Karen Wills

Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial

Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting. Design Cluster randomised controlled parallel group trial. Setting Ambulance service in Hobart, Tasmania, Australia. Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years. Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting. Main outcome measure Prehospital or in-hospital mortality. Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen. Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting. Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291.

Seasonal not annual rainfall determines grassland biomass response to carbon dioxide

The rising atmospheric concentration of carbon dioxide (CO2) should stimulate ecosystem productivity, but to what extent is highly uncertain, particularly when combined with changing temperature and precipitation. Ecosystem response to CO2 is complicated by biogeochemical feedbacks but must be understood if carbon storage and associated dampening of climate warming are to be predicted. Feedbacks through the hydrological cycle are particularly important and the physiology is well known; elevated CO2 reduces stomatal conductance and increases plant water use efficiency (the amount of water required to produce a unit of plant dry matter). The CO2 response should consequently be strongest when water is limiting; although this has been shown in some experiments, it is absent from many. Here we show that large annual variation in the stimulation of above-ground biomass by elevated CO2 in a mixed C3/C4 temperate grassland can be predicted accurately using seasonal rainfall totals; summer rainfall had a positive effect but autumn and spring rainfall had negative effects on the CO2 response. Thus, the elevated CO2 effect mainly depended upon the balance between summer and autumn/spring rainfall. This is partly because high rainfall during cool, moist seasons leads to nitrogen limitation, reducing or even preventing biomass stimulation by elevated CO2. Importantly, the prediction held whether plots were warmed by 2 °C or left unwarmed, and was similar for C3 plants and total biomass, allowing us to make a powerful generalization about ecosystem responses to elevated CO2. This new insight is particularly valuable because climate projections predict large changes in the timing of rainfall, even where annual totals remain static. Our findings will help resolve apparent differences in the outcomes of CO2 experiments and improve the formulation and interpretation of models that are insensitive to differences in the seasonal effects of rainfall on the CO2 response.

The TasFACE climate-change impacts experiment: design and performance of combined elevated CO2 and temperature enhancement in a native Tasmanian grassland

The potential impacts of climate change on both natural and managed ecosystems are far-reaching and are only beginning to be understood. Here we describe a new experiment that aims to determine the impacts of elevated concentration of CO2 ((CO2)) and elevated temperature on a native Themeda-Austrodanthonia-dominated grassland ecosystem in south-eastern Tasmania. The experimental site contains 60 vascular plant species. The experiment combines the latest developments in free-air CO2 enrichment (FACE) technology with the use of infrared (IR) heaters to mimic environmental conditions expected to exist in the year 2050. The CO2 concentration in the FACE treatments is reliably maintained at 550 µmol mol −1 and leaf temperature is elevated by an average of 2.1 ◦ C by the IR treatment, with 1-cm soil temperature being elevated by 0.8 ◦ C. Measurements being made in the experiment cover plant ecophysiological responses, plant population dynamics and community interactions. Soil processes and ecosystem effects, including nutrient cycling and plant animal interactions, are also being investigated. Collaborations are invited from interested parties.

Flowering phenology in a species‐rich temperate grassland is sensitive to warming but not elevated CO2

* Flowering is a critical stage in plant life cycles, and changes might alter processes at the species, community and ecosystem levels. Therefore, likely flowering-time responses to global change drivers are needed for predictions of global change impacts on natural and managed ecosystems. * Here, the impact of elevated atmospheric CO2 concentration ([CO2]) (550 micromol mol(-1)) and warming (+2 masculineC) is reported on flowering times in a native, species-rich, temperate grassland in Tasmania, Australia in both 2004 and 2005. * Elevated [CO2] did not affect average time of first flowering in either year, only affecting three out of 23 species. Warming reduced time to first flowering by an average of 19.1 d in 2004, acting on most species, but did not significantly alter flowering time in 2005, which might be related to the timing of rainfall. Elevated [CO2] and warming treatments did not interact on flowering time. * These results show elevated [CO2] did not alter average flowering time or duration in this grassland; neither did it alter the response to warming. Therefore, flowering phenology appears insensitive to increasing [CO2] in this ecosystem, although the response to warming varies between years but can be strong.

