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Background: QMF149 is an inhaled fixed-dose combination of indacaterol acetate and mometasone furoate (MF) delivered via Breezhaler®, under development for once-daily treatment of asthma. MF delivered via Twisthaler® is approved as Asmanex® Twisthaler® for the treatment of asthma. Bridging of MF delivered via Twisthaler® to MF delivered via Breezhaler® was undertaken as part of QMF149 development to enable dose comparisons between the devices. Pharmacokinetics (PK) of MF were characterized in two studies; a single dose PK study in healthy volunteers and a pharmacokinetic/pharmacodynamic (PK/PD) study in asthma patients., Objectives: The PK study in healthy volunteers evaluated the PK of single doses of MF via Breezhaler® (50-400 μg) and compared systemic exposure of MF following administration via Breezhaler® and Twisthaler® 400 μg (2 inhalations of 200 μg). The study in patients with asthma characterized the MF PK profile following once-daily inhalation of MF via Breezhaler® and Twisthaler® devices for 4 weeks., Methods: In the open-label, single-dose, crossover study, healthy subjects sequentially received MF via Twisthaler® (400 μg, medium-dose inhaled corticosteroid [ICS]) and escalating doses via Breezhaler® (50, 100, 200, 400 μg). PK data were obtained up to 72 h post-dose. In the double-blind, double-dummy, parallel-group study, asthma patients were randomised to receive either MF 80 μg (low-dose ICS) or 320 μg (high-dose ICS) via Breezhaler®, or 200 μg (low-dose ICS) or 800 μg (2 inhalations of 400 μg; high-dose ICS) via Twisthaler® once daily for 4 weeks. PK sampling was performed on Days 1 and 28 at pre-dose and up to 24 h post-dose., Results: In the healthy volunteer PK study, 20 healthy subjects completed all treatments. Dose-normalised AUC last of MF was 1.8-1.9-fold higher when delivered via Breezhaler® versus Twisthaler®. AUC and C max of MF increased in a dose-proportional manner over the range of 50-400 μg via Breezhaler®. Results from this study guided dose selection of MF via Breezhaler® for the asthma study. In the asthma study, in a subset of 96 patients, mean systemic exposure (AUC last and C max ) for MF 80 and 320 μg via Breezhaler® was comparable with MF 200 and 800 μg via Twisthaler®, respectively, on Day 28., Conclusion: PK characterization in a healthy volunteer PK study and subsequently an asthma study enabled selection of 80 μg (low), 160 μg (medium), and 320 μg (high) delivered via Breezhaler® as MF doses comparable to the 200 μg, 400 μg and 800 μg doses delivered by Twisthaler®, respectively, as part of QMF149 formulation development., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Mometasone furoate (MF) is the inhaled corticosteroid (ICS) component in the long-acting β 2 -agonist (LABA)/ICS fixed-dose combination of indacaterol/MF, delivered via Breezhaler®, in development for asthma. MF at low (80 μg) and high (320 μg) doses delivered via Breezhaler® is expected to be comparable to MF at low (200 μg) and high (800 μg) doses respectively, delivered via Twisthaler®., Methods: This was a randomized, double-blind, double-dummy, four-week, parallel-group study of 739 adolescents and adults with persistent asthma. Eligible patients were receiving ICS treatment up to the maximum dose per day on a stable regimen for at least four weeks before screening. The study population was enriched for patients who were responsive to ICS therapy. The primary objective of the present study was to show non-inferiority of these doses, i.e. the low (80 μg) and high (320 μg) doses of MF delivered via Breezhaler® once daily, compared with the corresponding low (200 μg) and high (800 μg) doses of MF delivered via Twisthaler® once daily. The primary endpoint was 24 h post-dose trough forced expiratory volume in 1 s (FEV 1 ), after four weeks of treatment in patients with asthma. A secondary objective was to evaluate the efficacy of MF 80 μg and 320 μg delivered via Breezhaler®, and MF 200 μg and 800 μg delivered via Twisthaler® in terms of Asthma Control Questionnaire-5 (ACQ-5) after one, two, three and four weeks of treatment., Results: The LS mean difference in trough FEV 1 after four weeks of treatment between MF low dose 80 μg (Breezhaler®) and MF low dose 200 μg (Twisthaler®) was 27 mL (95% CI -34, 89); for MF high dose 320 μg (Breezhaler®) and MF high dose 800 μg (Twisthaler®) the difference was 0 mL (95% CI -60, 61). These differences were neither clinically nor statistically significant. All treatment arms provided similar clinically relevant improvements in ACQ-5 after four weeks of treatment compared with baseline. Both treatments showed a similar safety profile with a low incidence of adverse events., Conclusion: The similarities in effects on lung function and ACQ after four weeks of treatment demonstrate the comparability of MF at low (80 μg) and high (320 μg) doses delivered with Breezhaler® with MF at low (200 μg) and high (800 μg) doses delivered with Twisthaler®, respectively. The study formally demonstrated that MF, delivered via Breezhaler®, is non-inferior to MF, delivered via Twisthaler® at corresponding ICS doses., Competing Interests: Declarations of competing interest RB reports grants to Mainz University and personal fees from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche, as well as personal fees from AstraZeneca, Chiesi, Cipla, Sanofi and Teva, all outside the submitted work. AMT, MH, ID, FP, BH and HCT are employees of Novartis Pharma AG and own Novartis Pharma AG shares. WC is an employee of Novartis Pharmaceuticals Corporation. CB and JJ are employees of Novartis Pharma AG. DZ is an employee of Novartis Pharma AG and owns Novartis Pharma AG shares. DZ has led the development of Breezhaler® dry powder inhaler and was the technical project leader for the development of the Breezhaler® mometasone drug product. FK reports personal grants or fees for scientific work, presentations and Advisory boards in the last 5 years from Mundipharma, Astra Zeneca, Novartis and TEVA. However, all of these are outside the submitted work., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background:  The efficacy of the German disease management programs (DMP) asthma and chronic obstructive pulmonary disease (COPD) cannot be shown with the legally bound documentations. Studies with control groups are rare. Aim of this work was to investigate in a cross-sectional study whether the disease control differs in participants (DMP+) and non-participants (DMP - ) of the DMPs asthma and COPD., Methods:  The study was a prospective multicenter cross-sectional study. Primary endpoints were the Asthma Control Test™ (ACT) in the asthma part of the study and the COPD Assessment Test™ (CAT) for the COPD part., Results:  A total of 1038 asthma patients and 846 COPD patients were included, of whom about 70 % participated in the corresponding DMP. The ACT total score was higher in asthma DMP+ patients than in DMP- patients (mean difference 0.86; 95 % CI: 0.29 - 1.43;p = 0.003), but not clinically relevant. For COPD there was no clinically relevant difference in COPD disease impact (0.52; 95 % CI: - 0.71 - 1.75; p = 0.405). Although DMP patients had to be enrolled in the respective DMP for at least one year, only 60 % of these patients had participated in a structured education. We did not observe a difference in disease control in DMP patients who respectively participated and did not participate in a structured education., Discussion:  There was no clinically relevant difference in disease control between DMP+ and DMP- patients. The efficacy of DMPs has been demonstrated internationally in randomized controlled trials. Randomized controlled trials should be conducted in Germany for demonstrating efficacy of DMPs asthma and COPD., Registration:  drks.de, DRKS00007664, Registration date: Jan 15, 2015., Competing Interests: Diese Studie wurde durch die Mundipharma GmbH finanziert. P. O. und B. L-B. sind Mitarbeiterinnen der Mundipharma GmbH. F. K. und A. Z. haben Beraterverträge mit der Mundipharma GmbH. A. Z. ist Mitglied der Schriftleitung der Dtsch Med Wochenschr., (© Georg Thieme Verlag KG Stuttgart · New York.)

Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force., Competing Interests: Conflict of interest: A. Bourdin reports personal and institutional fees for advisory board work from AstraZeneca, Novartis, GSK, Boehringher Ingelheim, Chiesi, Actelion, Pfizer and Teva, outside the submitted work. Conflict of interest: L. Bjermer has nothing to disclose. Conflict of interest: C. Brightling reports grants and personal fees for consultancy from GlaxoSmithKline, AstraZeneca/Medimmune, Novartis, Chiesi, Roche/Genentech and Boehringer Inglheim, personal fees for consultancy from Vectura, Theravance, PreP, Gilead, Sanofi/Regeneron, Teva, Gossamer and 4DPharma, grants from Pfizer and Mologic, outside the submitted work. Conflict of interest: G.G. Brusselle reports personal fees for advisory board work and lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, personal fees for advisory board work from Sanofi, outside the submitted work. Conflict of interest: P. Chanez reports research grants and personal fees for consultancy, advisory board work and lectures from ALK, Almirall, Boehringer Ingelheim, GSK, AstraZeneca, Novartis, TEVA and Chiesi, grants from AMU, outside the submitted work. Conflict of interest: K.F. Chung has received honoraria for participating in advisory board meetings of GSK, AZ, Novartis, Merck, BI and TEVA regarding treatments for asthma and COPD, and has also been renumerated for speaking engagements. Conflict of interest: A. Custovic reports personal fees for consultancy from Novartis, Regeneron/Sanofi, Boehringer Ingelheim and Philips, personal fees for lectures from Thermo Fisher Scientific and Novartis, outside the submitted work. Conflict of interest: Z. Diamant reports personal fees from AstraZeneca and Sanofi-Genzyme, during the conduct of the study; personal fees from Aquilon, ALK, Boehringer Ingelheim, Gilead, Hal Allergy and MSD, outside the submitted work; and in addiction to academic affiliations, also works at a phase I/II unit performing clinical studies for different biotech and pharma companies. Conflict of interest: S. Diver has nothing to disclose. Conflict of interest: R. Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline; in addition, is a co-founder and current consultant, and has shares in, Synairgen, a University of Southampton spin out company. Conflict of interest: D. Hamerlijnck has nothing to disclose. Conflict of interest: I. Horvath reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GSK, Novartis, CSL-Behring and Roche, outside the submitted work. Conflict of interest: S.L. Johnston reports personal fees for advisory board work from Therapeutic Frontiers and Virtus Respiratory Research, personal fees for consultancy from Myelo Therapeutics GmbH, Concert Pharmaceuticals, Bayer, Gerson Lehrman Group, resTORbio, Bioforce, Materia Medical Holdings, PrepBio Pharma, Pulmotect, Virion Health and Lallemand Pharma, personal and insititutional fees for consultancy from Synairgen, Novartis, Boehringer Ingelheim and Chiesi; and has received personal fees for the following patents planned, issued or pending: transgenic animal models of HRV with human ICAM-1 sequences (UK patent application number 02 167 29.4, and international patent application number PCT/EP2003/007939); anti-virus therapy for respiratory diseases (UK patent application number GB 0405634.7); interferon-beta for anti-virus therapy for respiratory diseases (international patent application number PCT/GB05/50031); interferon lambda therapy for the treatment of respiratory disease (UK patent application number 6779645.9, granted); induction of cross-reactive cellular response against rhinovirus antigens (European patent number 13305152), outside the submitted work. Conflict of interest: F. Kanniess reports personal fees for lectures and advisory board work from AstraZeneca, Novartis, Mundipharma and TEVA, outside the submitted work. Conflict of interest: N. Papadopoulos reports personal fees for advisory board work and lectures from Novartis, Nutricia, HAL, personal fees from Menarini/Faes Farma and Mylan/Meda, personal fees for lectures from Sanofi, Biomay, MSD, ASIT Biotech and Boehringer Ingelheim, personal fees for advisory board work from AstraZeneca and GSK, grants from Gerolymatos International SA and Capricare, outside the submitted work. Conflict of interest: A. Papi reports grants, personal fees for lectures, advisory board work and consultancy, and travel expenses reimbursement from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline and Teva, personal fees for advisory board work and consultancy from Sanofi/Regeneron, personal fees for lectures and travel expenses reimbursement from Zambon and Novartis, personal fees for lectures, advisory board work and consultancy, and travel expenses reimbursement from Mundipharma, personal fees for lectures and advisory board work, and travel expenses reimbursement Almirall, grants, personal fees for lectures and travel expenses reimbursement from Menarini, grants from Fondazione Maugeri, grants from Fondazione Chiesi Farmaceutici, outside the submitted work. Conflict of interest: R.J. Russell has nothing to disclose. Conflict of interest: D. Ryan reports personal fees for advisory board work from GSK and Trudell Medical, personal fees for advisory board work and lectures from AZ, personal fees for lectures from Mylan and Chiesi, personal fees for consultancy from Optimum Patient Care, outside the submitted work. Conflict of interest: K. Samitas has nothing to disclose. Conflict of interest: T. Tonia acts as ERS methodologist. Conflict of interest: E. Zervas reports personal fees consultancy and lectures from Astra, Bristol-Myers Squibb, Chiesi, GSK, Elpen, Merck, MSD, Novartis, Menarini and Pfizer, non-financial support for travel, accommodation and meeting expenses from Astra, Bristol-Myers Squibb, Galenica, Chiesi, Elpen, Novartis, Menarini and Roche, outside the submitted work. Conflict of interest: M. Gaga reports grants and personal fees from AZ, grants from BI, Elpen, Novartis and Menarini, personal fees from BMS, MSD, Chiesi and Pharmaten, outside the submitted work., (Copyright ©ERS 2019.)

