Impact of shift work and other work-related factors on anti-SARS-CoV-2 spike-protein serum concentrations in healthcare workers after primary mRNA vaccination - a retrospective cohort study.

BACKGROUND: Knowing whether shift work negatively affects the immune system's response to COVID-19 vaccinations could be valuable for planning future vaccination campaigns for healthcare workers. We aimed to determine the impact of working late or night shifts on serum anti-SARS-CoV-2 spike protein immunoglobulin G (anti-S) antibody levels after primary SARS-CoV-2-mRNA vaccination. METHODS: To obtain detailed information on shift work, we sent a separate online questionnaire to 1475 eligible healthcare workers who participated in a prospective longitudinal study conducted in 15 healthcare institutions in Switzerland. We asked all vaccinated healthcare workers with available anti-S antibody levels after vaccination to complete a brief online survey on their working schedules within one week before and after primary mRNA vaccination. We used multivariate regression to evaluate the association between work shifts around primary vaccination and anti-S antibody levels. We adjusted for confounders already known to influence vaccine efficacy (e.g. age, sex, immunosuppression, and obesity) and for variables significant at the 0.05 alpha level in the univariate analyses. RESULTS: The survey response rate was 43% (n = 638). Ninety-eight responders were excluded due to unknown vaccination dates, different vaccines, or administration of the second dose shortly (within 14 days) after or before serologic follow-up. Of the 540 healthcare workers included in our analysis, 175 (32.4%) had worked at least one late or night shift within seven days before and/or after primary vaccination. In the univariate analyses, working late or night shifts was associated with a nonsignificant -15.1% decrease in serum anti-S antibody levels (p = 0.090). In the multivariate analysis, prior infection (197.2% increase; p <0.001) and immunisation with the mRNA-1273 vaccine (63.7% increase compared to the BNT162b2 vaccine; p <0.001) were the strongest independent factors associated with increased anti-S antibody levels. However, the impact of shift work remained statistically nonsignificant (-13.5%, p = 0.108). CONCLUSION: Working late or night shifts shortly before or after mRNA vaccination against COVID-19 does not appear to significantly impact serum anti-S antibody levels. This result merits consideration since it supports flexible vaccination appointments for healthcare workers, including those working late or night shifts.

Clinical characteristics governing treatment adjustment in COPD patients: results from the Swiss COPD cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a widespread chronic disease characterised by irreversible airway obstruction [1]. Features of clinical practice and healthcare systems for COPD patients can vary widely, even within similar healthcare structures. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is considered the most reliable guidance for the management of COPD and aims to provide treating physicians with appropriate insight into the disease. COPD treatment adaptation typically mirrors the suggestions within the GOLD guidelines, depending on how the patient has been categorised. However, the present study posits that the reasons for adjusting COPD-related treatment are hugely varied. OBJECTIVES: The objective of this study was to assess the clinical symptoms that govern both pharmacological and non-pharmacological treatment changes in COPD patients. Using this insight, the study offers suggestions for optimising COPD management through the implementation of GOLD guidelines. METHODS: In this observational cohort study, 24 general practitioners screened 260 COPD patients for eligibility from 2015-2019. General practitioners were asked to collect general information from patients using a standardised questionnaire to document symptoms. During a follow-up visit, the patient's symptoms and changes in therapy were assessed and entered into a central electronic database. Sixty-five patients were removed from the analysis due to exclusion criteria, and 195 patients with at least one additional visit within one year of the baseline visit were included in the analysis. A change in therapy was defined as a change in either medication or non-medical treatment, such as pulmonary rehabilitation. Multivariable mixed models were used to identify associations between given symptoms and a step up in therapy, a step down, or a step up and a step down at the same time. RESULTS: For the 195 patients included in analyses, a treatment adjustment was made during 28% of visits. In 49% of these adjustments, the change in therapy was a step up, in 33% a step down and in 18% a step up (an increase) of certain treatment factors and a step down (a reduction) of other prescribed treatments at the same time. In the multivariable analysis, we found that the severity of disease was linked to the probability of therapy adjustment: patients in GOLD Group C were more likely to experience an increase in therapy compared to patients in GOLD Group A (odds ratio [OR] 3.43 [95% confidence interval {CI}: 1.02-11.55; p = 0.135]). In addition, compared to patients with mild obstruction, patients with severe (OR 4.24 [95% CI: 1.88-9.56]) to very severe (OR 5.48 [95% CI: 1.31-22.96]) obstruction were more likely to experience a therapy increase (p <0.0001). Patients with comorbidities were less likely to experience a treatment increase than those without (OR 0.42 [95% CI: 0.24-0.73; p = 0.002]). A therapy decrease was associated with both a unit increase in COPD Assessment Test (CAT) score (OR 1.07 [95% CI: 1.01-1.14; p = 0.014]) and having experienced an exacerbation (OR 2.66 [95% CI: 1.01-6.97; p = 0.047]). The combination of steps up as well as steps down in therapy was predicted by exacerbation (OR 8.93 [95% CI: 1.16-68.28; p = 0.035]) and very severe obstruction (OR 589 [95% CI: 2.72 - >999; p = 0.109]). CONCLUSIONS: This cohort study provides insight into the management of patients with COPD in a primary care setting. COPD Group C and airflow limitation GOLD 3-4 were both associated with an increase in COPD treatment. In patients with comorbidities, there were often no treatment changes. Exacerbations did not make therapy increases more probable. The presence of neither cough/sputum nor high CAT scores was associated with a step up in treatment.

