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Background: Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This is the first systematic review with the objective of summarising evidence on HZ burden in adults with asthma., Methods: A global systematic literature review and meta-analysis was conducted (MEDLINE and Embase, 2003-2024) on HZ burden (incidence, risk and complications) in adults (≥18 years) with asthma., Results: There were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% CI 4.68-6.96) in adults aged ≥18 years (4.20 (95% CI 3.09-5.70) in those aged <60 years versus 10.33 (95% CI 9.17-11.64) in those aged ≥60 years). The pooled rate ratio for developing HZ was 1.23 (95% CI 1.11-1.35) in those aged ≥18 years and 1.36 (95% CI 1.15-1.61) in those aged ≥50 years. The risk of HZ was higher in people with asthma using systemic corticosteroids, long-acting β-agonists plus inhaled corticosteroids and "add-on therapy". Asthma was also associated with an increased risk of post-herpetic neuralgia (OR 1.21, 95% CI 1.06-1.37) and HZ ophthalmicus (OR 1.9, 95% CI 1.1-3.2). Differences in study design, setting, case definitions and follow-up durations led to heterogeneity., Conclusions: This systematic literature review and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care., Competing Interests: Conflict of interest: A. Jorga and C. Williams are employed by GSK. A. Jorga holds shares in Pfizer and GSK. H. Vroling and I.T. Sepúlveda-Pachón are employees of P95/Pallas. P95/Pallas received funding from GSK for the submitted work. P95/Pallas holds/held contracts with AstraZeneca, GSK, Pfizer, Sanofi, Seqirus, Merck, Takeda, Orchard, Biomarin, Daiichi, Bavarian Nordic and Bayer (work for the non-GSK companies was not related to HZ). K.J. Mortimer declares grants and sponsorship from AstraZeneca and GSK to support the Global Asthma Network, consulting fees from AstraZeneca and GSK on asthma and COPD-related advisory boards, and honorarium from GSK for lectures on improving vaccine access for people with asthma, outside the submitted work. A.A. Cruz declares grants and sponsorship from GSK to support the ProAR Foundation, and consulting or lecture fees from Abdi-Ibrahim, AstraZeneca, Boehringer Ingelheim, Chiesi, Crossject, Eurofarma, Farmoquimica, Glennmark, GSK, Mylan, Novartis and Sanofi on asthma-related activities. The authors declare no other financial or non-financial relationships and activities or conflicts of interest., (Copyright ©The authors 2024.)

Background: Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings., Methods: First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy., Results: In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex., Conclusions: Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding., Competing Interests: Conflict of interest: C.A. Valencia-Hernández, F. Del Greco M, L. Portas, V. Sundaram and C. Minelli have no conflicts of interest to disclose. C.I. Bloom reports awards and grants from the National Institute for Health and Care Research and Asthma + Lung UK, outside the submitted work., (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: The relationship between objectively measured cough and type 2 (T2) biomarkers and other measures of asthma control and severity is poorly understood. The objective of this study was to assess the relationship between objective and subjective cough measurement tools and clinical biomarkers of asthma., Methods: Patients with severe asthma and mild-to-moderate asthma completed validated asthma and cough-related measurement tools (including ambulatory cough monitoring) and measurement of spirometry and T2 biomarkers (exhaled nitric oxide fraction ( F ENO ) and peripheral blood eosinophil count). Patients were classified according to T2 status based on T2-low ( F ENO <20 ppb and peripheral blood eosinophils <150 cells·µL -1 ), T2-intermediate ( F ENO ≥20 ppb or peripheral blood eosinophils ≥150 cells·µL -1 ) or T2-high ( F ENO ≥20 ppb and peripheral blood eosinophils ≥150 cells·µL -1 )., Results: 61 patients completed the study measurements (42 severe asthma and 19 mild-to-moderate asthma). Patients with severe asthma had higher rates of cough than those with mild-to-moderate asthma in terms of total 24-h cough counts (geometric mean±sd 170.3±2.7 versus 60.8±4.1; p=0.002) and cough frequency (geometric mean±sd 7.1±2.7 versus 2.5±4.1 coughs·h -1 ; p=0.002). T2-low patients with severe asthma had significantly lower 24-h cough frequency compared with T2-intermediate and T2-high patients., Conclusions: In patients with low biomarkers of T2 inflammation, cough frequency measurements were not elevated, suggesting that the mechanism for cough in asthma is underlying T2 eosinophilic inflammation and the logical first step for treating cough in asthma may be to achieve adequate suppression of T2 inflammation with currently available therapies., Competing Interests: Conflict of interest: L.G. Heaney reports grants from Medimmune, Novartis, Roche/Genentech, GlaxoSmithKline, Amgen, AstraZeneca, Aerocrine and Vitalograph; lecture honoraria from Novartis, Hoffman la Roche/Genentech, Sanofi, GlaxoSmithKline, AstraZeneca, Teva and Circassia; travel support from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Napp Pharmaceuticals; and participation on advisory boards with Novartis, Hoffman la Roche/Genentech, Sanofi, Evelo Biosciences, GlaxoSmithKline, AstraZeneca, Teva, Theravance and Circassia; outside the submitted work. L.P.A. McGarvey reports grants from Chiesi, Merck, Bellus Health, Bayer and Shionogi; consulting fees from Merck, NeRRe Pharmaceuticals, Menlo, Bellus, Bayer, Genentech, Shionogi, Nocion, Bionorica and Applied Clinical Intelligence; travel support from Boehringer Ingelheim and Chiesi; and participation on advisory boards with Applied Clinical Intelligence; outside the submitted work. S.S. Birring reports consulting fees from Merck, Bayer, Shionogi, CSA and Gala; outside the submitted work. J. Holmes and H. Fletcher have nothing to disclose., (Copyright ©The authors 2022.)

Background: Obese children with asthma are more vulnerable to air pollution, especially fine particulate matter (PM 2.5 ), but reasons are poorly understood. We hypothesised that differences in breathing patterns (tidal volume, respiratory rate and minute ventilation) due to elevated body mass index (BMI) may contribute to this finding., Objective: To investigate the association of BMI with breathing patterns and deposition of inhaled PM 2.5 ., Methods: Baseline data from a prospective study of children with asthma were analysed (n=174). Tidal breathing was measured by a pitot-tube flowmeter, from which tidal volume, respiratory rate and minute ventilation were obtained. The association of BMI z-score with breathing patterns was estimated in a multivariable model adjusted for age, height, race, sex and asthma severity. A particle dosimetry model simulated PM 2.5 lung deposition based on BMI-associated changes in breathing patterns., Results: Higher BMI was associated with higher tidal volume (adjusted mean difference (aMD) between obese and normal-range BMI of 25 mL, 95% CI 5-45 mL) and minute ventilation (aMD 453 mL·min -1 , 95% CI 123-784 mL·min -1 ). Higher tidal volumes caused higher fractional deposition of PM 2.5 in the lung, driven by greater alveolar deposition. This translated into obese participants having greater per-breath retention of inhaled PM 2.5 (aMD in alveolar deposition fraction of 3.4%, 95% CI 1.3-5.5%), leading to worse PM 2.5 deposition rates., Conclusions: Obese children with asthma breathe at higher tidal volumes that may increase the efficiency of PM 2.5 deposition in the lung. This finding may partially explain why obese children with asthma exhibit greater sensitivity to air pollution., Competing Interests: Conflict of interest: N. Afshar-Mohajer has nothing to disclose. Conflict of interest: T.D. Wu has nothing to disclose. Conflict of interest: R. Shade has nothing to disclose. Conflict of interest: E. Brigham reports grants from the National Institute for Environmental Health Sciences, during the conduct of the study. Conflict of interest: H. Woo has nothing to disclose. Conflict of interest: M. Wood has nothing to disclose. Conflict of interest: R. Koehl has nothing to disclose. Conflict of interest: K. Koehler has nothing to disclose. Conflict of interest: J. Kirkness reports other (salary) from 4DMedical, outside the submitted work. Conflict of interest: N.N. Hansel reports grants from NIH and COPD Foundation, grants and personal fees for advisory board work from AstraZeneca and GSK, grants from Boehringer Ingelheim, personal fees for advisory board work from Mylan during the conduct of the study. Conflict of interest: G. Ramachandran has nothing to disclose. Conflict of interest: M.C. McCormack reports grants from National Institutes of Health (P50ES018176) and Environmental Protection Agency (83615201), during the conduct of the study; other (authorship royalties) from UpToDate, personal fees for consultancy from Aridis, GlaxoSmithKline and Celgene, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV 1 /FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood., Competing Interests: Conflict of interest: A. Marcon has nothing to disclose. Conflict of interest: F. Locatelli has nothing to disclose. Conflict of interest: S.C. Dharmage has nothing to disclose. Conflict of interest: C. Svanes has nothing to disclose. Conflict of interest: J. Heinrich has nothing to disclose. Conflict of interest: B. Leynaert has nothing to disclose. Conflict of interest: P. Burney has nothing to disclose. Conflict of interest: A. Corsico has nothing to disclose. Conflict of interest: G. Caliskan has nothing to disclose. Conflict of interest: L. Calciano has nothing to disclose. Conflict of interest: T. Gislason has nothing to disclose. Conflict of interest: C. Janson has nothing to disclose. Conflict of interest: D. Jarvis has nothing to disclose. Conflict of interest: R. Jõgi received grants from the Estonian Research Council (Personal Research Grant n. 562), and personal fees for consultancy and lecturing from GSK, Boehringer and Novartis, and for travels/accommodation/meetings from GSK and Boehringer. Conflict of interest: T. Lytras has nothing to disclose. Conflict of interest: A. Malinovschi has nothing to disclose. Conflict of interest: N. Probst-Hensch has nothing to disclose. Conflict of interest: K. Toren has nothing to disclose. Conflict of interest: L. Casas has nothing to disclose. Conflict of interest: G. Verlato has nothing to disclose. Conflict of interest: J. Garcia-Aymerich has nothing to disclose. Conflict of interest: S. Accordini has nothing to disclose., (Copyright ©The authors 2021.)