Background: The fixed-dose combination of budesonide/formoterol (B/F) has been available in the Spiromax® dry powder inhaler since 2014., Objectives: To assess patient satisfaction, inhaler use errors, and disease control in patients with asthma or chronic obstructive pulmonary disease (COPD) treated with B/F Spiromax., Methods: This non-interventional, prospective, 12-week study enrolled consecutive asthma or COPD patients who had recently begun treatment with B/F Spiromax or were switched from another inhaled corticosteroid/long-acting β2-agonist combination to B/F Spiromax in routine clinical practice. Patients recruited from 243 specialist respiratory clinics or general practices in Germany were assessed for patient satisfaction (Satisfaction with Inhalers and Preference questionnaire), inhaler application errors (modified Easy Low Instruction over Time checklist), disease control, and safety., Results: The population included 3,943 patients: asthma n = 2,707 (68.7%); COPD n = 1,236 (31.3%). At baseline, 60.1% of patients were "satisfied" or "very satisfied" with their previous inhaler, and this increased to 88.8% at week 12 of B/F Spiromax use. Overall, 62.1% of pre-treated patients preferred B/F Spiromax to their old inhaler. The frequency of any handling error observed with B/F Spiromax at week 12 was lower than at baseline (11.9 vs. 25.5% of patients, respectively). After 12 weeks, 77.4% were assessed as having improved (minimally, much, or very much) overall health status versus baseline. Guideline-defined disease severity (as rated by physicians) and patient-reported symptom severity improved during the study in both asthma and COPD patients. B/F Spiromax was well tolerated., Conclusion: B/F Spiromax was associated with high patient satisfaction, low device handling error rate, and improvements in clinical outcomes in real-world clinical practice., (© 2018 S. Karger AG, Basel.)

Background: The efficacy of the German disease management programs (DMP) asthma and chronic obstructive pulmonary disease (COPD) cannot be shown with the legally bound documentations. Studies with control groups are rare. Aim of this work was to investigate in a cross-sectional study whether the disease control differs in participants (DMP+) and non-participants (DMP-) of the DMPs asthma and COPD., Methods: The study was a prospective multicenter cross-sectional study. Primary endpoints were the Asthma Control Test™ (ACT) in the asthma part of the study and the COPD Assessment Test™ (CAT) for the COPD part., Results: A total of 1038 asthma patients and 846 COPD patients were included, of whom about 70 % participated in the corresponding DMP. The ACT total score was higher in asthma DMP+ patients than in DMP- patients (mean difference 0.86; 95 %CI:0.29 - 1.43;p = 0.003), but not clinically relevant. For COPD there was no clinically relevant difference in COPD disease impact (0.52; 95 %CI:-0.71 - 1.75;p = 0.405). Although DMP patients had to be enrolled in the respective DMP for at least one year, only 60 % of these patients had participated in a structured education. We did not observe a difference in disease control in DMP patients who respectively participated and did not participate in a structured education., Discussion: There was no clinically relevant difference in disease control between DMP+ and DMP- patients. The efficacy of DMPs has been demonstrated internationally in randomized controlled trials. Randomized controlled trials should be conducted in Germany for demonstrating efficacy of DMPs asthma and COPD., Registration: drks.de, DRKS00007664, Registration date: Jan 15, 2015., Competing Interests: Diese Studie wurde durch die Mundipharma GmbH finanziert. P. O. und B.L-B. sind Mitarbeiterinnen der Mundipharma GmbH. F.K. und A.Z. haben Beraterverträge mit der Mundipharma GmbH. A.Z. ist Mitglied der Schriftleitung der Dtsch Med Wochenschr., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Prospective, non-interventional study of fixed-dose inhaled corticosteroid (ICS)/long-acting beta 2 -agonist (LABA) combination therapy with fluticasone propionate/formoterol fumarate (FP/FORM) across a spectrum of community-based patients with asthma in a real-life setting., Methods: In FP/FORM-treated patients aged ≥12 years, asthma control (Asthma Control Test™ [ACT]), incidence of severe exacerbations, lung function, quality of life (asthma quality of life questionnaire [AQLQ]) and adverse events (AEs) were assessed over one year., Results: Almost 40% (n = 555) of the full analysis population (N = 1410) were receiving ICS/LABA therapy prior to enrolment; 69.8% completed the study. Asthma control (mean ACT ± standard deviation) improved from 16.3 ± 5.0 at baseline to 19.8 ± 4.5 at study end. ACT scores were significantly (p < 0.0001) higher than baseline at all observation timepoints, including the first assessment at 4-6 weeks. The percentage of patients with asthma control increased (baseline: 30.9%; study end: 62.4%), and the percentage of patients with ≥1 severe asthma exacerbation decreased (12 months before: 35.8%; during study: 5.9%). Lung function (forced expiratory volume in one second, peak expiratory flow) improved from baseline to each observation timepoint (p < 0.0001 for all). Improvement in asthma status was accompanied by ameliorated quality of life: AQLQ scores improved significantly from baseline to all observation timepoints (p < 0.0001 for all). AEs accorded with the summary of product characteristics. After study completion, 70% of patients continued FP/FORM treatment., Conclusion: In this one-year study, FP/FORM treatment was associated with clinically relevant improvements in asthma status in a diverse population of patients under real-life conditions., (Copyright © 2017. Published by Elsevier Ltd.)

