZeneca, Sanofi and Valeo. C. Lemière reports royalties from UptoDate; consulting fees from GlaxoSmithKline, AstraZeneca and Sanofi; payments for presentations from GlaxoSmithKline, AstraZeneca and Sanofi. M.D. Lougheed reports grants from the Manitoba Workers Compensation Board, Ontario Lung Association, Ontario Thoracic Society, Government of Ontario's Innovation Fund, Queen's University, AstraZeneca and GlaxoSmithKline; payments for co-development and co-presentation of a severe asthma preparation course from the Canadian Thoracic Society and for co-development of an accredited CME module on severe asthma from MDBriefcase; participation on advisory board for AstraZeneca; membership on the Canadian Thoracic Society Asthma Clinical Assembly and Canadian Thoracic Society Asthma Clinical Assembly Steering Committee, Health Quality Ontario's Asthma in Adults and Asthma in Children Quality Standard Advisory Committee; is past chair of the Canadian Thoracic Society Asthma Clinical Assembly, is a Canadian Thoracic Society representative on the Lung Association's board of directors and a Canadian Thoracic Society representative to the European Respiratory Society. K.L. Vandemheen has nothing to declare. S.D. Aaron reports payments for lectures from AstraZeneca, GlaxoSmithKline and Sanofi; participation on advisory boards for AstraZeneca, GlaxoSmithKline, Sanofi and Covis., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD., Methods: Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD., Results: Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97)., Conclusions: Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms., Competing Interests: Conflict of interest: M. Cherian reports no conflict of interest. K.M.A. Magner reports no conflict of interest. G.A. Whitmore reports no conflict of interest. K.L. Vandemheen reports no conflict of interest. C. Bergeron reports grants, contracts or honoraria from Novartis, Biohaven, AstraZeneca, Sanofi, Valeo and Grifols; and advisory board participation Sanofi, AstraZeneca, GlaxoSmithKline, Takeda and Valeo. L-P. Boulet reports grants, contracts, consulting fees or honoraria from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Sanofi-Regeneron, Covis and Novartis; royalties or licences from UptoDate and Taylor & Francis; leadership roles with the Global Initiative for Asthma (GINA), Global Asthma Association (INTERASMA) and Canadian Thoracic Society; and holds the Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. A. Cote reports grants, contracts, consulting fees or honoraria from GlaxoSmithKline, AstraZeneca, Valeo, Sanofi-Regeneron and Covis; and advisory board participation with AstraZeneca, Sanofi and Valeo. S.K. Field reports grants, contracts, consulting fees or honoraria from Bayer, Insmed, Merck, Valeo and GlaxoSmithKline. E. Penz reports grants, contracts, consulting fees or honoraria from the Saskatchewan Health Research Foundation, CIHR, Respiratory Research Centre, SCPOR, AstraZeneca, Saskatchewan Cancer Agency, GlaxoSmithKline, Sanofi, Genzyme, ICBEM and Boehringer Ingelheim; and leadership roles with the Canadian Thoracic Society COPD Assembly, CIHR Institute Advisory Board and Youth4Change. R.A. McIvor reports no conflict of interest. C. Lemière repots grants, contracts, consulting fees or honoraria from GlaxoSmithKline, AstraZeneca, Sanofi and Novartis; and royalties or licences from UptoDate. S. Gupta reports no conflict of interest. I. Mayers reports no conflict of interest. M. Bhutani reports grants, contracts, consulting fees, support for travel or honoraria from the CIHR, AstraZeneca, GlaxoSmithKline, Novartis, Grifols, Sanofi, Covis, Valeo, Lung Association of Saskatchewan, Canadian Thoracic Society and Lung Association of Alberta and Northwest Territories; and leadership roles with the Canadian Thoracic Society and Alberta Health Services. P. Hernandez reports grants, contracts, support for travel or honoraria from the CIHR, Cyclomedia, Boehringer Ingelheim, Vertex, Grifols, AstraZeneca, Boehringer Ingelheim, Janssen and Canadian Thoracic Society; advisory board participation with Acceleron, AstraZeneca, Boehringer Ingelheim, Covis, GlaxoSmithKline, Grifols, Janssen, Novartis, Sanofi, Takeda and Valeo; and leadership roles with the Canadian Thoracic Society. M.D. Lougheed reports grants, contracts or honoraria from the CIHR, AstraZeneca, GlaxoSmithKline, Canadian