[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: 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.
[show abstract][hide abstract] ABSTRACT: Transcutaneous measurement of carbon dioxide is routinely done at the earlobe site. In patients receiving non invasive ventilation or in the intensive care setting with necklines, an alternate measurement site would be useful. We started to use the infraclavicular site for transcutaneous measurements of carbon dioxide using a new digital sensor.
Comparison of transcutaneous carbon dioxide with arterial carbon dioxide at the infraclavicular site.
We retrospectively compared transcutaneous carbon dioxide at the infraclavicular site with arterial carbon dioxide in 50 samples. The Sentec Digital Monitoring System (Sentec AG, Therwil, Switzerland) was used. The V-Sign digital sensor was placed on the infraclavicular site at the medial two third and one third point from the sternoclavicular joint and acromioclavicular joint.
When comparing P(c)CO(2) with P(a)CO(2) values, the Bland-Altman analysis revealed a bias of 0.02 kPa (95% CI: [- 0.1; 0.14]) with a precision of 0.42 kPa. Linear regression analysis describes the relationship between the two methods. The slope of the linear model was 0.85 ± 0.04 and the intercept was 0.77 ± 0.21 (RSE = 0.37, R(2) = 0.91).
The measurement of transcutaneous carbon dioxide at the infraclavicular site is feasible with a digital sensor and has a good correlation with the carbon dioxide values obtained from the arterial blood gas. The findings of the current study form the basis for further clinical studies for its regular application in clinical use.
Scandinavian journal of clinical and laboratory investigation 03/2012; 72(4):340-2. · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: The existence of nasal mucosa remodeling in allergic rhinitis is controversial. Few data are available on the dynamics of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in nasal fluid after an allergen challenge. We examined whether an immediate allergic reaction that induces nasal congestion and inflammation is able to also induce changes in remodeling parameters in nasal fluid.
Controlled experimental study.
Ten patients with allergic occupational rhinitis due to flour underwent a control and active inhalation challenge with serial monitoring of nasal congestion and nasal symptoms with acoustic rhinometry and a visual analogue scale. Levels of remodeling markers (MMP-2, MMP-7, MMP-9, MMP-13, TIMP-1, TIMP-2) and inflammatory cells in nasal fluid were measured before the challenge and at 30 minutes, 6 hours, and 24 hours following the challenge.
In contrast to the control challenge, the flour challenge induced nasal symptoms and significant decreases in nasal volume in all subjects. After the flour challenge, a significant increase in nasal levels of TIMP-2 and a nonsignificant increase in TIMP-1 levels were observed, whereas no significant changes in nasal levels of MMPs were documented.
This study showed that after an inhalation challenge with an occupational allergen, the nasal mucosa displayed an imbalance in favor of TIMPs enzymes activity as compared to MMPs enzymes activity, represented in an increase in nasal levels of TIMP-2 during the course of the early reaction following the allergen challenge.
The Laryngoscope 02/2012; 122(4):730-5. · 1.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines aim to optimise chronic obstructive pulmonary disease (COPD) diagnosis and treatment. However, little is known about the extent to which general practitioners' (GP) adherence to GOLD guidelines improves patient outcomes.
In this questionnaire-based study, COPD patients were screened and enrolled; exacerbation history was recorded, and demographic, spirometric and management data were collected for 12 months. Spirometry was performed at least every 6 months according to American Thoracic Society guidelines. Based on these data, patients were grouped into GOLD COPD severity classifications. Data were expressed as the difference between baseline and month 12.
Among 139 GPs, 454 patients were analysed regarding baseline and 12 month data. There was no significant change in distribution of GOLD COPD severity grades, lung function or guideline adherence. Chronic cough and sputum production were significantly reduced (p <0.001; p <0.020), as was exacerbation rate (p = 0.041). Factors associated with exacerbations were male sex, asthma and cerebrovascular insult as a co-morbidity. Exacerbation rate was significantly reduced in patients treated with combination therapy (long-acting β2-agonist (LABA)+ inhaled corticosteroids (ICS); p = 0.0178) and long-acting anticholinergics (LAAC; p = 0.0011). Patients treated per guidelines had no advantage in lung function, estimation of symptom prevalence or, most importantly, exacerbation rate.
While there was no improvement in adherence to GOLD guidelines, disease severity was not affected detrimentally, suggesting that guideline adherence does not seem to impact symptom prevalence, exacerbation rate or lung function decline after one year of follow up.
[show abstract][hide abstract] ABSTRACT: There is conflicting evidence about resting carbon dioxide levels in asthmatic individuals. We wanted to determine if transcutaneously measured carbon dioxide levels prior and during bronchial provocation testing differ according to asthma status reflecting dysfunctional breathing.
We investigated active firefighters and policemen by means of a validated questionnaire on respiratory symptoms, spirometry, bronchial challenge testing with methacholine (MCT) and measurement of transcutaneous blood carbon dioxide partial pressure (PtcCO(2)) at rest prior performing spirometry, one minute and five minutes after termination of MCT. A respiratory physician blinded to the PtcCO(2) results assigned a diagnosis of asthma after reviewing the available study data and the files of the workers medical screening program.
The study sample consisted of 128 male and 10 female individuals. Fifteen individuals (11%) had physician-diagnosed asthma. There was no clinically important difference in median PtcCO(2) at rest, one and five minutes after recovery from MCT in asthmatics compared to non-asthmatics (35.6 vs 35.7 mmHg, p = 0.466; 34.7 vs 33.4 mmHg, p = 0.245 and 37.4 vs 36.4 mmHg, p = 0.732). The median drop in PtcCO(2) during MCT and the increase after MCT was lower in asthmatics compared to non-asthmatics (0.1 vs 3.2 mmHg, p = 0.014 and 1.9 vs 2.9 mmHg, p = 0.025).
