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Arschang Valipour,1 Michael Tamm,2 Jana Kociánová,3 Valentina Bayer,4 Maria Sanzharovskaya,5 Alexey Medvedchikov,6 Monika Haaksma-Herczegh,6 János Mucsi,7 Zvi Fridlender,8 Claudia Toma,9,10 Andrey Belevskiy,11 Bohumil Matula,12 Jurij Šorli13 1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord – Klinik Floridsdorf, Vienna, Austria; 2Lung Centre/Pneumology Department, University Hospital Basel, Basel, Switzerland; 3Pneumological Outpatient Department, MephaCentrum, a.s., Ostrava-Poruba, Czech Republic; 4Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5Respiratory TA, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 6Medical Affairs Regional Center, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 7Elizabeth Nursing Home, Gödöllő, Hungary; 8Department of Internal Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel; 9Department of Pneumology, Institute of Pneumatology “Marius Nasta”, Bucharest, Romania; 10Department Of Pneumology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 11Department of Pulmonology, Pirogov Russian National Research Medical University, Pletnev Hospital, Moscow, Russian Federation; 12Department of Functional Diagnostics, Specialized Hospital of Saint Zoerardus, Teaching Facility of the Slovak Medical University, Nitra, Slovakia; 13Topolšica Hospital, Topolšica, SloveniaCorrespondence: Arschang ValipourDepartment of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord-Klinik, Floridsdorf Brünnerstrasse 68, Wien, Vienna 1210, AustriaTel +43 1 910 600Email arschang.valipour@wienkav.atBackground: Reduced physical activity is associated with increased morbidity and mortality in patients with COPD. Studies suggest that treatment with the long-acting muscarinic antagonist tiotropium and the long-acting β2-agonist olodaterol increases exercise capacity. This study assessed the effects of a fixed-dose combination (FDC) of tiotropium/olodaterol (delivered via Respimat®) on physical functioning in patients with stable COPD in a “real-world setting”.Methods: An international, open-label, single-arm, non-interventional study conducted in nine countries measuring changes in self-reported physical functioning in COPD patients treated with tiotropium/olodaterol 5/5 μg FDC for approximately 6 weeks. The primary endpoint was therapeutic success, defined as a minimum 10-point increase in the 10-question Physical Functioning Questionnaire (PF-10) score. Secondary endpoints included absolute change in PF-10 from Visit 1 to Visit 2, patient general condition (measured by Physician’s Global Evaluation score) and patient satisfaction with the treatment and device (assessed by Patient Satisfaction Questionnaire at the end of the study period).Results: Therapeutic success was observed in 67.8% of 7218 patients (95% CI 66.7, 68.8) in the final analysis set after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 16.6 points (95% CI 16.2, 17.0). Therapeutic success was 64.3% (95% CI 63.0–65.6%) in patients with infrequent (≤1) and 76.1% (95% CI 74.3–77.9%) in patients with frequent (≥2) exacerbations (p

Andreas Scherr, Jerome Schmidlin, Silvio Albisser, Michael Tamm, Daiana Stolz Clinic for Pneumology and Respiratory Cell Research, University Hospital of Basel, Basel, Switzerland Background: In contrast to cigarette smoking, the association between water pipe smoking and airway hyperresponsiveness remains widely unexplored.Methods: A bronchoprovocation challenge with mannitol was performed in young adults recruited at the University of Basel, Switzerland. Subjects were categorized as acute water pipe smokers (single episode of water pipe smoking, no or

Frank Rassouli,1 Florent Baty,1 Daiana Stolz,2 Werner Christian Albrich,3 Michael Tamm,2 Sandra Widmer,1 Martin Hugo Brutsche1 1Department of Pulmonary and Sleep Medicine, Cantonal Hospital St Gallen, St Gallen, Switzerland; 2Department of Pulmonary and Sleep Medicine, University Hospital Basel, Basel, Switzerland; 3Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, St Gallen, Switzerland Background: There are only scarce data regarding the evolution of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) over time. Our aim was to investigate the evolution of the CAT in a telehealthcare (THC) cohort and to evaluate its potential to predict exacerbations.Patients and methods: The CAT was measured weekly over up to 1 year in 40 COPD patients undergoing a THC intervention. The evolution of the CAT was analyzed using linear regression. The association between this evolution and the occurrence of exacerbations was evaluated using the Andersen–Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors.Results: The median CAT at inclusion was 17 (interquartile range 13–22) points. During the study, 25% of patients had a significant negative slope (median –7 points per year [ppy]), 38% were stable (median +0 ppy) and 38% had a significant positive slope (median +6 ppy). The median slope of the CAT in the overall cohort was +1 (interquartile range –3 to +6) ppy. A significant positive association was found between the change in CAT scores and the risk of exacerbations (hazard ratio =1.08, 95% CI: 1.03–1.13; p

