Characteristics of Severe Asthma Patients and Predictors of Asthma Control in the Swiss Severe Asthma Registry.

BACKGROUND: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5-10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. OBJECTIVES: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. METHOD: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. RESULTS: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13-87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting ß2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. CONCLUSION: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients.

The Occupational Burden of Nonmalignant Respiratory Diseases. An Official American Thoracic Society and European Respiratory Society Statement.

Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.

Diagnosis and Management of Asthma - The Swiss Guidelines.

The Global Initiative for Asthma (GINA) is a network of individuals, organizations, and public health officials that was established to disseminate information about the care of patients with asthma and to improve asthma care. The GINA ("Global Strategy for Asthma Management and Prevention") report has been updated annually since 2002. Due to new knowledge and therapeutic development in the field, the Swiss Respiratory Society felt the need to provide a new document that is based on both the available literature and the recommendations of the 2016 GINA report. Key new features of the 2016 GINA report include a "new" definition of asthma, underscoring its heterogeneous nature, and the core elements of variable symptoms and variable expiratory airflow limitation; the importance of confirming the diagnosis of asthma in order to minimize both under- and overtreatment; practical tools for the assessment of symptom control and risk factors for adverse outcomes; a comprehensive approach to asthma management that acknowledges the foundational role of inhaled corticosteroid therapy, but also provides a framework for individualizing patient care; an emphasis on maximizing the benefit of available medications by addressing common problems such as incorrect inhaler technique and poor adherence; a continuum of care for worsening asthma, starting with early self-management and progressing to primary care or acute care management; and diagnosis of the asthma/chronic obstructive pulmonary disease overlap syndrome. This document is meant to advice the key stakeholders on the diagnosis and management of asthma and highlights the need to individualize the care of each and every asthmatic patient.

Analysis of nocturnal actigraphic sleep measures in patients with COPD and their association with daytime physical activity.

BACKGROUND: Sleep disturbances are common in patients with chronic obstructive pulmonary disease (COPD) with a considerable negative impact on their quality of life. However, factors associated with measures of sleep in daily life have not been investigated before nor has the association between sleep and the ability to engage in physical activity on a day-to-day basis been studied. AIMS: To provide insight into the relationship between actigraphic sleep measures and disease severity, exertional dyspnoea, gender and parts of the week; and to investigate the association between sleep measures and next day physical activity. METHODS: Data were analysed from 932 patients with COPD (66% male, 66.4±8.3 years, FEV1% predicted=50.8±20.5). Participants had sleep and physical activity continuously monitored using a multisensor activity monitor for a median of 6 days. Linear mixed effects models were applied to investigate the factors associated with sleep impairment and the association between nocturnal sleep and patients' subsequent daytime physical activity. RESULTS: Actigraphic estimates of sleep impairment were greater in patients with worse airflow limitation and worse exertional dyspnoea. Patients with better sleep measures (ie, non-fragmented sleep, sleeping bouts ≥225 min, sleep efficiency ≥91% and time spent awake after sleep onset <57 min) spent significantly more time in light (p<0.01) and moderate-to-vigorous physical activity (p<0.01). CONCLUSIONS: There is a relationship between measures of sleep in patients with COPD and the amount of activity they undertake during the waking day. Identifying groups with specific sleep characteristics may be useful information when designing physical activity-enhancing interventions.

The Integrated Care of Asthma in Switzerland (INCAS) Study: Changes in Asthma Control and Perception of Health Care through Asthma Education.