Adherence to the GOLD Guidelines in Primary Care: Data from the Swiss COPD Cohort.

(1) Introduction: Chronic obstructive pulmonary disease (COPD) and its associated morbidity and mortality are a global burden on both affected patients and healthcare systems. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) issues guidelines with the aim of improving COPD management. Previous studies reported significant variability in adherence to these recommendations. The objective of this study was to evaluate Swiss primary practitioners' adherence to the GOLD guidelines for the pharmacological treatment of stable COPD. (2) Methods: We studied patients who were included in the Swiss COPD cohort study, an ongoing prospective study in a primary care setting, between 2015 and 2022. The key inclusion criteria are age ≥ 40 years, FEV1/FVC ratio < 70%, and a smoking history of at least 20 pack-years. Adherence to the GOLD guidelines was assessed per visit and over time. (3) Results: The data of 225 COPD patients (mean age 67 ± 9 years, 64% male) and their respective 1163 visits were analyzed. In 65% of visits (726/1121), treatment was prescribed according to the GOLD guidelines. Non-adherence was most common in GOLD groups A and B (64% and 33%) and mainly consisted of over-treatment (two long-acting bronchodilators in group A (98/195, 50%) and ICS in groups A (21/195, 11%) and B (198/808, 25%)). In group D, the prescriptions conformed with the guidelines in 99% of cases (109/108). Guideline adherence was associated with high symptom load (COPD Assessment Test) (OR 1.04, p = 0.002), high number of exacerbations (OR = 2.07, p < 0.001), asthma overlap (OR 3.36, p = 0.049), and diabetes mellitus (OR 2.82, p = 0.045). (4) Conclusion: These results confirm a conflict between the GOLD recommendations and primary practice, mainly concerning over-treatment in GOLD groups A and B. Patients with high symptom load, high exacerbation risk, asthma overlap, and diabetes mellitus are more likely to be treated in conformity with the guidelines. Further research is needed to uncover the reasons for the discrepancies and to design strategies for improvement.

Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. METHODS: COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. RESULTS: Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). CONCLUSION: Nomograms built from these models can assist clinicians in the decision-making process of COPD care.

Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled «TOASST" (Taper Or Abrupt Steroid STop) multicenter trial.

