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

Chronic obstructive lung disease (COPD) is a common cause of death in industrialized countries often induced by exposure to tobacco smoke. A substantial number of patients with COPD also suffer from pulmonary hypertension that may be caused by hypoxia or other hypoxia-independent stimuli - inducing pulmonary vascular remodeling. The Ca2+ binding protein, S100A4 is known to play a role in non-COPD-driven vascular remodeling of intrapulmonary arteries. Therefore, we have investigated the potential involvement of S100A4 in COPD induced vascular remodeling. Lung tissue was obtained from explanted lungs of five COPD patients and five non-transplanted donor lungs. Additionally, mice lungs of a tobacco-smoke-induced lung emphysema model (exposure for 3 and 8 month) and controls were investigated. Real-time RT-PCR analysis of S100A4 and RAGE mRNA was performed from laser-microdissected intrapulmonary arteries. S100A4 immunohistochemistry was semi-quantitatively evaluated. Mobility shift assay and siRNA knock-down were used to prove hypoxia responsive elements (HRE) and HIF binding within the S100A4 promoter. Laser-microdissection in combination with real-time PCR analysis revealed higher expression of S100A4 mRNA in intrapulmonary arteries of COPD patients compared to donors. These findings were mirrored by semi-quantitative analysis of S100A4 immunostaining. Analogous to human lungs, in mice with tobacco-smoke-induced emphysema an up-regulation of S100A4 mRNA and protein was observed in intrapulmonary arteries. Putative HREs could be identified in the promoter region of the human S100A4 gene and their functionality was confirmed by mobility shift assay. Knock-down of HIF1/2 by siRNA attenuated hypoxia-dependent increase in S100A4 mRNA levels in human primary pulmonary artery smooth muscle cells. Interestingly, RAGE mRNA expression was enhanced in pulmonary arteries of tobacco-smoke exposed mice but not in pulmonary arteries of COPD patients. As enhanced S100A4 expression was observed in remodeled intrapulmonary arteries of COPD patients, targeting S100A4 could serve as potential therapeutic option for prevention of vascular remodeling in COPD patients.     

A comparative study of clinical manifestations,haematological and serological responses after experimental infection with <Emphasis Type="Italic">Anaplasma phagocytophilum</Emphasis> in two Norwegian sheep breeds

Background  

It has been questioned if the old native Norwegian sheep breed, Old Norse Sheep (also called Norwegian Feral Sheep), normally distributed on coastal areas where ticks are abundant, is more protected against tick-borne infections than other Norwegian breeds due to a continuously high selection pressure on pasture. The aim of the present study was to test this hypothesis in an experimental infection study.     

Cardio-Respiratory Reference Data in 4631 Healthy Men and Women 20-90 Years: The HUNT 3 Fitness Study

Purpose

To provide a large reference material on key cardio-respiratory variables in a healthy population of Norwegian men and women aged 20–90 years.

Methods

Sub maximal and peak levels of cardio-respiratory variables were measured using cardiopulmonary exercise testing during treadmill running.

Results

The highest peak ventilation among men (141.9±24.5 L·min⁻¹) and women (92.0±16.5 L·min⁻¹) was observed in the youngest age group (20–29 years, sex differences p<0.001) with an average 7% reduction per decade. The highest tidal volumes were observed in the 30–39 and 40–49 year age groups among men (2.94±0.46 L) and women (2.06±0.32 L) (sex differences p<0.001), with a subsequent average 6% reduction per decade. Ventilatory threshold and respiratory compensation point were observed at approximately 77% and 87% of peak oxygen uptake (VO_2peak) among men and women, respectively. The best ventilatory efficiency (EqVCO_2Than) was observed in the youngest age group (20–29 years) in both men (26.2±2.8) and woman (27.5±2.7) (sex differences p<0.001) with an average 3% deterioration in ventilatory efficiency per decade.

Conclusion

This is the largest European reference material of cardio-respiratory variables in healthy men and women aged 20–90 years, establishing normal values for, and associations between key cardio-respiratory parameters. This will be useful in clinical decision making when evaluating cardiopulmonary health in similar populations.     