BACKGROUND: Despite great efforts in establishing optimal asthma management, asthma may remain uncontrolled. To effectively manage chronic diseases, such as asthma, it is important to train patients in self-management skills. OBJECTIVES: The aim of this study was to assess the potential benefit of standardised asthma education in Switzerland for asthma control and patients' perception of received asthma care and of self-management support. METHODS: For this multicentre longitudinal controlled study, asthma patients were recruited in Switzerland. The Asthma Control Test (ACT) was used to assess asthma control. The Patient Assessment of Chronic Illness Care questionnaire (PACIC 5A) was applied to evaluate received health-care services and self-management support. Patients were offered the possibility to attend asthma education sessions conducted by the Swiss Lung League and Swiss Allergy Centre. After 1 year, attenders and non-attenders completed the questionnaires again. Changes in ACT and PACIC 5A scores were analysed using dependent t tests. RESULTS: Overall, 223 patients with asthma were investigated (mean age 43 ± 12 years, 38% male, 13% current smokers, 29% ex-smokers). Sixty-one (27%) patients attended education sessions. Both groups had improved asthma control at follow-up (attenders: t(56) = -3.2, r = 0.4 [medium effect size], p = 0.002; non-attenders: t(141) = -2.6, r = 0.2 [small effect size], p = 0.010). Attenders improved in PACIC and 5A sum scores (t(50) = -3.6, r = 0.5 [medium effect size], p = 0.001). CONCLUSIONS: A comprehensive self-management asthma education programme in Switzerland improved asthma control and patients' perception of received asthma care and of self-management support. Professionals should motivate patients to attend asthma education in order to become active partners in managing their disease.

Physical activity patterns and clusters in 1001 patients with COPD.

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

The integrated care of asthma in Switzerland (INCAS)-study: Patients' perspective of received asthma care and their interest in asthma education.

OBJECTIVE: For successful long-term asthma care, self-management education is a cornerstone. Little is known about associations between patients' interest in education, asthma control and care delivery. We compared patients' characteristics, asthma control and patients' perspective about asthma care in subjects with and without interest in asthma education. Moreover, we assessed reasons, why patients denied participating in asthma education. METHODS: Baseline data of 223 patients with asthma (age 43 ± 12 years, 38% male, 58% non-smokers, 13% current smokers), who participated in a multicentre longitudinal controlled study, are reported. At baseline, patients completed the Asthma Control Test (ACT), the Patient Assessment Chronic Illness Care questionnaire (PACIC 5A) and stated their interest in an asthma education programme. RESULTS: Overall, 34% of all participants showed uncontrolled asthma. One hundred and twenty-five (56%) patients were interested in education. Compared to patients without interest, they were characterised by male gender (p = 0.013), worse asthma control (p < 0.001), and perception of lower quality of chronic asthma care delivery, in particular lower self-management support (p < 0.001). Main reasons for rejecting asthma education were having sufficient asthma knowledge, having only mild asthma, receiving adequate medical support and lack of time. CONCLUSIONS: More than half of the patients were interested in asthma education. Interest was associated with worse asthma control and lower receipt of care according to the Chronic Care Model. Considering these aspects, this approach may help to improve care quality and allow targeting interventions to those patients who are interested in becoming active participants in their care and who might benefit most.

Ultrafast 3D balanced steady-state free precession MRI of the lung: Assessment of anatomic details in comparison to low-dose CT.

PURPOSE: To evaluate the anatomical details offered by a new single breath-hold ultrafast 3D balanced steady-state free precession (uf-bSSFP) sequence in comparison to low-dose chest computed tomography (CT). MATERIALS AND METHODS: This was an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant prospective study. A total of 20 consecutive patients enrolled in a lung cancer screening trial underwent same-day low-dose chest CT and 1.5T MRI. The presence of pulmonary nodules and anatomical details on 1.9 mm isotropic uf-bSSFP images was compared to 2 mm lung window reconstructions by two readers. The number of branching points on six predefined pulmonary arteries and the distance between the most peripheral visible vessel segment to the pleural surface on thin slices and 50 mm maximum intensity projections (MIP) were assessed. Image quality and sharpness of the pulmonary vasculature were rated on a 5-point scale. RESULTS: The uf-bSSFP detection rate of pulmonary nodules (32 nodules visible on CT and MRI, median diameter 3.9 mm) was 45.5% with 21 false-positive findings (pooled data of both readers). Uf-bSSFP detected 71.2% of branching points visible on CT data. The mean distance between peripheral vasculature and pleural surface was 13.0 ± 4.2 mm (MRI) versus 8.5 ± 3.3 mm (CT) on thin slices and 8.6 ± 3.9 mm (MRI) versus 4.6 ± 2.5 mm (CT) on MIPs. Median image quality and sharpness were rated 4 each. CONCLUSION: Although CT is superior to MRI, uf-bSSFP imaging provides good anatomical details with sufficient image quality and sharpness obtainable in a single breath-hold covering the entire chest.

