Alexander Turk

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

RATIONALEnThere is limited evidence from population-based studies demonstrating incidence of spirometric-defined chronic obstructive pulmonary disease (COPD) in association with occupational exposures.nnnOBJECTIVESnWe 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).nnnMEASUREMENTS AND MAIN RESULTSnPrebronchodilator 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.nnnCONCLUSIONSnIn 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.

Nocturnal periodic breathing during acclimatization at very high altitude at Mount Muztagh Ata (7,546 m)

RATIONALEnQuantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m).nnnOBJECTIVESnTo investigate whether periodic breathing persists during prolonged stay at very high altitude.nnnMETHODSnA total of 34 mountaineers (median age, 46 yr; 7 women) climbed from 3,750 m within 19-20 days to the summit at 7,546 m. During ascent, repeated nocturnal recordings of calibrated respiratory inductive plethysmography, pulse oximetry, and scores of acute mountain sickness were obtained.nnnMEASUREMENTS AND MAIN RESULTSnNocturnal oxygen saturation decreased, whereas minute ventilation and the number of periodic breathing cycles increased with increasing altitude. At the highest camp (6,850 m), median nocturnal oxygen saturation, minute ventilation, and the number of periodic breathing cycles were 64%, 11.3 L/min, and 132.3 cycles/h. Repeated recordings within 5-8 days at 4,497 m and 5,533 m, respectively, revealed increased oxygen saturation, but no decrease in periodic breathing. The number of periodic breathing cycles was positively correlated with days of acclimatization, even when controlled for altitude, oxygen saturation, and other potential confounders, whereas symptoms of acute mountain sickness had no independent effect on periodic breathing.nnnCONCLUSIONSnOur field study provides novel data on nocturnal oxygen saturation, breathing patterns, and ventilation at very high altitude. It demonstrates that periodic breathing increases during acclimatization over 2 weeks at altitudes greater than 3,730 m, despite improved oxygen saturation consistent with a progressive increase in loop gain of the respiratory control system. Clinical trial registered with www.clinicaltrials.gov (NCT00514826).

Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m.

Investigations studying the secretion of EPO (erythropoietin) in response to acute hypoxia have produced mixed results. Further, the errors associated with the various methods used to determine EPO are not well documented. The purpose of the current study was to determine the EPO response of 17 trained male subjects to either an acute bout of normobaric hypoxia (Hy; n = 10) or normoxia (Con; n = 7). A secondary aim was to determine the error associated with the measurement of EPO. After baseline tests, the treatment group (Hy) underwent a single bout of hypoxic exposure (F(I(O(2))) approximately 0.148; 3100 m) consisting of a 90-min rest period followed by a 30-min exercise phase (50% V(O)(2max)). Venous blood samples were drawn pre (0 min) and post (120 min) each test to assess changes in plasma EPO (DeltaEPO). The control (Con) group was subjected to the same general experimental design, but placed in a normoxic environment (F(I(O(2))) approximately 0.2093). The Hy group demonstrated a mean increase in EPO [19.3 (4.4) vs. 24.1 (5.1) mU/mL], p < 0.04, post 120 min of normobaric hypoxia. The calculated technical error of measurement for EPO was 2.1 mU/mL (9.8%). It was concluded that an acute bout of hypoxia, has the capacity to elevate plasma EPO. This study also demonstrates that the increase in EPO accumulation was 2 times greater than the calculated measurement of error.

Recruitment barriers in a randomized controlled trial from the physicians' perspective – A postal survey

BackgroundThe feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment.MethodsWe identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease. We developed and pilot-tested a self-administered questionnaire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 (full agreement with statement = very substantial recruitment barrier) to 7 (no agreement with statement = no recruitment barrier).Results38 of 55 recruiting physicians returned questionnaires (69% response rate), of which 35 could be analyzed (64% useable response rate). Recruiting physicians reported that time constraints (median agreement of 3, interquartile range 2–5) had the most negative impact on recruitment followed by difficulties including identified eligible patients (median agreement of 5, IQR 3–6). Other barriers such as trial design barriers, lack of access to treatment, individual barriers of recruiting physicians or insufficient training of recruiting physicians were perceived to have little or no impact on patient recruitment.ConclusionPhysicians perceived time constraints as the most relevant recruitment barrier in a randomized trial. To overcome recruitment barriers interventions, that are affordable for both industry- and investigator-driven trials, need to be developed and tested in randomized trials.Trial registrationISRCTN84612310

High Incidence of Optic Disc Swelling at Very High Altitudes

OBJECTIVESnTo determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema.nnnMETHODSnThis multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores.nnnRESULTSnSixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001).nnnCONCLUSIONnOptic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.

Early versus late pulmonary rehabilitation in chronic obstructive pulmonary disease patients with acute exacerbations: a randomized trial.