Thoracic Society and MDBriefcase; advisory board participation with AstraZeneca; leadership roles with the Canadian Thoracic Society, Health Quality Ontario and the Lung Association. C.J. Licskai reports no conflict of interest. T. Azher reports no conflict of interest. M. Ainslie reports no conflict of interest. N. Ezer reports grants, contracts or honoraria from the CIHR, Rossy Cancer Network, Covis Pharma, GlaxoSmithKline, AstraZeneca, Fédération des Omnipracticiens du Québec and Médecin du Québec Magazine; advisory board participation with GlaxoSmithKline; leadership role with the Quebec Ministry of Health Lung Cancer Screening Implementation Committee; and receipt of study drug from Covis. S. Mulpuru reports no conflict of interest. S.D. Aaron reports honoraria from AstraZeneca, Sanofi and GlaxoSmithKline; and advisory board participation with AstraZeneca, GlaxoSmithKline and Sanofi., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: COPD is a major comorbidity in lung cancer screening (LCS) cohorts, with a high prevalence of undiagnosed COPD. Combining symptom assessment with spirometry in this setting may enable earlier diagnosis of clinically significant COPD and facilitate increased understanding of lung cancer risk in COPD. In this study, we wished to understand the prevalence, severity, clinical phenotype and lung cancer risk of individuals with symptomatic undiagnosed COPD in a LCS cohort., Methods: 16 010 current or former smokers aged 55-77 years attended a lung health check as part of the SUMMIT Study. A respiratory consultation and spirometry were performed alongside LCS eligibility assessment. Those with symptoms, no previous COPD diagnosis and airflow obstruction were labelled as undiagnosed COPD. Baseline low-dose computed tomography (LDCT) was performed in those at high risk of lung cancer (PLCO m2012 score ≥1.3% and/or meeting USPSTF 2013 criteria)., Results: Nearly one in five (19.7%) met criteria for undiagnosed COPD. Compared with those previously diagnosed, those undiagnosed were more likely to be male (59.1% versus 53.2%; p<0.001), currently smoking (54.9% versus 47.6%; p<0.001) and from an ethnic minority group (p<0.001). Undiagnosed COPD was associated with less forced expiratory volume in 1 s impairment (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 and 2: 85.3% versus 68.4%; p<0.001) and lower symptom/exacerbation burden (GOLD A and B groups: 95.6% versus 77.9%; p<0.001) than those with known COPD. Multivariate analysis demonstrated that airflow obstruction was an independent risk factor for lung cancer risk on baseline LDCT (adjusted OR 2.74, 95% CI 1.73-4.34; p<0.001), with a high risk seen in those with undiagnosed COPD (adjusted OR 2.79, 95% CI 1.67-4.64; p<0.001)., Conclusions: Targeted case-finding within LCS detects high rates of undiagnosed symptomatic COPD in those most at risk. Individuals with undiagnosed COPD are at high risk for lung cancer., Competing Interests: Conflict of interest: S. Tisi, J.L. Dickson, C. Horst, H. Hall and P. Verghese are all funded or part-funded through GRAIL Inc., as part of the SUMMIT Study. S.M. Janes was a Wellcome Trust Senior Fellow in Clinical Science (WT107963AIA); is supported by Cancer Research UK (CRUK) programme grant EDDCPGM\100002, the Rosetrees Trust, the Roy Castle Lung Cancer foundation, the Garfield Weston Trust and UCLH Charitable Foundation; and reports fees for advisory board work from AstraZeneca, Bard1 Bioscience, Achilles Therapeutics and Jansen, assistance for travel to meetings from AstraZeneca and Takeda, grant income from GRAIL Inc. and Owlstone, and share options from Optellum and Bard1 Lifescience Ltd. S.L. Quaife is supported by a Cancer Research UK (CRUK) Population Research Fellowship (C50664/A24460) and Barts Charity (MRC&U0036). A. Nair is part-funded through the UCLH Biomedical Research Centre. A. Devaraj reports personal fees from Boehringer Ingelheim, Roche, Galacto Biotech, Galapagos and Vicore. A. Hackshaw reports consulting fees from Evidera Inc. and assistance for travel to meetings from GRAIL Inc. J.R. Hurst reports assistance for travel from AstraZeneca and Boehringer Ingelheim, and payment for lectures and presentations from AstraZeneca, Boehringer Ingelheim, Nutricia and Takeda. There are no disclosures from K. Gyertson, V. Bowyer, C. Levermore, A-M. Mullin, J. Teague and L. Farrelly., (Copyright ©The authors 2022.)