Background: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort., Methods: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis., Results: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses., Conclusion: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications., Competing Interests: Conflict of interest: H.K. Reddel reports grants, personal fees and non-financial support from AstraZeneca, during the conduct of the study; grants and personal fees for data monitoring committee work, advisory board work and providing independent medical education from AstraZeneca and GlaxoSmithKline, personal fees for data monitoring committee work from Merck, personal fees for data monitoring committee work, advisory board work and grant for registry from Novartis, personal fees for providing independent medical education from Teva, personal fees for advisory board work and providing independent medical education from Boehringer Ingelheim, and personal fees for advisory board work from Sanofi Genzyme and Chiesi, outside the submitted work; and is Chair of the GINA Scientific Committee and a member of the GINA Board. Conflict of interest: J. Vestbo reports personal fees for steering committee work from AstraZeneca, during the conduct of the study; and personal fees for consultancy and lectures from GlaxoSmithKline, Chiesi Pharmaceuticals, Novartis and AstraZeneca, and grants and personal fees for consultancy and lectures from Boehringer Ingelheim, outside the submitted work. Conflict of interest: A. Agusti reports personal fees for scientific committee work from AstraZeneca, during the conduct of the study; and grants and personal fees for lectures and advisory board work from GlaxoSmithKline and Menarini, and personal fees for lectures and advisory board work from Chiesi, outside the submitted work. Conflict of interest: G.P. Anderson reports personal fees for consultancy and share options from Pieris Pharmaceuticals, ENA Therapeutics and ENA Respiratory, personal fees for scientific committee work from AstraZeneca, and personal fees for lectures from GlaxoSmithKline, AstraZeneca, Menarini and Novartis, outside the submitted work; and has US Patent 7,455,836 licensed to MorphoSys, sublicensed to GlaxoSmithKline. Conflict of interest: A.T. Bansal has nothing to disclose. Conflict of interest: R. Beasley reports personal fees for steering committee work from AstraZeneca, during the conduct of the study; and grants and personal fees from AstraZeneca and GlaxoSmithKline, personal fees from Avillion and Theravance, and grants from Genentech, outside the submitted work. Conflict of interest: E.H. Bel reports grants and personal fees from AstraZeneca, GlaxoSmithKline, Novartis and Teva, and personal fees from Sanofi/Regeneron, Sterna and Chiesi, outside the submitted work. Conflict of interest: C. Janson reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, outside the submitted work. Conflict of interest: B. Make reports grants, non-financial support and other (advisory board and presentations) from AstraZeneca, grants, non-financial support and other from GlaxoSmithKline, non-financial support for data monitoring committee work from Spiration, grants, non-financial support and other (advisory board) from Sunovion, other (CME activity) from Mt. Sinai, Web MD, National Jewish Health, Novartis, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, Medscape, Ultimate Medical Academy, Eastern Pulmonary Society, Catamount Medical, Eastern VA Medical Center, Academy Continued Health Care Learning and Wolters Kluwer Health, grants from Pearl Research and NHLBI, other (advisory board) from Verona, Boehringer Ingelheim, Theravance and Science 24/7, non-financial support and other (advisory board) from Circassia and Phillips, personal fees and non-financial support for consultancy from Third Pole, non-financial support and other (data monitoring committee) from Shire, and personal fees for data monitoring committee work from Takeda, outside the submitted work. Conflict of interest: I.D. Pavord reports personal fees for lectures, advisory board work, meeting attendance and organising educational events from AstraZeneca, personal fees for lectures, advisory board work and meeting attendance from Boehringer Ingelheim and GlaxoSmithKline, personal fees for lectures from Aerocrine and Chiesi, personal fees for lectures and advisory board work from Almirall and Novartis, personal fees for advisory board work from Genentech, Regeneron, Sanofi, Circassia and Knopp, personal fees for lectures, meeting attendance and organising educational events from Teva, and grants from NIHR, outside the submitted work. Conflict of interest: D. Price reports study funding from AstraZeneca, during the conduct of the study; personal fees for advisory board work and consultancy from Amgen, grants and personal fees for advisory board work, lectures, consultancy and travel/accommodation/meeting expenses from AstraZeneca and Boehringer Ingelheim, grants and personal fees for advisory board work, lectures and consultancy from Chiesi, Mylan and Teva, grants and personal fees for advisory board work from Circassia, personal fees for lectures from Cipla and Kyorin, personal fees for consultancy and lectures from GlaxoSmithKline, grants and personal fees for advisory board work, lectures, consultancy, travel/accommodation/meeting expenses and educational activities from Mundipharma and Novartis, grants and personal fees for consultancy from Pfizer and Theravance, grants and personal fees for advisory board work and lectures from Regeneron Pharmaceuticals and Sanofi Genzyme, grants from Respiratory Effectiveness Group and UK National Health Service, personal fees for advisory board work and travel/accommodation/meeting expenses from ThermoFisher, non-financial support for grant committee reviewing from Efficacy and Evaluation Mechanism Programme and Health Technology Assessment, outside the submitted work; has stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; and is part owner of the social enterprise Optimum Patient Care Ltd (Australia and UK) and of the Observational and Pragmatic Research Institute Pte Ltd (Singapore). Conflict of interest: E. Rapsomaniki is an employee of AstraZeneca (UK). Conflict of interest: N. Karlsson is an employee of AstraZeneca. Conflict of interest: D.K. Finch was an employee of AstraZeneca at the time of authorship. Conflict of interest: J. Nuevo is an employee of AstraZeneca. Conflict of interest: A. de Giorgio-Miller has nothing to disclose. Conflict of interest: M. Alacqua has nothing to disclose. Conflict of interest: R. Hughes reports personal fees from GlaxoSmithKline, Novartis, Boehringer Ingelheim and AstraZeneca, outside the submitted work; and is an employee of AstraZeneca. Conflict of interest: H. Müllerová is an employee of AstraZeneca. Conflict of interest: M. Gerhardsson de Verdier is an employee of AstraZeneca., (Copyright ©The authors 2021.)

