Sabrina Maier

Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: The REDUCE randomized clinical trial

IMPORTANCE International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown. OBJECTIVE To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. DESIGN, SETTING, AND PATIENTS REDUCE: (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (≥20 pack-years) without a history of asthma, from March 2006 through February 2011. INTERVENTIONS Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%. MAIN OUTCOME AND MEASURE Time to next exacerbation within 180 days. RESULTS Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently. CONCLUSIONS AND RELEVANCE In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN19646069.

Daily physical activity, functional capacity and quality of life in patients with COPD.

Abstract Introduction: In the therapy of chronic obstructive pulmonary disease (COPD), it is a major goal to improve health-related quality of life (HRQOL). Patients with COPD often suffer from exertional dyspnea and adopt a sedentary lifestyle, which could be associated with poorer HRQOL. The aim of this study was to investigate the independent association of objectively measured daily physical activity and functional capacity with HRQOL in patients with COPD. Methods: In this cross-sectional study conducted at the University Hospital Basel, Switzerland, 87 stable patients (58.6% male, mean age: 67.3 ± 9.6 yrs) with COPD in GOLD grades I (n = 23), II (n = 46), III (n = 12) and IV (n = 6) were investigated. To assess HRQOL, the COPD assessment test (CAT) was completed. Patients performed spirometry and 6-min walk test. Physical activity was measured by the SenseWear Mini Armband on 7 consecutive days. By performing a multiple linear regression analysis, independent predictors of CAT score were identified. Results: Age (β = −0.39, p = 0.001), average daily steps (β = −0.31, p = 0.033) and 6-min walk distance (β = −0.32, p = 0.019) were found to be independent predictors of CAT score, whereas physical activity duration above 3 METs (p = 0.498) and forced expiratory volume in 1 s in% of predicted (p = 0.364) showed no significant association. Conclusions: This study showed that average daily steps and functional capacity are independent determinants of HRQOL in patients with COPD. This emphasizes the importance to remain active and mobile, which is associated with better HRQOL.

Response to Add-on Inhaled Corticosteroids in COPD Based on Airway Hyperresponsiveness to Mannitol

BACKGROUND The use of inhaled corticosteroids in mild to moderate COPD is controversial. The aim of this study was to determine whether airway hyperresponsiveness to mannitol might identify patients who are likely to respond to add-on inhaled corticosteroids. METHODS Ninety subjects with mild to moderate COPD were recruited and 68 subsequently randomized in a double-blind manner to receive inhaled budesonide (1,600 μg/d, n = 31) or placebo (n = 37) for 3 months. Thirty-eight subjects had airway hyperresponsiveness to mannitol (17 received budesonide, 21 placebo). All subjects received tiotropium throughout the study, including 4 weeks before randomization. Spirometry, quality of life (St. George Respiratory Questionnaire), degree of dyspnea, airway responsiveness to mannitol, and exhaled nitric oxide were assessed at week 0 (recruitment), week 4 (baseline prior to randomization), and week 16 (posttreatment). RESULTS Compared with placebo, budesonide was associated with improved quality of life in subjects showing airway hyperresponsiveness to mannitol (difference of changes in quality of life score between randomization and study completion, −9.1; 95% CI, −15.8 to −2.3; P < .01). Treatment with inhaled budesonide also led to a reduction in airway responsiveness to mannitol compared with placebo (difference in log10 response-dose ratio, −0.3; 95% CI, −0.6 to −0.04; P < .01). However, postrandomization changes in FEV1 % predicted, quality of life, and exhaled nitric oxide showed no difference between budesonide and placebo. CONCLUSIONS In subjects with mild to moderate COPD and airway hyperresponsiveness to mannitol, quality of life and airway responsiveness improved after treatment with inhaled corticosteroids added to long-acting bronchodilator therapy.

