Habitat alteration or climate: What drives the densities of an invading ungulate?

Anthropogenic habitat alteration and climate change are two well-known contributors to biodiversity loss through changes to species distribution and abundance; yet, disentangling the effects of these two factors is often hindered by their inherent confound across both space and time. We leveraged a contrast in habitat alteration associated with the jurisdictional boundary between two Canadian provinces to evaluate the relative effects of spatial variation in habitat alteration and climate on white-tailed deer (Odocoileus virginianus) densities. White-tailed deer are an invading ungulate across much of North America, whose expansion into Canada's boreal forest is implicated in the decline of boreal caribou (Rangifer tarandus caribou), a species listed as Threatened in Canada. We estimated white-tailed deer densities using 300 remote cameras across 12 replicated 50 km2 landscapes over 5 years. White-tailed deer densities were significantly lower in areas where winter severity was higher. For example, predicted deer densities declined from 1.83 to 0.35 deer/km2 when winter severity increased from the lowest value to the median value. There was a tendency for densities to increase with increasing habitat alteration; however, the magnitude of this effect was approximately half that of climate. Our findings suggest that climate is the primary driver of white-tailed deer populations; however, understanding the mechanisms underpinning this relationship requires further study of over-winter survival and fecundity. Long-term monitoring at the invasion front is needed to evaluate the drivers of abundance over time, particularly given the unpredictability of climate change and increasing prevalence of extreme weather events.

Microplastics analytics: why we should not underestimate the importance of blank controls.

Recent years have seen considerable scientific attention devoted towards documenting the presence of microplastics (MPs) in environmental samples. Due to omnipresence of environmental microplastics, however, disentangling environmental MPs from sample contamination is a challenge. Hence, the environmental (collection site and laboratory) microplastics contamination of samples during processing is a reality that we must address, in order to generate reproducible and reliable data. Here we investigated published literature and have found that around 1/5 of studies failed to use blank controls in their experiments. Additionally, only 34% of the studies used a controlled air environment for their sample processing (laminar flow, fume hood, closed laboratory, clean room, etc.). In that regard, we have also shown that preparing samples in the fume hood, leads to more microplastics > 1 µm) contamination than preparing it in the laboratory bench and the laminar flow. Although it did not completely prevent microplastics contamination, the processing of sample inside the laminar flow is the best option to reduce sample contamination during processing. Overall, we showed that blank controls are a must in microplastics sample preparation, but it is often overlooked by researchers. Supplementary Information: The online version contains supplementary material available at 10.1186/s43591-023-00065-3.

The need for environmentally realistic studies on the health effects of terrestrial microplastics.

Plastic pollution is now so widespread that microplastics are regularly detected in biological samples surveyed for their presence. Despite their pervasiveness, very little is known about the effects of microplastics on the health of terrestrial vertebrates. While emerging studies are showing that microplastics represent a potentially serious threat to animal health, data have been limited to in vivo studies on laboratory rodents that were force fed plastics. The extent to which these studies are representative of the conditions that animals and humans might actually experience in the real world is largely unknown. Here, we review 114 papers from the peer-reviewed literature in order to understand how the concentrations and types of microplastics being administered to rodents in lab studies compare to those found in terrestrial soils. From 73 in vivo lab studies, and 41 soil studies, we found that lab studies have heretofore fed rodents microplastics at concentrations that were hundreds of thousands of times greater than they would be exposed to in nature. Furthermore, health effects have been studied for only 20% of the microplastic polymers that are known to occur in soils. Plastic pollution is arguably one of the most pressing ecological and public health issues of our time, yet existing lab-based research on the health effects of terrestrial microplastics does not reflect the conditions that free-ranging vertebrates are actually experiencing. Going forward, performing more true-to-life research will be of the utmost importance to fully understand the impacts of microplastics and maintain the public's faith in the scientific process. Supplementary Information: The online version contains supplementary material available at 10.1186/s43591-023-00059-1.

Effects of body size on estimation of mammalian area requirements.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum.

