Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

AIMS: The aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults. METHODS AND RESULTS: Older adults aged 70-77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak). CCR was not significantly lower [-0.19, 99% confidence interval (CI) -0.46 to 0.07] and VO2peak was not significantly higher (0.39 mL/kg/min, 99% CI -0.22 to 1.00) for ExComb vs. control. HIIT showed higher VO2peak (0.76 mL/kg/min, 99% CI 0.02-1.51), but not lower CCR (-0.32, 99% CI -0.64 to 0.01) vs. control. MICT did not show significant differences compared to control or HIIT. Individual risk factors mostly did not show significant between-group differences, with some exceptions for HIIT being better than control. There was no significant effect modification by sex. The number of cardiovascular events was similar across groups. The healthy and fit study sample, and contamination and cross-over between intervention groups, challenged the possibility of detecting between-group differences. CONCLUSIONS: Five years of supervised exercise training in older adults had little effect on cardiovascular risk profile and did not reduce cardiovascular events. REGISTRATION: ClinicalTrials.gov: NCT01666340.

Chemical characterization of combustion engine exhaust and assessment of helicopter deck operator occupational exposures on an offshore frigate class ship.

Diesel engine exhaust (DE) consists of a complex mixture of gases and aerosols, originating from sources such as engines, turbines, and power generators. It is composed of a wide range of toxic compounds ranging from constituents that are irritating to those that are carcinogenic. The purposes of this work were to characterize DE originating from different engine types on a ship operating offshore and to quantify the potential exposure of workers on the ship's helicopter deck to select DE compounds. Sampling was conducted on a Norwegian Nansen-class frigate that included helicopter operations. Frigate engines and generators were fueled by marine diesel oil, while the helicopter engine was fueled by high flash point kerosene-type aviation fuel. Exhaust samples were collected directly from the stack of the diesel engine and one of the diesel generator exhaust stacks, inside a gas turbine exhaust stack, and at the exhaust outlet of the helicopter. To characterize the different exhaust sources, non-targeted screening of volatile and semi-volatile organic compounds was performed for multiple chemical classes. Some of the compounds detected at the sources are known irritants, such as phthalic anhydride, 2,5-dyphenyl-p-benzoquinone, styrene, cinnoline, and phenyl maleic anhydride. The exhaust from the diesel engine and diesel generator was found to contain the highest amounts of particulate matter and gaseous compounds, while the gas turbine had the lowest emissions. Personal exposure samples were collected outdoors in the breathing zone of a helicopter deck operator over nine working shifts, simultaneously with stationary measurements on the helicopter deck. Elemental carbon, nitrogen dioxide, and several volatile organic compounds are known to be present in DE, such as formaldehyde, acrolein, and phenol were specifically targeted. Measured DE exposures of the crew on the helicopter deck were variable, but less than the current European occupational exposure limits for all compounds, except elemental carbon, in which concentration varied between 0.5 and 37 µg/m3 over nine work shifts. These findings are among the first published for this type of working environment.

Acute respiratory distress after exposure to chlorine dioxide-based disinfectant.

A hospital cleaner developed acute respiratory distress after working with a chlorine dioxide-based disinfectant. The content of chlorine dioxide in the product is below the limit that would require the product to be labelled as hazardous to health, but we show with a simple estimation that the relevant threshold limit values for chlorine dioxide in the working atmosphere may be exceeded under normal use of the product. This may have implications for risk assessment of the use of such chlorine dioxide-based disinfectants and may warrant stricter regulations for labelling these products.

The association between dynamic lung volume and peak oxygen uptake in a healthy general population: the HUNT study.