Background: The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform(®), 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints)., Methods: Patients aged ≥18 years with forced expiratory volume in 1 s (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg (low dose) or placebo, during 2 periods of 28 ± 3 days each, separated by 2-3 weeks. AMP challenges were performed pre-dose and 12 h after last dose at the end of each treatment period. A series of post hoc analyses were performed only in patients allocated to both fluticasone/formoterol doses, who completed the study and had evaluable AMP PD20 data for both treatments ("fluticasone/formoterol subgroup"). Changes in AMP PD20 FEV1, percentage sputum eosinophils and FeNO levels (Day 1 vs Day 28) between treatments were compared by an analysis of covariance (ANCOVA)., Results: Sixty-two patients were randomised and 46 completed the study. Fifteen patients received both high- and low-dose fluticasone/formoterol (post hoc subgroup). The difference in AMP PD20 for the overall population was not statistically significant between high- and low-dose fluticasone/formoterol (LS mean fold difference: 1.3; p = 0.489), although both dose levels were superior to placebo: high-dose vs placebo LS mean fold difference: 4.4, p < 0.001; low-dose vs placebo LS mean fold difference: 3.5, p < 0.001. In the post hoc subgroup, the difference in AMP PD20 between the doses was statistically significant in favour of the high-dose (LS mean fold difference: 2.4, p = 0.012). Other inflammatory parameters (sputum eosinophil counts and FeNO) showed small differences and statistically non-significant changes between high- and low-dose fluticasone/formoterol., Conclusions: A significant dose-response was found between low- and high-dose fluticasone/formoterol in the post hoc subgroup (patients who received both doses), but not in the overall population, with the higher dose demonstrating a greater reduction in airway responsiveness to AMP., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The efficacy profile of roflumilast, a phosphodiesterase-4 inhibitor used for the treatment of chronic obstructive pulmonary disease (COPD), is well known. In asthma treatment, much less is understood about the role of roflumilast, particularly its mechanism of action and potential bronchodilatory effects., Aim: To evaluate the therapeutic efficacy and mechanism of action of roflumilast in patients with asthma using data from eight placebo-controlled, double-blind phase I-III studies., Methods: The studies were conducted at 14 sites in Europe, North America and South Africa from 1997 to 2005. The effect of treatment with 250 μg, 500 μg or 1000 μg roflumilast was compared with placebo in seven cross-over studies and one parallel-group study in 197 patients 18-70 years of age. Primary endpoints focused on the extent of the late allergic response after an allergen challenge, change in sputum cell eosinophil counts or exhaled nitric oxide (eNO), forced expiratory volume in 1 s (FEV1) and exercise-induced bronchoconstriction. Secondary endpoints included the extent of the early allergic response and measurements of tumour necrosis factor α (TNFα), sputum cells and inflammatory markers., Results: Roflumilast attenuated allergen-induced bronchoconstriction (FEV1) in patients with asthma. Significant reductions in allergen-induced airway inflammation, including a reduction in both eosinophil and neutrophil counts were also observed and physiologic responses to allergen-induced challenge were confirmed by a significant reduction in TNFα. Side effects were similar to COPD, but did not include weight loss., Conclusions: The results from these studies indicate that the anti-inflammatory effects of roflumilast observed in COPD are also seen in asthma and advance our understanding of its mechanism of action. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT01365533., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The fixed combination of extrafine beclomethasone dipropionate and formoterol fumarate (BDP/FF) pMDI (Foster(®)) is approved for treatment of adult asthmatic patients. In order to provide an alternative drug delivery system for BDP/FF to physicians and patients, a dry powder inhaler (NEXThaler(®)) has been developed, capable to deliver extrafine particles to the lungs and therefore improve the dosing of the drugs, especially in patients with poor hand-breath coordination., Objective: This trial was performed to compare efficacy and safety of extrafine BDP/FF NEXThaler(®) with extrafine BDP/FF pMDI or non-extrafine BDP DPI alone in adult patients with controlled asthma., Methods: In this 8-week randomised, double-blind, parallel-group trial, patients were randomized to receive either extrafine BDP/FF NEXThaler(®) 100/6 μg bid, extrafine BDP/FF 100/6 μg pMDI bid or non-extrafine BDP DPI 100 μg bid. The primary efficacy variable was change from baseline to the entire 8-week randomised treatment period in average pre-dose morning PEF., Results: The ITT population comprised 754 patients. Extrafine BDP/FF NEXThaler(®) was non-inferior (pre-defined margin: -15 L/min) relative to extrafine BDP/FF pMDI (mean difference: -1.84; 95% CI: -6.73, 3.05) in terms of the primary efficacy variable, change from baseline in average pre-dose morning PEF. Statistical superiority of both extrafine BDP/FF formulations over non-extrafine BDP DPI was demonstrated for the primary efficacy variable (providing evidence of assays sensitivity of the trial), ACQ score and percentage of rescue medication use-free days. No significant safety signals were observed., Conclusion: NEXThaler(®) is an effective and well-tolerated delivery device for treatment of patients with asthma who need a regular treatment., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Asthma is an inflammatory disease of the airways, but in clinical practice inflammation is rarely monitored. The aim of this study was to assess the level of airway inflammation in steroid naïve adult and pediatric patients with intermittent asthma over one year., Methods: 54 children and 50 adults with intermittent asthma (GINA step 1) were included. On up to 6 visits lung function, airway hyperresponsiveness to methacholine (PC20FEV1), sputum eosinophils and exhaled nitric oxide (FeNO) were assessed., Results: 36 pediatric and 34 adult patients were able to produce at least three adequate sputum samples over the study period and were included into the analysis.In 8 children (22%) the percentage of sputum eosinophils was always below 2.5%. A higher level of eosinophils (>2.5%) was found on at least one visit in 16 (44%) and always >2.5% in 12 children (33%). In the adult group the respective numbers were 14 patients (41%) with always low (<2.5%), 17 (50%) with at least once over 2.5% and three patients (9%) were always above the threshold of 2.5% sputum eosinophils., Conclusion: These results demonstrate that a substantial number of children and adults with intermittent asthma under ß-agonist treatment only, have variable or persistently high levels of eosinophilic airway inflammation. Long-term studies are needed to observe the progression of asthma severity in such patient populations.

