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Introduction: Small airway disease (SAD) represents a common and critical feature of Chronic Obstructive Pulmonary Disease (COPD). Introduced in the '60s, SAD has gradually gained increasing interest as assessment methodologies have improved. Chronic exposure to smoking and noxious particles or gases induces inflammation and remodeling, leading to airway obstruction and SAD, eventually resulting in complete airway loss., Areas Covered: A literature search up to June 2024 was performed in PubMed to identify articles on SAD and airway diseases mainly COPD, but also to the extent that it seemed relevant in the uncontrolled/severe asthma field, where SAD is better studied. We provide clinicians and translational scientists with a comprehensive analysis of the existing literature on SAD in COPD, concentrating on the underlying pathophysiological mechanisms, diagnostic techniques, and current pharmacological approaches targeting airflow obstruction in small airways., Expert Opinion: Small airways are the primary site for the onset and progression of airflow obstruction in patients with COPD, with significant clinical consequences associated with poor lung function, hyperinflation, and impaired quality of life. The early identification of individuals with subclinical SAD may allow us to prevent its further progress from airway loss and potential development of emphysema and choose the appropriate therapeutic approach.

The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review., Competing Interests: G.M. Gauvreau declares grants from AstraZeneca, Biohaven, Novartis and Genentech; consulting fees from AstraZeneca, Biohaven, Novartis, Sterna Biologicals and Certior Consulting; and payment or honoraria from AstraZeneca, Genzyme and Genentech, all in the 36 months prior to manuscript submission. B.E. Davis declares no competing interests. G. Scadding declares support from ALK-Abelló (provision of active and placebo medication for the GRASS clinical trial referenced in the article) and the Immune Tolerance Network (NIAID, NIH, USA; sponsor of the GRASS clinical trial) related to the present manuscript; as well as payment for lectures from ALK-Abelló in 2020 and 2021; and support from GlaxoSmithKline for attendance at the 2021 European Academy of Allergy and Clinical Immunology meeting. L-P. Boulet declares research grants for participation in multicentre studies or research projects proposed by the investigator from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron; royalties from UptoDate and Taylor & Francis; lecture fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck and Sanofi, all in the 36 months prior to manuscript submission; and the following unpaid contributions: Chair of the Global Initiative for Asthma (GINA) Board of Directors; President of the Global Asthma Organisation (Interasma); Member of the Canadian Thoracic Society Respiratory Guidelines Committee; and Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. L. Bjermer declares no competing interests. A. Chaker declares grants or contracts, via Technical University Munich, from EIT Health (European Institute of Technology), BMBF (German Federal Ministry of Education and Research), AstraZeneca, Sanofi-Genzyme, Roche, GlaxoSmithKline and ALK-Abelló; payments or honoraria, via Technical University Munich, from ALK-Abelló, Allergopharma, AstraZeneca, GlaxoSmithKline, Immunotek, Novartis, Regeneron, Sanofi-Genzyme, Leti, Zeller and Bencard; travel reimbursement to attend European Academy of Allergy and Clinical Immunology meetings (2018 and 2021 from the European Academy of Allergy and Clinical Immunology; 2019 from ALK-Abelló); patents, via Technical University Munich, relating to allergen-specific immunotherapy and treatment of SARS-CoV-2 infection; participation, via Technical University Munich, on a data safety monitoring board or advisory board for ALK-Abelló, Allergopharma, AstraZeneca, GlaxoSmithKline, Immunotek, Novartis, Regeneron and Sanofi-Genzyme; and the following unpaid roles: Past Chair of the Allergy, Clinical Immunology and Environmental Medicine Section of the German ENT