Background: There are few data to support accurate interpretation of spirometry data in South Asia, a major global region with a high reported burden of chronic respiratory disease., Method: We measured lung function in 7453 healthy men and women aged ≥18 years, from Bangladesh, North India, South India, Pakistan and Sri Lanka, as part of the South Asia Biobank study. First, we assessed the accuracy of existing equations for predicting normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ) and FEV 1 /FVC ratio. Then, we used our data to derive (n=5589) and internally validate (n=1864) new prediction equations among South Asians, with further external validation among 339 healthy South Asians living in Singapore., Results: The Global Lung Initiative (GLI) and National Health and Nutrition Examination Survey consistently overestimated expiratory volumes (best fit GLI-African American, mean±sd z-score: FEV 1 -0.94±1.05, FVC -0.91±1.10; n=7453). Age, height and weight were strong predictors of lung function in our participants (p<0.001), and sex-specific reference equations using these three variables were highly accurate in both internal validation (z-scores: FEV 1 0.03±0.99, FVC 0.04±0.97, FEV 1 /FVC -0.03±0.99) and external validation (z-scores: FEV 1 0.31±0.99, FVC 0.24±0.97, FEV 1 /FVC 0.16±0.91). Further adjustment for study regions improves the model fit, with highest accuracy for estimation of region-specific lung function in South Asia., Conclusion: We present improved equations for predicting lung function in South Asians. These offer the opportunity to enhance diagnosis and management of acute and chronic lung diseases in this major global population., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2022.)

Background: Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma., Methods: In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models., Results: Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgA + memory B-cells were associated with impaired lung function and specifically with parameters indicative for augmented resistance in the peripheral airways. Accordingly, asthma patients with small airway dysfunction (SAD) defined by impulse oscillometry showed increased frequencies of IgA + memory B-cells, particularly in patients with mild-moderate asthma. Additionally, IgA + memory B-cells significantly correlated with clinical features of SAD such as exacerbations., Conclusions: With this study we demonstrate for the first time a significant association of increased IgA + memory B-cells with asthma and SAD, pointing towards future options for B-cell-directed strategies in preventing and treating asthma., Competing Interests: Conflict of interest: C. Happle reports grants from Novartis and Pari, outside the submitted work. M.V. Kopp reports grants from Allergopharma GmbH and Vertex GmbH; honoraria for lectures from Allergopharma GmbH, Sanofi GmbH, Infectopharm GmbH, Vertex GmbH and Leti GmbH; advisory board membership at Allergopharma GmbH and Sanofi GmbH; outside the submitted work. E. von Mutius reports royalties from Elsevier GmbH, Georg Thieme Verlag, Springer-Verlag GmbH and Elsevier Ltd; consulting fees from the Chinese University of Hong Kong, European Commission, HiPP GmbH & Co KG and AstraZeneca; lecture honoraria from Massachusetts Medical Society, Springer-Verlag GmbH, Elsevier Ltd, Boehringer Ingelheim International GmbH, European Respiratory Society, Universiteit Utrecht – Faculteit Diergeneeskunde, Universität Salzburg, Springer Medizin Verlag GmbH, Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI), Klinikum Rechts der Isar, University of Colorado, Paul-Martini-Stiftung and Imperial College London; travel support from Verein zur Förderung der Pneumologie am Krankenhaus Großhansdorf eV, Pneumologie Développement, Mondial Congress & Events GmbH & Co. KG, American Academy of Allergy, Asthma & Immunology, Imperial College London, Margaux Orange, Volkswagen Stiftung, Boehringer Ingelheim International GmbH, European Respiratory Society, Universiteit Utrecht – Faculteit Diergeneeskunde, Österreichische Gesellschaft für Allergologie und Immunologie, Massachusetts Medical Society, OM Pharma SA, Hanson Wade Ltd, iKOMM GmbH, DSI Dansk Borneastma Center, American Thoracic Society, HiPP GmbH & Co. KG and Universiteit Utrecht – Faculteit Bètawetenschappen; outside the submitted work. In addition, E. von Mutius has patent LU101064 (Barn dust extract for the prevention and treatment of diseases) pending, royalties paid to ProtectImmun for