Background: Whether a combination of glucocorticoid and antifungal triazole is superior to glucocorticoid alone in reducing exacerbations in patients with allergic bronchopulmonary aspergillosis (ABPA) remains unknown. We aimed to compare the efficacy and safety of prednisolone-itraconazole combination versus prednisolone monotherapy in ABPA., Methods: We randomised subjects with treatment-naïve acute-stage ABPA complicating asthma to receive either prednisolone alone (4 months) or a combination of prednisolone and itraconazole (4 and 6 months, respectively). The primary outcomes were exacerbation rates at 12 months and glucocorticoid-dependent ABPA within 24 months of initiating treatment. The key secondary outcomes were response rates, percentage decline in serum total IgE at 6 weeks, time to first ABPA exacerbation and treatment-emergent adverse events (TEAEs)., Results: We randomised 191 subjects to receive either prednisolone (n=94) or prednisolone-itraconazole combination (n=97). The 1-year exacerbation rate was 33% and 20.6% in the prednisolone monotherapy and prednisolone-itraconazole combination arms, respectively (p=0.054). None of the participants progressed to glucocorticoid-dependent ABPA. All of the subjects experienced a composite response at 6 weeks, along with a decline in serum total IgE (mean decline 47.6% versus 45.5%). The mean time to first ABPA exacerbation (417 days) was not different between the groups. None of the participants required modification of therapy due to TEAEs., Conclusions: There was a trend towards a decline in ABPA exacerbations at 1 year with the prednisolone-itraconazole combination versus prednisolone monotherapy. A three-arm trial comparing itraconazole and prednisolone monotherapies with their combination, preferably in a multicentric design, is required to define the best treatment strategy for acute-stage ABPA., Competing Interests: Conflict of interest: R. Agarwal has received grant support for conducting research in ABPA from Cipla Pharmaceuticals, Mumbai, India, outside the submitted work. Conflict of interest: V. Muthu has nothing to disclose. Conflict of interest: I.S. Sehgal has nothing to disclose. Conflict of interest: S. Dhooria has nothing to disclose. Conflict of interest: K.T. Prasad has nothing to disclose. Conflict of interest: M. Garg has nothing to disclose. Conflict of interest: A.N. Aggarwal has nothing to disclose. Conflict of interest: A. Chakrabarti has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown., Aims: To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions., Methods: Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (<25 kg·m -2 , 25-29.9 kg·m -2 , ≥30 kg·m -2 ) and followed for 12 years as part of the Seinäjoki Adult Asthma Study. Self-reported and dispensed OCS were assessed for the 12-year period. Data on hospital admissions were analysed based on medical records., Results: 12 years after diagnosis, 86% of the patients who were obese (BMI ≥30 kg·m -2 ) at diagnosis remained obese. During the follow-up, no difference was found in weight gain between the BMI categories. During the 12-year follow-up, patients obese at diagnosis reported more frequent use of OCS courses (46.9% versus 23.1%, p=0.028), were dispensed OCS more often (81.6% versus 56.9%, p=0.014) and at higher doses (median 1350 (interquartile range 280-3180) mg versus 600 (0-1650) mg prednisolone, p=0.010) compared to normal-weight patients. Furthermore, patients who were obese had more often one or more respiratory-related hospitalisations compared to normal-weight patients (38.8% versus 16.9%, p=0.033). In multivariate logistic regression analyses, obesity predicted OCS use and hospital admissions., Conclusions: In adult-onset asthma, patients obese at diagnosis mostly remained obese at long-term and had more exacerbations and respiratory-related hospital admissions compared to normal-weight patients during 12-year follow-up. Weight loss should be a priority in their treatment to prevent this outcome., Competing Interests: Conflict of interest: P. Ilmarinen reports grants and personal fees for lectures from AstraZeneca, personal fees for lectures from Mundipharma, GlaxoSmithKline and Novartis, outside the submitted work. Conflict of interest: A. Pardo has nothing to disclose. Conflict of interest: L.E. Tuomisto reports personal fees for lectures and meeting attendance from Boehringer Ingelheim and AstraZeneca, outside the submitted work. Conflict of interest: I. Vähätalo has nothing to disclose. Conflict of interest: O. Niemelä has nothing to disclose. Conflict of interest: P. Nieminen has nothing to disclose. Conflict of interest: H. Kankaanranta reports grants, personal fees for lectures and consultancy, and non-financial support for meeting attendance from AstraZeneca, personal fees for lectures and consultancy from Chiesi Pharma AB, Novartis and GlaxoSmithKline, personal fees for lectures from Mundipharma, personal fees for lectures and consultancy, and non-financial support for meeting attendance from Boehringer Ingelheim and Orion Pharma, personal fees for consultancy from SanofiGenzyme, outside the submitted work., (Copyright ©ERS 2021.)

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide rapidly. However, the effects of asthma, asthma medication and asthma severity on the clinical outcomes of COVID-19 have not yet been established., Methods: The study included 7590 de-identified patients, who were confirmed to have COVID-19 using the severe acute respiratory syndrome coronavirus 2 RNA-PCR tests conducted up to May 15, 2020; we used the linked-medical claims data provided by the Health Insurance Review and Assessment Service. Asthma and asthma severity (steps suggested by the Global Initiative for Asthma) were defined using the diagnostic code and history of asthma medication usage., Results: Among 7590 COVID-19 patients, 218 (2.9%) had underlying asthma. The total medical cost associated with COVID-19 patients with underlying asthma was significantly higher than that of other patients. Mortality rate for COVID-19 patients with underlying asthma (7.8%) was significantly higher than that of other patients (2.8%; p<0.001). However, asthma was not an independent risk factor for the clinical outcomes of COVID-19 after adjustment, nor did asthma medication use and asthma severity affect the clinical outcomes of COVID-19. However, use of oral short-acting β 2 -agonists was an independent factor to increase the total medical cost burden. Patients with step 5 asthma showed significant prolonged duration of admission compared to those with step 1 asthma in both univariate and multivariate analysis., Conclusions: Asthma led to poor outcomes of COVID-19; however, underlying asthma, use of asthma medication and asthma severity were not independent factors for poor clinical outcomes of COVID-19, generally., Competing Interests: Conflict of interest: Y.J. Choi has nothing to disclose. Conflict of interest: J-Y. Park has nothing to disclose. Conflict of interest: H.S. Lee has nothing to disclose. Conflict of interest: J. Suh has nothing to disclose. Conflict of interest: J.Y. Song has nothing to disclose. Conflict of interest: M.K. Byun has nothing to disclose. Conflict of interest: J.H. Cho has nothing to disclose. Conflict of interest: H.J. Kim has nothing to disclose. Conflict of interest: J-H. Lee has nothing to disclose. Conflict of interest: J-W. Park has nothing to disclose. Conflict of interest: H.J. Park has nothing to disclose., (Copyright ©ERS 2021.)

Background: Obesity is a common comorbidity in asthma and associated with poorer asthma control, more frequent/severe exacerbations, and reduced response to asthma pharmacotherapy., Objective: This review aims to compare use of all classes of asthma medications in obese (body mass index (BMI) ≤30 kg·m -2 ) versus healthy-weight (BMI <25 kg·m -2 ) subjects with asthma., Design: Databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, Embase and MEDLINE were searched up to July 2019 for English-language studies that recorded medication use or dose in obese and healthy-weight adults with asthma. A critical appraisal checklist was utilised for scrutinising methodological quality of eligible studies. Meta-analysis was performed and heterogeneity was examined with the use of the Chi-squared test. This review was conducted based on a published protocol (www.crd.york.ac.uk/PROSPERO CRD42020148671)., Results: Meta-analysis showed that obese subjects are more likely to use asthma medications, including short-acting β 2 -agonists (OR 1.75, 95% CI 1.17-2.60; p=0.006, I 2 =41%) and maintenance oral corticosteroids (OR 1.86, 95% CI 1.49-2.31; p<0.001, I 2 =0%) compared to healthy-weight subjects. Inhaled corticosteroid (ICS) dose (µg·day -1 ) was significantly higher in obese subjects (mean difference 208.14, 95% CI 107.01-309.27; p<0.001, I 2 =74%). Forced expiratory volume in 1 s (FEV 1 ) % predicted was significantly lower in obese subjects (mean difference -5.32%, 95% CI -6.75--3.89; p<0.001, I 2 =42%); however, no significant differences were observed in FEV 1 /forced vital capacity (FVC) ratio between groups., Conclusions: We found that obese subjects with asthma have higher use of all included asthma medication classes and higher ICS doses than healthy-weight asthma subjects, despite lower FEV 1 and a similar FEV 1 /FVC %. A better understanding of the factors driving increased medication use is required to improve outcomes in this subgroup of asthmatics., Competing Interests: Conflict of interest: C.A. Thompson has nothing to disclose. Conflict of interest: S.R. Eslick has nothing to disclose. Conflict of interest: B.S. Berthon has nothing to disclose. Conflict of interest: L.G. Wood has nothing to disclose., (Copyright ©ERS 2021.)