PtcCO(2) levels at rest prior and during recovery after MCT do not differ in individuals with or without physician diagnosed asthma. The fall and subsequent increase in PtcCO(2) levels are higher in non-asthmatics than in asthmatics and seems to be related with increased number of respiratory maneuvers during MCT.
PLoS ONE 01/2012; 7(3):e32464. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The GINA guidelines have redefined the primary goal of asthma treatment as achieving optimum control.
To document the level of asthma control in Switzerland, the correlations between the international guidelines by GINA and the ACT's rating of asthma control, current treatment in adolescent and adult Swiss asthma patients and factors associated with asthma control.
General practitioners and specialists (pulmonologists, allergologists and paediatricians) were invited to participate in the cross-sectional survey. Asthma control was assessed in 1093 asthma patients using both the ACT and the GINA classification for asthma control.
According to the GINA guidelines controlled asthma was found in 290 (27%) patients, when measured with the ACT 124 (11.5%) patients showed sufficient asthma control. Of the test results 65% were in accordance with each other, whereas in 85% of the non-matching results the ACT underestimated control according to GINA classification. An ACT cut-off score of ≤17 best identified uncontrolled asthma according to GINA guidelines. A total of 956 (87.7%) patients received controller medication and 849 (77.9%) patients received reliever medication. The following parameters were consistently identified to be significantly associated with insufficient asthma control in both GINA and ACT measurements: presence of exacerbation, use of reliever medication, switch of therapy and smoking. STUDY LIMITATION: For this study only the ACT version for adults was used.
Asthma control remains insufficient in the majority of patients, despite prescription of regular controller medication. This survey confirms the validated ACT to be useful and important in everyday practice as an objective measure for asthma control according to GINA guidelines in order to monitor control and adjust treatment.
Current Medical Research and Opinion 12/2011; 27(12):2301-8. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Smoking is a major health risk in young adults. We undertook a study in young Swiss military recruits to determine the impact of intensive training and of help offered on smoking cessation during Basic Military Training (BMT). A questionnaire including questions according to their smoking status, sporting activities and, alcohol use was administered to 999 conscripts at beginning and at the end of the BMT. The results were compared to a control group of BMT schools where no such intervention took place. The study shows that the prevalence of smokers in the intervention group decreased (start BMT 31.9%, end BMT 25.5%; p = 0.021), while the prevalence of smokers increased in the control group (start BMT 26.4%, end BMT 32.6%; p = 0.038). A motivation to serve in the armed forces, as well as the willingness to stop smoking in the next month were the factors associated with a subsequent cessation of smoking during BMT. A smoke stop intervention during BMT is viable and can lead to a decrease in the prevalence of smoking at the end of BMT.
[show abstract][hide abstract] ABSTRACT: The Juniper Asthma Specific Quality of Life Questionnaire (AQLQ(S)) is a questionnaire that allows measurement of disease specific quality of life. We wanted to examine correlations between the (AQLQ(S)) general and different subscale scores and both psychiatric morbidity and levels of psychological distress in individuals with occupational asthma (OA) and to determine if results in the emotional function subscale allow identification of individuals with clinically significant psychological distress or current psychiatric disorders.
This was a cross-sectional study of individuals with OA who were assessed during a re-evaluation for permanent disability, after they were no longer exposed to the sensitizing agent. Patients underwent a general sociodemographic and medical history evaluation, a brief psychiatric interview (Primary Care Evaluation of Mental Disorders, PRIME-MD) and completed a battery of questionnaires including the AQLQ(S), the St-Georges Respiratory Questionnaire (SGRQ), and the Psychiatric Symptom Index (PSI).
There was good internal consistency (Cronbach alpha = 0.936 for the AQLQ(S) total score) and construct validity for the AQLQ(S) (Spearman rho = -0.693 for the SGRQ symptom score and rho = -0.650 for the asthma severity score). There were medium to large correlations between the total score of the AQLQ(S) and the SGRQ symptom score (r = -.693), and PSI total (r = -.619) and subscale scores (including depression, r = -.419; anxiety, r = -.664; anger, r = -.367; cognitive disturbances, r = -.419). A cut-off of 5.1 on the AQLQ(S) emotional function subscale (where 0 = high impairment and 7 = no impairment) had the best discriminative value to distinguish individuals with or without clinically significant psychiatric distress according to the PSI, and a cut-off of 4.7 best distinguished individuals with or without a current psychiatric disorder according to the PRIME-MD.
Impaired quality of life is associated with psychological distress and psychiatric disorders in individuals with OA. Findings suggest that the AQLQ(S) questionnaire may be used to identify patients with potentially clinically significant levels of psychological distress.
Health and Quality of Life Outcomes 09/2011; 9:76. · 2.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Smoking is one of the leading preventable risk factors for the development of lung-, cardio-vascular diseases and cancer. We report results of a prospective survey regarding smoking behaviour and willingness to stop smoking in patients of an internal medicine clinic. Twenty percent of participants admitted smoking cigarettes in the previous 7 days. Smokers were more often males and were younger than non- or ex-smokers. Every second smoker reported being told to stop smoking by a physician before but only about a third was offered active support in doing so. About half of the smoking participants were interested to quit smoking and to participate in a hospital-based smoking cessation program. In patients admitted to the hospital, smoking behaviour and willingness to quit smoking should be recorded and help in quitting smoking should be offered actively. Beside recording smoking behaviour and willingness to quit, patients who are admitted in the hospital should be offered help to quit smoking or to join a proactive structured smoking cessation program.