BACKGROUND: Despite the widespread use of glucocorticoids in inflammatory and autoimmune disorders, there is uncertainty about the safe cessation of long-term systemic treatment, as data from prospective trials are largely missing. Due to potential disease relapse or glucocorticoid-induced hypocortisolism, the drug is often tapered to sub-physiological doses rather than stopped when the underlying disease is clinically stable, increasing the cumulative drug exposure. Conversely, the duration of exposure to glucocorticoids should be minimized to lower the risk of side effects. METHODS: We designed a multicenter, randomized, triple-blinded, placebo-controlled trial to test the clinical noninferiority of abrupt glucocorticoid stop compared to tapering after ≥28 treatment days with ≥420 mg cumulative and ≥7.5 mg mean daily prednisone-equivalent dose. 573 adult patients treated systemically for various disorders will be included after their underlying disease has been stabilized. Prednisone in tapering doses or matching placebo is administered over 4 weeks. A 250 mg ACTH-test, the result of which will be revealed a posteriori, is performed at study inclusion; all patients are instructed on glucocorticoid stress cover dosing. Follow-up is for 6 months. The composite primary outcome measure is time to hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis. Secondary outcomes include the individual components of the primary outcome, cumulative glucocorticoid doses, signs and symptoms of hypocortisolism, and the performance of the ACTH test in predicting the clinical outcome. Cox proportional hazard, linear, and logistic regression models will be used for statistical analysis. CONCLUSION: This trial aims to demonstrate the clinical noninferiority and safety of abrupt treatment cessation after ≥28 days of systemic glucocorticoid therapy in patients with stabilized underlying disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03153527; EUDRA-CT: 2020-005601-48 https://clinicaltrials.gov/ct2/show/NCT03153527?term=NCT03153527&draw=2&rank=1.

Are Predictors for Overall Mortality in COPD Patients Robust over Time?

(1) Background: Mortality is a major outcome in research on chronic obstructive pulmonary disease (COPD) with various predictors described. However, the dynamic courses of important predictors over time are disregarded. This study evaluates if longitudinal assessment of predictors provides additional information on the mortality risk in COPD when compared with a cross-sectional analysis.; (2) In a longitudinal, prospective, non-interventional cohort study including mild to very severe COPD patients, mortality and its various possible predictors were annually assessed up to seven years.; (3) Results: 297 patients were analysed. Mean (SD) age was 62.5 (7.6) years and 66% males. Mean (SD) FEV1 was 48.8 (21.4)%. A total of 105 events (35.4%) happened with a median (95% CI) survival time of 8.2 (7.2/NA) years. No evidence for a difference between the raw variable and the variable history on the predictive value for all tested variables over each visit was found. There was no evidence for changing effect estimates (coefficients) across the study visits due to the longitudinal assessment; (4) Conclusions: We found no evidence that predictors of mortality in COPD are time dependent. This implies that cross-sectional measured predictors show robust effect estimates over time and multiple assessments seem not to change the predictive value of the measure.

[Pulmonary Opacities - What Lies Beneath?] / Pulmonale Verschattungen ­ was steckt dahinter?

Pulmonary Opacities - What Lies Beneath? Abstract. Abstract: Pulmonary opacities are among the most common findings that general practitioners and internists have to interpret in everyday life. Conventional chest x-rays are still important, but computed tomograms often provide additional information. Patient history, clinical examination but also additionally collected laboratory findings are important prerequisites for the interpretation of imaging studies. Likewise, radiological patterns should be recognized and correctly described. The density, distribution to one or both sides, basal or apical, unifocal or multifocal, also the involvement of the interstitial tissue, bronchioles, the alveolar space and pleura can provide decisive differential diagnostic information. Space-occupying or shrinking processes may be suspected on behalf of the course of pleural lines. Tumours may be differentiated from shrinking lung volume as seen in atelectasis by shift of the mediastinum or the shape of pleural lines. Occasionally control images can support the interpretation of the radiological results.

Prediction of Acute COPD Exacerbation in the Swiss Multicenter COPD Cohort Study (TOPDOCS) by Clinical Parameters, Medication Use, and Immunological Biomarkers.

BACKGROUND AND OBJECTIVE: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. METHOD: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. RESULTS: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. CONCLUSIONS: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD.