BACKGROUND: Although dynamic lung volume is not considered a limiting factor of peak oxygen uptake (VO2peak) in healthy subjects, an association between forced expiratory lung volume in one second (FEV1) and VO2peak has been reported in a healthy population aged 69 - 77 years. We hypothesized that a corresponding association could be found in a healthy general population including young and middle-aged subjects. METHODS: In a population-based study in Norway, we investigated the association between FEV1 above the lower limit of normal (LLN) and VO2peak using linear regression and assessed the ventilatory reserve (VR) in healthy subjects aged 20 - 79 years (n = 741). RESULTS: On average, one standard deviation (SD) increase in FEV1 was associated with 1.2 ml/kg/min (95% CI 0.7 - 1.6) higher VO2peak. The association did not differ statistically by sex (p-value for interaction = 0.16) and was similar (0.9 ml/kg/min, 95% CI 0.2 - 1.5) in a sensitivity analysis including only never-smokers (n = 376). In subjects below and above 45 years of age, corresponding estimates were 1.2 ml/kg/min (95% CI 0.5 - 1.8) and 1.2 ml/kg/min (95% CI 0.5 - 1.9), respectively. Preserved VR (≥ 20%) was observed in 66.6% of men and 86.4% of women. CONCLUSIONS: Normal dynamic lung volume, defined as FEV1 above LLN, was positively associated with VO2peak in both men and women, in never-smokers and in subjects below and above 45 years of age. The majority of subjects had preserved VR, and the results suggest that FEV1 within normal limits may influence VO2peak in healthy subjects even when no ventilatory limitation to exercise is evident.

Association between pulmonary function and peak oxygen uptake in elderly: the Generation 100 study.

BACKGROUND: Although reduced function of the respiratory system limits peak oxygen uptake in diseases affecting the lungs or airways, the healthy respiratory system is thought to have a spare capacity for oxygen transport and uptake, and is not considered a limiting factor for peak oxygen uptake in healthy people. However, lung function declines with age and could theoretically limit peak oxygen uptake in elderly. We examined the association between peak oxygen uptake and lung function indices in an elderly population with the hypothesis that lung function indices would be associated with VO2peak up to a threshold value situated above the lower limits of normal lung function for our population. METHODS: Spirometry, gas diffusion tests and incremental work tests were performed in 1443 subjects (714 women) aged 69-77 years. Association between lung function indices and peak oxygen uptake was studied with hockey-stick regression. RESULTS: Forced expiratory volume in 1 s (FEV1) had a positive association with peak oxygen uptake up to, but not above, a threshold value of 2.86 l for men, and 2.13 l for women (lower limit of normal 2.73 and 1.77 l respectively). A corresponding threshold was found for diffusing capacity of the lung for carbon monoxide (DLCO) for men at 9.18 mmol/min/kPa (lower limit of normal 6.84 mmol/min/kPa). DLCO for women and DLCO divided by alveolar volume (DLCO/VA) for both sexes had a significant linear relationship to VO2peak (p < 0.05), but no significant threshold value was found in these associations. CONCLUSIONS: Threshold values for FEV1 for both sexes and DLCO for men were identified. These lung function indices had a positive association with VO2peak up to these threshold values, but not above. The identified threshold values were above lower limits of normal for FEV1 and DLCO.

Effects of exercise training on pulmonary vessel muscularization and right ventricular function in an animal model of COPD.

BACKGROUND: Right ventricular dysfunction in COPD is common, even in the absence of pulmonary hypertension. The aim of the present study was to examine the effects of high intensity interval training (HIIT) on right ventricular (RV) function, as well as pulmonary blood vessel remodeling in a mouse model of COPD. METHODS: 42 female A/JOlaHsd mice were randomized to exposure to either cigarette smoke or air for 6 hours/day, 5 days/week for 14 weeks. Mice from both groups were further randomized to sedentariness or HIIT for 4 weeks. Cardiac function was evaluated by echocardiography and muscularization of pulmonary vessel walls by immunohistochemistry. RESULTS: Smoke exposure induced RV systolic dysfunction demonstrated by reduced tricuspid annular plane systolic excursion. HIIT in smoke-exposed mice reversed RV dysfunction. There were no significant effects on the left ventricle of neither smoke exposure nor HIIT. Muscularization of the pulmonary vessels was reduced after exercise intervention, but no significant effects on muscularization were observed from smoke exposure. CONCLUSIONS: RV function was reduced in mice exposed to cigarette smoke. No Increase in pulmonary vessel muscularization was observed in these mice, implying that other mechanisms caused the RV dysfunction. HIIT attenuated the RV dysfunction in the smoke exposed mice. Reduced muscularization of the pulmonary vessels due to HIIT suggests that exercise training not only affects the heart muscle, but also has important effects on the pulmonary vasculature.

Lung function and peak oxygen uptake in chronic obstructive pulmonary disease phenotypes with and without emphysema.

