Background Uncontrolled severe asthma often remains unidentified in clinical practice. There is clearly an unmet need to identify patients with uncontrolled severe asthma and design new strategies to improve and sustain asthma control.

Background Chronic obstructive pulmonary disease is a progressive and debilitating disease associated with substantial morbidity and mortality. Patients with COPD often suffer episodes of disease instability reflected by worsening of symptoms and exacerbations leading to a sustained worsening of patient`s condition beyond day-to-day variability and frequently require adjustment of treatment. It has been shown that exacerbation history is a main driver of future exacerbation risk in COPD patients; thus, identification and adequate management of these patients in everyday practice is pivotal in order to improve functional status and quality of life.

Introduction/Background: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item asthma control tool that assesses both symptom impairment and exacerbation risk. To date, only the English version of the AIRQ has been validated in a United States (US) population (1). Aims/objectives: To validate the German-language version of the AIRQ in patients aged ≥12 years with different levels of asthma control. Methods: Cross-sectional, multicenter study conducted in Germany. A total of 300 patients completed the AIRQ (7 impairment and 3 risk items) to assess asthma control. The receiver operating characteristic (ROC) curve, area under the curve (AUC), sensitivity, and specificity of the AIRQ were calculated relative to a composite of Asthma Control Test (ACT) score (impairment) and prior-year exacerbations (risk). Results: The AIRQ yielded an AUC of 0.91 to identify well-controlled vs not well-/very poorly controlled asthma with a sensitivity of 85.8% and a specificity of 82.3% using a cut-point of ≥2. An AUC of 0.90 to identify well-/not well-controlled vs very poorly controlled asthma with a sensitivity of 64.8% and a specificity of 91.8% was observed using a cut-point of ≥5 (Figure). Conclusions: The German version of the AIRQ demonstrated the ability to identify patients with poor asthma control. These results confirm the validity of the AIRQ in a non-US population. References 1. Murphy, K. R., et al. J. Allergy Clin. Immunol. Pract. 2020; 8:2263-2274

Die bisher vorliegenden Daten zur Effektivität von Disease Management Programmen (DMP) entstammen ausschließlich der in den Programmen geforderten Dokumentation. Kontrollgruppenuntersuchungen fehlen bisher, mit denen die Auswirkung der Teilnahme an einem DMP oder an einer Schulung belegt werden kann.

Die bisher vorliegenden Daten zur Effektivität entstammen aus der DMP-Dokumentation; Kotrollgruppenuntersuchungen fehlen bisher, mit denen die Auswirkungen der Teilnahme an einem DMP und/oder der Schulung belegt werden kann.

Severe asthma is difficult to treat, and identifying patients who may be suitable for specific biologic therapy through the development of high quality severe asthma care pathways will be a key factor in managing patients appropriately.

Objective: Prospective, non-interventional study of fixed-dose inhaled corticosteroid (ICS)/long-acting betas-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 TestTM [ACM, 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 Acr 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. (C) 2017 Published by Elsevier Ltd.

Background The ICS fluticasone propionate (FP) and the LABA formoterol fumarate (FORM) have now been combined in a single aerosol inhaler (FP/FORM; flutiform®). The effect of low- (2 puffs 50/5 µg bid) vs high-dose (2 puffs 250/10 µg bid) FP/FORM on airway responsiveness to AMP was compared in an incomplete block, placebo-controlled, 2-way crossover study. Post hoc data analysis from patients who received both FP/FORM doses is presented. Methods 62 patients (33M, 29F; =18yrs; reversible FEV1 =60% pred.) discontinued maintenance ICS medication for 2 - 3wks; those showing a provocative dose of AMP producing a 20% decline in FEV1 (AMP PD20 FEV1) of <60 mg were randomised to receive 2 of 3 treatments (FP/FORM high-, low-dose or placebo) during 2 periods of 28 ± 3 days each, separated by 2 - 3wks. AMP challenges were performed pre-dose and repeated 12h after last dose at the end of each treatment period. The difference in changes in AMP PD20 FEV1 (day 1 vs day 28) between treatments were compared by an ANCOVA. Results 15 patients were randomised to receive both high- and low-dose FP/FORM. The change in AMP PD20 FEV1 was greater with FP/FORM high- compared with low-dose (LS means: high dose = 11 mg; 95% CI 4.3, 27.9; low dose = 4.6 mg, 95% CI 1.8, 11.8), with a statistically significant 2.4 fold difference in AMP PD20 FEV1 (1.2 doubling doses) between doses (LS mean: 2.4; 95% CI 1.3, 4.5; p = 0.012). FP/FORM was well-tolerated; only few (mild or moderate) AEs occurred. Conclusions A significant dose-response was found between low- and high-dose FP/FORM with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.