Trends in incidence of occupational asthma, contact dermatitis, noise-induced hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in European countries from 2000 to 2012.

OBJECTIVES: The European Union (EU) strategy for health and safety at work underlines the need to reduce the incidence of occupational diseases (OD), but European statistics to evaluate this common goal are scarce. We aim to estimate and compare changes in incidence over time for occupational asthma, contact dermatitis, noise-induced hearing loss (NIHL), carpal tunnel syndrome (CTS) and upper limb musculoskeletal disorders across 10 European countries. METHODS: OD surveillance systems that potentially reflected nationally representative trends in incidence within Belgium, the Czech Republic, Finland, France, Italy, the Netherlands, Norway, Spain, Switzerland and the UK provided data. Case counts were analysed using a negative binomial regression model with year as the main covariate. Many systems collected data from networks of 'centres', requiring the use of a multilevel negative binomial model. Some models made allowance for changes in compensation or reporting rules. RESULTS: Reports of contact dermatitis and asthma, conditions with shorter time between exposure to causal substances and OD, were consistently declining with only a few exceptions. For OD with physical causal exposures there was more variation between countries. Reported NIHL was increasing in Belgium, Spain, Switzerland and the Netherlands and decreasing elsewhere. Trends in CTS and upper limb musculoskeletal disorders varied widely within and between countries. CONCLUSIONS: This is the first direct comparison of trends in OD within Europe and is consistent with a positive impact of European initiatives addressing exposures relevant to asthma and contact dermatitis. Taking a more flexible approach allowed comparisons of surveillance data between and within countries without harmonisation of data collection methods.

Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349. Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma. Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.

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.

Predictors of the overlap syndrome and its association with comorbidities in patients with chronic obstructive pulmonary disease.

BACKGROUND: The occurrence of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in an individual patient has been described as 'overlap syndrome', which has been associated with poor prognosis. Little is known about the possible predictors of the overlap syndrome and its association with comorbidities contributing to impaired outcome. OBJECTIVES: This study aimed to evaluate the prevalence and possible predictors of the overlap syndrome and its association with comorbidities in a cohort of COPD patients. METHODS: Individuals with COPD (GOLD stages I-IV, risk groups A-D) were recruited from outpatient clinics. Information on age, gender, body mass index (BMI), smoking status, Epworth sleepiness scale (ESS), COPD assessment test, comorbidities, medications and exacerbations in the past year was collected and a spirometry was performed. Participants underwent a nocturnal polygraphy using the ApneaLink™ device at home. An apnea-hypopnea index (AHI) >10 per hour was considered to indicate OSA. RESULTS: We enrolled 177 COPD patients (112 men) with a mean age of 64 years (range 42-90), of whom 35 (20%) had an ESS score above 10. During nocturnal polygraphy, 33 patients (19%) had evidence of OSA. In multivariate analysis, BMI and pack years were positively associated with AHI, independent of other significant AHI determinants from univariate analysis. Arterial hypertension and diabetes were more common in patients with the overlap syndrome. CONCLUSIONS: Almost 20% of COPD patients also have OSA. BMI and smoking history seem to be predictors of the overlap syndrome, and these patients may be more often affected by hypertension and diabetes.

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.