Society; board member at large of the German Allergy Society (DGAKI); scientific advisor/board member to the German Society for Applied Allergy (AeDA); board member of the Allergen Immuntherapy Interest Group, European Academy of Allergy and Clinical Immunology. D.W. Cockcroft reports the following research grants in the 36 months prior to manuscript submission: research grant Dept of Medicine University of Saskatchewan (Effect of tiotropium on airway response to allergen); Canadian Society of Allergy and Clinical Immunology (The effect of deep inhalation on mannitol responsiveness); AstraZeneca (A phase 2a double blind randomised parallel group placebo controlled multicentre study to evaluate the effect of AZD8154 administered via nebuliser once daily on allergen-induced inflammation in subjects with mild allergic asthma challenged with inhaled allergen); AllerGen NCE (Methacholine challenge comparison of a jet nebuliser and vibrating mesh nebuliser); Novartis (Inhaled CSJ117 in adult asthmatics with mild atopic asthma). B. Dahlén declares payment to their institution in 2004 for a clinical trial by AstraZeneca, related to the present work; and grants to support the Karolinska Severe Asthma Centre from GlaxoSmithKline and Novartis; consulting fees from Teva, AstraZeneca and Sanofi; and payment for lectures from AstraZeneca and Sanofi, all in the 36 months prior to manuscript submission. W. Fokkens declares grants to their institution from ALK, Mylan, Allergy Therapeutics, GlaxoSmithKline, Sanofi, Novartis and Chordate; consulting fees from Sanofi and Bioinspire; payment or honoraria from Sanofi, GlaxoSmithKline and Novartis; and participation on a data safety monitoring board or advisory board for Lyra, Sanofi and GlaxoSmithKline, all in the 36 months prior to manuscript submission; and that they are Secretary General of the European Rhinologic Society. P. Hellings declares no competing interests. N. Lazarinis declares no competing interests. P.M. O'Byrne reports grants from AstraZeneca, GlaxoSmithKline, Biohaven, Merck, Bayer and Novartis; consulting fees from AstraZeneca, Covis, GlaxoSmithKline, Amgen and Novartis; and payment or honoraria from AstraZeneca, Covis and Novartis, all in the 36 months prior to manuscript submission; and that they are a Section Editor of the European Respiratory Journal. E. Tufvesson declares no competing interests. S. Quirce declares consulting fees and payment or honoraria from GlaxoSmithKline, Sanofi and AstraZeneca; and payment or honoraria from Novartis, Chiesi, Mundipharma and Teva, all in the 36 months prior to manuscript submission. M. Van Maaren declares payment or honoraria from ALK-Abelló, Takeda and CSL Behring, in the 36 months prior to manuscript submission; and an unpaid role as Chairman of the Dutch Society of Allergology and Clinical Immunology since 2020. F. H. de Jongh declares an unpaid role as European Respiratory Society Assessment Director. Z. Diamant reports that until May 2020 they worked as Research Director Respiratory & Allergy at a CRO (QPS-NL), which received funding from biotech and several pharma companies for conduct of phase I–II clinical studies (drug development); and declares consulting fees from ALK-Abelló, AstraZeneca, Antabio, GlaxoSmithKline, HAL Allergy, QPS-NL and Sanofi-Genzyme; and payment or honoraria from BMR, Boehringer Ingelheim, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Merck Sharp & Dohme and Sanofi-Genzyme, all in the 36 months prior to manuscript submission; and unpaid roles as the European Academy of Allergy and Clinical Immunology Asthma Section Chair (2017–2019) and EUFOREA Asthma Expert Panel Chair (since 2020)., (Copyright ©The authors 2022.