Health Preference Measures in Patients with Obstructive Sleep Apnea Syndrome Undergoing Continuous Positive Airway Pressure Therapy: Data from a Randomized Trial.

BACKGROUND: In patients with obstructive sleep apnea syndrome (OSAS), the preference-based, health-related quality of life in terms of utility has not been extensively studied. OBJECTIVE: To address this point, we compared the performance of different instruments assessing utility in patients with OSAS undergoing continuous positive airway pressure (CPAP) therapy. MATERIALS AND METHODS: Data of 208 patients with OSAS (28 women, mean ± SE age 54.4 ± 0.7 years, apnea-hypopnea index (AHI) 51.9 ± 1.8/h, Epworth sleepiness score 13.4 ± 0.2) participating in a randomized trial of different CPAP modalities over 2 years were analyzed. Evaluations included sleep studies, Epworth sleepiness scale, and several utility instruments that measure subjective health preference on a scale ranging from 1 (most preferred and perfect health) to 0 (least preferred and very poor health). RESULTS: After 2 years of CPAP therapy, the mean ± SE AHI was 6.7 ± 1.5/h and Epworth score 7.9 ± 0.4, both p < 0.001 versus baseline. Baseline utilities and changes (95% confidence interval) after 2 years of CPAP therapy were EuroQol 5-dimensions 0.79 ± 0.01, 0.02 (0.00-0.05, p = 0.064); short-form 6-dimension medical outcome questionnaire 0.72 ± 0.01, 0.06 (0.04-0.08, p < 0.001); Euro-thermometer visual analog scale 0.70 ± 0.01, 0.09 (0.07-0.12, p < 0.001); time trade-off 0.82 ± 0.01, 0.03 (0.01-0.06, p = 0.002); and standard gamble 0.82 ± 0.01, -0.01 (-0.03 to 0.02, p = 0.712). CONCLUSION: The short-form 6-dimensions questionnaire, the Euro-thermometer, and the time trade-off instruments reflected the major clinical improvements in OSAS, while the EuroQoL 5-dimensions and standard gamble tests were not sensitive to CPAP effects. These results indicate that the evaluation of utility of a treatment for OSAS depends critically on the instrument used, which is important from an individual and societal perspective.

Obstructive sleep apnoea and the progression of thoracic aortic aneurysm: a prospective cohort study.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with an increased prevalence of aortic aneurysms and it has also been suggested that severe OSA furthers aneurysm expansion in the abdomen. We evaluated whether OSA is a risk factor for the progression of ascending thoracic aortic aneurysm (TAA). METHODS: Patients with TAA underwent yearly standardised echocardiographic measurements of the ascending aorta over 3 years and two level III sleep studies. The primary outcome was the expansion rate of TAA in relation to the apnoea-hypopnoea index (AHI). Secondary outcomes included surveillance for aortic events (composite end-points of rupture/dissection, elective surgery or death). RESULTS: Between July 2014 and March 2020, 230 patients (median age 70 years, 83.5% male) participated in the cohort. At baseline, 34.8% of patients had AHI ≥15 events·h-1. There was no association between TAA diameter and AHI at baseline. After 3 years, mean±sd expansion rates were 0.55±1.25 mm at the aortic sinus and 0.60±1.12 mm at the ascending aorta. In the regression analysis, after controlling for baseline diameter and cardiovascular risk factors, there was strong evidence for a positive association of TAA expansion with AHI (aortic sinus estimate 0.025 mm, 95% CI 0.009-0.040 mm; p<0.001 and ascending aorta estimate 0.026 mm, 95% CI 0.011-0.041 mm; p=0.001). 20 participants (8%) experienced an aortic event; however, there was no association with OSA severity. CONCLUSION: OSA may be a modest but independent risk factor for faster TAA expansion and thus potentially contributes to life-threatening complications in aortic disease.

Compliance of Pharmacotherapy with GOLD Guidelines: A Longitudinal Study in Patients with COPD.

Objective: 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.

Handgrip Strength Seems Not to Be Affected by COPD Disease Progression: A Longitudinal Cohort Study.

