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Background: Anti-interleukin (IL)-5 biologics effectively reduce exacerbations and the need for maintenance oral corticosteroids (mOCS) in severe eosinophilic asthma. However, it is unknown how long anti-IL-5 treatment should be continued. Data from clinical trials indicate a gradual but variable loss of control after treatment cessation. In this pilot study of titration, we evaluated a dose-titration algorithm in patients who had achieved clinical control on an anti-IL-5 biologic., Methods: In this open-label randomised controlled trial conducted over 52 weeks, patients with clinical control (no exacerbations or mOCS) on anti-IL-5 treatment were randomised to continue with unchanged intervals or have dosing intervals adjusted according to a titration algorithm that gradually extended dosing intervals and reduced them again at signs of loss of disease control. The OPTIMAL algorithm was designed to down-titrate dosing until signs of loss of control, to enable assessment of the longest dosing interval possible., Results: Among 73 patients enrolled, 37 patients were randomised to the OPTIMAL titration arm; 78% of patients tolerated down-titration of treatment. Compared to the control arm, the OPTIMAL arm tended to have more exacerbations during the study (32% versus 17%; p=0.13). There were no severe adverse events related to titration, and lung function and symptoms scores remained stable and comparable in both study arms throughout., Conclusion: This study serves as a proof of concept for titration of anti-IL-5 biologics in patients with severe asthma with clinical control on treatment, and the OPTIMAL algorithm provides a potential framework for individualising dosing intervals in the future., Competing Interests: Conflict of interest: M.B. Soendergaard reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and AstraZeneca, and participation on a data safety monitoring board or advisory board with AstraZeneca. A-S. Bjerrum reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and AstraZeneca. L.M. Rasmussen reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GSK, Teva and ALK, support for attending meetings from AstraZeneca and Chiesi, and participation on a data safety monitoring board or advisory board with AstraZeneca, GSK, Teva and Sanofi. A. von Bulow reports consultancy fees from Novartis, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Novartis and GSK, and participation on a data safety monitoring board or advisory board with AstraZeneca and Novartis. C. Porsbjerg reports grants paid to their institution from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, consultancy fees (paid both to institution and as personal honoraria) from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, payment or honoraria for lectures, presentations, manuscript writing or educational events (paid both to institution and as personal honoraria) from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, and participation on a data safety monitoring board or advisory board (fees paid both to institution and as personal honoraria) with AstraZeneca, Novartis, Teva, Sanofi and ALK. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal., Research Question: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment?, Study Design and Methods: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV 1 > 80%) and a six-question Asthma Control Questionnaire score ≤ 1.5 following 12 months of treatment., Results: Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy., Interpretation: Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. H. reports speaker fees from AstraZeneca; M. B. S. reports speaker fees from GSK; A. v. B. reports consulting fees from Novartis, speaker fees from Novartis, GSK, and AstraZeneca, travel grants from AstraZeneca, and participation in advisory boards with AstraZeneca and Novartis; A.-S. B. reports lecture fees from AstraZeneca and GSK; L. M. R. has received lecture fees from AstraZeneca, GSK, and Teva, support for attending meetings and/or travel received from AstraZeneca and Chiesi, and participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, GSK, and Teva; K. E. J. H. reports grants from SanofiGenzyme and AstraZeneca, lecture fees from AstraZeneca, GSK, Chiesi, TEVA, and SanofiGenzyme; O. H. reports support attending meetings from Sanofi, and participation in advisory boards with GSK, MSD, Sanofi, AstraZeneca, TEVA, and ALK; C. U. reports grants from Sanofi, Boehringer Ingelheim, AstraZeneca, and Novartis, consulting fees from Chiesi, Orion Pharma, AstraZeneca, GSK, Teva, Menarini, and Takeda, lecture fees from Orion Pharma, AstraZeneca, and TEVA, and participation in advisory boards with Novartis, GSK, AstraZeneca, Pfizer, Sanofi, Chiesi, and Boehringer Ingelheim; C. P. reports grants from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi, and ALK, consulting fees from AstraZeneca, GSK, Novartis, TEVA, Sanofi, Chiesi, and ALK, lecture fees from AstraZeneca, GSK, Novartis, TEVA, Sanofi, Chiesi, and ALK, participation in advisory boards with AstraZeneca, Novartis, TEVA, Sanofi, and ALK. None declared (J. S., C. R. J., T. I., S. L. J., M. B., K. D. A.)