Background: An association between the severity of coronavirus disease 2019 (COVID-19) and the presence of certain chronic conditions has been suggested. However, unlike influenza and other viruses, the disease burden of COVID-19 in patients with asthma has been less evident., Objective: To understand the impact of COVID-19 in patients with asthma., Methods: Using big-data analytics and artificial intelligence through the SAVANA Manager clinical platform, we analysed clinical data from patients with asthma from January 1 to May 10, 2020., Results: Out of 71 182 patients with asthma, 1006 (1.41%) suffered from COVID-19. Compared to asthmatic individuals without COVID-19, patients with asthma and COVID-19 were significantly older (55 versus 42 years), predominantly female (66% versus 59%), smoked more frequently and had higher prevalence of hypertension, dyslipidaemias, diabetes and obesity. Allergy-related factors such as rhinitis and eczema were less common in asthmatic patients with COVID-19 (p<0.001). In addition, higher prevalence of these comorbidities was observed in patients with COVID-19 who required hospital admission. The use of inhaled corticosteroids (ICS) was lower in patients who required hospitalisation due to COVID-19, as compared to non-hospitalised patients (48.3% versus 61.5%; OR 0.58, 95% CI 0.44-0.77). Although patients treated with biologics (n=865; 1.21%) showed increased severity and more comorbidities at the ear, nose and throat level, COVID-19-related hospitalisations in these patients were relatively low (0.23%)., Conclusion: Patients with asthma and COVID-19 were older and at increased risk due to comorbidity-related factors. ICS and biologics are generally safe and may be associated with a protective effect against severe COVID-19 infection., Competing Interests: Conflict of interest: J.L. Izquierdo reports personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Grifols, Menarini, Novartis, Orion, Pfizer, Sandoz and Teva. Conflict of interest: C. Almonacid reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis and ALK. Conflict of interest: Y. González reports that they are an employee at Savana Medica. Conflict of interest: C. Del Rio-Bermudez reports that they are an employee at Savana Medica. Conflict of interest: J. Ancochea has nothing to disclose. Conflict of interest: R. Cárdenas has nothing to disclose. Conflict of interest: S. Lumbreras has nothing to disclose. Conflict of interest: J.B. Soriano has nothing to disclose., (Copyright ©ERS 2021.)

Most children diagnosed with asthma have respiratory symptoms such as cough, dyspnoea and wheezing, which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated genetic susceptibility to asthma itself, but few have focused on important respiratory symptoms that characterise childhood asthma.Using whole-genome sequencing (WGS) data for 894 asthmatic trios from a Costa Rican cohort, we performed family-based association tests (FBATs) to assess the association between genetic variants and multiple asthma-relevant respiratory phenotypes: cough, phlegm, wheezing, exertional dyspnoea and exertional chest tightness. We tested whether genome-wide significant associations were replicated in two additional studies: 1) 286 asthmatic trios from the Childhood Asthma Management Program (CAMP), and 2) 2691 African American current or former smokers from the COPDGene study.In the 894 Costa Rican trios, we identified a genome-wide significant association (p=2.16×10 -9 ) between exertional dyspnoea and the single nucleotide polymorphism (SNP) rs10165869, located on chromosome 2q37.3, that was replicated in the CAMP cohort (p=0.023) with the same direction of association (combined p=3.28×10 -10 ). This association was not found in the African American participants from COPDGene. We also found suggestive evidence for an association between SNP rs10165869 and the atypical chemokine receptor 3 ( ACKR3 ).Our finding encourages the secondary association analysis of a wider range of phenotypes that characterise respiratory symptoms in other airway diseases/studies., Competing Interests: Conflict of interest: S. Lee has nothing to disclose. Conflict of interest: J.A. Lasky-Su has nothing to disclose. Conflict of interest: C. Lange has nothing to disclose. Conflict of interest: W. Kim has nothing to disclose. Conflict of interest: P.L. Kumar has nothing to disclose. Conflict of interest: M-L.N. McDonald has nothing to disclose. Conflict of interest: C.A. Vaz Fragoso has nothing to disclose. Conflict of interest: C. Laurie has nothing to disclose. Conflict of interest: B.A. Raby has nothing to disclose. Conflict of interest: J.C. Celedon has received research materials from GSK and Merck (inhaled steroids) and Pharmavite (vitamin D and placebo capsules), in order to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work. Conflict of interest: M.H. Cho has nothing to disclose. Conflict of interest: S. Won has nothing to disclose. Conflict of interest: S.T. Weiss reports that he is an author for UpToDate, PI of several NIH grants and an unpaid advisor to Novartis Pharmaceuticals. Conflict of interest: J. Hecker has nothing to disclose., (Copyright ©ERS 2021.)

Introduction: Osteoporosis and fragility fractures are associated with corticosteroids which are the mainstay treatment for asthma; however, these bone comorbidities within asthma need to be better described., Methods: A matched cohort study was conducted using the UK Clinical Practice Research Database (CPRD). Adults with an incident asthma code were identified and matched, with up to four randomly selected people without asthma, by age, sex and practice. Osteoporosis and fragility fracture incidence rates were calculated, and Cox regression was performed comparing hazard rates to the general population. We report the impact of age, sex, glucocorticoids and the risk of specific fractures., Results: Patients with asthma had a higher risk of osteoporosis (adjusted hazard ratio (aHR) 1.18, 95% CI 1.13-1.23) and were 12% (aHR 1.12, 95% CI 1.07-1.16) more likely to sustain fragility fractures than the general population. Age modified the effect of asthma on osteoporosis and fragility fractures, such that the effect was stronger in younger people (p interaction <0.0001). The vertebra (aHR 1.40, 95% CI 1.33-1.48) and forearm/wrist (aHR 1.27, 95% CI 1.22-1.32) were the sites linked with a larger incidence. A dose-response relationship between oral corticosteroids (OCS) and osteoporosis was observed, whereas the risk of fragility fractures increased in those with six or more OCS courses per year. Regular use of inhaled corticosteroids (ICS) increased the risk of both bone conditions., Conclusions: Patients with asthma are more likely to develop osteoporosis or sustain fragility fractures than the general population, with a particular concern in younger people and those more frequently using OCS and ICS., Competing Interests: Conflict of interest: C.V. Chalitsios has nothing to disclose. Conflict of interest: T.M. McKeever has nothing to disclose. Conflict of interest: D.E. Shaw has nothing to disclose., (Copyright ©ERS 2021.)