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care., Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021., Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%)., Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic., Competing Interests: Conflict of interest: A. Bourdin reports receiving grants or contracts outside the submitted work from AstraZeneca and Boeringher Ingelheim; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events as well as support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Chiesi and Amgen, outside the submitted work. Z. Csoma reports receiving honoraria for presentations from Astra/Zeneca, TEVA and Sanofi/Aventis (Hungary) outside the submitted work. E. Heffler reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Sanofi-Genzyme, Regeneron, Novartis, GSK, Circassia; Stallergenes-Greer and Nestlè Purina outside the submitted work. G.W. Canonica reports receiving consulting fees from AstraZeneca GSK, Novartis, Sanofi and Stallergenes Greer; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GSK, Novartis, Sanofi, Stallergenes Greer, Menarini, Chiesi and Mylan; participation on data safety monitoring or advisory boards for AstraZeneca, GSK, Novartis, Sanofi, Stallergenes Greer and Chiesi; all disclosures made outside the submitted work. G-J. Braunstahl reports grants or contracts from GSK, AstraZeneca and ALK Abello; consulting fees from GSK, Sanofi, ALK Abello, AstraZeneca and Novartis; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from GSK, Sanofi, ALK Abello, AstraZeneca and Novartis; and is on the scientific board of the Dutch Lung Foundation, task force Asthma NVALT and editorial board NTVAAKI; all disclosures made outside the submitted work. S. van der Sar reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca and GSK; and support received from ALK for attending meetings and/or travel; all disclosures made outside the submitted work. N. Nenasheva reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca plc., Sanofi S.A., Teva Pharmaceuticals, Novartis International AG and Chiesi Farmaceutici S.p.A., outside the submitted work. A. Bossios reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AZ, GSK and Teva; support for attending meetings and/or travel received from Novartis; and participation on a data safety monitoring or advisory boards for AZ, GSK, Novartis, Teva and Sanofi; and is a member of the steering Committee of SHARP, Secretary of Assembly 5 (Airway diseases, asthma, COPD and chronic cough) of the European Respiratory Society and vice-chair of Nordic Severe Asthma Network; all disclosures made outside the submitted work. D. Aronsson reports receiving grants or contracts from ALK-Abello outside the submitted work. A. Egesten reports receiving honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, outside the submitted work. L. Ahlbeck reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca; and participation on data safety monitoring or advisory boards for AstraZeneca, Sanofi and GSK; all disclosures made outside the submitted work. S. Škrgat reports receiving honoraria for lectures and educational events supported by GSK, AstraZeneca, Sanofi, Chiesi, Pliva Teva and Medis; and participation on advisory boards of GSK, AstraZeneca, Chiesi and Sanofi; all disclosures made outside the submitted work. N. Edelbaher reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GSK, Astra Zeneca, Chiesi, Pliva Teva, Krka, Novartis, Boehringer Ingelheim and Sanofi; and participation on advisory boards of GSK, Astra Zeneca, Chiesi, Novartis and Boehringer Ingelheim; all disclosures made outside the submitted work. J. Rüdiger reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from the Education of Swiss Emergency physicians; and participation on a data safety monitoring board or board for Boehringer Ingelheim; and is a member of the Board of the Swiss Society of Pneumology and President of the Thorax section of the Swiss Ultrasound Society; all disclosures made outside the submitted work. N. Pavlov reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GSK, Novartis and OM Pharma; support for attending meetings and/or travel received from Boehringer Ingelheim; participation on data safety monitoring or advisory boards for AstraZeneca, GSK, Novartis and Sanofi; all disclosures made outside the submitted work. P. Gianella reports participation on an advisory board for Novartis about Xolair for nasal polyps, outside the submitted work. F. Charbonnier reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Sanofi, Novartis, Mundipharma, AstraZeneca and GSK; participation on data safety monitoring or advisory boards for