Search

Richard Kraemer,1,2,* Fabian Gardin,3,* Hans-Jürgen Smith,4 Florent Baty,5 Jürg Barandun,3 Andreas Piecyk,3 Stefan Minder,1 Jörg Salomon,1 Martin Frey,6 Martin H Brutsche,5 Heinrich Matthys7 1Centre of Pulmonary Medicine, Hirslanden Private Hospital Group, Salem-Hospital, Bern, Switzerland; 2Center for Translational Medicine and Biomedical Entrepreneurship, University of Bern, Bern, Switzerland; 3Centre of Pulmonary Medicine, Hirslanden Private Hospital Group, Clinic Hirslanden, Zürich, Switzerland; 4Medical Development, Research in Respiratory Diagnostics, Berlin, Germany; 5Department of Pneumology, Cantonal Hospital St, Gallen, Switzerland; 6Department of Pneumology, Barmelweid Hospital, Barmelweid, Switzerland; 7Department of Pneumology, University Hospital of Freiburg, Freiburg, Germany*These authors contributed equally to this workCorrespondence: Richard Kraemer, Center of Pulmonary Medicine, Hirslanden Private Hospital Group, Schänzlistrasse 39, Berne, CH-3013, Switzerland, Tel +41 79 300 26 53, Email richard.kraemer@hirslanden.chBackground: A significant proportion of patients with obstructive lung disease have clinical and functional features of both asthma and chronic obstructive pulmonary disease (COPD), referred to as the asthma–COPD overlap (ACO). The distinction of these phenotypes, however, is not yet well-established due to the lack of defining clinical and/or functional criteria. The aim of our investigations was to assess the discriminating power of various lung function parameters on the assessment of ACO.Methods: From databases of 4 pulmonary centers, a total of 540 patients (231 males, 309 females), including 372 patients with asthma, 77 patients with ACO and 91 patients with COPD, were retrospectively collected, and gradients among combinations of explanatory variables of spirometric (FEV1, FEV1/FVC, FEF25-75), plethysmographic (sReff, sGeff, the aerodynamic work of breathing at rest; sWOB), static lung volumes, including trapped gases and measurements of the carbon monoxide transfer (DLCO, KCO) were explored using multiple factor analysis (MFA). The discriminating power of lung function parameters with respect to ACO was assessed using linear discriminant analysis (LDA).Results: LDA revealed that parameters of airway dynamics (sWOB, sReff, sGeff) combined with parameters of static lung volumes such as functional residual capacity (FRCpleth) and trapped gas at FRC (VTGFRC) are valuable and potentially important tools discriminating between asthma, ACO and COPD. Moreover, sWOB significantly contributes to the diagnosis of obstructive airway diseases, independent from the state of pulmonary hyperinflation, whilst the diffusion capacity for carbon monoxide (DLCO) significantly differentiates between the 3 diagnostic classes.Conclusion: The complexity of COPD with its components of interaction and their heterogeneity, especially in discrimination from ACO, may well be differentiated if patients are explored by a whole set of target parameters evaluating, interactionally, flow limitation, airway dynamics, pulmonary hyperinflation, small airways dysfunction and gas exchange disturbances assessing specific functional deficits.Keywords: COPD, COPD and coexisting asthma, ACO, aerodynamic work of breathing, airway dynamics, pulmonary hyperinflation, small airways dysfunction, precision medicine, multiple factor analysis, MFA, linear discriminant analysis, LDA

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

Sarah Crook,1 Gilbert Büsching,2 Stephan Keusch,3 Stephan Wieser,4 Alexander Turk,3,5 Martin Frey,2 Milo A Puhan,1 Anja Frei1 1Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; 2Pulmonary Rehabilitation, Klinik Barmelweid, Barmelweid, Switzerland; 3Pulmonology, Zürcher RehaZentrum Wald, Wald, Switzerland; 4Pulmonology, Stadtspital Waid, Zurich, Switzerland; 5Department of Internal Medicine, See-Spital Horgen, Horgen, Switzerland Background: Evidence from longitudinal studies on the impact of exacerbation symptoms on physical activity in chronic obstructive pulmonary disease (COPD) is lacking. The aim of this first exploratory study was to assess the association between exacerbation symptoms and physical activity, and to quantify the relative influence of specific symptoms. Methods: We recruited COPD patients at high risk for exacerbations from 2 pulmonary rehabilitation clinics and 1 acute care clinic in Switzerland. For 3 months after discharge, patients completed a daily symptom diary on a smartphone application, the EXAcerbations of Chronic pulmonary disease Tool (EXACT), and wore a pedometer to measure daily steps. We used mixed-effects models to determine the association of daily steps with exacerbation symptoms. Results: A total of 21 patients (Global Initiative for Chronic Obstructive Lung Disease grades 2–4) were enrolled for a mean of 94.4 days (standard deviation 4.2). The baseline median number of daily steps was 3,264.6 (interquartile range [IQR]: 1,851.3–4,784.1) and EXACT score was 37.0 (IQR: 30.9–41.4). A 12-point increase in EXACT score (indicating the start of an exacerbation) was statistically significantly associated with a decrease in daily steps of 653.3 (95% CI 969.7–336.9). Chest symptoms (tightness, discomfort and congestion) were more strongly associated with change in steps than breathlessness, and cough and sputum (z-value -4.5 vs -2.9 and -3.0). Conclusion: This is the first study to show that, in a small cohort of COPD patients, increases in exacerbation symptoms were associated with a statistically and clinically significant reduction in daily physical activity. These results underscore the importance for symptom control and exacerbation prevention in COPD patients. Keywords: longitudinal, management, step count, PRO, COPD, exacerbation, physical activity, symptoms