Background: Viral respiratory infections are the main causes of asthma exacerbation. The susceptibility of patients with asthma to develop an exacerbation when they present with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. The objective of this study was to investigate the characteristics and outcomes of asthmatic patients with coronavirus disease 2019 (COVID-19) pneumonia who required hospitalisation during the spring 2020 outbreak in Paris, France., Methods: A prospective cohort follow-up was carried out from 15 March to 15 April 2020 in Bicêtre Hospital, University Paris-Saclay, France. All hospitalised patients with a SARS-CoV-2 infection who reported a history of asthma were included., Results: Among 768 hospitalised patients, 37 (4.8%) reported a history of asthma, which had been previously confirmed by a pulmonologist in 85% of cases. These asthmatic patients were mainly female (70%) and nonsmokers (85%), with a median age of 54 years (interquartile range (IQR) 42-67 years). None of them presented with an asthma exacerbation. 22 (59%) had major comorbidities and 31 (84%) had a body mass index ≥25 kg·m -2 . The most common comorbidities were obesity (36%), hypertension (27%) and diabetes (19%). All patients had a confirmed diagnosis of COVID-19 pneumonia on computed tomography of the chest. Eosinopenia was a typical biological feature with a median count of 0 cells·mm -3 (IQR 0-0 cells·mm -3 ). 11 patients (30%) were admitted into the intensive care unit, with three deaths (8.1%) occurring in the context of comorbidities., Conclusion: Asthma patients were not overrepresented among those with severe pneumonia due to SARS-CoV-2 infection who required hospitalisation. The worst outcomes were observed mainly in patients with major comorbidities., Competing Interests: Conflict of interest: A. Beurnier has nothing to disclose. Conflict of interest: E-M. Jutant has nothing to disclose. Conflict of interest: M. Jevnikar has nothing to disclose. Conflict of interest: A. Boucly has nothing to disclose. Conflict of interest: J. Pichon has nothing to disclose. Conflict of interest: M. Preda has nothing to disclose. Conflict of interest: M. Frank has nothing to disclose. Conflict of interest: J. Laurent has nothing to disclose. Conflict of interest: C. Richard has nothing to disclose. Conflict of interest: X. Monnet has nothing to disclose. Conflict of interest: J. Duranteau has nothing to disclose. Conflict of interest: A. Harrois has nothing to disclose. Conflict of interest: M-C. Chaumais has nothing to disclose. Conflict of interest: M-F. Bellin has nothing to disclose. Conflict of interest: N. Noël has nothing to disclose. Conflict of interest: S. Bulifon has nothing to disclose. Conflict of interest: X. Jaïs has nothing to disclose. Conflict of interest: F. Parent has nothing to disclose. Conflict of interest: A. Seferian has nothing to disclose. Conflict of interest: L. Savale has nothing to disclose. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and MSD, personal fees from Acceleron Pharmaceuticals, Gossamer Bio and Ferrer, grants and personal fees from Bayer, grants from GlaxoSmithKline, outside the submitted work. Conflict of interest: D. Montani has nothing to disclose. Conflict of interest: M. Humbert reports grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from AstraZeneca, Novartis, Roche, Sanofi and Teva, outside the submitted work., (Copyright ©ERS 2020.)

Objective: To determine the short-term and long-term effects of a high intensity pulmonary rehabilitation programme on asthma control, body composition, lung function and exercise capacity in obese asthma patients., Methods: Patients with obesity (body mass index (BMI)≥30 kg·m -2 ) and suboptimal controlled asthma (Asthma Control Questionnaire (ACQ)≥0.75) were randomly assigned to a 3-month pulmonary rehabilitation programme (PR only), pulmonary rehabilitation programme with the use of an internet based self-management support programme (PR+SMS) or usual care. The pulmonary rehabilitation programme included high-intensity interval training, nutritional intervention and psychological group sessions. Patients in the usual care group were advised to lose weight and to exercise. The primary outcome was the difference of change of ACQ between PR only and PR+SMS after 3 months. Total follow-up was 12 months., Results: 34 patients were included in the study (14 PR only, nine PR+SMS, 11 control). Compared with patients in usual care, patients in the PR only group had a significant reduction in BMI and significant improvements in asthma control, exercise capacity and aerobic capacity after 3 months. These improvements persisted during 12 months of follow-up. No difference in ACQ between PR+SMS and PR only groups was observed. However, users of the SMS programme had a significantly lower BMI after 12 months compared with subjects in the PR only group., Conclusion: A high-intensity pulmonary rehabilitation programme provides sustained improvements in asthma control, body composition and exercise capacity in obese asthmatics that are not optimally controlled and, therefore, should be considered in the treatment of these patients., Competing Interests: Conflict of interest: Y. Türk reports grants from GSK, TEVA, Novartis and Chiesi, during the conduct of the study. Conflict of interest: W. Theel has nothing to disclose Conflict of interest: A. van Huisstede has nothing to disclose. Conflict of interest: G-J.M. van de Geijn reports personal fees for lectures and non-financial support (travel and accommodation reimbursement, reagents and equipment for research) from Beckman Coulter, outside the submitted work. Conflict of interest: E. Birnie has nothing to disclose. Conflict of interest: P.S. Hiemstra has nothing to disclose. Conflict of interest: J.K. Sont has nothing to disclose. Conflict of interest: C. Taube has nothing to disclose. Conflict of interest: G-J. Braunstahl reports grants from GSK, Teva, Novartis and Chiesi, during the conduct of the study; personal fees from ALK Abello, GSK, AstraZeneca, Sanofi, Chiesi and Novartis, outside the submitted work., (Copyright ©ERS 2020.)

The association between asthma exacerbation during pregnancy and adverse maternal and child health outcomes have not been investigated appropriately. Our objective was to determine the short- and long-term intergenerational effect of asthma exacerbation in pregnant women with asthma.A population cohort study was conducted using data from the Ontario asthma surveillance system and population-level health administrative data. Asthma exacerbation in pregnant women with asthma was defined as at least one of the following criteria: at least five physician visits, or one emergency department visit or one hospital admission for asthma during pregnancy. Pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders were identified using International Classification of Disease codes (9th and 10th revisions).The cohort consisted of 103 424 singleton pregnancies in women with asthma. Asthma exacerbation in pregnant women with asthma was associated with higher odds of pre-eclampsia (OR 1.30, 95% CI 1.12-1.51) and pregnancy-induced hypertension (OR 1.17, 95% CI 1.02-1.33); babies had higher odds of low birthweight (OR 1.14, 95% CI 1.00-1.31), preterm birth (OR 1.14, 95% CI 1.01-1.29) and congenital malformations (OR 1.21, 95% CI 1.05-1.39). Children born to women with asthma exacerbation during pregnancy had elevated risk of asthma (OR 1.23, 95% CI 1.13-1.33) and pneumonia (OR 1.12, 95% CI 1.03-1.22) during the first 5 years of life.Asthma exacerbation during pregnancy in women with asthma showed increased risk of pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders in their children, indicating that appropriate asthma management may reduce the risk of adverse health outcomes., Competing Interests: Conflict of interest: K. Abdullah has nothing to disclose. Conflict of interest: J. Zhu has nothing to disclose. Conflict of interest: A. Gershon has nothing to disclose. Conflict of interest: S. Dell has nothing to disclose. Conflict of interest: T. To has nothing to disclose., (Copyright ©ERS 2020.)

Introduction: The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns., Methods: This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters., Results: 782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old., Conclusions: The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns., Competing Interests: Conflict of interest: M.T. Krishna reports support from Thermo Fisher (sponsorship to attend EAACI conference, Helsinki, in 2017 and support for department for conducting an educational meeting (PracticAllergy course)), ALK Abello (sponsorship to attend EAACI conference, Helsinki, in 2017), GSK, Mylan, Abbott, Allergy Therapeutics, Nutricia Danone and Biodiagnostics (support for conducting an educational meeting (PracticAllergy course)), outside the submitted work. Conflict of interest: A. Subramanian has nothing to disclose. Conflict of interest: N.J. Adderley has nothing to disclose. Conflict of interest: D.T. Zemedikun has nothing to disclose. Conflict of interest: G.V. Gkoutos has nothing to disclose. Conflict of interest: K. Nirantharakumar reports grants from NIHR, MRC, Diabetes UK and AstraZeneca, and personal fees from MSD, Sanofi and Boehringer Ingelheim, outside the submitted work., (Copyright ©ERS 2019.)