Skeletal muscle dysfunction, functional exercise capacity impairment and reduced physical activity are characteristic features in patients with chronic obstructive pulmonary disease (COPD). Assessments addressing muscle strength of the upper limb, such as measurement of handgrip strength (HGS), are rarely performed and reported. We aimed to analyze the course of HGS and possible predictors of changes in HGS over time in COPD. Yearly assessments of various disease markers were performed for a follow-up of up to seven years in a cohort of COPD patients to assess the longitudinal disease process. Data of 194 patients with at least one follow-up measurement were analyzed. HGS decreased significantly by B = -0.86 (95% CI -1.09/-0.62, p < 0.001) over time. The multivariate mixed effects model showed an independent association between greater annual declines in HGS and lower numbers of steps per day by B = 0.11 (95% CI 0.03/0.18, p = 0.006) and an enhanced change in COPD Assessment Test scores by B = -0.01 (95% CI -0.01/-0.00, p = 0.034). No evidence for an independent association between annual decline in HGS and FEV1% pred. by B = -0.01 (95% CI -0.03/0.01, p = 0.297) was shown. Patients who died during follow-up did not exhibit greater declines in HGS compared to survivors (p = 0.884). Although HGS significantly decreased over time, no pathophysiological link with COPD disease progression could be demonstrated. Previous cross-sectional associations between HGS and mortality could not be confirmed in this longitudinal setting. Our data suggests that repeated monitoring of HGS in clinical settings seems not to be helpful to predict COPD specific disease progression.

"Can do, don't do" are not the lazy ones: a longitudinal study on physical functioning in patients with COPD.

BACKGROUND AND OBJECTIVE: Reduced physical capacity (PC) and physical activity (PA) are common in COPD patients and associated with poor outcome. However, they represent different aspects of physical functioning and interventions do not affect them in the same manner. To address this, a new PC-PA quadrant concept was recently generated to identify clinical characteristics of sub-groups of physical functioning. The objective of this study was to I) proof the new concept and to verify their differentiating clinical characteristics, II) evaluate the consistency of the concept over time, III) assess whether patients changed their quadrant affiliation over time, IV) and to test if changes in quadrant affiliations are associated with changes in clinical characteristics. METHODS: In a longitudinal, prospective, non-interventional cohort with mild to very severe COPD patients, PC and PA as well as respiratory variables, COPD-specific health status, comorbidities, survival, and exacerbations were yearly assessed. RESULTS: Data from 283 patients were analysed at baseline. Mean (min/max) follow-up time was 2.4 (0.5/6.8) years. The PC-PA quadrants could be characterized as follows: I) "can't do, don't do": most severe and symptomatic, several comorbidities II) "can do, don't do": severe but less symptomatic, several comorbidities III) "can't do, do do": few patients, severe and symptomatic, less comorbidities IV) "can do, do do": mildest and less symptomatic, less comorbidities, lowest exacerbation frequency. Of the 172 patients with at least one follow-up, 58% patients never changed their quadrant affiliation, while 17% declined either PC, PA or both, 11% improved their PC, PA or both, and 14% showed improvement and decline in PC, PA or both during study period. None of the clinical characteristics or their annual changes showed consistent significant and relevant differences between all individual sub-groups. CONCLUSION: Our findings suggest that there are no clinical characteristics allowing to distinguish between the PC-PA quadrants and the concept seems not able to illustrate disease process. However, the already low PA but preserved PC in the "can do, don't do" quadrant raises the question if regularly assessment of PA in clinical practice would be more sensitive to detect progressive deterioration of COPD compared to the commonly used PC. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01527773.

[Pulmonary Infiltrate - Not Always Due to Bacterial Infection]. / Pneumonisches Infiltrat ­ nicht immer eine bakterielle Infektion.

Pulmonary Infiltrate - Not Always Due to Bacterial Infection Abstract. A 65-year-old female patient with a history of controlled asthma was diagnosed with community-acquired pneumonia (CAP). After two weeks of treatment on co-amoxicillin, she failed to respond and was referred for further investigations. Clinical symptoms and laboratory results were suggestive for eosinophilic granulomatosis with polyangiitis (EGPA). Diagnosis and treatment of this disease are still challenging, especially in cases with vital organ involvement.