Effects of telephone health mentoring in community-recruited chronic obstructive pulmonary disease on self-management capacity, quality of life and psychological morbidity: a randomised controlled trial

Objectives To assess benefits of telephone-delivered health mentoring in community-based chronic obstructive pulmonary disease (COPD). Design Cluster randomised controlled trial. Setting Tasmanian general practices: capital city (11), large rural (3), medium rural (1) and small rural (16). Participants Patients were invited (1207) from general practitioner (GP) databases with COPD diagnosis and/or tiotropium prescription, response rate 49% (586), refused (176) and excluded (criteria: smoking history or previous study, 68). Spirometry testing (342) confirmed moderate or severe COPD in 182 (53%) patients. Randomisation By random numbers code, block stratified on location, allocation by sequentially numbered, opaque and sealed envelopes. Intervention Health mentor (HM) group received regular calls to manage illness issues and health behaviours from trained community health nurses using negotiated goal setting: problem solving, decision-making and action planning. Control: usual care (UC) group received GP care plus non-interventional brief phone calls. Outcomes Measured at 0, 6 and 12 months, the Short Form 36 (SF-36) and St George’s Respiratory Questionnaire (SGRQ, primary); Partners In Health (PIH) Scale for self-management capacity, Hospital Anxiety and Depression Scale (HADS), Center for Epidemiologic Studies-Depression (CES-D) questionnaire, Post-Traumatic Stress Disorder Checklist, Satisfaction with life and hospital admissions (secondary). Results 182 participants with COPD (age 68±8 years, 62% moderate COPD and 53% men) were randomised (HM=90 and UC=92). Mixed model regression analysis accounting for clustering, adjusting for age, gender, smoking status and airflow limitation assessed efficacy (regression coefficient, β, reported per 6-month visit). There was no difference in quality of life between groups, but self-management capacity increased in the HM group (PIH overall 0.15, 95% CI 0.03 to 0.29; knowledge domain 0.25, 95% CI 0.00 to 0.50). Anxiety decreased in both groups (HADS A 0.35; 95% CI −0.65 to −0.04) and coping capacity improved (PIH coping 0.15; 95% CI 0.04 to 0.26). Conclusions Health mentoring improved self-management capacity but not quality of life compared to regular phone contact, which itself had positive effects where decline is generally expected.

A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial–mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study

Background We recently reported that epithelial–mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma. With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study. Methods Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo). The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers). Results Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance. From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study. Conclusion Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways. A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important. Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD.

Influence of warming on soil water potential controls seedling mortality in perennial but not annual species in a temperate grassland

In a water-limited system, the following hypotheses are proposed: warming will increase seedling mortality; elevated atmospheric CO2 will reduce seedling mortality by reducing transpiration, thereby increasing soil water availability; and longevity (i.e. whether a species is annual or perennial) will affect the response of a species to global changes. Here, these three hypotheses are tested by assessing the impact of elevated CO2 (550 micromol mol(-1) and warming (+2 degrees C) on seedling emergence, survivorship and establishment in an Australian temperate grassland from autumn 2004 to autumn 2007. Warming impacts on seedling survivorship were dependent upon species longevity. Warming reduced seedling survivorship of perennials through its effects on soil water potential but the seedling survivorship of annuals was reduced to a greater extent than could be accounted for by treatment effects on soil water potential. Elevated CO2 did not significantly affect seedling survivorship in annuals or perennials. These results show that warming will alter recruitment of perennial species by changing soil water potential but will reduce recruitment of annual species independent of any effects on soil moisture. The results also show that exposure to elevated CO2 does not make seedlings more resistant to dry soils.