Background: Patients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown., Study Setting: A prospective observational study of adults with PCR-confirmed influenza in 11 UK hospitals, measuring nasal, nasopharyngeal and systemic immune mediators and whole-blood gene expression., Results: Of 133 admissions, 40 (30%) had previous asthma; these were more often female (70% versus 38.7%, OR 3.69, 95% CI 1.67-8.18; p=0.0012), required less mechanical ventilation (15% versus 37.6%, Chi-squared 6.78; p=0.0338) and had shorter hospital stays (mean 8.3 versus 15.3 days, p=0.0333) than those without. In patients without asthma, severe outcomes were more frequent in those given corticosteroids (OR 2.63, 95% CI 1.02-6.96; p=0.0466) or presenting >4 days after disease onset (OR 5.49, 95% CI 2.28-14.03; p=0.0002). Influenza vaccination in at-risk groups (including asthma) were lower than intended by national policy and the early use of antiviral medications were less than optimal. Mucosal immune responses were equivalent between groups. Those with asthma had higher serum interferon (IFN)-α, but lower serum tumour necrosis factor, interleukin (IL)-5, IL-6, CXCL8, CXCL9, IL-10, IL-17 and CCL2 levels (all p<0.05); both groups had similar serum IL-13, total IgE, periostin and blood eosinophil gene expression levels. Asthma diagnosis was unrelated to viral load, IFN-α, IFN-γ, IL-5 or IL-13 levels., Conclusions: Asthma is common in those hospitalised with influenza, but may not represent classical type 2-driven disease. Those admitted with influenza tend to be female with mild serum inflammatory responses, increased serum IFN-α levels and good clinical outcomes., Competing Interests: Conflict of interest: A. Jha holds a clinical lectureship at the University of Cambridge that is supported jointly by the University of Cambridge Experimental Medicine Training Initiative (EMI) programme in partnership with GlaxoSmithKline (EMI-GSK) and Cambridge University Hospitals NHS Foundation Trust. The funding received by A. Jha from the EMI-GSK programme is not relevant to the content of this manuscript. Conflict of interest: J. Dunning has nothing to disclose. Conflict of interest: T. Tunstall has nothing to disclose. Conflict of interest: R.S. Thwaites has nothing to disclose. Conflict of interest: L.T. Hoang has nothing to disclose. Conflict of interest: O.M. Kon has nothing to disclose. Conflict of interest: M.C. Zambon has nothing to disclose Conflict of interest: T.T. Hansel and Imperial Innovations are involved in setting up a medical device company called Mucosal Diagnostics (MD), which is an Imperial College spin-off company. Conflict of interest: P.J. Openshaw reports personal fees for consultancy from Janssen, grants from MRC, EU, NIHR Biomedical Research Centre, MRC/GSK, Wellcome Trust, NIHR and MRC Global Challenge Research Fund, personal fees for online presentations from European Respiratory Society, non-financial support from AbbVie, outside the submitted work; and is past president and trustee of British Society for Immunology, vice-chair and member of NERVTAG (New and Emerging Respiratory Virus Threats Advisory Group; Department of Health)., (Copyright ©ERS 2019.)

Asthma has been linked with prolonged time to pregnancy. Our aim was to explore a possible association between asthma and need for fertility treatment among women with live births.All women enrolled in the Management of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital, Denmark were each matched with the next three consecutive women giving birth at Hvidovre Hospital. Information from the Danish National Assisted Reproductive Technology (ART) registry was cross-linked with the Danish Medical Birth registry to identify live births. The primary outcome of interest was births following fertility treatment.Our sample comprised pregnancies from asthmatic mothers (n=932, described as "cases") and non-asthmatic mothers (n=2757, described as "controls"), with 12% (n=114) and 8% (n=212), respectively, having had fertility treatment (OR 1.67, 95% CI 1.32-2.13; p<0.001). This association remained statistically significant after adjusting for confounders, including body mass index (OR 1.31, 95% CI 1.00-1.70; p=0.047). In women ≥35 years, 25% of cases (n=63) and 13% of controls (n=82) received fertility treatment (OR 2.12, 95% CI 1.47-3.07; p<0.001), which also remained statistically significant after adjusting for confounders (OR 1.65, 95% CI 1.11-2.46; p=0.013).A higher proportion of the births from asthmatic mothers involved fertility treatment compared to non-asthmatic mothers, not least among women aged ≥35 years., Competing Interests: Conflict of interest: A. Vejen Hansen has nothing to disclose. Conflict of interest: Z. Ali has nothing to disclose. Conflict of interest: S.S. Malchau has nothing to disclose. Conflict of interest: J. Blafoss has nothing to disclose. Conflict of interest: A. Pinborg has nothing to disclose. Conflict of interest: C.S. Ulrik has nothing to disclose., (Copyright ©ERS 2019.)

We investigated whether the combination of increased exhaled nitric oxide fraction ( F eNO ) level and blood eosinophil count had an additive value in chronic airway disease in the general population.We included 4677 individuals aged 20-100 years from the Copenhagen General Population Study. Based on pre- and post-bronchodilator spirometry, self-reported asthma and smoking history, participants were subdivided into healthy never-smokers (n=1649), healthy ever-smokers (n=1581), asthma (n=449), chronic obstructive pulmonary disease (COPD) (n=404), asthma-COPD overlap (ACO) (n=138) and nonspecific airflow limitation (n=456).Compared to individuals with F eNO <25 ppb and blood eosinophils <0.3×10 9  cells·L -1 , age- and sex-adjusted odds ratios (95% CI) for wheezing were 1.54 (1.29-1.84) for individuals with F eNO ≥25 ppb or blood eosinophils ≥0.3×10 9  cells·L -1 and 2.14 (1.47-3.10) for individuals with F eNO ≥25 ppb and blood eosinophils ≥0.3×10 9  cells·L -1 Corresponding odds ratios were 1.13 (0.91-1.41) and 1.83 (1.20-2.79) for sputum production, 1.54 (1.22-1.94) and 3.26 (2.16-4.94) for asthma, 1.03 (0.80-1.32) and 0.67 (0.36-1.27) for COPD and 1.32 (0.88-1.96) and 2.14 (1.05-4.36) for ACO. Among individuals reporting respiratory symptoms, predicting the type of chronic airway disease did not differ between the two biomarkers and did not improve by combining them.Combination of F eNO and blood eosinophils may have an additive value in characterising chronic airway disease in the general population but still needs to be investigated further with regard to clinical application., Competing Interests: Conflict of interest: Y. Çolak reports personal fees from Boehringer Ingelheim and AstraZeneca outside the submitted work. Conflict of interest: P. Lange reports grants from AstraZeneca and GlaxoSmithKline, and personal fees from Boehringer Ingelheim, AstraZeneca, Novartis and GlaxoSmithKline, outside the submitted work., (Copyright ©ERS 2018.)