Sleep quality and the risk of work injury: a Swiss case-control study

Sleep problems are a well‐known risk factor for work injuries, but less is known about which vulnerable populations are most at risk. The aims of this study were to investigate the association between sleep quality and the risk of work injury and to identify factors that may modify the association. A case–control study including 180 cases and 551 controls was conducted at the University Hospital in Basel, Switzerland, from 1 December 2009 to 30 June 2011. Data on work injuries and sleep quality were collected. Adjusted odds ratios and 95% confidence intervals of the association between sleep quality and work injury were estimated in multivariable logistic regression analyses and were stratified by hypothesized effect modifiers (age, gender, job risk, shift work, sleep duration and working hours). Poor sleep quality was associated significantly with work injury of any type (P < 0.05) and with being caught in particular (P < 0.05). The association between poor sleep quality and work injury was significantly higher for workers older than 30 years (odds ratio>30 1.30 versus odds ratio≤30 0.91, P < 0.01), sleeping 7 h or less per night (odds ratio≤7 1.17 versus odds ratio>7 0.79, P < 0.05) and working 50 h or more per week (odds ratio≥50 1.79 versus odd ratio<50 1.10, P < 0.01). Work injury risk increased with increasing severity of sleep problems (P < 0.05). Prior work injury frequency increased with decreasing sleep quality (P < 0.05). Older age, short sleep duration and long working hours may enhance the risk of work injuries associated with sleep quality.

Differences in classification of COPD patients into risk groups A-D: a cross-sectional study

BackgroundThe Global Initiative for Chronic Obstructive Lung Disease proposed in 2011 a new system to classify chronic obstructive pulmonary disease (COPD) patients into risk groups A-D, which considers symptoms and future exacerbation risk to grade disease severity. The aim of this study was to investigate the agreement between COPD risk group classifications using COPD assessment test (CAT) or modified Medical Research Council (mMRC) and severity grades or past-year exacerbations. Furthermore, physical activity across risk groups was examined.Methods87 patients with stable COPD were classified into risk groups A-D. CAT and mMRC were completed. Severity grades I-IV were determined using spirometry and the number of past-year exacerbations was recorded. To test the interrater agreement, Cohen’s Kappa was calculated. Daily physical activity was measured by the SenseWear Mini armband.ResultsUsing CAT, 65.5% of patients were in high-symptom groups (B and D). With mMRC, only 37.9% were in B and D. Using severity grades, 20.7% of patients were in high-exacerbation risk groups (C and D). With past-year exacerbations, 9.2% were in C and D. Interrater agreement between CAT and mMRC (κ = 0.21) and between severity grades and past-year exacerbations (κ = 0.31) was fair. Daily steps were reduced in risk groups B and C + D compared to A (p < 0.01), using either classification.ConclusionsWhen classifying COPD patients into risk groups A-D, the use of CAT or mMRC and severity grades or past-year exacerbations does not provide equal results. Daily steps decreased with increasing COPD risk groups.

Sleep problems and work injury types: a study of 180 patients in a Swiss emergency department.

INTRODUCTION Sleep problems present a risk for work injuries and are a major occupational health concern worldwide. Knowledge about the influence of sleep problems on work injury patterns is limited. Therefore, the aim of this study was to identify potential associations between different types of work injuries and sleep quality, sleep duration, and daytime sleepiness. METHODS In this hospital-based study, 180 male and female patients with work injuries were recruited at the Emergency Department of the University Hospital Basel, Switzerland, from December 1st 2009 to June 30th 2011. The data on work injury characteristics, sleep problems, and potential confounders, such as demographic, health, lifestyle, occupational and environmental factors, were collected. Multivariable logistic regression analyses were performed to investigate the relationship between sleep problems and various types of work injury. RESULTS Each dimension of sleep problems - sleep quality, sleep duration and daytime sleepiness - was a significant risk factor for at least one type of work injury. The strongest association was found for musculoskeletal injuries and falls with short sleep duration (odds ratio [OR] 5.41, 95% confidence interval [CI] 1.81-16.22). The standardised scores of the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS) did not discriminate between injury types. CONCLUSION Employees with sleep problems were more likely to suffer from certain types of work injuries. This should be considered by employers monitoring work injuries and implementing prevention measures in the companys health and safety management.