No impact of exacerbation frequency and severity on the physical activity decline in COPD: a long-term observation.

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.

Predictive factors for exacerbation and re-exacerbation in chronic obstructive pulmonary disease: an extension of the Cox model to analyze data from the Swiss COPD cohort.

BACKGROUND: The Swiss COPD cohort was established in 2006 to collect data in a primary care setting. The objective of this study was to evaluate possible predictive factors for exacerbation and re-exacerbation. METHODS: In order to predict exacerbation until the next visit based on the knowledge of exacerbation since the last visit, a multistate model described by Therneau and Grambsch was performed. RESULTS: Data of 1,247 patients (60.4% males, 46.6% current smokers) were analyzed, 268 (21.5%) did not fulfill spirometric diagnostic criteria for COPD. Data of 748 patients (63% males, 44.1% current smokers) were available for model analysis. In order to predict exacerbation an extended Cox Model was performed. Mean FEV1/FVC-ratio was 53.1% (±11.5), with a majority of patients in COPD GOLD classes 2 or 3. Hospitalization for any reason (HR1.7; P = 0.04) and pronounced dyspnea (HR for mMRC grade four 3.0; P < 0.001) at most recent visit as well as prescription of short-acting bronchodilators (HR1.7; P < 0.001), inhaled (HR1.2; P = 0.005) or systemic corticosteroids (HR1.8; P = 0.015) were significantly associated with exacerbation when having had no exacerbation at most recent visit. Higher FEV1/FVC (HR0.9; P = 0.008) and higher FEV1 values (HR0.9; P = 0.001) were protective. When already having had an exacerbation at the most recent visit, pronounced dyspnea (HR for mMRC grade 4 1.9; P = 0.026) and cerebrovascular insult (HR2.1; P = 0.003) were significantly associated with re-exacerbation. Physical activity (HR0.6; P = 0.031) and treatment with long-acting anticholinergics (HR0.7; P = 0.044) seemed to play a significant protective role. In a best subset model for exacerbation, higher FEV1 significantly reduced and occurrence of sputum increased the probability of exacerbation. In the same model for re-exacerbation, coronary heart disease increased and hospitalization at most recent visit seemed to reduce the risk for re-exacerbation. CONCLUSION: Our data confirmed well-established risk factors for exacerbations whilst analyzing their predictive association with exacerbation and re-exacerbation. This study confirmed the importance of spirometry in primary care, not only for diagnosis but also as a risk evaluation for possible future exacerbations. TRIAL REGISTRATION: Our study got approval by local ethical committee in 2006 (EK Nr. 170/06) and was registered retrospectively on ClinicalTrials.gov (NCT02065921, 19th of February 2014).

Enhancing Visibility of the Hypopharyngeal-Esophageal Region by Introduction of a Physiological Eructation Maneuver.

BACKGROUND: In routine medical examination, the hypopharyngeal-esophageal area (HER) is difficult to assess due to its position and anatomical complexity. The purpose of this study was to evaluate the feasibility of a volitional eructation maneuver during transnasal flexible laryngoscopy and its influence on the visibility of the HER. METHODS: Twenty healthy volunteers underwent flexible laryngoscopy. Once the larynx was freely visible during laryngoscopy, the subjects were asked to trigger a "burp." The volitional belching during the study was assisted by drinking a carbonated cold drink. The triggered relaxation of the upper esophageal sphincter along with the widening of the hypopharynx region was recorded and subsequently analyzed frame by frame. RESULTS: Out of 20 volunteers, 16 (80%) were able to volitionally induce an eructation. Significant widening of the hypopharynx region up to the relaxant upper esophageal sphincter could be recorded. The structures were clearly visible in the offline analysis. In 13 (81%) of the 16 subjects who could induce an eructation, the upper esophageal sphincter was partially visible or free for full inspection. CONCLUSION: The eructation method as a simple physiological function can be used as a complementary method during flexible transnasal endoscopy to enhance visibility of the entire hypopharynx region as well as the upper esophageal sphincter.