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important., Objective: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma., Methods: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment., Results: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years., Conclusion: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Hydrofluorocarbons, the propellants used in metered dose inhalers, are powerful greenhouse gases. However, this review investigates the use of metered dose inhalers which continue to be on the rise in Denmark despite evidence that most patients are treated equally well with dry powder inhalers. If the use of metered dose inhalers in Denmark were reduced to approximately the level seen in Sweden it would lead to a reduction in CO2e comparable with the emissions from the electricity used in 16,500 typical Danish households., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: There is limited evidence on the pathways leading to severe asthma and we are presently unable to effectively predict the progression of the disease. We aimed to describe the longitudinal trajectories leading to severe asthma and to describe clinical events preceding disease progression in a nationwide population of patients with severe asthma., Methods: We conducted an observational study based on Swedish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. We identified adult patients with severe asthma in 2018 according to the European Respiratory Society/American Thoracic Society definition and used latent class analysis to identify trajectories of asthma severity over a 10-year retrospective period from 2018., Results: Among 169 128 asthma patients, we identified 4543 severe asthma patients. We identified four trajectories of severe asthma that were labelled as: trajectory 1 "consistently severe asthma" (n=389 (8.6%)), trajectory 2 "gradual onset severe asthma" (n=942 (20.7%)), trajectory 3 "intermittent severe asthma" (n=1685 (37.1%)) and trajectory 4 "sudden onset severe asthma" (n=1527 (33.6%)). "Consistently severe asthma" had a higher daily inhaled corticosteroid dose and more prevalent osteoporosis compared with the other trajectories. Patients with "gradual onset severe asthma" and "sudden onset severe asthma" developed type 2-related comorbidities concomitantly with development of severe asthma. In the latter group, this primarily occurred within 1-3 years preceding onset of severe asthma., Conclusions: Four distinct trajectories of severe asthma were identified illustrating different patterns of progression of asthma severity. This may eventually enable the development of better preventive management strategies in severe asthma., Competing Interests: Conflict of interest: A. von Bülow reports consulting fees from Novartis, speaker fees from Novartis, GSK and AstraZeneca, travel grants from AstraZeneca, and participation in advisory boards with AstraZeneca and Novartis. S. Hansen reports speaker fees from AstraZeneca. P. Sandin reports no conflicts of interest. O. Ernstsson reports no conflicts of interest. C. Janson reports no conflicts of interest. L. Lehtimäki reports fees for lectures, consultations or advisory board meetings from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Mundipharma, Novartis, Orion and Sanofi. H. Kankaanranta reports consulting fees from AstraZeneca, GSK, Chiesi, MSD, Orion Pharma, Novartis and Sanofi-Genzyme, and speaker fees from AstraZeneca, GSK, Orion Pharma and Boehringer Ingelheim. C. Ulrik reports grants from Sanofi, Boehringer Ingelheim, AstraZeneca and Novartis, consulting fees from Chiesi, Orion Pharma, Menarini, Takeda, AstraZeneca, Teva and GSK, lecture fees from Orion, Pharma, AstraZeneca and Teva, and participation in advisory boards with Novartis, GSK, Pfizer, AstraZeneca, Sanofi, Chiesi and Boehringer Ingelheim. B.B. Aarli reports grants from Novartis, consulting fees from AstraZeneca, lecture fees from GSK, AstraZeneca, Sanofi-Aventis, Novartis and Boehringer Ingelheim, and participation in advisory boards with GSK, AstraZeneca, Chiesi Pharma, Novartis and Sanofi. K. Geale is a board member of Quantify Research AB, Quantify Research ApS, Quantify Research AS and Quantify HEOR Private Limited, is CEO of Quantify Research AB, Quantify Research ApS and Quantify Research AS, and has stock and stock options in Quantify Research AB. S.T. Tang is an employee at Sanofi and holds stocks in Sanofi. M. Wolf is an employee at Novartis Finland. V. Backer reports no conflicts of interest. O. Hilberg reports consulting fees from Novartis, Sanofi, AstraZeneca, GSK, ALK, MSD and Teva, and travel grants from Sanofi. A. Altraja reports consulting fees from AstraZeneca, Boehringer Ingelheim, GSK and Sanofi, speaker fees from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, Norameda (Chiesi), GSK, Sanofi and Zentiva, expert testimony for AstraZeneca, Boehringer Ingelheim, GSK and Sanofi, travel grants from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim and Norameda (Chiesi), participation in advisory boards with AstraZeneca, Boehringer Ingelheim, GSK and Sanofi, and receipt of equipment from Berlin-Chemie Menarini. H. Backman reports speaker fees from AstraZeneca, Boehringer Ingelheim and GSK. D. Lúdvíksdóttir reports speaker fees from GSK and Boehringer Ingelheim. U.S. Björnsdóttir reports speaker fees from Sanofi, AstraZeneca and Novartis, support for travel from Sanofi, and participation in advisory boards with