Elevated serum immunoglobulin (Ig)E is the hallmark of atopy, and contributes to asthma and bronchial hyperresponsiveness in atopic individuals. In contrast, the significance of IgE in nonallergic subjects is less clear. The aim of the present study is to clarify a potential association of IgE and asthma in absence of clinical allergy.To this purpose 1,219 consecutive patients of a pulmonary practice were evaluated. Nonallergic patients were defined by negative skin prick test, history of atopy and specific IgE, 509 subjects (42%) were nonallergic. Among these, 80 patients (16%) had elevated total IgE levels (>150 U . mL -1 ). Prevalence and severity of asthma in nonallergic subjects with IgE>150 U . mL -1 were compared with subjects with normal IgE levels, and lung function parameters were correlated with serum IgE in all nonallergic subjects and asthmatics.Asthma was more prevalent in nonallergic subjects with elevated IgE levels than in nonallergic subjects with normal IgE (39% versus 14%; p<0.001). Lung function values of nonallergic asthmatics were lower for forced expiratory volume in one second (FEV1) % predicted (66+20% versus 8317%; p<0.001), FEV1% forced vital capacity (FVC) (7014% versus 818%; p<0.001) and forced mid expiratory flow (FEF25±75) (1.70.9 L . s -1 versus 2.80.9 L . s -1 ; p=0.002) in patients with high IgE compared to asthmatics with normal IgE, and were negatively correlated with log IgE levels in all nonallergic asthmatics. (FEV1 % pred: r=-0.5, p<0.001; FEV1 % FVC: r=-0.53, p<0.001; FEF25±75: r=-0.52, p<0.001). In the whole study population, multivariate analysis showed a greater than fivefold asthma risk for nonallergic individuals with serum IgE>150 U . mL -1 . These data support the role of IgE as risk factor for asthma independent of allergy, and they further challenge the definition of intrinsic asthma as "non-IgE mediated" entity. Eur Respir J 2000; 16: 609±614.

Poster sessionsThorax 2012;67(Suppl 2):A1-A204 A147 completed the study. At Day 21, QVA149 significantly improved exercise endurance time by 59.5 seconds versus placebo (p=0.006), which was of a similar magnitude to the improvement seen with tiotropium versus placebo (66.3 seconds; p=0.002). More patients stopped exercise due to dyspnoea with placebo (43% versus 36% with both QVA149 and tiotropium) and due to muscle fatigue with QVA149 and tiotropium (44-46% versus 38% with placebo). QVA149 also produced significant and clinically meaningful improvements in trough FEV 1 , dynamic IC at exercise isotime, trough IC and trough FVC versus placebo and tiotropium ( Introduction QVA149 is a novel inhaled once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β 2 -agonist indacaterol and the long-acting muscarinic antagonist NVA237 (glycopyrronium) in development for the maintenance treatment of COPD. This study evaluated the effect of QVA149 on P192Michael Rudolf: he has been reimbursed by the following companies for speaking at educational meetings, for consultancy work, or for attending scientific conferences: Almirall, Astra-Zeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck Sharp and Dohme, Napp, Novartis, Pfizer, Schering-Plough, and Teva.Rajendra Mehta: he has no conflicts of interest. Introduction QVA149 is a novel once-daily fixed-dose combination of the long-acting β 2 -agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237) in development for the treatment of chronic obstructive pulmonary disease (COPD). The BRIGHT study evaluated the effects of QVA149 versus placebo and tiotropium on exercise tolerance and lung function in patients with moderate-to-severe COPD. Methods In a double-blind, double-dummy, 3-period crossover study, patients with moderate-to-severe COPD were randomised to QVA149 110/50 µg, placebo or tiotropium 18 µg once daily for 3 weeks. The primary endpoint was exercise endurance time for QVA149 versus placebo during a submaximal exercise tolerance test (SMETT) via cycle ergometry at Day 21. Dynamic inspiratory capacity (IC) at isotime during exercise, trough IC, trough FEV 1 and trough forced vital capacity (FVC) were also measured. Results Eighty five patients were randomised; mean age was 62 years, mean post-bronchodilator FEV 1 56% predicted. 86% patients QVA149 ONCE DAILY IMPROVES EXERCISE TOLERANCE AND LUNG FUNCTION IN PATIENTS WITH MODERATE TO SEVERE COPD: THE BRIGHT STUDY