Previous studies of associations of forced expiratory lung volume in one second (FEV1) with peak oxygen uptake (VO2peak) in chronic obstructive pulmonary disease (COPD) have not taken sex, age and height related variance of dynamic lung volumes into account. Nor have such demographic spread of spirometric measures been considered in studies comparing VO2peak between COPD phenotypes characterized by degree of emphysema. We aimed to assess the association of FEV1Z-score with VO2peak in COPD (n = 186) and investigate whether this association differs between emphysema (E-COPD) and non-emphysema (NE-COPD) phenotypes. Corresponding assessments using standardized percent predicted FEV1 (ppFEV1) were performed for comparison. Additionally, phenotype related differences in VO2peak were compared using FEV1Z-score and ppFEV1 as alternative expressions of FEV1. E-COPD and NE-COPD were defined by transfer factor of the lung for carbon monoxide below and above lower limits of normal (LLN), respectively. The associations were assessed in linear regression models. One unit reduction in FEV1Z-score was associated with 1.9 (95% CI 1.4, 2.5) ml/kg/min lower VO2peak. In stratified analyses, corresponding estimates were 2.2 (95% CI 1.4, 2.9) and 1.2 (95% CI 0.2, 2.2) ml/kg/min lower VO2peak in E-COPD and NE-COPD, respectively. The association did not differ statistically by COPD phenotype (p-value for interaction = 0.153). Similar estimates were obtained in analyses using standardized ppFEV1. Compared to NE-COPD, VO2peak was 2.2 (95% CI 0.8, 3.6) and 2.1 (95% CI 0.8, 3.5) ml/kg/min lower in E-COPD when adjusted for FEV1Z-score and ppFEV1, respectively. In COPD, FEV1Z-score is positively associated with VO2peak. This association was stronger in E-COPD but did not differ statistically by phenotype. Both the association of FEV1 with VO2peak and the difference in VO2peak comparing COPD phenotypes seems independent of sex, age and height related variance in FEV1. Mechanisms leading to reduction in FEV1 may contribute to lower VO2peak in E-COPD.

The association between normal lung function and peak oxygen uptake in patients with exercise intolerance and coronary artery disease.

In coronary artery disease (CAD), exercise intolerance with reduced oxygen uptake at peak exercise (VO2peak) is assumed to primarily reflect cardiovascular limitation. However, oxygen transport and utilization depends on an integrated organ response, to which the normal pulmonary system may influence overall capacity. This study aimed to investigate the associations between normal values of lung function measures and VO2peak in patients with exercise intolerance and CAD. We hypothesized that forced expiratory lung volume in one second (FEV1), transfer factor of the lung for carbon monoxide (TLCO) and TLCO/alveolar volume (TLCO/VA) above lower limits of normal (LLN) are associated with VO2peak in these patients. We assessed patients with established CAD (n = 93; 21 women) referred for evaluation due to exercise intolerance from primary care to a private specialist clinic in Norway. Lung function tests and cardiopulmonary exercise testing (CPET) were performed. Z-scores of FEV1, FEV1/forced vital capacity (FVC), TLCO and TLCO/VA were calculated using the Global Lung Function Initiative (GLI) software and LLN was defined as the fifth percentile (z = -1.645). Non-obstructive patients, defined by both FEV1 and FEV1/FVC above LLN, were assessed. The associations of FEV1Z-score, TLCOZ-score and TLCO/VAZ-score above LLN with VO2peak were investigated using linear regression models. Mean VO2peak ± standard deviation (SD) was 23.8 ± 6.4 ml/kg/min in men and 19.7 ± 4.4 ml/kg/min in women. On average, one SD increase in FEV1, TLCO and TLCO/VA were associated with 1.4 (95% CI 0.2, 2.6), 2.6 (95% CI 1.2, 4.0) and 1.3 (95% CI 0.2, 2.5) ml/kg/min higher VO2peak, respectively. In non-obstructive patients with exercise intolerance and CAD, FEV1, TLCO and TLCO/VA above LLN are positively associated with VO2peak. This may imply a clinically significant influence of normal lung function on exercise capacity in these patients.

Acute exercise is not cardioprotective and may induce apoptotic signalling in heart surgery: a randomized controlled trial.