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed.Colony-stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated.Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes., Competing Interests: Conflict of interest: K. Takahashi received personal fees from Asahi General Hospital, during the conduct of the study. Conflict of interest: M. Loza is employed by and owns stock in Johnson & Johnson, the parent company of Janssen R&D. Conflict of interest: F. Baribaud is an employee and shareholder of Janssen R&D. Conflict of interest: P. Chanez has provided consultancy services for Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, Merck Sharp & Dohme, AstraZeneca, Novartis, Teva, Chiesi, Sanofi and SNCF; has served on advisory boards for Almirall, Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi and Sanofi; has received lecture fees from Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific and ALK; and has received industry-sponsored grants from Roche, Boston Scientific, Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, ALK, Novartis, Teva and Chiesi. Conflict of interest: I. Horvath has received personal fees from Astra Zeneca, Boehringer Ingelheim, Novartis, CSL, Chiesi, Roche, GSK, Berlin-Chemie and Sandoz, outside the submitted work. Conflict of interest: P. Montuschi reports personal fees from advisory board meetings with AstraZeneca, outside the submitted work. Conflict of interest: F. Singer has received personal fees and honoraria for speaking engagements from Vertex and Novartis, outside the submitted work. Conflict of interest: S-E. Dahlén has received research grants from several Swedish funding bodies such as MRC, Heart-Lung-Foundation and the Strategic Research Foundation, during the conduct of the study; and has received personal fees for advisory board meetings from GSK, AZ, Novartis, Teva, Regeneron/Sanofi, Merck and RSPR AB, grants on asthma phenotyping from AZ, and honoraria for speaking engagements from GSK and Teva, outside the submitted work. Conflict of interest: B. Dahlén has received personal fees from Teva (for advisory board membership) and AstraZeneca (payments for lectures), outside the submitted work. Conflict of interest: N. Krug reports grants from IMI (U-BIOPRED consortium IMI number 115010), during the conduct of the study. Conflict of interest: T. Sandström has received personal fees from advisory board meetings with pharmaceutical companies GSK, AZ, Novartis, Teva and Boehringer Ingelheim, and honoraria for speaking engagements for AZ, Novartis, Boehringer Ingelheim, outside the submitted work. Conflict of interest: D.E. Shaw has received personal fees for advisory board work from GSK, AZ, Teva and Boehringer Ingelheim, outside the submitted work. Conflict of interest: R. Lutter has received personal fees for advisory board meetings from GSK and Boehringer Ingelheim, and grants on asthma and COPD from GSK, Lung Foundation and MedImmune, outside the submitted work. Conflict of interest: P. Bakke has received personal fees for advisory board meetings from GSK, AZ, Novartis and Teva, and honoraria for speaking engagements from AZ and Boehringer Ingelheim, outside the submitted work. Conflict of interest: L.J. Fleming has received personal fees for advisory board meetings from Novartis, Vectura and Boehringer Ingelheim, grants from Asthma UK and BLF, and honoraria for speaking engagements for Novartis, outside the submitted work. Conflict of interest: P.H. Howarth was employed part time by GSK as Global Medical Expert. Conflict of interest: M. Caruso received grants (paid to institute) from the Innovative Medicines Initiative (IMI), during the conduct of the study. Conflict of interest: C. Auffray received grants from the Innovative Medicine Initiative (U-BIOPRED Consortium IMI number 115010 and eTRIKS Consortium IMI number 115446), during the conduct of the study. Conflict of interest: B. De Meulder received grants from the Innovative Medicine Initiative (U-BIOPRED Consortium IMI number 115010 and eTRIKS Consortium IMI number 115446), during the conduct of the study. Conflict of interest: D. Lefaudeux received grants from the Innovative Medicine Initiative (U-BIOPRED Consortium IMI number 115010 and eTRIKS Consortium IMI number 115446), during the conduct of the study. Conflict of interest: R. Djukanovic has received personal fees for lectures at company sponsored symposia and consulting in advisory boards from TEVA, grants (for an investigator led study of mechanisms of action of omalizumab) and personal fees (for lectures at company sponsored symposia and consulting in advisory boards) from Novartis, and is a consultant to, co-founder of, and holds shares in Synairgen, outside the submitted work. Conflict of interest: P.J. Sterk has received a public-private grant (paid to institute) from Innovative Medicines Initiative (IMI) covered by the European Union (EU) and the European Federation of Pharmaceutical Industries and Associations (EFPIA), during the conduct of the study. Conflict of interest: I.M. Adcock has received personal fees for advisory board meetings from GSK, AZ, Novartis, Boehringer Ingelheim and Vectura, grants on asthma and COPD from Pfizer, GSK, MRC, EU, BI and IMI, and honoraria for speaking engagements for AZ and BI, outside the submitted work. Conflict of interest: K.F. Chung has received personal fees for advisory board meetings from GSK, AZ, Novartis, Teva, Boehringer Ingelheim and J&J, grants on asthma and COPD from Pfizer, GSK, MRC, EU IMI and NIH, and honoraria for speaking engagements for AZ and Merck, outside the submitted work., (Copyright ©ERS 2018.)

Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in small airways have been found in asthma. If the "one airway, one disease" concept is consistent, such dysfunctions should also be detected in the peripheral airways of patients suffering from allergic rhinitis.We investigated whether peripheral airway reactivity and NO overproduction could be documented in distal airways in patients with allergic rhinitis. Exhaled NO fraction ( F eNO ) and the slope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfur hexafluoride (SF 6 ) were measured in 31 patients with allergic asthma, 23 allergic rhinitis patients and 24 controls, before and after sputum induction. SBWT is sensitive to airway calibre change occurring in the lung periphery.The F eNO decrease was more significant in asthma and rhinitis than in controls (-55.1% and -50.0%, respectively, versus -40.8%) (p=0.007 and p=0.029, respectively). S SF 6 and S He increased in all groups. Change in S He (ΔS He ) > ΔS SF 6 was observed in rhinitis (p=0.004) and asthma (p<0.001), whereas ΔS SF 6 = ΔS He in controls (p=0.431).This study provides evidence of peripheral airway dysfunction in patients with allergic rhinitis quite similar to that described in asthma. Furthermore, a large proportion of the increased NO production reported in allergic rhinitis appears to originate in the peripheral airways., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

Asthma and chronic obstructive pulmonary disease (COPD) are complex and overlapping diseases that include inflammatory phenotypes. Novel anti-eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping, which might be accessible from exhaled breath.Our objective was to capture clinical/inflammatory phenotypes in patients with chronic airway disease using an electronic nose (eNose) in a training and validation set.This was a multicentre cross-sectional study in which exhaled breath from asthma and COPD patients (n=435; training n=321 and validation n=114) was analysed using eNose technology. Data analysis involved signal processing and statistics based on principal component analysis followed by unsupervised cluster analysis and supervised linear regression.Clustering based on eNose resulted in five significant combined asthma and COPD clusters that differed regarding ethnicity (p=0.01), systemic eosinophilia (p=0.02) and neutrophilia (p=0.03), body mass index (p=0.04), exhaled nitric oxide fraction (p<0.01), atopy (p<0.01) and exacerbation rate (p<0.01). Significant regression models were found for the prediction of eosinophilic (R 2 =0.581) and neutrophilic (R 2 =0.409) blood counts based on eNose. Similar clusters and regression results were obtained in the validation set.Phenotyping a combined sample of asthma and COPD patients using eNose provides validated clusters that are not determined by diagnosis, but rather by clinical/inflammatory characteristics. eNose identified systemic neutrophilia and/or eosinophilia in a dose-dependent manner., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

The association between obesity and bronchial hyperresponsiveness (BHR) is incompletely characterised. Using the 2006 follow-up of the Tasmanian Longitudinal Health Study, we measured the association between obesity and BHR and whether it was mediated by small airway closure or modified by asthma and sex of the patient.A methacholine challenge measured BHR. Multivariable logistic regression measured associations between body mass index (BMI) and BHR, adjusting for sex, asthma, smoking, corticosteroid use, family history and lung function. Mediation by airway closure was also measured.Each increase in BMI of 1 kg·m -2 was associated with a 5% increase in the odds of BHR (OR 1.05, 95% CI 1.01-1.09) and 43% of this association was mediated by airway closure. In a multivariable model, BMI (OR 1.06, 95% CI 1.00-1.16) was associated with BHR independent of female sex (OR 3.26, 95% CI 1.95-5.45), atopy (OR 2.30, 95% CI 1.34-3.94), current asthma (OR 5.74, 95% CI 2.79-11.82), remitted asthma (OR 2.35, 95% CI 1.27-4.35), low socioeconomic status (OR 2.11, 95% CI 1.03-4.31) and forced expiratory volume in 1 s/forced vital capacity (OR 0.86, 95% CI 0.82-0.91). Asthma modified the association with an increasing probability of BHR as BMI increased, only in those with no or remitted asthma.An important fraction of the BMI/BHR association was mediated via airway closure. Conflicting findings in previous studies could be explained by failure to consider this intermediate step., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) seems an important clinical phenotype, but multiple definitions have been proposed. This study's objectives were to assess the effect of different ACOS definitions on prevalence, patient characteristics and exacerbations.5675 individuals aged 45-65 years, with 846 asthma/COPD patients, were included in the Netherlands Epidemiology of Obesity study between 2008 and 2012, and followed-up for a median of 1.8 years. ACOS was defined by recent consensus criteria and five other definitions, based on registry, questionnaires and lung function.Prevalence of ACOS in the asthma/COPD population ranged between 4.4% and 38.3%, depending on the definition used. Agreement between registry-based and self-reported ACOS was 0.04 and 0.41 when lung function (forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) <0.7) was added. With registry or self-report defined ACOS, only 51% and 33% had FEV 1 /FVC <0.7. Patient characteristics were similar, but asthma duration was longer with self-reported compared with registry-based ACOS (mean difference 22 years (95% CI 12-33)). Exacerbation risk was highest with registry-based ACOS compared with asthma (adjusted incidence rate ratio 1.6 (95% CI 1.2-2.1)).This study adds important knowledge about agreement between ACOS definitions and their relation with exacerbations. Given the low agreement, differences in prevalence, patient characteristics and risk of exacerbations, consensus about ACOS definition in different care settings is urgently needed., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Differences between asthma-COPD overlap syndrome (ACOS) and adult-onset asthma are poorly understood. This study aimed to evaluate these differences in a clinical cohort of patients with adult-onset asthma, as a part of the Seinäjoki Adult Asthma Study (SAAS).188 patients were diagnosed with adult-onset asthma and re-evaluated 12 years after diagnosis. They were divided into three groups based on smoking history and post bronchodilator spirometry values: 1) never- and ex-smokers with <10 smoked pack-years; 2) non-obstructive (forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ≥0.7) patients with ≥10 pack-years; and 3) ACOS patients with ≥10 pack-years and FEV 1 /FVC <0.7.ACOS patients had lower diffusing capacity ( D LCO /V A 86% predicted versus 98 or 96% predicted; p<0.001), higher blood neutrophil levels (4.50 versus 3.60 or 3.85×10 9 L -1 ; p=0.008), and higher IL-6 levels (2.88 versus 1.52 or 2.10 pg·mL -1 , p<0.001) as compared to never- and ex-smokers with <10 pack-years, or non-obstructive patients with ≥10 pack-years smoking history, respectively. ACOS patients also showed reduced lung function, higher remaining bronchial reversibility and a higher number of comorbidities.This study shows distinct differences in diffusing capacity, blood neutrophil and IL-6 levels, bronchial reversibility, lung function and comorbidities between ACOS and adult-onset asthma. The present findings should be considered in the comprehensive assessment of adult asthma patients., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Due to the high prevalence rates of cigarette smoking and asthma, current and ex-smokers frequently develop chronic airway disease without spirometric evidence of chronic obstructive pulmonary disease (COPD), either alone or associated with asthma. This review considers the classification, clinical outcomes, inflammatory and imaging variables, phenotypes, and management of current and ex-smokers with airway disease without COPD, focusing on overlaps in those with and without asthma. These individuals have more respiratory symptoms, worse quality of life, increased exacerbation rates, reduced lung function and more comorbidities than never-smokers with asthma or healthy never-smokers. As well as clinical features, airway inflammatory and structural changes in smoking-induced airway disease without COPD overlap with those found in smokers with asthma. Cigarette smoking is associated with worse clinical outcomes in some phenotypes of asthma. Management involves public health measures to control exposure to tobacco smoke, personal advice on smoking cessation and the use of appropriate targeted therapies, although evidence is limited on their effectiveness. Understanding the mechanisms, natural history and management of current and ex-smokers with asthma and smoking-induced airway disease without COPD is a priority for future research., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