Einleitung: Mit dem DuoResp Spiromax® (Budesonid/Formoterol DPI) ist seit Sommer 2014 ein neuer ICS/LABA-Inhalator verfügbar. Dessen Akzeptanz und die Häufigkeit von Anwendungsfehler wird in einer Real-Life Studie überprüft.

Einleitung: Die Fülle neuer Asthma- und COPD-Präparate inkl. der neuen Inhalertypen, die in kontrollierten Studien kaum noch bedeutsame Effektivitätsunterschiede aufweisen, werfen die Frage nach deren Akzeptanz im praktischen Alltag auf. Ziel ist es, unter real-life Bedingungen die Patientenzufriedenheit bzw. Probleme in der Anwendung der Budesonid/Formoterol Fix-Kombination (DuoResp® Spiromax®) zu untersuchen.

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 mu g, 500 mu g or 1000 mu g 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 alpha (TNF alpha), 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 TNF alpha. 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. (C) 2015 Elsevier Ltd. All rights reserved.

Die Studie untersucht die Sicherheit und Wirksamkeit der Fluticasonpropionat/Formoterolfumarat-Kombination (FP/FORM; flutiform®) an 1500 Asthmapatienten (Pat.) über 1 Jahr (J.). In die Zwischenanalyse gingen 1213 Pat. (Safety Population; 59,8% weiblich; Alter 48,8 ± 17,7 J.) bzw. 986 Pat. (Full Analysis Population; 60,4% weiblich; Alter 48,8 ± 17,6 J.; Asthmadauer 10,8 ± 12,6 J.) ein. 572 Pat. (58%) wurden neu auf eine ICS/LABA-Kombination eingestellt, 345 Pat. (35%) von einer ICS/LABA-Kombination umgestellt (bei 7% keine Angaben). Die zu Beginn am häufigsten verwendeten FP/FORM-Tagesdosen waren 500/20 µg (45%), 250/10 µg (30%) und 1000/40 µg (11%). Bei 83% der Pat. blieb die Dosierung im Therapieverlauf stabil. Asthmakontrolle, Lebensqualität und Lungenfunktion sind in der Tabelle dargestellt. Verbesserungen im Asthma Control Test (ACTTM) bzw. Asthma Quality of Life Questionnaire (AQLQ) zeigten sich in allen Fragen bzw. Domänen. Der Anteil gut kontrollierter Pat. (ACT™ ≥ 20) stieg von 32% auf 55% (M1), 62% (M3) und 62% (M6), der Anteil schlecht kontrollierter Pat. (ACT™ ≤ 15) sank von 42% auf 18% (M1), 13% (M3) und 15% (M6).

Hintergrund: ICS-Fluticasonpropionat (FP) und LABA-Formoterolfumarat (FORM) werden inzwischen in einem einzigen Aerosolinhalator (FP/FORM; flutiform®) kombiniert. Die Wirkung von niedrig- (50/5 µg 2 Hübe zweimal täglich) vs. hochdosiertem (250/10 µg 2 Hübe zweimal täglich) FP/FORM auf die Reagibilität der Atemwege auf AMP wurde in einer placebokontrollierten, Zweifach-Crossover-Studie mit unvollständigem Blockdesign verglichen. Es wird die Post-hoc-Analyse der Daten von Patienten präsentiert, die beide FP/FORM-Dosen erhielten.

Eine nicht-interventionelle Studie an 1500 Patienten (Pat.) mit Asthma untersucht die Sicherheit und Wirksamkeit der Kombination Fluticasonpropionat (FP)/Formoterolfumarat (FORM) in einem Dosieraerosol (flutiform®); die Beobachtungszeit pro Pat. beträgt 1 Jahr. Die Studie begann im November 2012 und soll im April 2015 beendet sein. In eine Zwischenanalyse gingen 360 Pat. (62,5% weiblich; 94,7% > 18 Jahre; Alter 50,3 ± 18,4 Jahre; Asthmadauer 10,8 ± 13,6 Jahre) ein; 325 Pat. hatten den 1. Kontrolltermin (ca. 1 Monat nach Therapiebeginn (M1)) und 179 Pat. den 2. Kontrolltermin (ca. 3 Monate nach Therapiebeginn (M3)) abgeschlossen. 163 Pat. (45,3%) inhalierten eine Tagesdosis von 500/20 µg FP/FORM, 125 Pat. (34,7%) 250/10 µg und 37 Pat. (10,3%) 1000/40 µg. Die FEV1 betrug vor Therapiebeginn 2,4 ± 0,9 l und stieg unter FP/FORM auf 2,6 ± 0,9 l an (M3), die FEV1% Soll verbesserte sich von 82,0 ± 18,7% auf 86,6 ± 19,5% (M3). Der ACT™-Score verbesserte sich unter Therapie mit FP/FORM von 17,1 ± 5,0 auf 19,2 ± 4,8 (M1) bzw. 19,7 ± 4,3 (M3); die Verbesserung zeigte sich bei allen 5 Fragen. Der Patientenanteil mit gut kontrolliertem Asthma (ACT™-Score ≥20) stieg von 39,2% auf 56,3% (M1) bzw. 60,3% (M3) deutlich an, der Anteil schlecht kontrollierter Pat. (ACT™-Score ≤15) sank von 38,7% auf 21,2% (M1) bzw. 14,0% (M3). Der AQLQ-Score verbesserte sich von 4,9 ± 1,2 auf 5,6 ± 1,1 (M3); die Verbesserung zeigte sich in allen Domänen. 31 Pat. (8,6%) entwickelten 43 unerwünschte Ereignisse, die mit der FP/FORM-Therapie in Zusammenhang standen (NW), darunter 2 Pat. kardiale NW, 2 Pat. Mundsoor, 3 Pat. Husten, 4 Pat. Mundtrockenheit, 12 Pat. Heiserkeit. 4 Pat. entwickelten je eine schwere Asthmaexazerbation (eine davon erforderte Hospitalisierung), die alle nicht in Zusammenhang mit FP/FORM standen. Die Zwischenergebnisse zeigen, dass die Therapie mit FP/FORM gut verträglich ist und sowohl die Lungenfunktion als auch die Asthmakontrolle und die Lebensqualität verbessert.