OBJECTIVES: During open-heart surgery, the myocardium experiences ischaemia-reperfusion injury. A single bout of moderate, 30-min exercise induces preconditioning and protects the heart from ischaemia-reperfusion injury in rats, but this has never been investigated in humans. We aimed to investigate whether 1 bout of moderate exercise 24 h prior to surgery protects against mitochondrial and cardiac damage. METHODS: Patients scheduled for elective coronary artery bypass were eligible for this pilot study. Twenty were included and randomized to the treadmill exercise group (the EX group, n = 10) 24 h preoperatively or to standard presurgical procedures (control n = 10). Right atrial (RA) and left ventricular (LV) biopsies were collected immediately before and as long as possible after aortic cross-clamping to assess the primary outcome of mitochondrial respiration by respirometry, in addition to reactive oxygen species production by fluorometry and apoptotic transcripts. Cardiac troponin T and creatine kinase myocardial brain were measured in plasma at arrival, before surgery and 6 and 24 h postoperatively. RESULTS: Mitochondrial respiration was lower in the EX group after surgery in the LV (Complex I -22%, P < 0.05 and maximal -23%, P < 0.05) and the right atrium (Complex I -25%, P < 0.05). Transcript level of the apoptosis-related marker caspase 3 was increased 1.5-fold in the LV prior to surgery in the EX group when compared with the control group, P < 0.05. Cardiac troponin T was 45% higher in the EX group than in the control group 6 h postoperatively (P = 0.03), although not significant when corrected for aortic cross-clamping time. CONCLUSIONS: Results indicate that exercise did not precondition the heart against surgery-related damage. Exercise may render the myocardium and mitochondria more vulnerable to perioperative damage. Clinical trials registration number: NCT00218985 (https://clinicaltrials.gov/ct2/show/NCT00218985).

Lung function parameters improve prediction of VO2peak in an elderly population: The Generation 100 study.

Peak oxygen uptake (VO2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO2peak, spirometry, and a gas diffusion test. Prediction models for VO2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p<0.001). FEV1, diffusing capacity of the lungs for carbon monoxide and hemoglobin concentration substantially improved the accuracy of VO2peak prediction when added to an established model in an elderly population.

Cardiorespiratory Reference Data in Older Adults: The Generation 100 Study.

PURPOSE: Cardiorespiratory fitness (CRF) is regarded a clinical vital sign, and accurate reference values for all age groups are essential. Little data exist on CRF and cardiorespiratory function in older adults. The aim of this study was to provide normative values for CRF and cardiorespiratory function in older adults, including people with history of cardiovascular diseases (CVD). METHODS: In total, 1537 (769 women) participants age 70 to 77 yr underwent clinical examinations and cardiopulmonary exercise tests. Peak oxygen uptake (V˙O2peak), ventilation (V˙Epeak), expiration of carbon dioxide (VV˙CO2peak), breathing frequency (BFpeak), tidal volume (VTpeak), oxygen pulse (O2 pulsepeak), ventilatory efficiency (EqV˙O2peak and EqV˙CO2peak), and 1-min HR recovery were assessed. RESULTS: Men compared with women had higher V˙O2peak (31.3 ± 6.7 vs 26.2 ± 5.0 mL·min·kg), BFpeak (41.8 ± 8.0 vs 39.7 ± 7.1 breaths per minute), VTpeak (2.3 ± 0.5 vs 1.6 ± 0.3), O2 pulsepeak (16.4 ± 3.2 vs 11.3 ± 2.0), V˙CO2peak (2.9 ± 0.2 and 1.9 ± 0.1 L·min), V˙Epeak (96.2 ± 21.7 vs 61.1 ± 21.6 L·min), EqV˙O2peak (38.0 ± 6.9 vs 35.1 ± 5.6), and EqV˙CO2peak (33.5 ± 5.7 vs 31.9 ± 4.5). Women and men with CVD had lower V˙O2peak (14% and 19%), peak HR (5% and 6%), V˙Epeak (8% and 10%), VTpeak (7% and 4%), and lower EqV˙CO2peak (4% and 6%) compared with their healthy counterparts, respectively. Compared with healthy women and men, 1-min HR recovery was 12% and 16% lower for women and men with CVD. CONCLUSIONS: This study represents the largest reference material on directly measured CRF and cardiorespiratory function in older men and women, with and without CVD. This novel information will help researchers and clinicians to interpret data form cardiopulmonary testing in older adults.