An open-label study examining the effect of pharmacological treatment on mannitol- and exercise-induced airway hyperresponsiveness in asthmatic children and adolescents with exercise-induced bronchoconstriction.

BACKGROUND: Mannitol- and exercise bronchial provocation tests are both used to diagnose exercise-induced bronchoconstriction. The study aim was to compare the short-term treatment response to budesonide and montelukast on airway hyperresponsiveness to mannitol challenge test and to exercise challenge test in children and adolescents with exercise-induced bronchoconstriction. METHODS: Patients were recruited from a paediatric asthma rehabilitation clinic located in the Swiss Alps. Individuals with exercise-induced bronchoconstriction and a positive result in the exercise challenge test underwent mannitol challenge test on day 0. All subjects then received a treatment with 400 µg budesonide and bronchodilators as needed for 7 days, after which exercise- and mannitol-challenge tests were repeated (day 7). Montelukast was then added to the previous treatment and both tests were repeated again after 7 days (day 14). RESULTS: Of 26 children and adolescents with exercise-induced bronchoconstriction, 14 had a positive exercise challenge test at baseline and were included in the intervention study. Seven of 14 (50%) also had a positive mannitol challenge test. There was a strong correlation between airway responsiveness to exercise and to mannitol at baseline (r = 0.560, p = 0.037). Treatment with budesonide and montelukast decreased airway hyperresponsiveness to exercise challenge test and to a lesser degree to mannitol challenge test. The fall in forced expiratory volume in one second during exercise challenge test was 21.7% on day 0 compared to 6.7% on day 14 (p = 0.001) and the mannitol challenge test dose response ratio was 0.036%/mg on day 0 compared to 0.013%/mg on day 14 (p = 0.067). CONCLUSION: Short-term treatment with an inhaled corticosteroid and an additional leukotriene receptor antagonist in children and adolescents with exercise-induced bronchoconstriction decreases airway hyperresponsiveness to exercise and to mannitol.

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

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 (ß = -0.39, p = 0.001), average daily steps (ß = -0.31, p = 0.033) and 6-min walk distance (ß = -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.

[Asthma and COPD in the workplace]. / Asthma und COPD am Arbeitsplatz.

Obstructive lung diseases are frequent in the Swiss general population. The course of these diseases can be influenced by several factors encountered in the workplace. The impact of these factors can be limited by engineered and administrative controls and then by the utilization of personal protective equipment. Surveillance programs aim to identify individuals with early symptoms of occupational disease. A change of workplace is indicated if the occupational exposures lead to a frequent exacerbation of a respiratory disorder.

Matrix metalloproteinase-9 increases in the sputum from allergic occupational asthma patients after specific inhalation challenge.

BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a role in the pathogenesis of asthma. MMP-9 increases in the sputum of asthmatic patients after bronchial challenge with common allergens. We sought to assess whether a high-molecular-weight occupational allergen was able to induce changes in MMP-9 as well as in other MMPs and TIMPs in subjects with occupational asthma. METHODS: Ten patients underwent specific inhalation challenge (SIC) on 2 consecutive days. We monitored changes in lung function by measuring FEV(1) for 7 h. Induced sputum test was performed at 6 h after sham and flour challenge. The total and differential cell counts were analyzed. Levels of MMPs (specifically MMP-2, MMP-7, MMP-9 and MMP-13) were measured using Fluorokine® MultiAnalyte Profiling kits and a Luminex® Bioanalyzer, while levels of TIMP-1 and TIMP-2 were measured by ELISA. RESULTS: Flour challenge increased the percentage of eosinophils in sputum samples. Asthmatic reactions induced by flour were associated with a significant increase in the sputum level of MMP-9 (p = 0.05), but not in the levels of MMP-2, MMP-7, MMP-13, TIMP-1 and TIMP-2. Sputum levels of MMP-9 measured after flour challenge were nearly significantly correlated (r = 0.67; p = 0.06) with the maximal fall in FEV(1) observed during the asthmatic reaction, but they did not correlate with the number of neutrophils (r = 0.18; p = 0.7) and eosinophils (r = 0.55; p = 0.2). CONCLUSIONS: This study showed that MMP-9 increases in sputum samples from sensitized occupational asthma patients after SIC with flour.