Prospective analysis of adrenal function in patients with acute exacerbations of COPD: the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial

OBJECTIVE To analyze prospectively the hypothalamic-pituitary-adrenal (HPA) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease (COPD). DESIGN Prospective observational study. SUBJECTS AND METHODS Patients presenting to the emergency department were randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner. The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline, on day 6 before blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of the test results. Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment. RESULTS A total of 311 patients were included in the analysis. Mean basal and stimulated serum total cortisol levels were highest on admission (496±398 and 816±413 nmol/l respectively) and lowest on day 6 (235±174 and 453±178 nmol/l respectively). Pathological stimulation tests were found in 63, 38, 9, 3, and 2% of patients on day 6, at discharge, and on days 30, 90, and 180 respectively, without significant difference between treatment groups. Clinical indicators of hypocortisolism did not correlate with stimulation test results, but cortisol levels were inversely associated with re-exacerbation risk. There were no hospitalizations or deaths as a result of adrenal crisis. CONCLUSION Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD. In hypocortisolemic patients who were provided with instructions about stress prophylaxis, the abrupt termination of prednisone appeared safe.

The ADO index as a predictor of two-year mortality in general practice-based chronic obstructive pulmonary disease cohorts.

Background: Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care. Objectives: Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2-year mortality in 2 general practice-based COPD cohorts. Methods: Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2-year all-cause mortality. Results: Fifty-two (8.1%) patients died during the 2-year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71). Conclusions: The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings.

Predictors of Increased Daytime Sleepiness in Patients with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study

Background. Patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from increased daytime sleepiness. The aim of this study was to identify potential predictors of subjective daytime sleepiness with special regard to sleep-related breathing disorder and nocturnal activity. Methods. COPD patients were recruited at the University Hospital Basel, Switzerland. COPD risk groups A–D were determined according to spirometry and COPD Assessment Test (CAT). Breathing disorder evaluation was performed with the ApneaLink device. Nocturnal energy expenditure was measured with the SenseWear Mini Armband. Subjective daytime sleepiness was recorded using the Epworth Sleepiness Scale (ESS). Results. Twenty-two patients (36%) were in COPD risk group A, 28 patients (45%) in risk group B, and 12 patients (19%) in risk groups C + D (n = 62). Eleven patients (18%) had a pathological ESS ≥ 10/24. ESS correlated positively with CAT (r = 0.386, p < 0.01) and inversely with age (r = −0.347, p < 0.01). In multiple linear regression age (β = −0.254, p < 0.05), AHI (β = 0.287, p < 0.05) and CAT score (β = 0.380, p < 0.01) were independent predictors of ESS, while nocturnal energy expenditure showed no significant association (p = 0.619). Conclusion. These findings provide evidence that daytime sleepiness in COPD patients may partly be attributable to nocturnal respiratory disturbances and it seems to mostly affect younger patients with more severe COPD symptoms.

Obstructive sleep apnea syndrome and sleep disorders in individuals with occupational injuries

BackgroundSome sleep disorders are known risk factors for occupational injuries (OIs). This study aimed to compare the prevalence of obstructive sleep apnea syndrome (OSAS) in a population of patients with OIs admitted to the emergency room (ER) with hospital outpatients as controls.MethodsSeventy-nine patients with OIs and 56 controls were recruited at the University Hospital of Basel, Switzerland between 2009 and 2011. All patients completed a questionnaire and underwent a full-night attended polysomnography (PSG). We considered an apnea–hypopnea index (AHI) > 5 as an abnormal finding suggestive of a diagnosis of OSAS.ResultsPatients with OIs did not differ from controls regarding sex, age, body mass index, and job risk of OI. Patients with OIs tended to have an abnormal AHI (n = 38 [48%] vs. n = 16 [29%], odds ratio [OR] = 2.32 [95% confidence interval (CI):1.05–5.13]), and a higher AHI (8.0 vs. 5.6 events/h; Cohen’s d 0.28, p = 0.028) compared with controls. Patients with OIs also had abnormal limb movement index, arousal index, and signs of sleep bruxism compared with controls. Compared with 36 controls (66%), 70 patients with OIs (89%) had either excessive daytime sleepiness (EDS), and/or an abnormal finding during PSG (OR = 4.32, 95% CI:1.65–11.52). However, patients with OIs did not differ from controls regarding EDS or oxygen desaturation index.ConclusionsPatients treated in the ER for OI had more abnormal findings suggestive of OSAS or other sleep disorders compared with a control group of hospital outpatients. Screening for these conditions should be part of the postaccident medical investigation.