A new approach of fitting biomass dynamics models to data

A non-traditional approach of fitting dynamic resource biomass models to data is developed in this paper. A variational adjoint technique is used for dynamic parameter estimation. In the variational formulation, a cost function measuring the distance between the model solution and the observations is minimized. The data assimilation method provides a novel and computationally efficient procedure for combining all available information, i.e., the data and the model in the analysis of a resource system. This technique will be used to analyze data for the North-east Arctic cod stock. Two alternative population growth models: the logistic and the Gompertz model are used for estimating parameters of simple bioeconomic models by the method of constrained least squares. Estimates of the parameters of the models dynamics are reasonable and can be accepted. The main inference from the work is that the average fishing mortality is found to be significantly above the maximum sustainable yield value.     

Phytoestrogens and Their Metabolites in Bulk-Tank Milk: Effects of Farm Management and Season

Phytoestrogens have structures similar to endogenous steroids and may induce or inhibit the response of hormone receptors. The objectives of the present study were to compare the effects of long-term vs. short-term grassland management in organic and conventional dairy production systems, compare organic and conventional production systems and assess seasonal variation on phytoestrogen concentrations in bulk-tank milk. The concentrations of phytoestrogens were analyzed in bulk-tank milk sampled three times in two subsequent years from 28 dairy farms: Fourteen organic (ORG) dairy farms with either short-term or long-term grassland management were paired with 14 conventional (CON) farms with respect to grassland management. Grassland management varied in terms of time since establishment. Short-term grassland management (SG) was defined as establishment or reseeding every fourth year or more often, and long-term grassland management (LG) was defined as less frequent establishment or reseeding. The proportion of red clover (Trifolium pretense L.) in the herbage was positively correlated with milk concentrations of the mammalian isoflavone equol. Therefore, organically produced bulk-tank milk contained more equol than conventionally produced milk, and milk from ORG-SG farms had more equol than milk from ORG-LG farms. Milk produced during the indoor-feeding periods had more equol than milk produced during the outdoor feeding period, because pastures contained less red clover than fields intended for silage production. Organically produced milk had also higher concentrations of the mammalian lignan enterolactone, but in contrast to equol, concentrations increased in the outdoor-feeding periods compared to the indoor-feeding periods. There were no indications of fertility problems on ORG-SG farms who had the highest red clover proportions in the herbage. This study shows that production system, grassland management, and season affect milk concentrations of phytoestrogens. However, compared to soy products, milk concentrations of phytoestrogens are low and future studies are required to investigate if the intake of phytoestrogens from dairy products has physiological effects in humans.     

Long term effects of an integrated care intervention on hospital utilization in patients with severe COPD: a single centre controlled study

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality globally. In Trondheim in 2008 an integrated care model (COPD-Home) consisting of an education program, self-management plan, home visits and a call centre for patient support and communication was developed. The objective was to determine the efficacy of an intervention according to the COPD-Home model in reducing hospital utilization among patients with COPD stage III and IV (GOLD 2007) discharged after hospitalization for acute exacerbations of COPD (AECOPD).

Methods

A single centre, prospective, open, controlled clinical study comparing COPD-Home integrated care (IC) with usual care (UC).

Results

Ninety-one versus 81 patients mean age 73.4 ± 9.3 years (57% women) were included in the IC group (ICG) and the UC group (UCG) respectively, and after 2 years 51 and 49 patients were available for control in the respective groups. During the year prior to study start there were 71 hospital admissions (HA) in the ICG and 84 in the UCG. There was a 12.6% reduction in HA in the ICG during the first year of follow-up and a 46.5% reduction during the second year (p = 0.01) compared to an 8.3% increase during the first year and no change during the second year in the ICG. During the year prior to study start, the number of hospital days (HD) was 468 in the ICG and 479 in the UCG. In the IC group, the number of HD was reduced by 48.3% during the first year (p = 0.01), and remained low during the second year of follow-up (p=0.02). In the UC group, the number of HD remained unchanged during the follow-up period. There was a trend towards a shorter survival time among patients in the ICG compared to the UCG, hazard ratio 1.33 [95% CI 0.77 to 2.33].

Conclusion

Intervention according to the COPD-Home model reduced hospital utilization in patients with COPD III and IV with a persisting effect throughout the 2 years of follow-up. However, there was a trend towards a shorter survival time in the intervention group.     

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.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0117-y) contains supplementary material, which is available to authorized users.