[Show abstract][Hide abstract] ABSTRACT: The 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
European Respiratory Journal 07/2014; · 6.36 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Sleep Research 06/2014; · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Isocyanates are among the most common causes of occupational asthma (OA) in Switzerland. Patients with OA have been shown to have unfavourable medical, socioeconomic and psychological outcomes. We investigated long-term asthma and the socio-economic outcomes of diisocyanate-induced asthma (DIA) in Switzerland.
Journal of occupational medicine and toxicology (London, England). 01/2014; 9:21.
[Show abstract][Hide abstract] ABSTRACT: We evaluated interactions between SERPINA1 PiMZ genotype, associated with intermediate α1-antitrysin deficiency, with outdoor particulate matter ≤10 µm (PM10), and occupational exposure to vapours, dusts, gases and fumes (VGDF), and their effects on annual change in lung function.
Pre-bronchodilator spirometry was performed in 3739 adults of the Swiss Cohort Study on Air Pollution and Lung Disease in Adults (SAPALDIA) for whom SERPINA1 genotypes were available. At baseline in 1991, participants were aged 18-62 years; follow-up measurements were conducted from 2001 to 2003. In linear mixed regression models of annual change in lung function, multiplicative interactions were evaluated between PiMZ genotype (PiMM as reference) and change in PM10 (μg/m(3)), and VGDF exposure (high-level, low-level or no exposure as reference) during follow-up.
Annual declines in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%) (-82 mL/s, 95% CI -125 to -39) and forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) (-0.3%, 95% CI -0.6% to 0.0%) in association with VGDF exposure were observed only in PiMZ carriers (Pinteraction<0.0001 and Pinteraction=0.03, respectively). A three-way interaction between PiMZ genotype, smoking and VGDF exposure was identified such that VGDF-associated FEF25-75% decline was observed only in ever smoking PiMZ carriers (Pinteraction=0.01). No interactions were identified between PiMZ genotype and outdoor PM10.
SERPINA1 PiMZ genotype, in combination with smoking, modified the association between occupational VGDF exposure and longitudinal change in lung function, suggesting that interactions between these factors are relevant for lung function decline. These novel findings warrant replication in larger studies.
Occupational and Environmental Medicine 11/2013; · 3.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
JAMA The Journal of the American Medical Association 05/2013; · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: Sleep problems are a potential risk factor for work injuries but the extent of the risk is unclear. We conducted a systematic review and meta-analysis to quantify the effect of sleep problems on work injuries. METHODS: A systematic literature search using several databases was performed. Sleep problems of any duration or frequency as well as work injuries of any severity were of interest. The effect estimates of the individual studies were pooled and relative risks (RR) and 95% confidence intervals (CI) were calculated through random effects models. Additionally, the population attributable risk was estimated. RESULTS: In total, 27 observational studies (n = 268,332 participants) that provided 54 relative risk estimates were included. The findings of the meta-analysis suggested that workers with sleep problems had a 1.62 times higher risk of being injured than workers without sleep problems (RR: 1.62, 95% CI: 1.43-1.84). Approximately 13% of work injuries could be attributed to sleep problems. CONCLUSION: This systematic review confirmed the association between sleep problems and work injuries and, for the first time, quantified its magnitude. As sleep problems are of growing concern in the population, these findings are of interest for both sleep researchers and occupational physicians.
Sleep Medicine Reviews 05/2013; · 8.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess airway hyperresponsiveness to eucapnic voluntary hyperventilation and dry powder mannitol challenge in athletes aiming to participate at the Paralympic Games 2008 in Beijing, especially in athletes with spinal cord injury.
Forty-four athletes with a disability (27 with paraplegia (group 1), 3 with tetraplegia (group 2) and 14 with other disabilities such as blindness or single limb amputations (group 3) performed spirometry, skin prick testing, measurement of exhaled nitric oxide, eucapnic voluntary hyperventilation challenge test (EVH) and mannitol challenge test (MCT). A fall in FEV1 of >=10% in either challenge test was deemed positive for exercise-induced bronchoconstriction.