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ZusammenfassungHintergrund: Mit dem monoklonalen anti-IgE-Antikörper Omalizumab steht eine Erweiterung der Behandlung des allergischen Asthma bronchiale zur Verfügung. Die Dosierung von Omalizumab erfolgt nach Serum-IgE und Körpergewicht. Eine nahezu vollständige Suppression des Serum-IgE ist für den Therapieerfolg wichtig. Viele Asthmatiker weisen neben perennialen auch saisonale Sensibilisierungen auf, und der saisonale IgE-¹Boostª könnte eine Dosisanpassung erforderlich machen, bzw. den Therapieerfolg negativ beeinflussen. Methode: Wir untersuchten Gesamt-IgE-Spiegel und spezifisches (Lieschgras g6) IgE bei 17 Patienten mit saisonaler allergischer Rhinitis und/oder saisonalem Asthma vor und während der Gräserpollensaison. Anhand des Dosierungsschemas für Omalizumab errechneten wir hypothetische Dosen vor und während der Pollensaison. Ergebnisse: Das Gesamt-IgE der Patienten lag präsaisonal bei 89 (50 ± 178) kU/l (geom. Mittelwert mit 95 % Konfidenzintervall) und stieg saisonal signifikant auf 126 (63 ± 251) kU/l an (p = 0,0006). Das spezifische IgE stieg parallel hierzu von 11 (6,3 ± 19) kU/l auf 15,1 (8,3 ± 29) kU/l (p = 0,0013). Die errechneten präsaisonalen Dosierungen von Omalizumab waren: keine Dosierung (IgE < 30 kU/l): n = 2; 150 mg alle 4 Wochen: n = 7; 300 mg alle 4 Wochen: n = 2; 225 mg alle 2 Wochen: n = 4; 300 mg alle 2 Wochen: n = 1; 375 mg alle 2 Wochen: n = 1. Auf der Grundlage der saisonalen IgE-Spiegel hätte sich für 5/17 Patienten eine ¾nderung der Omalizumab-Dosis in die nächsthöhere Dosisstufe ergeben, davon wären zwei Patienten aus dem Dosierungsbereich herausgefallen. Schlussfolgerung: Ein saisonaler Anstieg des Serum-IgE lässt sich bei Patienten mit Pollenallergie beobachten. Dieser wäre für die Mehrzahl der Patienten ohne Einfluss auf die DosisAbstract Background: The anti-IgE antibody Omalizumab has been approved for the treatment of perennial allergic asthma. Dosing of omalizumab is adjusted according to total IgE levels and body weight, and a near complete suppression of free IgE is deemed to be necessary for optimal efficacy. Many asthmatics, however, have additional sensitisations against seasonal allergens, e. g. pollen, and seasonal exposure may increase total and specific IgE levels (ªboostº), thus leading to an imbalance between IgE levels and omalizumab with possible impact on therapeutic outcome. Methods: We studied serum total and specific (timothy grass) IgE levels in 17 patients with seasonal allergic rhinitis and/ or asthma prior to and during the grass pollen season. Based on total IgE levels, we then calculated hypothetical doses of omalizumab required for treatment at each time point. Results: During the pollen season, total IgE increased significantly from a preseasonal mean of 89 (50 ± 178) kU/l (geom. mean with 95 % confidence interval) to 126 (63 ± 251) kU/l (p = 0.0006). Accordingly, specific IgE increased from 11 (6.3 ± 19) kU/l to 15.1 (8.3 ± 29) kU/l (p = 0.0013). Calculated doses of omalizumab based on pre-seasonal IgE levels were: no dosing (IgE < 30 kU/l): ...

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