Background: Objective measures are required that may be used as a proxy for exacerbations in asthma. The aim was to determine the sensitivity and specificity of electronic diary data to detect severe exacerbations (SEs) of asthma. A secondary aim was to identify phenotypic variables associated with a higher risk of exacerbation., Methods: In the BIOAIR study, 169 patients with asthma (93 severe (SA); 76 mild to moderate (MA)) recorded lung function, symptoms and medication use in electronic diaries for 1 year. Data were analysed using receiver-operator characteristics curves and related to physician-diagnosed exacerbations. Medical history and baseline clinical data were used to assess risk of exacerbation., Results: Of 122 physician-diagnosed exacerbations, 104 occurred in the SA group (1.1 per patient/year), 18 in the MA group (0.2 per patient/year) and 63 were severe using American Thoracic Society/European Respiratory Society criteria. During exacerbations, peak expiratory flow (PEF) and forced expiratory volume in 1 s significantly decreased, whereas day and night symptoms significantly increased. An algorithm combining a 20% decrease in PEF or a 20% increase in day symptoms on 2 consecutive days was able to detect SEs with 65% sensitivity and 95% specificity. The strongest risk factors for SEs were low Asthma Control Questionnaire score, sputum eosinophils ≥ 3%, body mass index >25 and low quality of life (St George's Respiratory Questionnaire), with ORs between 3.61 and 2.22 (p<0.05)., Conclusions: Regular electronic monitoring of PEF and asthma symptoms provides an acceptable sensitivity and specificity for the detection of SEs and may be suitable for personal internet-based monitoring of asthma control.

Background: Allergen-specific TH2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a TH1 response, and thereby suppresses the allergic TH2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a TH1-mediated protective response., Objective: We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma., Methods: In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734)., Results: All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n = 33) despite steroid withdrawal, compared with deteriorations observed under placebo (n = 30, P < .05). At week 12, two thirds of the QbG10-treated patients had their asthma "well controlled" (Asthma Control Questionnaire score ≤0.75) compared with one third under placebo. FEV1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in QbG10 patients. Adverse events were mostly injection site reactions occurring after QbG10 administration., Conclusion: Treatment with QbG10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

In asthma, airways constrict in response to emotion and stress, but underlying mechanisms, potential extrathoracic contributions, and associations with airway pathophysiology have not been elucidated. We therefore investigated the role of the cholinergic pathway in emotion-induced airway responses in patients with asthma and the association of these responses with airway pathophysiology. Patients with asthma (n=54) and healthy participants (n=25) received either 40 microg ipratropium bromide or a placebo in a double-blind double-dummy cross-over design in two laboratory sessions with experimental emotion induction. Stimuli were preevaluated films and pictures of pleasant, unpleasant, and neutral quality. Respiratory resistance and reactance at 5 and 20 Hz were measured continuously before and during presentations, together with respiration by impedance plethysmography and end-tidal PCO2 by capnometry. In addition, measures of airway inflammation (fraction of exhaled nitric oxide), airway hyperreactivity (methacholine challenge), and reversibility of obstruction were obtained. Respiratory resistance at 5 and 20 Hz increased during unpleasant stimuli in asthma patients. This response was blocked by ipratropium bromide and was not substantially associated with asthma severity, airway inflammation, hyperreactivity and reversibility, or pattern of ventilation and PCO2. Under the placebo condition, changes in resistance during unpleasant films were positively correlated with patients' reports of psychological asthma triggers. In conclusion, airway constriction to unpleasant stimuli in asthma depends on an intact cholinergic pathway, is largely due to the central airways, and is not substantially associated with other indicators of airway pathology. Its link to the perceived psychological triggers in patients' daily lives suggests a physiological basis for emotion-induced asthma.