Background: Around the world, the timing of referral of chronic obstructive pulmonary disease (COPD) patients for pulmonary rehabilitation differs from immediately after exacerbation (early) to later on when patients are in a stable state (late). There are no trials comparing the different time points of referral for pulmonary rehabilitation. Objectives: Our aim was to compare the effects of early and late pulmonary rehabilitation on exacerbation rates and health-related quality of life (HRQOL) in COPD patients with exacerbations. Methods: We randomized COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages II–IV) with a recent exacerbation to early (within 2 weeks) or late pulmonary rehabilitation (starting 6 months after randomization and in a stable state). The primary outcome was the exacerbation rate over 18 months, and secondary outcomes included HRQOL and mortality. We used multivariate analyses and an intention-to-treat analysis approach. Results: We randomized 36 patients to pulmonary rehabilitation. On average, patients with early rehabilitation (n = 19) had 2.61 (SD 2.96) exacerbations requiring systemic corticosteroids and/or antibiotics, compared to 2.77 (SD 3.41) in patients with late rehabilitation (adjusted incidence rate ratio 0.83, 95% confidence interval 0.43–1.63; p = 0.60). Over the 18-month period, patients with late rehabilitation experienced more dyspnea (difference on Chronic Respiratory Questionnaire dyspnea domain 0.74 and on the Medical Research Council dyspnea scale 0.37), but neither these differences nor any difference in HRQOL domains reached statistical significance. Conclusions: We did not find any statistically significant differences between early and late pulmonary rehabilitation. However, our trial indicates that early rehabilitation may lead to faster recovery of HRQOL after exacerbations compared to rehabilitation later on when patients are in a stable state.

New Insights Into Changes in Corneal Thickness in Healthy Mountaineers During a Very-High-Altitude Climb to Mount Muztagh Ata

OBJECTIVEnTo investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT).nnnMETHODSnTwenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO(2)) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m.nnnRESULTSnCentral corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 microm. Mean CCT in group 2 increased from 534 to 563 microm (P = .048). The amount of decrease in SpO(2) paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO(2) and age.nnnCONCLUSIONSnCorneal swelling during high-altitude climbs is promoted by low SpO(2). Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness-related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.

Population-based reference values for the 1-min sit-to-stand test

ObjectivesTo determine reference values for the 1-min sit-to-stand (STS) test in an adult population.MethodsCross-sectional study nested within a nationwide health promotion campaign in Switzerland. Adults performed the STS test and completed questions on demographics and health behavior.Results6,926 out of 7,753 (89.3 %) adults were able to complete the STS test. The median number of repetitions ranged from 50/min (25–75th percentile 41–57/min) in young men and 47/min (39–55/min) in young women aged 20–24xa0years to 30/min (25–37/min) in older men and 27/min (22–30/min) in older women aged 75–79xa0years.ConclusionsThe reference values support the interpretation of 1-min STS test performance and identification of subjects with decreased lower body muscular strength and endurance.

Early detection of subjects at risk for vascular remodelling - results from the Swiss population-based study SAPALDIA

QUESTIONS UNDER STUDYnAs the burden of cardiovascular disease (CVD) increases globally, its prevention and risk assessment becomes ever more important. We thus investigated the longitudinal association of the cardiovascular risk scores in the population-based cohort SAPALDIA with carotid intima media thickening (CIMT), an indicator of sub-clinical disease, and CVD incidence.nnnMETHODSnIn 2,832 SAPALDIA participants, the Swiss and ESC heart risk score (AGLA, SCORE) were calculated based on 2001 data and CIMT was measured in 2010/11. We ran multi-level linear regression analyses between scores and CIMT, stratified for CVD status and gender, and logistic analyses for doctor-diagnosed CVD incidence. Path analyses investigated direct and indirect effects on CIMT.nnnRESULTSnAGLA and SCORE were positively associated with increasing CIMT in both healthy and CVD diagnosed subjects and men and women. Participants in highest risk categories showed a significant CIMT difference of >0.20 mm compared to the reference risk category (<1%), even larger in CVD healthy subjects and men. With increasing risk the odds of CVD incidence increased (Ref. <1%; 10 yr. risk AGLA >10% OR 2.1, >20% OR 3.7). Path analyses yield risk factors direct and indirect effects through blood pressure.nnnCONCLUSIONnThe positive longitudinal association between risk estimations and CIMT confirms the use of risk scores in assessing individuals and populations at risk. Systolic blood pressure appears to be a main pathological mechanism, underscoring the importance of optimal blood pressure control and the importance of prevention strategies of risk factors, indirectly affecting CIMT through the haemodynamic pathway.

Physical activity is associated with lower arterial stiffness in older adults: results of the SAPALDIA 3 Cohort Study

AbstractnAssociations of physical activity (PA) intensity with arterial stiffness in older adults at the population level are insufficiently studied. We examined cross-sectional associations of self-reported PA intensities with arterial stiffness in elderly Caucasians of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults. Mixed central and peripheral arterial stiffness was measured oscillometrically by the cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). The self-reported International Physical Activity Questionnaire long version was administered to classify each subject’s PA level. We used univariable and multivariable mixed linear and logistic regression models for analyses in 1908 persons aged 50xa0years and older. After adjustment for several confounders moderate, vigorous and total PA were inversely associated with CAVI (pxa0=xa00.02–0.03). BaPWV showed negative and marginally significant associations with vigorous and moderate PA (each pxa0=xa00.06), but not with total PA (pxa0=xa00.28). Increased arterial stiffness (CAVIxa0≥xa09, upper tertile) was inversely and significantly associated with vigorous PA [odds ratio (OR) 0.65, 95xa0% confidence interval (CI) 0.48–0.88], and marginally significantly with total PA (OR 0.76, 95xa0% CI 0.57–1.02) and moderate PA (OR 0.75, 95xa0% CI 0.56–1.01). The odds ratio for baPWVxa0≥xa014.4 was 0.67 (95xa0% CI 0.48–0.93) across the vigorous PA levels, and was non-significant across the total (OR 0.91, 95xa0% CI 0.66–1.23) and moderate PA levels (OR 0.94, 95xa0% CI 0.69–1.28). In this general Caucasian population of older adults higher levels especially of vigorous PA were associated with lower arterial stiffness. These data support the importance of PA for improving cardiovascular health in elderly people.