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

Rüdiger Sauer,1 Michaela Hänsel,2 Roland Buhl,3 Roman A Rubin,4 Marcel Frey,5 Thomas Glaab2,3 1Lung Centre Ulm, Ulm, Germany; 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 3Pulmonary Department, Mainz University Hospital, Mainz, Germany; 4Pulmonary Specialist Practice, Wiesbaden, Germany; 5Biometrics, Alcedis GmbH, Gießen, Germany Background: Maintaining and improving physical functioning is key to mitigating the cycle of deconditioning associated with chronic obstructive pulmonary disease (COPD). We evaluated the impact of free combination of the long-acting anticholinergic tiotropium plus the long-acting β2-agonist olodaterol on physical functioning in a real-world clinical setting. Methods: In this open-label noninterventional study, Global initiative for chronic Obstructive Lung Disease (GOLD) B–D patients with COPD aged ≥40 years were treated for 4–6 weeks with either tiotropium 5 µg + olodaterol 5 µg (both via Respimat® inhaler) or tiotropium 18 µg (HandiHaler®) + olodaterol 5 µg (Respimat®) once daily. Physical functioning was assessed by the self-reported 10-item Physical Functioning Questionnaire (PF-10). The primary end point was the percentage of patients achieving therapeutic success, defined as a 10-point increase in the PF-10 between baseline (visit 1) and weeks 4–6 (visit 2). Secondary end points included absolute PF-10 scores, Physicians’ Global Evaluation, satisfaction with Respimat® and adverse events. Results: A total of 1,858 patients were treated: 1,298 (69.9%) with tiotropium 5 µg + olodaterol 5 µg and 560 (30.1%) with tiotropium 18 µg + olodaterol 5 µg. At study end, 1,683 (92.6%) and 1,556 patients (85.6%) continued using tiotropium and olodaterol, respectively; 48.9% (95% confidence interval: 46.5, 51.3) achieved the primary end point. Therapeutic success rates were significantly higher for maintenance-naïve patients compared to those who had received prior therapy (59.1% vs 44.5%; P

Various fire emission estimates for southern Africa during 2019, derived with multiple burned area data sets with resolutions ranging from 500 to 20 m, are evaluated using satellite carbon monoxide (CO) observations. Southern African emissions derived from burned area generated by 20 m Sentinel‐2 satellite imagery are up to 120% higher than other estimates because small fires are better detected with a higher‐resolution satellite instrument. A comprehensive comparison between simulated and observed atmospheric CO indicates that the Sentinel‐2 burned area data significantly improves emission estimates, with up to 15% reduction in CO concentration biases in comparison to emissions based on coarser resolution burned area data. We also found that the temporal lag between emissions and atmospheric CO concentrations during the peak fire month was related to atmospheric transport. These findings emphasize the importance of utilizing higher‐resolution satellite instruments in accurately estimating emissions and understanding the impact of small fires on global climate. Plain Language Summary: We studied how much carbon monoxide (CO) was released into the air in southern Africa due to fires. To derive CO emissions we used different remotely sensed data of area burned, with varying levels of detail, from 500 to 20 m, and used these emissions in a model to mimic atmospheric transport and chemistry of CO. We found that emissions derived from the very detailed 20‐m satellite images from Sentinel‐2 produced a similar large amount of CO in the atmosphere over southern Africa as seen by CO satellite observations. This is because the smaller fires, which are harder to spot, were detected with the 20‐m burned area satellite observations. We also found that the air movement and inflow of polluted air from outside Africa impacted the peak of air pollution. Key Points: Sentinel‐2 burned area detects small fires, resulting in up to 120% higher fire emissions compared to conventional resolution estimatesImproved fuel load modeling and new emission factors yield more trustworthy fire emissions that can be evaluated with top‐down constraintsAtmospheric modeling and TROPOMI CO observations indicate a 15% bias reduction using Sentinel‐2 burned area compared with coarser fire data [ABSTRACT FROM AUTHOR]