Considerable individual differences exist in asthma patients' airway responses to emotional stimuli, but little is known about the generalization of such responses across situations or states of airways constriction. Fifty-four asthma patients and 25 healthy controls viewed in two separate sessions, films and blocks of pictures from each of three emotional qualities, pleasant, unpleasant, and neutral. At the beginning of each session, patients received a placebo or anti-cholinergic bronchodilator (ipratropium bromide), respectively, in a randomized double-blind design. Respiratory resistance, reactance and impedance were recorded throughout stimulus presentations with impulse oscillometry. Resistance increases showed a moderate degree of generalization across unpleasant films and pictures, unpleasant and pleasant pictures, as well as cholinergic blockade and placebo. Thus, the intensity of airway responses to unpleasant emotional stimuli is a moderately stable characteristic of asthma patients. In addition to the central airway, peripheral and extrathoracic airways may also contribute the consistency of such responses., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Rationale: Oral corticosteroids effectively treat asthma exacerbations but are associated with well-described side effects., Objective: This study compared the efficacy and safety of a high dose of an inhaled corticosteroid with oral prednisolone in patients with worsening of their asthma after medication withdrawal., Methods: Patients tapered off their inhaled corticosteroids until they reached predefined criteria of "worsening asthma". Randomized patients (n=130) were treated double blind with either ciclesonide 800mug twice daily (starting with 800mug hourly for 3h after randomization) or prednisolone 40mg once daily for 2 weeks. Spirometry, daily asthma symptoms, morning and evening peak expiratory flow and blood parameters were assessed in all, methacholine challenge and inflammatory measures were determined in induced sputum in a subset of patients., Results: Ciclesonide was as effective as prednisolone in improving forced expiratory flow in 1s, morning peak expiratory flow and symptoms, the latter improving more rapidly with ciclesonide. No differences were found in methacholine responsiveness or inflammatory measures in sputum or blood. Ciclesonide caused significantly less reduction in morning plasma cortisol levels (p<0.0001)., Conclusion: This study shows that inhaled ciclesonide (800mug twice daily) has comparable efficacy to oral prednisolone (40mg once daily) to regain asthma control in patients with asthma worsening. The more rapid onset and smaller effect on cortisol suppression suggest a better safety profile of ciclesonide.

Background: Indacaterol is a new once-daily inhaled beta(2)-agonist in clinical development for asthma as a component of a fixed-dose combination with an inhaled corticosteroid., Objectives: To investigate the efficacy and safety of indacaterol in patients with chronic persistent asthma., Methods: A total of 115 patients were randomized in a double-blind, incomplete-block cross-over design to sequences of four 7-day treatment periods (separated by 7-day washouts) with indacaterol 100, 200, 300, 400, or 600 micro g or placebo, once daily, via single-dose dry-powder inhaler. After the fourth washout, patients received 1 day of open-label formoterol 12 mu g twice daily. Forced expiratory volume in 1 second (FEV(1)) was measured for 24 hours post-dose on days 1 and 7., Results: For standardized (with respect to time) FEV(1) area under the curve at 22 to 24 hours (AUC(22-24h)) on day 1, indacaterol doses >or=200 micro g were superior to placebo (p < 0.05) and similar or greater than formoterol 12 micro g twice daily. By day 7, mean differences from placebo in FEV(1) standardized AUC(22-24h) were 0.08, 0.16, 0.15, 0.11, and 0.16 L for indacaterol 100, 200, 300, 400, and 600 micro g, respectively (all p < 0.05 vs. placebo). Mean FEV(1) for indacaterol doses >or= 200 micro g on day 7 was higher than placebo (p < 0.05) pre-dose and at all post-dose time points. AEs were generally mild in severity; no serious AEs occurred. No clinically meaningful differences were observed between treatments in any safety assessments., Conclusions: Once-daily indacaterol demonstrated sustained 24-hour bronchodilator efficacy, with similar efficacy on days 1 and 7, and was generally well tolerated.

Objective: To examine the association of changes in current negative mood and long-term daily hassles with changes in lung function and airway inflammation in patients suffering from asthma and in healthy controls. Associations between psychological factors and asthma symptoms have been documented, but the relationship between airway inflammation and psychological factors has been largely unexplored., Method: Data were analyzed from 46 asthma patients and 25 controls who completed questionnaires on current mood and daily hassles at two assessments 3 months apart. Lung function was measured by spirometry (forced expiratory volume in the first second (FEV(1))) and airway inflammation by the fraction of nitric oxide in exhaled air (FeNO). Regression analyses controlling for allergen load and air pollution (ozone) were calculated to study the association between changes in psychological factors and changes in lung function and airway inflammation, and to examine the mediational role of airway inflammation in the stress-lung function association., Results: In patients with asthma, increases in negative affect were associated with decreases in FEV(1) and increases in FeNO. For daily hassles, a reverse pattern of associations was found, with decreases in daily hassles linked to decreases in FEV(1) and increases in FeNO. Mediation analyses showed that FeNO was a significant mediator of the association of both negative affect and daily hassles with lung function changes. No significant associations were found for healthy controls., Conclusion: Psychological variables are consistently associated with spirometric lung function and airway inflammation in asthma patients. For asthma patients, effects of acute negative affect must be distinguished from more chronic distress due to daily hassles.

Background: Anecdotal accounts have identified hyperventilation as one route through which psychological factors can trigger bronchoconstriction. However, little is known about the empirical association between psychological and other trigger factors and hyperventilation in asthma exacerbations., Objective: To study the cross-sectional association between perceived triggers and hyperventilation symptoms in 1 British and 1 German sample of patients with asthma who were recruited from the community and from primary care clinics., Method: Patients completed relevant language versions of the Asthma Trigger Inventory and the Asthma Symptom Checklist., Results: After controlling for demographics and asthma severity, perceived asthma triggers measured by subscales of the Asthma Trigger Inventory explained 12.5% to 37.3% of the variance in Asthma Symptom Checklist hyperventilation-hypocapnia symptoms. Psychological triggers accounted for 10.6% to 26.7% of the variance alone and 4.3% to 11.0% of the variance over and above other trigger factors. In contrast, perceived animal and pollen allergen triggers did not contribute unique variance to the hyperventilation symptom report. Psychological triggers did not explain variance in classic airway obstruction symptoms, thus arguing against a general bias toward inflated symptom reports in patients with psychologically induced asthma., Conclusion: Differences in perceived asthma triggers are substantially associated with hyperventilation symptoms, and patients with more frequent psychological triggers also tend to report that they experience more hyperventilation symptoms during their asthma symptom episodes.