Occupational exposure to dusts, gases, and fumes and incidence of chronic obstructive pulmonary disease in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults.

RATIONALE: There is limited evidence from population-based studies demonstrating incidence of spirometric-defined chronic obstructive pulmonary disease (COPD) in association with occupational exposures. OBJECTIVES: We evaluated the association between occupational exposures and incidence of COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). MEASUREMENTS AND MAIN RESULTS: Prebronchodilator ratio of forced expiratory volume in 1 second over forced vital capacity (FEV(1)/FVC) was measured in 4,267 nonasthmatic SAPALDIA participants ages 18-62 at baseline in 1991 and at follow-up in 2001-2003. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (FEV(1)/FVC < 0.70) and Quanjer reference equation (FEV(1)/FVC < lower limit of normal [LLN]), and categorized by severity (≥ 80% and <80% predicted FEV(1) for stage I and stage II+, respectively). Using a job-exposure matrix, self-reported occupations at baseline were assigned exposures to biological dusts, mineral dusts, gases/fumes, and vapors, gases, dusts, or fumes (VGDF) (high, low, or unexposed as reference). Adjusted incident rate ratios (IRRs) of stage I and stage II+ COPD were estimated in mixed Poisson regression models. Statistically significant (P < 0.05) IRRs of stage II+ GOLD and LLN-COPD, indicating risks between two- and fivefold, were observed for all occupational exposures at high levels. Occupational exposure-associated risk of stage II+ COPD was observed mainly in males and ages ≥ 40 years, and remained elevated when restricted to nonsmokers. CONCLUSIONS: In a Swiss working adult population, occupational exposures to biological dusts, mineral dusts, gases/fumes, and VGDF were associated with incidence of COPD of at least moderate severity.

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.

Predictors for Unplanned Readmissions within 18 Days after Hospital Discharge: a Retrospective Cohort Study.

Since the introduction of the reimbursement system based on diagnosis-related groups (DRG) in Swiss hospitals in 2012, most readmissions occurring within 18 days and appertaining to the same major diagnostic category (MDC) are merged and thus often reimbursed to a lesser extent. While readmissions reflect increased distress for patients and their relatives, the causes are mainly patient-related and difficult to influence. However, it may be possible to identify cases at higher risk for readmission. Therefore, the aim of this study was to find predictors for early readmissions in the same MDC, to identify high-risk index hospitalizations and possibly prevent unnecessary readmissions. The data of all patients admitted to the Clinic of Internal Medicine at the University Hospital of Basel, Switzerland, hospitalized for longer than 24 hours during the pre-DRG period between October 2009 and September 2010 were retrospectively collected. Data were examined for predictors of unplanned readmission within 18 days under the same MDC ('relevant readmission') by means of logistic regression. 7479 patients (median age 67.8 years, 56% male) were admitted to the Clinic of Internal Medicine, with 232 patients (3.1%) being readmitted at least once. Logistic regression revealed male sex (p =0.035) and a high number of prescribed drugs at discharge (p <0.005) as patient-related predictors. The MDCs respiratory system, cardiovascular system, and gastrointestinal/hepatobiliary system were identified as high-risk categories (each p <0.005). Age and length of index hospital stay added no significant explanatory value to the regression model. Unplanned readmissions under the same MDC within 18 days were infrequent and not related to patients' age or length of hospital stay. Overall, multimorbid patients, and hospitalizations regarding the cardiovascular, respiratory, or gastrointestinal system appear to be most at risk and should therefore be specifically targeted in the prevention of early readmissions.