Flowering, seed production and seed mass in a species-rich temperate grassland exposed to FACE and warming

Long-term effects of climate change on plant communities must be mediated by reproductive and recruitment responses of component species. From spring 2003 until autumn 2006, we monitored flowering and seed-production responses to free air CO2 enrichment (FACE) and 2°C warming in a species-rich, nutrient-poor southern temperate grassland, by using the TasFACE experiment. There were no effects of either FACE or warming on the proportion of species flowering in any year. Flowering, seed production and seed mass were not significantly affected by FACE, warming or their interaction in most species. Some species, however, did respond significantly to simulated global changes. These responses generally were not governed by life history, but there were two distinct trends. First, warming increased the proportion of the population that flowered in perennial grasses but not in other species types. Second, flowering and seed production of both perennial woody dicots responded strongly to the interaction of FACE and warming, with Bossiaea prostrata producing most seeds in warmed FACE plots and Hibbertia hirsuta producing the most in unwarmed FACE plots. FACE increased seed mass 4-fold in the perennial C3 grass Elymus scaber (P < 0.01) but substantially reduced seed mass of the perennial C3 grass Austrodanthonia caespitosa (P < 0.02) and the perennial forb Hypochaeris radicata (P < 0.02), with the remainder of species unaffected. Our results indicate that warming and elevated CO2 had little effect on seed production in the temperate grassland ecosystem. The few significant affects there were, however, are likely to have substantial implications for community composition and structure.

Effects of Individualized Bone Density Feedback and Educational Interventions on Osteoporosis Knowledge and Self-Efficacy: A 12-Yr Prospective Study

This is 12-yr follow-up of a randomized controlled trial aimed to evaluate the long-term effects of bone density feedback and osteoporosis education on osteoporosis knowledge and self-efficacy. We examined the effects of feedback of bone density-defined fracture risk (high [T-score <0] vs normal [T-score ≥0] risk) and 2 different educational interventions (the group-based Osteoporosis Prevention and Self-Management Course [OPSMC] vs an osteoporosis leaflet) on osteoporosis knowledge and self-efficacy in women aged 25-44. Seventy-four percent (N = 347) of 470 participants at baseline participated at 12 yr. Overall, the scores were higher for osteoporosis knowledge but lower for self-efficacy at 12 yr. However, neither intervention had an effect on the change in knowledge (T-score, β = 0.4, 95% confidence interval [CI] = -0.3 to 1.1; OPSMC, β = 0.2, 95% CI = -0.5 to 0.9) or self-efficacy (T-score, β = -1.1, 95% CI = -2.5 to 0.4; OPSMC, β = -0.2, 95% CI = -1.6 to 1.3). Women in households with an unemployed main financial provider had a decrease in knowledge at 12 yr compared with those in households with an employed main financial provider in whom knowledge increased (β = -1.95, 95% CI = -3.40 to -0.50), but there were no other predictors of change identified for knowledge or self-efficacy. In conclusion, beneficial effects of both OPSMC and feedback of high fracture risk on osteoporosis knowledge seen previously at 2 yr were not sustained after 12 yr although overall knowledge was still significantly higher than at baseline. Neither intervention improved osteoporosis self-efficacy. More frequent osteoporosis education and bone density feedback may be required to maintain knowledge, and other approaches to improve self-efficacy are necessary.

Elevated CO2 and warming impacts on flowering phenology in a southern Australian grassland are related to flowering time but not growth form, origin or longevity

Flowering is a critical stage in plant life cycles, and changes in phenology might alter processes at the species, community and ecosystem levels. Therefore, likely flowering-time responses to global-change drivers are needed for predictions of global-change impacts on natural and managed ecosystems. Predicting responses of species to global changes would be simplified if functional, phylogenetic or biogeographical traits contributed substantially to a species’ response. Here we investigate the role of growth form (grass, graminoid, forb, subshrub), longevity (annual, perennial), origin (native, exotic) and flowering time in determining the impact of elevated [CO2] (550 μmol mol-1) and infrared warming (mean warming of +2°C) on flowering times of 31 co-occurring species of a range of species-types in a temperate grassland in 2004, 2005 and 2007. Warming reduced time to first flowering by an average of 20.3 days in 2004, 2.1 days in 2005 and 7.6 days in 2007; however, the response varied among species and was unrelated to growth form, origin or longevity. Elevated [CO2] did not alter flowering times; neither was there any [CO2] by species-type interaction. However, both warming and elevated [CO2] tended to have a greater effect on later-flowering species, with time to first flowering of later-flowering species being reduced by both elevated [CO2] (P < 0.001) and warming (P < 0.001) to a greater extent than that of earlier-flowering species. These results have ramifications for our predictions of community and ecosystem interactions in native grasslands in response to global change.