Background and Objective: Patients' perception of asthma triggers has been explored in a largely unstructured fashion in the past. Therefore, we developed the Asthma Trigger Inventory (ATI), a questionnaire that allows for a psychometrically valid measurement of patients' perceived asthma triggers. Here we evaluate a German language version of the ATI and studied the relationship of subscales with self-reported health status, health care use, psychopathology, and results of allergy skin testing., Method: Data were obtained from 370 asthma patients recruited from the community, primary care, and in-patient asthma treatment and education., Results: Analysis revealed a five-factor structure that largely confirmed results with the English original. Reliability was good to satisfactory (Cronbach's alpha=0.77-0.89) for allergy, exercise, air pollution/irritants, infection, and psychological trigger subscales. In hierarchical regression analysis adjusting for demographics and asthma severity, asthma patients with stronger non-allergic triggers showed less physical and mental well-being and more asthma-related health care use. Psychological triggers showed unique associations with anxious and depressed mood. Pollen and animal allergen scores of the ATI were significantly related to skin test results for relevant allergens. Non-allergic but not allergic triggers showed substantial associations with asthma control., Conclusion: The German version of the ATI reliably measures asthma patients' trigger perceptions. Non-specific asthma triggers exert a greater burden on patients' well-being and primary health care use.

Corticosteroids are effective anti-inflammatory medications that are recommended for the control of persistent asthma. Little, however, is known about their influence on the perception of dyspnea, which, in turn, is important to the successful self-management of asthma. This paper provides a synopsis of available studies examining the impact of corticosteroids on the sensitivity to perceive dyspnea and presents possible mechanisms underlying this relationship. The results of these investigations are conflicting with some studies showing improved perception and other studies showing worsened perception of dyspnea after corticosteroid treatment. Thus, firm conclusions cannot be derived from the currently available data. Implications for future research, which is required to increase our understanding of potential influences of corticosteroids on the perception of dyspnea, are provided.

The present study examined the bronchodilator and safety profiles of single-dose indacaterol in intermittent or persistent asthma. In the present double-blind crossover study, 42 patients were randomised to receive single doses of indacaterol (50, 100, 200 and 400 microg) or placebo via a hydrofluoroalkane pressurised metered-dose inhaler. The primary efficacy comparisons were the per cent changes in forced expiratory volume in one second (FEV(1 )) between indacaterol and placebo 30 min and 21 h post-dose. All doses resulted in prolonged bronchodilation, with indacaterol 200 and 400 microg meeting pre-specified efficacy criteria. The mean percentage increases in FEV(1) from placebo with indacaterol 200 and 400 microg were 7.6 and 14.9%, respectively, at 30 min, and 7.5 and 10.4%, respectively, at 21 h post-dose. At these doses, changes in mean FEV(1) relative to placebo were statistically significant from 5 min to 25 h, inclusive. At 5 min, the geometric least squares mean values for FEV(1) were 3.08 and 3.22 L for the 200 and 400 microg doses, respectively, compared with 2.99 L for placebo. At 24 h after dosing, the baseline-adjusted geometric least square mean FEV(1) was 3.13, 3.11, 3.24 and 3.30 L for indacaterol 50, 100, 200 and 400 microg, respectively, and 2.98 L for placebo. All treatments were well tolerated. Once-daily indacaterol at doses of 200 and 400 microg provided sustained 24-h bronchodilation, with a rapid onset and a good tolerability and safety profile.

Introduction: Demographic factors, symptom severity, and psychopathology, in particular anxiety and depression, are known to influence health care use and quality of life in asthma. Because depression and anxiety are typically correlated, we sought to explore whether depression specifically is associated with health care utilization and quality of life when effects of anxiety are controlled for., Method: In a cross-sectional questionnaire study, 88 asthma patients (46 women; age range 27-70 years) reported on symptoms and treatment of their disease, as well as anxiety and depression (Hospital Anxiety and Depression Scale, HADS), general quality of life (Short Form 12 Health Survey Questionnaire, SF-12) and asthmatic-specific quality of life (Living with Asthma, LAQ)., Results: While no considerable associations between anxiety and health care use were found, the associations between higher scores in depression and hospital visits as well as days of corticosteroid intake were significant. Furthermore, considerable variance in all subscales of quality of life questionnaires was explained by higher scores in depression, even when controlling for anxiety. For anxiety scores these associations were comparable, except for physical well-being., Conclusion: Depression is an important issue in asthma, as it is substantially related to quality of life and intake of corticosteroids, and marginally to hospitalization. Routine screening for depression should be considered in hospital and primary care.

The aim of the present study was to assess the reproducibility of changes in forced inspiratory volumes after bronchodilator inhalation. Thirteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 32-75%pred) and 10 patients with asthma (FEV1, 43-75%pred) inhaled either 200 microg fenoterol or 200 microg oxitropium bromide or placebo, each of them on three occasions, on nine different days in a randomised, cross-over, double-blind fashion. Forced expiratory (FEV1) and inspiratory (FIV1) volumes were measured before and 30 min after inhalation. In patients with COPD, the increase in FEV1 (coefficient of variation) was 221 ml (43%) after fenoterol and 235 ml (33%) after oxitropium; changes in FIV1 were 301 ml (45%) and 360 ml (29%). In patients with asthma, FEV1 improved by 618 ml (26%) and 482 ml (25%), FIV1 by 553 ml (41%) and 475 ml (23%). In less severe COPD or asthma, the reduction in dyspnoea was associated with the improvements in both FIV1 and FEV1, but in severe COPD with the improvement in FIV1 only. The data demonstrate that, at least in terms of relative changes, the reproducibility of bronchodilator responses in terms of FIV1 is similar to that of FEV1 and they underline the assertion of FIV1 being a sensible parameter particularly in severe COPD.