Fourteen (32%) athletes were atopic and 7 (16%) had a history of physician-diagnosed asthma. Absolute lung function values were significantly lower in patients of group 1 and 2 compared to group 3. Nine (20%) athletes were positive to EVH (8 paraplegics, 1 tetraplegic), and 8 (18%) athletes were positive to MCT (7 paraplegics, 1 tetraplegic). Fourteen (22.7%) subjects were positive to at least one challenge; only three athletes were positive to both tests. None of the athletes in group 3 had a positive test. Both challenge tests showed a significant association with physician-diagnosed asthma status (p = 0.0001). The positive and negative predictive value to diagnose physician-diagnosed asthma was 89% and 91% for EHV, and 75% and 86% for MCT, respectively.
EVH and MCT can be used to identify, but especially exclude asthma in Paralympic athletes.
BMC sports science, medicine and rehabilitation. 04/2013; 5(1):7.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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 company's health and safety management.
[Show abstract][Hide abstract] ABSTRACT: 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.
International Archives of Allergy and Immunology 09/2012; 160(2):161-164. · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Work-related rhinitis and asthma symptoms frequently co-exist.
To determine the prevalence and nature of nasal, pharyngeal, laryngeal and sinus symptoms among individuals with work-related respiratory symptoms.
Individuals referred to a tertiary occupational asthma clinic for investigations with specific inhalation challenges were evaluated using the RHINASTHMA quality of life questionnaire and a questionnaire that assessed the nature and frequency of upper airway symptoms, their relationship to the workplace and their temporal relationship with the onset of asthma symptoms.
There were 83 study participants. At least one upper airway symptom was reported by all of these individuals: nasal in 92%; pharyngeal in 82%; laryngeal in 65% and sinus in 53% of participants. Overall, there were no significant differences in the frequencies of nasal, pharyngeal, laryngeal and sinus symptoms when comparing these with occupational asthma (OA), work-exacerbated asthma (WEA) and work-related respiratory symptoms (WRS), except that nasal bleeding was most frequent among those with WRS. The presence of laryngeal symptoms was significantly associated with rhinitis-specific quality of life impairment. Individuals with workplace exposures to high molecular weight agents had greater impaired quality of life than those who were exposed to low molecular weight agents (RHINASTMA Upper Airway sub-scores: 24.0±10.4 versus 19.8±6.8; P < 0.05).
Individuals who were referred for work-related respiratory symptoms experienced high rates of work-related nasal, pharyngeal, laryngeal and sinus symptoms, regardless of having OA, WEA or WRS.
Occupational Medicine 07/2012; 62(6):427-34. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is limited evidence from population-based studies demonstrating incidence of spirometric-defined chronic obstructive pulmonary disease (COPD) in association with occupational exposures.
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).
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.
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.
American Journal of Respiratory and Critical Care Medicine 04/2012; 185(12):1292-300. · 11.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allergic rhinoconjunctivits and asthma are frequent diseases. About one in ten asthma cases is caused by an occupational hazard, either by an allergic or a non-immunologic mechanism. Primary or secondary preventive measures should be able to prevent these cases. Often, occupational rhinitis precedes the development of occupational asthma. Important causative agents are flours, plant and enzyme powders, laboratory animals, latex, isocyanates and hardeners, epoxy resins, acrylates, formaldehyde and welding fumes. Early diagnosis and the installation of protective measures are decisive for the prognosis of occupational respiratory disease.
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT BACKGROUND: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 randomised in a double-blind manner to receive inhaled budesonide (1600 mcg/day, 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 randomisation. Spirometry, quality of life (St George Respiratory Questionnaire), degree of dyspnoea, airway responsiveness to mannitol and exhaled nitric oxide were assessed at week 0 (recruitment), week 4 (baseline prior to randomisation) and week 16 (posttreatment). RESULTS:Compared to 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 randomisation and study completion: -9.1, 95% CI [-15.8; -2.3] p< 0.01). Treatment with inhaled budesonide also led to a reduction in airway responsiveness to mannitol compared with the placebo group (difference in log response-dose-ratio change: -0.3 95% CI [-0.6;-0.04] p< 0.01). However, post - randomisation changes in FEV(1) % predicted, quality of life and 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.