RATIONALE:An antagonist (MK-7123) of the cytokine receptor CXCR2 reduces neutrophil chemotaxis and thus may alleviate airway inflammation in chronic obstructive pulmonary disease (COPD).OBJECTIVES:To assess the efficacy, safety, and tolerability of three dose levels of MK-7123, compared with placebo, in patients with moderate to severe COPD.METHODS:This 6-month, double-blind study randomized patients with moderate to severe COPD (already on standard therapy) to daily MK-7123 at 10, 30, or 50 mg or placebo. The primary endpoint was change from baseline in post-bronchodilator FEV1.MEASUREMENTS AND MAIN RESULTS:A total of 616 patients (71% male; mean age, 63 yr; 45% current smokers; baseline FEV1 [SD], 1.43 L [0.45]; mean FEV1 percent predicted, 43.9%) were randomized. Only MK-7123 50 mg led to significant improvement in FEV1 over placebo (mean difference [SE], 67 ml [32]). Reduced sputum neutrophil count was observed among the 122 patients examined; P = 0.003 (3 mo) and P = 0.092 (6 mo) (MK-7123 50 mg vs. placebo). The stratum of current smokers, but not that of nonsmokers, showed significant improvement versus placebo in FEV1 (168 ml) and time-to-first exacerbation, and showed numerical improvement in St. George's Respiratory Questionnaire for COPD score. MK-7123 caused a dose-dependent decrease in absolute neutrophil count (ANC) and reduced inflammatory biomarkers matrix metallopeptidase-9 and myeloperoxidase in plasma and sputum; ANC lower than 1.5 × 10(9)/L led to discontinuations with higher doses of MK-7123 (18% in the MK-7123 50-mg group vs. 1% in placebo). Plasma C-reactive protein and fibrinogen increased with MK-7123 treatment. Rates of infections at 6 months were similar in all groups.CONCLUSIONS:Treatment with MK-7123 50 mg versus placebo led to significant improvement in FEV1 in patients with COPD, suggesting clinically important antiinflammatory effects with CXCR2 antagonism, although dose-related discontinuations were observed because of ANC decreases with MK-7123. Greater response was observed in smokers versus ex-smokers. Clinical trial registered with www.clinicaltrials.gov (NCT 01006616).

BACKGROUND:Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist bronchodilator currently in Phase III clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacodynamics, pharmacokinetics, safety and tolerability of ascending doses of aclidinium bromide in patients with COPD. METHODS:This double-blind, randomised, placebo-controlled, crossover study was conducted in patients with moderate to severe COPD (forced expiratory volume in 1s [FEV(1)] <65% predicted). Patients were randomly assigned to one of four treatment sequences of aclidinium bromide 100, 300, 900microg and placebo with a washout period between doses. The primary outcome was area under the FEV(1) curve over the 0-24h time interval. RESULTS:Seventeen patients with COPD were studied. Mean FEV(1) over 24h was 1.583L for placebo, and 1.727L, 1.793L and 1.815L for aclidinium bromide 100, 300 and 900microg, respectively (p<0.001 vs. placebo, all doses). Significant changes from baseline in FEV(1) were detected 15min post-dose for aclidinium bromide 300 and 900microg, with a peak effect 2h post-dose (all doses). Aclidinium bromide was undetected in plasma. The majority of adverse events was unrelated to study medication and did not result in discontinuation. CONCLUSION:Aclidinium bromide 100-900microg produced sustained bronchodilation over 24h in patients with COPD.