patent EP2361632 (Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders, granted on 19 March 2014), and patents EP1411977 (Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases, granted on 18 April 2007), EP1637147 (Stable dust extract for allergy protection, granted on 10 December 2008) and EP1964570 (Pharmaceutical compound to protect against allergies and inflammatory diseases, granted on 21 November 2012) licensed to ProtectImmun. In addition, E. von Mutius is a member of the EXPANSE (funded by European Commission) Scientific Advisory Board, member of the BEAMS External Scientific Advisory Board (ESAB), member of the Editorial Board of the Journal of Allergy and Clinical Immunology: In Practice, member of the Scientific Advisory Board of the Children's Respiratory and Environmental Workgroup (CREW), member of the International Scientific and Societal Advisory Board (ISSAB) of Utrecht Life Sciences (ULS), University of Utrecht, member of the External Review Panel of the Faculty of Veterinary Science, University of Utrecht, member of the Selection Committee for the Gottfried Wilhelm Leibniz Programme (DFG), member of the International Advisory Board of the Asthma UK Centre for Applied Research (AUKCAR), member of the International Advisory Board of The Lancet Respiratory Medicine, and member of the Scientific Advisory Board of the CHILD (Canadian Healthy Infant Longitudinal Development) study, McMaster University, Hamilton, Canada. T. Bahmer reports grants from Network University Medicine (NUM): National Pandemic Cohort Network (NAPKON); consulting fees and lecture honoraria from AstraZeneca, Novartis, GlaxoSmithKline, Roche and Chiesi; travel support from Chiesi and AstraZeneca; outside the submitted work. K.F. Rabe reports lecture honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, Novartis, Sanofi Regeneron, GlaxoSmithKline, Berlin-Chemie and Roche; advisory board membership at AstraZeneca and Sanofi Regeneron; leadership roles with the German Center for Lung Research (DZL), German Chest Society (DGP) and American Thoracic Society; outside the submitted work. A. Meyer-Bahlburg reports lecture honoraria from Pfizer; travel support from CSL Behring; advisory board membership with Pfizer; outside the submitted work. G. Hansen reports consulting fees from Sanofi GmbH; lecture honoraria from MedUpdate and AbbVie; outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2022.)

Background: Many people with asthma and COPD remain undiagnosed. We developed and validated a new case-finding questionnaire to identify symptomatic adults with undiagnosed obstructive lung disease., Methods: Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialling. Pre- and post-bronchodilator spirometry was used to confirm asthma or COPD. Predictive questions were selected using multinomial logistic regression with backward elimination. Questionnaire performance was assessed using sensitivity, predictive values and area under the receiver operating characteristic curve (AUC). The questionnaire was assessed for test-retest reliability, acceptability and readability. External validation was prospectively conducted in an independent sample and predictive performance re-evaluated., Results: A 13-item Undiagnosed COPD and Asthma Population Questionnaire (UCAP-Q) case-finding questionnaire to predict undiagnosed asthma or COPD was developed. The most appropriate risk cut-off was determined to be 6% for either disease. Applied to the derivation sample (n=1615), the questionnaire yielded a sensitivity of 92% for asthma and 97% for COPD; specificity of 17%; and an AUC of 0.69 (95% CI 0.64-0.74) for asthma and 0.82 (95% CI 0.78-0.86) for COPD. Prospective validation using an independent sample (n=471) showed sensitivities of 93% and 92% for asthma and COPD, respectively; specificity of 19%; with AUCs of 0.70 (95% CI 0.62-0.79) for asthma and 0.81 (95% CI 0.74-0.87) for COPD. AUCs for UCAP-Q were higher compared to AUCs for currently recommended case-finding questionnaires for asthma or COPD., Conclusions: The UCAP-Q demonstrated high sensitivities and AUCs for identifying undiagnosed asthma or COPD. A web-based calculator allows for easy calculation of risk probabilities for each disease., Competing Interests: Conflict of interest: C. Huynh reports no conflicts of interest. G.A. Whitmore reports no conflicts of interest. K.L. Vandemheen reports no conflicts of interest. J.M. FitzGerald reports no conflicts of interest. C. Bergeron reports no conflicts of interest. L-P. Boulet reports receiving