Peter Grendelmeier, Michael Tamm, Kathleen Jahn, Eric Pflimlin, Daiana Stolz Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben, Basel, Switzerland Background: Flexible bronchoscopy is increasingly used for diagnostic and therapeutic purposes. We aimed to examine the safety of flexible bronchoscopy with moderate sedation in patients with COPD. Methods: This study is a prospective, longitudinal, case–control, single-center study including 1,400 consecutive patients. After clinical and lung function assessments, patients were dichotomized in COPD or non-COPD groups. The primary end point was the combined incidence of complications. Results: The incidence of complications was similar in patients with and without COPD and independent of forced expiratory volume in the first second % predicted. Patients with COPD more frequently required insertion of a naso- or oropharyngeal airway; however, this difference was no longer significant after adjustment for age, gender, and duration of the procedure. Hypotension was significantly more common among patients with COPD. The number of episodes of hypoxemia ≤90% did not differ between the groups. However, patients with COPD had a lower mean and nadir transcutaneous oxygen saturation. Transcutaneous carbon dioxide tension (PtcCO2) change over the time course was similar in both groups, but both peak PtcCO2 and time on PtcCO2 >45 mmHg were higher in the COPD group. There were no differences in patient-reported outcomes. Conclusion: The safety of flexible bronchoscopy is similar in patients with and without COPD. This finding confirms the suitability of the procedure for both clinical and research indications. Keywords: bronchoalveolar lavage, propofol, complication, risk, respiratory insufficiency

The antipsoriatic dimethylfumarate (DMF) has been anecdotically reported to reduce asthma symptoms and to improve quality of life of asthma patients. DMF decreases the expression of proinflammatory mediators by inhibiting the transcription factor NF-KB and might therefore be of interest for the therapy of inflammatory lung diseases. In this study, we determined the effect of DMF on platelet-derived growth factor (PDGF)-BB- and TNF[alpha]-induced asthma-relevant cytokines and NF-KB activation by primary human asthmatic and nonasthmatic airway smooth muscle ceils (ASMC). Confluent nonasthmatic and asthmatic ASMC were incubated with DMF (0.1-100 [micro]M) and/or dexamethasone (0.0001-0.1 [micro]M), NF-KB p65 siRNA (100 nM), the NF-[kappa]B inhibitor helenalin (1 [micro]M) before stimulation with PDGF-BB or TNF[alpha] (10 ng/ml). Cytokine release was measured by ELISA. NF-[kappa]B, mitogen and stress-activated kinase (MSK-1 ), and CREB activation was determined by immunoblotting and EMSA. TNF[alpha]-induced eotaxin, RANTES, and IL-6 as well as PDGF-BB-induced IL-6 expression was inhibited by DMF and by dexamethasone from asthmatic and nonasthmatic ASMC, but the combination of both drugs showed no glucocorticoid sparing effect in either of the two groups. NF-[kappa]B p65 siRNA and/or the NF-KB inhibitor helenalin reduced PDGF-BB- and TNF[alpha]-induced cytokine expression, suggesting the involvement of NF-[kappa]B signaling. DMF inhibited TNF[alpha]-induced NF-[kappa]B p65 phosphorylation, NF-[kappa]B nuclear entry, and NF-[kappa]B-DNA complex formation, whereas PDGF-BB appeared not to activate NF-[kappa]B within 60 min. Both stimuli induced the phosphorylation of MSK-1, NF-[kappa]B p65 at Ser276, and CREB, and all were inhibited by DMF. These data suggest that DMF downregulates cytokine secretion not only by inhibiting NF-[kappa]B but a wider range of NF-[kappa]B-linked signaling proteins, which may explain its potential beneficial effect in asthma. mitogen and stress-activated kinase; CREB; DMF anti-inflammatory action; chronic lung inflammation; DMF steroid sparing effect