We aimed to describe the differences and similarities between patients with chronic obstructive airway disease classified on the basis of classical diagnostic labels (asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACOS)) or according to the underlying inflammatory pattern (Th-2 signature, either Th-2-high or Th-2-low).We performed a cross-sectional study of patients aged ≥40 years and with a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio ≤0.7 with a previous diagnosis of asthma (non-smoking asthmatics (NSA)), COPD or ACOS, the latter including both smoking asthmatics (SA) and patients with eosinophilic COPD (COPD-e). Clinical, functional and inflammatory parameters (blood eosinophil count, IgE and exhaled nitric oxide fraction ( F eNO )) were compared between groups. Th-2 signature was defined by a blood eosinophil count ≥300 cells·μL -1 and/or a sputum eosinophil count ≥3%.Overall, 292 patients were included in the study: 89 with COPD, 94 NSA and 109 with ACOS (44 SA and 65 with COPD-e). No differences in symptoms or exacerbation rate were found between the three groups. With regards the underlying inflammatory pattern, 94 patients (32.2%) were characterised as Th-2-high and 198 (67.8%) as Th-2-low. The Th-2 signature was found in 49% of NSA, 3.3% of patients with COPD, 30% of SA and 49.3% of patients with COPD-e. This classification yielded significant differences in demographic, functional and inflammatory characteristics.We conclude that a classification based upon the inflammatory profile, irrespective of the taxonomy, provides a more clear distinction of patients with chronic obstructive airway disease., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Asthma is associated with an increased risk of pulmonary embolism (PE) but little is known about whether asthma is associated with an increased risk of deep venous thrombosis (DVT). The aim in this study was to determine the risk of the first event of PE, DVT or a combination of PE and DVT in patients with asthma.We conducted this nationwide case-control study using data from Swedish nationwide registries. We included 114 366 Swedish-born patients with a first hospital diagnosis of PE, 76 494 patients with DVT and 6854 patients with both PE and DVT in Sweden between 1981 and 2010. We also included five age-, sex- and education-matched population controls. All previous hospital diagnoses of asthma were identified. Conditional logistic regression was used to compute odds ratios with adjustment for potential confounders.Asthma was associated with an adjusted odds ratio for PE of 1.43 (95% CI 1.37-1.50), for DVT of 1.56 (95% CI 1.47-1.65) and for combined PE and DVT of 1.60 (95% CI 1.32-1.93). Asthma was associated with an increased risk of PE, DVT and combined PE and DVT.Thus, the inflammation conferred by asthma seems to have systemic (and not just local) prothrombotic effects with increased risk of both DVT and PE., (Copyright ©ERS 2017.)

Asthmatic patients frequently have comorbidities, but the role of comorbidities in the economic burden of asthma is unclear. We examined the excess direct medical costs, including asthma- and comorbidity-related costs, in patients with asthma.We created a propensity score-matched cohort of patients newly diagnosed with asthma and non-asthmatic comparison subjects, both aged 5-55 years, from health administrative data (1997-2012) in British Columbia, Canada. Health services use records were categorised into 16 major disease categories based on International Classification of Diseases codes. Excess costs (in 2013 Canadian dollars ($)) were estimated as the adjusted difference in direct medical costs between the two groups.Average overall excess costs were estimated at $1058/person-year (95% CI 1006-1110), of which $134 (95% CI 132-136) was attributable to asthma and $689 (95% CI 649-730) to major comorbidity classes. Psychiatric disorders were the largest component of excess comorbidity costs, followed by digestive disorders, diseases of the nervous system, and respiratory diseases other than asthma. Comorbidity-attributable excess costs greatly increased with age but did not increase over the time course of asthma.These findings suggest that both asthma and comorbidity-related outcomes should be considered in formulating evidence-based policies and guidelines for asthma management., (Copyright ©ERS 2016.)

To estimate the association between obesity and poor asthma control or risk of exacerbations in asthmatic children and adolescents, and to assess whether these associations are different by sex.A meta-analysis was performed on unpublished data from three North-European paediatric asthma cohorts (BREATHE, PACMAN (Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects) and PAGES (Pediatric Asthma Gene Environment Study)) and 11 previously published studies (cross-sectional and longitudinal studies). Outcomes were poor asthma control (based on asthma symptoms) and exacerbations rates (asthma-related visits to the emergency department, asthma-related hospitalisations or use of oral corticosteroids). Overall pooled estimates of the odds ratios were obtained using fixed- or random-effects models.In a meta-analysis of 46 070 asthmatic children and adolescents, obese children (body mass index ≥95th percentile) compared with non-obese peers had a small but significant increased risk of asthma exacerbations (OR 1.17, 95% CI 1.03-1.34; I 2 : 54.7%). However, there was no statistically significant association between obesity and poor asthma control (n=4973, OR 1.23, 95% CI 0.99-1.53; I 2 : 0.0%). After stratification for sex, the differences in odds ratios for girls and boys were similar, yet no longer statistically significant.In asthmatic children, obesity is associated with a minor increased risk of asthma exacerbations but not with poor asthma control. Sex does not appear to modify this risk., (Copyright ©ERS 2016.)

Patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) have been largely excluded from pivotal therapeutic trials and, as a result, its treatment remains poorly defined and lacking firm evidence. To date, there is no universally accepted definition of ACOS, which has made it difficult to understand its epidemiology or pathophysiology. Despite many uncertainties, there is emerging agreement that some of the key features of ACOS include persistent airflow limitation in symptomatic individuals 40 years of age and older, a well-documented history of asthma in childhood or early adulthood and a significant exposure history to cigarette or biomass smoke. In this perspective, we propose a case definition of ACOS that incorporates these key features in a parsimonious algorithm that may enable clinicians to better diagnose patients with ACOS and most importantly enable researchers to design therapeutic and clinical studies to elucidate its epidemiology and pathophysiology and to ascertain its optimal management strategies., (Copyright ©ERS 2016.)