grants, consulting fees or honoraria from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron. A. Cote reports receiving honoraria from GlaxoSmithKline, AstraZeneca, Sanofi and Covis. S.K. Field reports receiving consulting fees or honoraria from Merck, GlaxoSmithKline, Novartis and Boehringer Ingelheim. E. Penz reports receiving honoraria from AstraZeneca, GlaxoSmithKline, Novartis, ICEBM and Boehringer Ingelheim. R.A. McIvor reports no conflicts of interest. C. Lemière reports receiving consulting fees or honoraria from Sanofi, TEVA, GlaxoSmithKline and AstraZeneca. S. Gupta reports no conflicts of interest. I. Mayers reports no conflicts of interest. M. Bhutani reports payments or honoraria from AZ, GSK, Novartis, Grifols, Sanofi, Covis and Valeo. P. Hernandez reports payments or honoraria from AZ, GSK, Novartis and Valeo. M.D. Lougheed reports receiving grants from AZ and GSK. C.J. Licskai reports receiving honoraria from AstraZeneca, GlaxoSmithKline, Novartis and Boehringer Ingelheim. T. Azher reports no conflicts of interest. M. Ainslee reports receiving honoraria from Boehringer Ingelheim. I. Fraser reports no conflicts of interest. M. Mahdavian reports no conflicts of interest. G.G. Alvarez reports no conflicts of interest. T. Kendzerska reports speaker honoraria from AstraZeneca. S.D. Aaron reports sitting on advisory boards and honoraria payments from GlaxoSmithKline, Sanofi and AstraZeneca., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Genetic susceptibility may be associated with earlier onset of chronic obstructive pulmonary disease (COPD). We hypothesised that a polygenic risk score (PRS) for COPD would be associated with earlier age of diagnosis of COPD., Methods: In 6647 non-Hispanic White (NHW) and 2464 African American (AA) participants from COPDGene, and 6812 participants from the Framingham Heart Study (FHS), we tested the relationship of the PRS and age of COPD diagnosis. Age at diagnosis was determined by: 1) self-reported age at COPD diagnosis or 2) age at visits when moderate-to-severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 2-4) was observed on spirometry. We used Cox regression to examine the overall and time-dependent effects of the PRS on incident COPD. In the COPDGene study, we also examined the PRS's predictive value for COPD at age <50 years (COPD50) using logistic regression and area under the curve (AUC) analyses, with and without the addition of other risk factors present at early life ( e.g. childhood asthma)., Results: In Cox models, the PRS demonstrated age-dependent associations with incident COPD, with larger effects at younger ages in both cohorts. The PRS was associated with COPD50 (OR 1.55 (95% CI 1.41-1.71) for NHW, OR 1.23 (95% CI 1.05-1.43) for AA and OR 2.47 (95% CI 2.12-2.88) for FHS participants). In COPDGene, adding the PRS to known early-life risk factors improved prediction of COPD50 in NHW (AUC 0.69 versus 0.74; p<0.0001) and AA (AUC 0.61 versus 0.64; p=0.04) participants., Conclusions: A COPD PRS is associated with earlier age of diagnosis of COPD and retains predictive value when added to known early-life risk factors., Competing Interests: Conflict of interest: E.K. Silverman received grant support from GlaxoSmithKline and Bayer. M.H. Cho has received grant support from GlaxoSmithKline and Bayer, consulting fees from Genentech and AstraZeneca, and speaking fees from Illumina. D.L. DeMeo has received support from Bayer and Honoraria from Novartis. J. Dupuis received NIH funding for salary coverage paid to Boston University. J. Zhang, H. Xu, D. Qiao, G.T. O'Connor, B.D. Hobbs and M. Moll have no conflict of interest to declare., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation., Methods: This technical standards document was developed by an international joint Task Force, appointed by the ERS/ATS with multidisciplinary expertise in conducting and interpreting PFTs and developing international standards. A comprehensive literature review was conducted and published evidence was reviewed., Results: Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments., Conclusions: Interpretation of PFTs must be complemented with clinical expertise and consideration of the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements., Competing Interests: Conflict of interest: S. Stanojevic reports grants, support for travel from the European Respiratory Society and was the Co-Chair of the Global Lung Function Initiative for the European Respiratory Society; and additionally acted on the Pulmonary