Sanofi, Novartis, Mundipharma, AstraZeneca and GSK; all disclosures made outside the submitted work. R. Chaudhuri reports receiving grants or contracts from AstraZeneca; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GSK, AstraZeneca, Teva, Chiesi, Sanofi and Novartis; support for attending meetings and/or travel received from Chiesi, Napp, Sanofi, Boehringer, GSK and AZ; and participation on data safety monitoring or advisory boards for GSK, AstraZeneca, Teva, Chiesi and Novartis; all disclosures made outside the submitted work. S.J. Smith is supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement number 831434 for Taxonomy, Targets, Treatment, and Remission; the JU receives support from the European Union's Horizon 2020 research and innovation programme, and the European Federation of Pharmaceutical Industries and Associates; all disclosures made outside the submitted work. S. Doe reports receiving support for attending meetings and/or travel from GSK and Sanofi, outside the submitted work. L. Heaney reports grants or contracts from Medimmune, Novartis UK, Roche/Genentech Inc., GlaxoSmithKline, Amgen, Genentech/Hoffman la Roche, AstraZeneca, Medimmune, Aerocrine and Vitalograph; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva and Circassia; support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Napp Pharmaceuticals; participation on data safety monitoring or advisory board for Novartis, Hoffman la Roche/Genentech Inc., Sanofi, Evelo Biosciences, GlaxoSmithKline, AstraZeneca, Teva, Theravance and Circassia; all disclosures made outside the submitted work. M. Masoli reports receiving grants or contracts from ERS SHARP to support the study “The burden of severe asthma on HRQoL across Europe”, outside the submitted work. P. Howarth is an employee of GSK. R. Djukanovic reports support for the present manuscript received from ERS, TEVA, GSK, Novartis, Sanofi and Chiesi; consulting fees from Synairgen for which the author is a co-founder and consultant and owns shares, outside the submitted work; and participation on a data safety monitoring or advisory board for Kymab (Cambridge), outside the submitted work. E. Bel reports support for the present manuscript from the ERS; grants or contracts received from GlaxoSmithKline and Teva, outside the submitted work; consulting fees received from AstraZeneca, GlaxoSmithKline, Sanofi, Sterna and Chiesi, outside the submitted work; honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from Teva; participation on a data safety monitoring or advisory board for AstraZeneca, outside the submitted work; and leadership or fiduciary roles, unpaid, for SHARP-CRC and RAPSODI (Dutch registry), outside the submitted work. M. Hyland reports receiving grants or contracts from TEVA; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for GSK; all disclosures made outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

Data-independent acquisition mass spectrometry (DIA-MS) is essential for information-rich spectral annotations in untargeted metabolomics. However, the acquired MS2 spectra are highly complex, posing significant annotation challenges. We have developed a correlation-based deconvolution (CorrDec) method that uses ion abundance correlations in multisample studies using DIA-MS as an update of our MS-DIAL software. CorrDec is based on the assumption that peak intensities of precursor and fragment ions correlate across samples and exploits this quantitative information to deconvolute complex DIA spectra. CorrDec clearly improved deconvolution of the original MS-DIAL deconvolution method (MS2Dec) in a dilution series of chemical standards and a 224-sample urinary metabolomics study. The primary advantage of CorrDec over MS2Dec is the ability to discriminate coeluting low-abundance compounds. CorrDec requires the measurement of multiple samples to successfully deconvolute DIA spectra; however, our randomized assessment demonstrated that CorrDec can contribute to studies with as few as 10 unique samples. The presented methodology improves compound annotation and identification in multisample studies and will be useful for applications in large cohort studies.