Sanofi. P. Kauppi reports consulting fees from Sobi, speaker fees from GSK and AstraZeneca, and fee for PI for Theravance. T. Sandström reports no conflicts of interest. A. Sverrild reports grants from AstraZeneca, and speaker fees from AstraZeneca, Chiesi, GSK, Sanofi-Genzyme and Novartis. V. Yasinska reports lecture fees from GSK and Sanofi, and participation in advisory boards with AstraZeneca and GSK. M. Kilpeläinen reports no conflicts of interest. B. Dahlén reports grants from GSK and Novartis. A. Viinanen reports consulting fees from AstraZeneca and GSK, speaker fees from GSK and Chiesi, and travel grants from AstraZeneca and Sanofi. L. Bjermer reports speaker fees from AstraZeneca, GSK, Airsonette, Birc, Chiesi, Novartis and Sanofi, and participation in advisory boards with AstraZeneca, Chiesi, GSK, Birc and Sanofi. A. Bossios reports speaker fees from GSK, AstraZeneca, Teva and Novartis, travel grants from AstraZeneca and Novartis, participation in advisory boards with GSK, AstraZeneca, Teva, Novartis and Sanofi, 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 is the vice-president of the Nordic Severe Asthma Network. C. Porsbjerg reports grants from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, consulting fees from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, lecture fees from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, and participation in advisory boards with AstraZeneca, Novartis, Teva, Sanofi and ALK., (Copyright ©The authors 2023.)

Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone., Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS., Methods: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models., Results: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48])., Conclusions: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life., Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions., Results: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43)., Conclusions: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: As a common chronic disease seen across all ages, asthma has the potential to incur high societal and individual costs from both direct healthcare costs and loss of productivity. Most previous studies use smaller, selected populations to assess the cost of asthma, possibly reducing generalisability. We, therefore, aimed to assess the total, nationwide economic burden of asthma by severity from both an individual and a societal perspective., Methods: The annual cost of asthma was assessed in a Danish nationwide cohort of patients aged 18-45 during 2014-2016 as excess healthcare costs, loss of income and welfare expenditure compared with controls (matched 1:4) using national registries. Asthma severity was defined as mild-to-moderate (steps 1-3 or step 4 without exacerbations) or severe (step 4 with exacerbations or step 5)., Results: Across 63 130 patients (mean age 33, 55% female), the annual excess cost of asthma compared with controls was predicted to €4095 (95% CI €3856 to €4334) per patient. Beyond direct costs related to treatment and hospitalisations (€1555 (95% CI €1517 to €1593)), excess indirect costs related to loss of income (€1060 (95% CI €946 to €1171)) and welfare expenditure (eg, sick pay and disability pensions) (€1480 (95% CI €1392 to €1570)) were seen. Crude pooling of excess costs resulted in an annual societal cost of €263 million for all included patients.Severe asthma (4.5%) incurred 4.4 times higher net costs (€15 749 (95% CI 13 928 to €17 638)) compared with mild-to-moderate disease (€3586 (95% CI €3349 to €3824)). Furthermore, patients with severe asthma experienced an annual loss of income of €3695 (95% CI €4106 to €3225) compared with controls., Conclusion: In young adults with asthma, a significant societal and individual financial burden of disease was seen across severities. Expenditure was mainly driven by loss of income and welfare utilisation, rather than direct healthcare costs., Competing Interests: Competing interests: KEJH has received personal fees from AstraZeneca, Chiesi, GSK, Sanofi and TEVA. AL has received personal fees from AstraZeneca, GSK, TEVA, Chiesi, Sanofi Genzyme, Boehringer-Ingelheim, Orion Pharma, Novartis, ALK-Abello, Mundipharma and Pfizer. RI has no conflicts to declare. OH has received personal fees AstraZeneca, GSK, TEVA, Chiesi, Sanofi Genzyme, Boehringer-Ingelheim. VB has received personal fees from AstraZeneca, GSK, TEVA, Sanofi Genzyme, MSD, Chiesi, Boehringer-Ingelheim, Novartis, ALK-Abello, Mundipharma and Pharmaxis. CSU has received personal fees from AstraZeneca, GSK, TEVA, Chiesi, Sanofi Genzyme, Boehringer-Ingelheim, Orion Pharma, Novartis, ALK-Abello, Mundipharma, Pfizer and Actelion., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This review describes the current Danish guidelines for inhaled asthma treatment. Monotherapy with short-acting beta-agonists (SABA) taken when needed is no longer recommended in asthma therapy for adults due to safety concerns. The recommended first-line treatment is now inhaled corticosteroids (ICS) taken with formoterol or ICS taken with SABA. The choice of inhaler can have a significant impact on compliance and symptom control, and an individualized approach is therefore needed. Biological treatment may be an alternative to oral corticosteroids in selected patient groups.

