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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

Purpose Acute exacerbations (AE) in patients with COPD are associated with a decline in lung function, increased risk of hospitalization, and mortality. In this cross-sectional study we tested whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. Methods In 210 patients with COPD (67 % men; mean (SD) age: 63 (8) years) enrolled in The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland (TOPDOCS) physical activity (PA) (steps per day, physical activity level, (PAL)), exercise capacity (6-min walking distance, (6MWD)), comorbidities, lung function, and medication were assessed. Differences between COPD patients with frequent (>2 year) and infrequent (0-1 year) exacerbations were assessed. Univariate and multivariate analyses were performed to investigate whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. Results Patients with frequent AE had a significantly lower [FEV.sub.1] and 6MWD compared to patients with infrequent AE. In univariate analysis, the number of exacerbations was inversely associated with [FEV.sub.1], 6MWD, BMI, and smoking status while there was a positive association with RV/TLC and combined inhaled medication. However, there was no significant association with PAL and steps per day. In multivariate analysis, [FEV.sub.1] and the use of combined inhaled medication were independently associated with the number of AE, after correction for covariates. Conclusions The findings of this study imply that [FEV.sub.1], independent of inhaled medication, is significantly associated with COPD exacerbations. Neither physical activity nor exercise capacity was independently associated with COPD exacerbations. Keywords COPD * Acute exacerbations * Objective assessment of daily physical activity * Exercise capacity, Introduction Acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) constitute a substantial burden for COPD patients. Characterized by a worsening of symptoms that is beyond the normal day to [...]

Background: Many patients with obstructive sleep apnea syndrome (OSA) are unable or unwilling to use continuous positive airway pressure (CPAP) therapy when traveling to the mountains for work or recreation even though they risk pronounced hypoxemia and exacerbation of sleep apnea. Because the treatment of OSA at altitude has not been established, we tested the hypothesis that acetazolamide improves hypoxemia, sleep, and breathing disturbances in otherwise untreated patients with OSA at altitude.Methods: Forty-five patients with OSA on long-term CPAP, median age 64 years, living at < 600 m underwent a placebo-controlled, double-blind, crossover trial randomized for the sequence of drug and altitude exposure (490 m, 1,860 m, and 2,590 m). Patients spent two 3-day periods at altitude and a 2-week wash-out period at < 600 m. At altitude, patients discontinued CPAP and received acetazolamide 2 × 250 mg daily or placebo. Polysomnography, vigilance, and symptoms were evaluated.Results: At 490 m, off CPAP, median nocturnal oxygen saturation was 93%, and the apnea/hypopnea index was 51.2/h. On placebo at 1,860 m and 2,590 m, the corresponding values were 89% and 85% and 63.6/h and 86.2/h, respectively (P < .01 vs 490 m, both instances). On acetazolamide at 1,860 m and 2,590 m, oxygen saturation was higher (91% and 88%) and apnea/hypopnea indices were lower (48.0/h and 61.4/h) than on placebo (P < .01 all instances). Acetazolamide reduced nocturnal transcutaneous Pco(2), improved sleep efficiency and subjective insomnia, and prevented excessive BP elevations at altitude.Conclusions: In patients with OSA discontinuing CPAP during an altitude sojourn, acetazolamide improves oxygenation, breathing disturbances, and sleep quality by stimulating ventilation. Therefore, patients with OSA may benefit from acetazolamide at altitude if CPAP therapy is not feasible.Trial Registry: ClinicalTrials.gov; No.: NCT00714740; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Rationale: To assess feasibility and yield of diagnostic procedures after active case finding for tuberculosis with radiologic screening at the three main entry points for asylum seekers to Switzerland. Method: Prospective multicenter study on the value of symptoms, spontaneous and induced sputum, and bronchoscopy for the confirmation of tuberculosis in radiologically selected cases. Results: Among 101 asylum seekers examined, spontaneous sputum was collected "on the spot" in 83 and yielded 7 (54%) of 13 smear-positive and 13 (39%) of 33 culture-positive cases. Morning sputum, collected in 84, yielded 8 (62%) and 16 (49%), and the two spontaneous sputa combined 9 (69%) and 20 (61%), respectively. Two additional induced sputa, collected in 91 persons, yielded no additional smear-positive, but yielded seven culture-positive cases (yield, 82%). Bronchoscopy, performed in 87 of 92 sputum smear-negative cases, yielded four additional smear-positive and six culture-positive cases. Culture confirmation was independently and significantly predicted by obtaining a specimen using bronchoscopy (adjusted odds ratio, 11.0; 95% confidence interval, 1.9-62) and a prior decision to treat (adjusted odds ratio, 3.0; confidence interval, 1.1-8.1). Conclusion: Radiographic anomalies compatible with tuberculosis found during screening are a poor guide to initiation of treatment. Respiratory and systemic symptoms correlated weakly with culture confirmation of tuberculosis. All radiologically selected cases must be examined with on-the-spot and early-morning sputum, regardless of symptoms. If both specimens are smear negative, the yield is increased by bronchoscopy and, to a lesser extent, by two samples of induced sputum. The examination of any single specimen has a low yield of 36 to 63% and is insufficient to exclude active tuberculosis. [ABSTRACT FROM AUTHOR]