Diagnosis, Prevention and Treatment of Stable COPD and Acute Exacerbations of COPD: The Swiss Recommendations 2018.

The Swiss National Guidelines 2013 for chronic obstructive pulmonary disease have been revised in order to acknowledge recent progress in diagnosis and management of this disease. The resulting new Swiss recommendations are based on best evidence from the literature, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 report and other published national guidelines. Misdiagnosis of chronic obstructive pulmonary disease is common and means that patients do not always receive optimal treatment. To improve the management of patients with chronic obstructive pulmonary disease in Switzerland, these recommendations encourage a more comprehensive assessment of patients, based on the combined assessment of symptoms, degree of airflow limitation, risk of exacerbation and the presence of comorbidities. Recommendations for evidence-based preventive measures, as well as pharmacological and non-pharmacological strategies for the management of both stable and acute exacerbations of chronic obstructive pulmonary disease are provided in this update.

Physical activity declines in COPD while exercise capacity remains stable: A longitudinal study over 5 years.

BACKGROUND AND OBJECTIVE: Daily physical activity (PA) and exercise capacity are reduced in patients with COPD. Whether the natural longitudinal course of both appears synchronically or one precedes the other is currently unclear. The aim was to assess the longitudinal relationship between exercise capacity and physical activity and their changes over time in patients with COPD. METHODS: In a longitudinal observation-study of heterogeneous COPD patients, recruited from pulmonary outpatient clinics or hospital settings, we annually investigated two exercise capacity tests (1-min sit to stand test (STS) and 6 min walking test (6MWT)) and daily physical activity assessed by number of steps per day for minimum one, up to seven years. Univariable and multivariable mixed effect models were used to investigate the annual change in STS, 6MWD and number of steps per day. RESULTS: 202 COPD patients (17% COPD risk group (considers symptoms and future exacerbation risk to grade disease severity) A, 49% B, 4% C and 34% D) with a mean (min/max) follow-up time of 2.4 (0.9/6.8) years were annually assessed. The number of steps per day decreased significantly over time (annual mean (95% CI) of -451.0 (-605.3/-296.6) steps, p < 0.001) while STS and 6MWD remained stable. CONCLUSION: Our findings suggest that COPD patients are increasingly impaired in their daily PA while exercise capacity remains stable during the study period. Thus, the longitudinal decline in PA seems not to be explained by a concomitant reduction in exercise tolerance. CLINICAL TRIAL REGISTRATION: www.Clinicaltrials.Gov, NCT01527773.

Autoadjusted versus fixed CPAP for obstructive sleep apnoea: a multicentre, randomised equivalence trial.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) is conventionally treated by continuous positive airway pressure set at a fixed level (fCPAP). Automatic mask pressure adjustment (autoCPAP) is increasingly used during home therapy. We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term. METHODS: In this multicentre equivalence trial, 208 patients with OSAS, with median Epworth sleepiness score (ESS) 13, apnoea/hypopnoea index 48.4/hour, were randomised to treatment with autoCPAP (5-15 mbar) or fCPAP (pressure set at the 90th percentile applied by autoCPAP during 2-4 weeks adaptation). Coprimary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment. Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals. RESULTS: At 2 years, in the intention to treat analysis, the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP (n=113, mean ESS-change -6.3, 95% CI -7.1 to -5.5; sleep resistance time +8.3 min, +6.9 to +9.7) and fCPAP (n=95, mean ESS-change -6.2, 95% CI -7.0 to -5.3; sleep resistance time +6.3 min, +4.7 to +7.8). The 95% CI of difference in ESS-reduction between autoCPAP and fCPAP was -0.9 to +1.4 and the 95% CI of difference in increase in sleep resistance time was -2.6 to +1.0 min. Blood pressure reduction and OSAS-related costs were similar between groups. CONCLUSIONS: AutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years. Costs of these treatments are similar. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00280800.