Function Testing Proficiency committee for the American Thoracic Society, all outside the submitted work. Conflict of interest: D.A. Kaminsky reports speaker fees from MGC Diagnostics, Inc. and honoraria from UpToDate, Inc., outside the submitted work. Conflict of interest: M.R. Miller has nothing to disclose. Conflict of interest: B. Thompson reports grants from the NHMRC; consulting fees from 4D Medical and Chiesi; lecture honoraria from 4D Medical, Chiesi and Mundipharma; and reports past academic work with the Global Lung Function Initiative for the European Respiratory Society, outside the submitted work. Conflict of interest: A. Aliverti reports patents on Forced Oscillation Technique from Philips and patents on Opto-Electronic Plethysmography from BTS Bioengineering, outside the submitted work. Conflict of interest: I. Barjaktarevic has nothing to disclose. Conflict of interest: B.G. Cooper acted as Co-Chair of the Global Lung Function Initiative at the European Respiratory Society, outside the submitted work. Conflict of interest: B. Culver has nothing to disclose. Conflict of interest: E. Derom has nothing to disclose. Conflict of interest: G.L. Hall was former Co-Chair of the Global Lung Function Initiative and reports previous academic and leadership work with the Global Lung Function Initiative, both with the European Respiratory Society, outside the submitted work. Conflict of interest: T.S. Hallstrand reports research grants from the NIH (NHLBI, NIAID), outside the submitted work. Conflict of interest: J.D. Leuppi reports grants from the Swiss National Science Foundation (SNF 160072 and 185592) and Swiss Personalised Health Network (SPHN 2018DR108); and has also received unrestricted grants from AstraZeneca AG Switzerland, Boehringer Ingelheim GmbH Switzerland, GSK AG Switzerland and Novartis AG Switzerland, outside the submitted work. Conflict of interest: N. MacIntyre reports consulting fees from Vyaire, outside the submitted work. Conflict of interest: M. McCormack reports royalties for authorship for PFT chapters from UpToDate; consulting fees related to PFT quality and reading from Aridis, outside the submitted work. Conflict of interest: M. Rosenfeld has nothing to disclose. Conflict of interest: E.R. Swenson has nothing to disclose., (The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Digital biomarkers are a promising novel method to capture clinical data in a home setting. However, clinical validation prior to implementation is of vital importance. The aim of this study was to clinically validate physical activity, heart rate, sleep and forced expiratory volume in 1 s (FEV 1 ) as digital biomarkers measured by a smartwatch and portable spirometer in children with asthma and cystic fibrosis (CF)., Methods: This was a prospective cohort study including 60 children with asthma and 30 children with CF (aged 6-16 years). Participants wore a smartwatch, performed daily spirometry at home and completed a daily symptom questionnaire for 28 days. Physical activity, heart rate, sleep and FEV 1 were considered candidate digital end-points. Data from 128 healthy children were used for comparison. Reported outcomes were compliance, difference between patients and controls, correlation with disease activity, and potential to detect clinical events. Analysis was performed with linear mixed effects models., Results: Median compliance was 88%. On average, patients exhibited lower physical activity and FEV 1 compared with healthy children, whereas the heart rate of children with asthma was higher compared with healthy children. Days with a higher symptom score were associated with lower physical activity for children with uncontrolled asthma and CF. Furthermore, FEV 1 was lower and (nocturnal) heart rate was higher for both patient groups on days with more symptoms. Candidate biomarkers appeared able to describe a pulmonary exacerbation., Conclusions: Portable spirometer- and smartwatch-derived digital biomarkers show promise as candidate end-points for use in clinical trials or clinical care in paediatric lung disease., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Although bronchopulmonary dysplasia (BPD) is associated with lung function deficits in childhood, many who develop BPD have normal lung function in childhood and many without BPD, including those born at 33-34 weeks of gestation, have lung dysfunction in childhood. Since the predictability of BPD for future lung deficits is increasingly doubted, we prospectively recruited preterm-born children