Competing Interests: Conflict of interest: K. Geale reports research project funding from Novartis for the current work; personal fees for consultancy from Quantify Research, during the conduct of the study and outside the submitted work. Conflict of interest: H. Darabi reports research project funding from Novartis for the current work; personal fees for consultancy from Quantify Research, during the conduct of the study and outside the submitted work. Conflict of interest: M. Lindh reports research project funding from Novartis for the current work; personal fees for consultancy from Quantify Research, during the conduct of the study and outside the submitted work. Conflict of interest: H. Fues Wahl reports research project funding from Novartis for the current work; personal fees for consultancy from Quantify Research, during the conduct of the study and outside the submitted work. Conflict of interest: O. Ström reports research project funding from Novartis for the current work; personal fees for consultancy from Quantify Research, during the conduct of the study and outside the submitted work. Conflict of interest: H. Cao is an employee of Novartis Pharmaceutical Company. Conflict of interest: L.A. Alvares is an employee of Novartis. Conflict of interest: R. Dodge has nothing to disclose. Conflict of interest: E. Loefroth is an employee of Novartis. Conflict of interest: A. Altraja reports personal fees and travel and educational support from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, CSL Behring, Roche, Teva and Sanofi, grants, personal fees and travel and educational support from Chiesi (Norameda) and GlaxoSmithKline, personal fees and travel support from MSD, grants and personal fees from Bayer, travel and educational support from Actelion (Johnson and Johnson), personal fees from Shire Pharmaceuticals, outside the submitted work. Conflict of interest: V. Backer has nothing to disclose. Conflict of interest: H. Backman reports personal fees for lectures from AstraZeneca, outside the submitted work. Conflict of interest: L. Bjermer reports personal fees from AstraZeneca, Boehringer, Chiesi, GSK, Novartis, Teva and ALK, outside the submitted work. Conflict of interest: A. Bossios reports personal fees for advisory board work and/or lectures from AZ, Teva, GSK and Novartis, outside the submitted work. Conflict of interest: B. Bøgvald Aarli reports personal fees for lectures from Boehringer Ingelheim, Novartis, AstraZeneca, Chiesi and Alere, personal fees for consultancy from GlaxoSmithKline, and has stock in from KBB Medic AS, outside the submitted work. Conflict of interest: B. Dahlén reports personal fees for lectures and advisory board work from AstraZeneca, GSK, Teva, Sanofi and Novartis, outside the submitted work. Conflict of interest: O. Hilberg has nothing to disclose. Conflict of interest: C. Jansson has nothing to disclose. Conflict of interest: H. Kankaanranta reports grants, personal fees for lectures and consultancy, and non-financial support to attend meetings from AstraZeneca, personal fees for lectures and consultancy from Chiesi Pharma AB, Novartis and GlaxoSmithKline, personal fees for lectures and consultancy, and non-financial support to attend meetings from Boehringer Ingelheim and Orion Pharma, personal fees for lectures from Mundipharma, personal fees for consultancy from Sanofi Genzyme, outside the submitted work. Conflict of interest: J. Karjalainen reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Novartis, Orion Pharma and Teva, outside the submitted work. Conflict of interest: P. Kauppi reports personal fees for lectures from GSK, Teva and Novartis, personal fees for manuscript preparation from Fimea, personal fees for consultancy from Sanofi, outside the submitted work. Conflict of interest: M. Kilpeläinen has nothing to disclose. Conflict of interest: S. Lehmann reports data analysis and manuscript preparation support from Novartis, during the conduct of the study; personal fees for lectures from AstraZeneca, personal fees for manuscript preparation from Boehringer Ingelheim, outside the submitted work. Conflict of interest: L. Lehtimäki reports personal fees from