The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.

Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue. The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast (10 mg, once a day) or low-dose inhaled fluticasone (100 microg b.i.d.) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma. Forty patients (forced expiratory volume in one second (FEV1), 60-80% predicted) were studied in a double-blind, randomised, crossover design. Treatment periods were separated by 3-8 weeks of washout. At the beginning and end of each period, FEV1, airway responsiveness to inhaled methacholine (provocative concentration causing a 20% fall in FEV1 (PC20)), the level of exhaled nitric oxide (NO) and sputum differential cell counts were determined. Only short-acting beta2-agonists were allowed for relief of symptoms. FEV1 increased by 0.50+/-0.07 L (mean+/-SEM) after fluticasone and by 0.37+/-0.07 L after montelukast (p<0.001, each), and PC20 by 1.33+/-0.13 (p<0.001) and 0.15+/-0.17 (NS) doubling doses, respectively. Correspondingly, percentages of sputum eosinophils were reduced by factor 2.7 (p<0.01) and 1.4 (nonsignificant (NS)), and the levels of exhaled NO (at 50 mL x s(-1)) by factor 2.1 (p<0.01) and 1.1 (NS). These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma, but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods.

Background: The combination of airway hyper-responsiveness, eosinophilic airway inflammation, and lung function impairment is considered as a hallmark of bronchial asthma. Since airway function might change with time in chronic asthma, the association between parameters which are characteristic of asthma could be different in subjects with different durations of the disease., Objective: We assessed whether in patients with asthma the relationship between airway hyperresponsiveness, non-invasive markers of airway inflammation, and baseline lung function depended on the duration of the disease., Methods: Sixty-six non-smoking patients with mild to moderate allergic asthma without corticosteroids were assigned to two groups, according to a duration of the disease (time interval since doctor's diagnosis) of either < or = 16 years (median 8 years; mean FEV1, 92.6% pred.; n = 34) or > 16 year (median 25 years; mean FEV1, 87.9% pred.; n = 32)., Results: Groups did not differ statistically in PC20FEV1 of methacholine, sputum composition, levels of exhaled nitric oxide (NO), lung function parameters, or history of treatment. There were significant correlations between PC20FEV1, eosinophils and NO in patients with a duration of the disease < or = 16 year, but no relation to lung function. In contrast, patients with a duration > 16 year showed a correlation between PC20FEV1 of methacholine and lung function but not eosinophils or NO. In both groups, eosinophils and NO were associated with each other. These results were corroborated by the statistical procedure of factor analysis that revealed 'inflammation' and 'lung function' as major entities and found 'responsiveness' to be associated with only one of them in each group., Conclusion: Our data demonstrate that with a shorter duration of the asthmatic disease airway hyper-responsiveness is associated with airway inflammation, whereas with a longer duration it is associated with impaired lung function, suggesting that in chronic asthma ongoing alterations become the primary determinant of functional characteristics.

To assess the efficacy of ciclesonide, a novel corticosteroid pro-drug, we compared its effect on lung function, airway responsiveness to inhaled AMP, the composition of induced sputum, and the level of exhaled nitric oxide (NO) with the effect of budesonide in patients with asthma. Fifteen non-smoking steroid-naive patients (mean FEV(1), 94%pred) inhaled either 400 microg ciclesonide or 400 microg budesonide as a single morning dose for two weeks each separated by a > or =3 week wash-out period. The study was performed in a double-observer, randomized, cross-over design. FEV(1)increased significantly during treatment with budesonide (3.38 vs. 3.64 l P=0,003), but not after ciclesonide (3.60 vs. 3.69 l). PC(20)FEV(1)of AMP increased (P<0,001, each) after both budesonide (4.59 vs. 32.48 mg/ml, 2.8 doubling doses) and ciclesonide (3.92 vs. 20.00 mg/ml, 2.4 doubling doses). The percentage of sputum eosinophils was significantly reduced after ciclesonide (7.9 vs. 3.4% P=0.01), but not budesonide (6.0 vs. 4.3%). After both budesonide and ciclesonide, a significant (P<0.001) reduction in the level of exhaled NO occurred. In none of the parameters studied, the changes differed significantly between treatment with budesonide or ciclesonide. These data suggest that ciclesonide is equi-effective to budesonide with regard to its potency to reduce the airway responsiveness to inhaled AMP as well as airway inflammation in patients with mild asthma., (Copyright Academic Press.)

The aim of this study was to assess the accuracy and applicability of a portable electronic peak flow meter combined with an asthma monitor (AM1, Jaeger, Germany) which measures peak expiratory flow (PEF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The technical accuracy in PEF, FEV1 and FVC measurement was tested according to American Thoracic Society (ATS) criteria for monitoring devices using a flow generator. In addition, the effect of connecting a heated screen pneumotachograph (PT) to the AM1 was determined and the accuracy in FEV1 determinations was evaluated by simultaneous measurements in 49 normal volunteers. The devices tested fulfilled all ATS criteria for monitoring devices with respect to the accuracy of PEF, FEV1, and FVC measurements. The conditions of intra- and interdevice variability were satisfied in all cases. Compared with the PT, the AM1 showed about 4% lower values in FEV1, as measured in the 49 subjects. In conclusion, the electronic peak flow meter and asthma monitor AM1 yielded valid measurements of peak expiratory flow and forced expiratory volume in one second, which matched the accuracy criteria of the American Thoracic Society standards for monitoring devices.