to identify early-life factors associated with lung function deficits after preterm birth., Methods: From 767 children aged 7-12 years who had their respiratory symptoms assessed, and had spirometry before and after a bronchodilator in our Respiratory Health Outcomes in Neonates (RHiNO) study, 739 (544 preterm-born at ≤34 weeks of gestation and 195 term-born) had satisfactory lung function. Data were analysed using multivariable logistic regression and mediation., Results: When preterm-born children were classified according to their lung function, low lung function (prematurity-associated lung disease (PLD)) was associated with BPD, gestation and intra-uterine growth restriction (IUGR) on univariable logistic regression analyses. However, on multivariable logistic regression analyses, gestation (β= -0.153, se 0.051; p=0.003) and IUGR (OR 1.783, 95% CI 1.06-3.00; p=0.029) remained significantly associated with later deficits of lung function, but BPD (OR 0.99, 95% CI 0.52-1.89; p=0.974) did not. Mediation analyses confirmed these results., Conclusions: Although traditionally BPD has been associated with low lung function in later life, the data show that gestation and IUGR are significantly associated with PLD in childhood, but BPD is not. By identifying children with PLD, we can better understand the underlying mechanisms and develop optimal therapies., Competing Interests: Conflict of interest: K. Hart has nothing to disclose. Conflict of interest: M. Cousins has nothing to disclose. Conflict of interest: W.J. Watkins reports grants from Moulton Foundation, outside the submitted work. Conflict of interest: S.J. Kotecha reports grants from Moulton Foundation and Nutricia Foundation, outside the submitted work. Conflict of interest: S. Kotecha reports grants from Medical Research Council and GSK, during the conduct of the study; grants from the NIHR/HTA, grants and personal fees from Aspire Pharma; grants from Moulton Foundation, outside the submitted work., (Copyright ©The authors 2022.)

Background: A significant number of children with asthma show remission in adulthood. Although these adults are often diagnosed with COPD in later life, the effect of clinically remitted childhood asthma on the decline in lung function during adulthood is uncertain. We examined whether clinical remission of childhood asthma was associated with an accelerated decline in lung function in apparently nonasthmatic adults., Methods: 3584 participants (mean (range) age 48.1 (35-65) years) who did not have adulthood asthma and other lung diseases and had normal lung function at the baseline visit were included. They were categorised as those with remitted childhood asthma (n=121) and healthy controls (n=3463) according to their self-reported childhood asthma history. Spirometry was performed at baseline and follow-up visits., Results: The mean follow-up was 5.3 years. Multivariate regression analysis showed that remitted childhood asthma and smoking were independently associated with a rapid decline in forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC). Smoking was an independent predictor of a rapid decline in FEV 1 /FVC. The annual decline in FEV 1 and FVC was significantly greater in participants with remitted childhood asthma than in healthy controls, and the differences remained significant after adjusting for the propensity score., Conclusions: A history of clinically remitted childhood asthma is an independent risk factor for accelerated decline in lung function in adults. Remitted childhood asthma and smoking may additively accelerate the development of obstructive lung disease., Competing Interests: Conflict of interest: S. Miura has nothing to disclose. Conflict of interest: H. Iwamoto has nothing to disclose. Conflict of interest: K. Omori has nothing to disclose. Conflict of interest: K. Yamaguchi has nothing to disclose. Conflict of interest: S. Sakamoto has nothing to disclose. Conflict of interest: Y. Horimasu has nothing to disclose. Conflict of interest: T. Masuda has nothing to disclose. Conflict of interest: S. Miyamoto has nothing to disclose. Conflict of interest: T. Nakashima has nothing to disclose. Conflict of interest: K. Fujitaka has nothing to disclose. Conflict of interest: H. Hamada has nothing to disclose. Conflict of interest: A. Yokoyama has nothing to disclose. Conflict of interest: N. Hattori reports grants from Teijin Pharma Co., Japan, during the conduct of the study. All other authors have nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)