Background: Leukotriene (LT) E 4 is the final active metabolite among the cysteinyl leukotrienes (CysLTs). Animal studies have identified a distinct LTE 4 receptor, suggesting that current cysteinyl leukotriene type 1 (CysLT 1 ) receptor antagonists can provide incomplete inhibition of CysLT responses., Objective: We tested this hypothesis by assessing the influence of the CysLT 1 antagonist montelukast on responses induced by means of inhalation of LTE 4 in asthmatic patients., Methods: Fourteen patients with mild intermittent asthma and 2 patients with aspirin-exacerbated respiratory disease received 20 mg of montelukast twice daily and placebo for 5 to 7 days in a randomized, double-blind, crossover study (NCT01841164). The PD 20 value was determined at the end of each treatment period based on an increasing dose challenge. Measurements included lipid mediators in urine and sputum cells 4 hours after LTE 4 challenge., Results: Montelukast completely blocked LTE 4 -induced bronchoconstriction. Despite tolerating an at least 10 times higher dose of LTE 4 after montelukast, there was no difference in the percentage of eosinophils in sputum. Urinary excretion of all major lipid mediators increased after LTE 4 inhalation. Montelukast blocked release of the mast cell product prostaglandin (PG) D 2 , as well as release of PGF 2α and thromboxane (Tx) A 2 , but not increased excretion of PGE 2 and its metabolites or isoprostanes., Conclusion: LTE 4 induces airflow obstruction and mast cell activation through the CysLT 1 receptor., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Omalizumab is an established anti-IgE therapy for the treatment of allergic diseases that prevents IgE from binding to its receptor. QGE031 is an investigational anti-IgE antibody that binds IgE with higher affinity than omalizumab., Objective: This study compared the effects of QGE031 with those of omalizumab on clinical efficacy, IgE levels, and FcεRI expression in a clinical model of allergic asthma., Methods: Thirty-seven patients with mild allergic asthma were randomized to subcutaneous omalizumab, placebo, or QGE031 at 24, 72, or 240 mg every 2 weeks for 10 weeks in a double-blind, parallel-group multicenter study. Inhaled allergen challenges and skin tests were conducted before dosing and at weeks 6, 12, and 18, and blood was collected until 24 weeks after the first dose., Results: QGE031 elicited a concentration- and time-dependent change in the provocative concentration of allergen causing a 15% decrease in FEV 1 (allergen PC 15 ) that was maximal and approximately 3-fold greater than that of omalizumab (P = .10) and 16-fold greater than that of placebo (P = .0001) at week 12 in the 240-mg cohort. Skin responses reached 85% suppression at week 12 in the 240-mg cohort and were maximal at week 18. The top doses of QGE031 consistently suppressed skin test responses among subjects but had a variable effect on allergen PC 15 (2-fold to 500-fold change). QGE031 was well tolerated., Conclusion: QGE031 has greater efficacy than omalizumab on inhaled and skin allergen responses in patients with mild allergic asthma. These data support the clinical development of QGE031 as a treatment of asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach., (Copyright ©ERS 2015.)

Background: In mild asthma exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting β2 agonists (SABAs) on demand., Objective: The hypothesis was that a combination of budesonide and formoterol on demand diminishes EIB equally to regular inhalation of budesonide and is more effective than terbutaline inhaled on demand., Methods: Sixty-six patients with asthma (>12 years of age) with verified EIB were randomised to terbutaline (0.5 mg) on demand, regular budesonide (400 μg) and terbutaline (0.5 mg) on demand, or a combination of budesonide (200 μg)  + formoterol (6 μg) on demand in a 6-week, double-blind, parallel-group study (ClinicalTrials.gov identifier: NCT00989833). The patients were instructed to perform three to four working sessions per week. The main outcome was EIB 24 h after the last dosing of study medication., Results: After 6 weeks of treatment with regular budesonide or budesonide+formoterol on demand the maximum post-exercise forced expiratory volume in 1 s fall, 24 h after the last medication, was 6.6% (mean; 95% CI -10.3 to -3.0) and 5.4% (-8.9 to -1.8) smaller, respectively. This effect was superior to inhalation of terbutaline on demand (+1.5%; -2.1 to +5.1). The total budesonide dose was approximately 2.5 times lower in the budesonide+formoterol group than in the regular budesonide group. The need for extra medication was similar in the three groups., Conclusions: The combination of budesonide and formoterol on demand improves asthma control by reducing EIB in the same order of magnitude as regular budesonide treatment despite a substantially lower total steroid dose. Both these treatments were superior to terbutaline on demand, which did not alter the bronchial response to exercise. The results question the recommendation of prescribing SABAs as the only treatment for EIB in mild asthma.