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Fabian A Grewe,1 Noriane A Sievi,1 Matteo Bradicich,1 Maurice Roeder,1 Thomas Brack,2 Martin H Brutsche,3 Martin Frey,4 Sarosh Irani,5 Jörg D Leuppi,6 Robert Thurnheer,7 Christian F Clarenbach,1 Malcolm Kohler1,8 1Pulmonary Division, University Hospital Zurich, Zurich, Switzerland; 2Pulmonary Division, Cantonal Hospital of Glarus, Glarus, Switzerland; 3Pulmonary Division, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland; 4Pulmonary Division, Clinic Barmelweid, Erlinsbach, Switzerland; 5Pulmonary Division, Cantonal Hospital of Aarau, Aarau, Switzerland; 6University Department of Medicine, Cantonal Hospital Baselland and University of Basel, Basel, Switzerland; 7Pulmonary Division, Cantonal Hospital of Münsterlingen, Münsterlingen, Switzerland; 8Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, SwitzerlandCorrespondence: Malcolm KohlerPulmonary Division, University Hospital Zurich, Raemistrasse 100, Zurich 8091, SwitzerlandEmail malcolm.kohler@usz.chObjective: To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting.Methods: This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland. Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016. For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline. We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication. Groups were compared via ANOVA.Results: Data of 305 patients (62± 7 years, 66% men) were analysed. In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline. Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines. Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively. Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%).Conclusion: The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups. The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement.Keywords: chronic obstructive pulmonary disease, Global Initiative for Chronic Obstructive Lung Disease guidelines, guideline-compliance

Noriane A Sievi,1 Malcolm Kohler,1 Robert Thurnheer,2 Joerg D Leuppi,3 Sarosh Irani,4 Martin Frey,5 Martin Brutsche,6 Thomas Brack,7 Christian F Clarenbach1 1Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland; 2Pulmonary Division, Cantonal Hospital of Münsterlingen, Münsterlingen, Switzerland; 3University Clinic of Medicine, Cantonal Hospital Baselland and University of Basel, Basel, Switzerland; 4Pulmonary Division, Cantonal Hospital of Aarau, Aarau, Switzerland; 5Pulmonary Division, Clinic Barmelweid, Barmelweid, Switzerland; 6Pulmonary Division, Cantonal Hospital of St Gallen, St Gallen, Switzerland; 7Pulmonary Division, Cantonal Hospital of Glarus, Glarus, Switzerland Introduction: COPD exacerbations are associated with a concomitant profound reduction in daily physical activity (PA). Thereby, exacerbation frequency and severity may have an amplifying effect. Whether the reduced level of PA returns to the level prior to exacerbation or has a sustained negative impact on activity behavior over time is unclear.Methods: The number of steps per day over 1 week, as a measure of daily PA, was assessed annually in a cohort of patients with COPD. Exacerbation frequency and severity were documented. Uni- and multivariate mixed effect models were used to investigate associations between change in number of steps per day (dependent variable) and exacerbations. Stratification by possible confounders was performed.Results: One hundred and eighty one COPD patients (median [quartile] age 64 [59/69] years, 65% male, median [quartiles] FEV1 % pred. 46 [33/65]) suffered a total of 273 exacerbations during the observation period (median [quartiles] follow-up time of 2.1 [1.6/3.1] years). Neither the frequency nor the severity of exacerbations was significantly related to the overall decline in PA over time. Stratification by different possible confounders such as age, sex and disease severity did not yield a subgroup in which exacerbations enhance the decrease in PA over time.Conclusion: The drop in PA during the phase of an acute exacerbation seems not to be a lasting phenomenon leading to a fundamental change in activity behavior.Trial registration: www.ClinicalTrials.gov, NCT01527773 Keywords: COPD, daily physical activity, exacerbation

Noriane A Sievi,1 Thomas Brack,2 Martin H Brutsche,3 Martin Frey,4 Sarosh Irani,5 Jörg D Leuppi,6 Robert Thurnheer,7 Malcolm Kohler,1,8 Christian F Clarenbach1 1Pulmonary Division, University Hospital of Zurich, Zurich, 2Pulmonary Division, Cantonal Hospital of Glarus, Glarus, 3Pulmonary Division, Cantonal Hospital of St Gallen, St Gallen, 4Pulmonary Division, Clinic Barmelweid, 5Pulmonary Division, Cantonal Hospital of Aarau, Aarau, 6University Clinic of Internal Medicine, Cantonal Hospital Baselland, 7Pulmonary Division, Cantonal Hospital of Münsterlingen, Münsterlingen, 8Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland Background and objective: Physical activity (PA) is an important outcome parameter in patients with COPD regarding hospitalizations and mortality. Both objective assessment by accelerometers and self-evaluation by questionnaires were used in studies investigating PA in COPD. Whether self-reported questionnaires can adequately reflect PA and its changes over time compared to objective assessments has not been thoroughly investigated in COPD. In this COPD cohort study, we evaluated whether PA measured by accelerometer and its annual changes can also be assessed by self-reported questionnaires. Methods: In 178 COPD patients with at least two assessments of PA, the agreement between objectively measured and self-reported activity was analyzed by Bland–Altman plots. Daily PA was assessed by a triaxial activity monitor over 1 week and by the self-reported German PA questionnaire 50+. Results: Comparison between the two methods of measurement revealed no convincing agreement with a mean difference and limits of agreement (±1.96 standard deviation [SD]) of time spent in at least moderate PA (>3 metabolic equivalent of task [MET]) of -77.6 (-340.3/185.2) min/day, indicating a self-reported overestimation of PA by the questionnaire. The mean difference and limits of agreement (±1.96SD) in the annual change of PA was 1.2 min/day (-208.2/282.6 min/day), showing also a poor agreement on an individual level. Conclusion: Evaluation of objectively measured and self-reported PA and their annual changes revealed no agreement in patients with COPD. Therefore, the evaluated questionnaire seems not helpful for measurement of PA and its changes over time. Keywords: activity monitor, activity questionnaire, airflow limitation, COPD