AstraZeneca, Chiesi, GSK, Boehringer Ingelheim, MSD, Novartis, pi tlsb -.005wOrionPharma, ALK, Teva and Sanofi, outside the submitted work. Conflict of interest: B. Lundbäck reports grants from AstraZeneca, personal fees for lectures and advisory board work from AstraZeneca, Novartis, GSK and Sanofi, outside the submitted work. Conflict of interest: T. Sandström has nothing to disclose. Conflict of interest: C. Suppli. Ulrik has nothing to disclose. Conflict of interest: A. Sverrild has nothing to disclose. Conflict of interest: A. Viinanen has nothing to disclose. Conflict of interest: A. von Bülow has nothing to disclose. Conflict of interest: V. Yasinska has nothing to disclose. Conflict of interest: C. Porsbjerg reports grants and personal fees from AstraZeneca, GSK, Novartis, Sanofi and Teva, outside the submitted work.

Fraction of exhaled nitric oxide (FeNO) is an easily available online biomarker, which correlates with the presence of type 2 inflammation in the airways. Measurements of FeNO together with clinical assessment and spirometry have the potential to improve diagnosis and management of patients with chronic airway symptoms. High values of FeNO in patients with relevant symptoms increase the probability of asthma and a favourable response to inhaled cortico-steroids, but low values can be seen in various subtypes of asthma and in asthmatic patients, who smoke.

Asthma is a chronic airway disease affecting many people worldwide. Less than 1% suffers from difficult-to-treat asthma and requires systemic corticosteroid treatment to achieve symptom control. The therapeutic options for these patients are limited and often we have to accept a lesser degree of symptom control. Methotrexate has been evaluated in 13 studies, where the mean corticosteroid dose reduction was 35%. Despite the adverse effects, we find that methotrexate may be a useful treatment of severe asthma in certain patients under close observation.

Asthma is a chronic airway disease affecting many people worldwide. Less than 1% suffers from difficult-to-treat asthma and requires systemic corticosteroid treatment to achieve symptom control. The therapeutic options for these patients are limited and often we have to accept a lesser degree of symptom control. Methotrexate has been evaluated in 13 studies, where the mean corticosteroid dose reduction was 35%. Despite the adverse effects, we find that methotrexate may be a useful treatment of severe asthma in certain patients under close observation.

Background: A number of occupational respiratory allergens are food related, and little is known about the responses these allergens elicit in sensitized persons that ingest them., Methods: Nine respiratory flour-allergic volunteers were exposed in a double-blind placebo-controlled food challenge with flour. Responses were monitored by spirometry, acoustic rhinometry, determination of urinary methyl histamine and tryptase and flow cytometric evaluation of basophil, dendritic and T cell numbers and markers., Results: Significant increases in serum tryptase (compared with placebo post-exposure levels) and methyl histamine and a coordinated decrease in blood basophils and nasal volume after ingestion of allergen compared with placebo suggest an allergic response to ingested allergen. There was no change in forced expiratory volume in 1 s. The number of blood plasmacytoid dendritic cells (DC), but not of myeloid DC, decreased after exposure (p = 0.001). DC HLA DR was reduced after both exposures (p < 0.001). Expression of CXCR4 on DC was reduced after allergen (p = 0.033) but not after placebo exposure. CD4+ T cell expression of CD25 was elevated after placebo (p = 0.021) but reduced after allergen provocation. The reduction in CD25 expression after allergen compared with placebo was significant (p = 0.024). CD152 was downregulated on these cells after allergen (p = 0.039) but less so after placebo exposure., Conclusion: Persons with respiratory allergy respond after ingestion of the relevant allergen. Response to this allergen challenge may selectively recruit plasmacytoid DC through CXCR4 and T cells expressing CD25 and CD152, which may be a regulatory phenotype.