Efectos del Tamaño Corporal sobre la Estimación de los Requerimientos de Área de Mamíferos Resumen La cuantificación precisa de los requerimientos de área de una especie es un prerrequisito para que la conservación basada en áreas sea efectiva. Esto comúnmente implica la recolección de datos de rastreo de la especie de interés para después realizar análisis de la distribución local. De manera problemática, la autocorrelación en los datos de rastreo puede resultar en una subestimación grave de las necesidades de espacio. Con base en trabajos previos, formulamos una hipótesis en la que supusimos que la magnitud de la subestimación varía con la masa corporal, una relación que podría tener implicaciones serias para la conservación. Para probar esta hipótesis en mamíferos terrestres, estimamos las áreas de distribución local con las ubicaciones en GPS de 757 individuos de 61 especies de mamíferos distribuidas mundialmente con una masa corporal entre 0.4 y 4,000 kg. Después aplicamos una validación cruzada en bloque para cuantificar el sesgo en estimaciones empíricas de la distribución local. Los requerimientos de área de los mamíferos <10 kg fueron subestimados por una media ∼15% y las especies con una masa ∼100 kg fueron subestimadas en ∼50% en promedio. Por lo tanto, encontramos que la estimación del área estaba sujeta al sesgo inducido por la autocorrelación, el cual era peor para las especies de talla grande. En combinación con el hecho de que el riesgo de extinción incrementa conforme aumenta la masa corporal, el escalamiento alométrico del sesgo que observamos sugiere que la mayoría de las especies amenazadas también tienen la probabilidad de ser aquellas especies con las estimaciones de distribución local menos acertadas. Como corrección, probamos si la reducción de datos o la estimación de la distribución local informada por la autocorrelación minimizan el efecto de escalamiento que tiene la autocorrelación sobre las estimaciones de área. La reducción de datos requirió una pérdida de datos del ∼93% para lograr la independencia estadística con un 95% de confianza y por lo tanto no fue una solución viable. Al contrario, la estimación de la distribución local informada por la autocorrelación resultó en estimaciones constantemente precisas sin importar la masa corporal. Cuando relacionamos la masa corporal con el tamaño de la distribución local, detectamos que la corrección de la autocorrelación resultó en un exponente de escalamiento significativamente >1, lo que significa que el escalamiento de la relación cambió sustancialmente en el extremo superior del espectro de la masa corporal.

Scale-insensitive estimation of speed and distance traveled from animal tracking data.

BACKGROUND: Speed and distance traveled provide quantifiable links between behavior and energetics, and are among the metrics most routinely estimated from animal tracking data. Researchers typically sum over the straight-line displacements (SLDs) between sampled locations to quantify distance traveled, while speed is estimated by dividing these displacements by time. Problematically, this approach is highly sensitive to the measurement scale, with biases subject to the sampling frequency, the tortuosity of the animal's movement, and the amount of measurement error. Compounding the issue of scale-sensitivity, SLD estimates do not come equipped with confidence intervals to quantify their uncertainty. METHODS: To overcome the limitations of SLD estimation, we outline a continuous-time speed and distance (CTSD) estimation method. An inherent property of working in continuous-time is the ability to separate the underlying continuous-time movement process from the discrete-time sampling process, making these models less sensitive to the sampling schedule when estimating parameters. The first step of CTSD is to estimate the device's error parameters to calibrate the measurement error. Once the errors have been calibrated, model selection techniques are employed to identify the best fit continuous-time movement model for the data. A simulation-based approach is then employed to sample from the distribution of trajectories conditional on the data, from which the mean speed estimate and its confidence intervals can be extracted. RESULTS: Using simulated data, we demonstrate how CTSD provides accurate, scale-insensitive estimates with reliable confidence intervals. When applied to empirical GPS data, we found that SLD estimates varied substantially with sampling frequency, whereas CTSD provided relatively consistent estimates, with often dramatic improvements over SLD. CONCLUSIONS: The methods described in this study allow for the computationally efficient, scale-insensitive estimation of speed and distance traveled, without biases due to the sampling frequency, the tortuosity of the animal's movement, or the amount of measurement error. In addition to being robust to the sampling schedule, the point estimates come equipped with confidence intervals, permitting formal statistical inference. All the methods developed in this study are now freely available in the ctmmR package or the ctmmweb point-and-click web based graphical user interface.

Knowing Me, Knowing You: Anal Gland Secretion of European Badgers (Meles meles) Codes for Individuality, Sex and Social Group Membership.

European badgers, Meles meles, are group-living in the UK, and demarcate their ranges with shared latrines. As carnivores, badgers possess paired anal glands, but olfactory information on the content of badger anal gland secretion (AGS) is largely uninvestigated. Here, we examined the volatile organic compounds (VOCs) of AGS samples from 57 free-living badgers using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry. AGS was rich in alkanes (C7-C15, 14.3% of identified compounds), aldehydes (C5-C14, 9.7%), phenols (C6-C15, 9.5%), alcohols (C5-C10, 7.3%), aromatic hydrocarbons (C6-C13, 6.8%), ketones (C6-C13, 6.3%) and carboxylic acids (C3-C12, 5.6%) and contained a variety of esters, sulfurous and nitrogenous compounds, and ethers. The number of VOCs per profile ranged from 20 to 111 (mean = 65.4; ± 22.7 SD), but no compound was unique for any of the biological categories. After normalization of the raw data using Probabilistic Quotient Normalization, we produced a resemblance matrix by calculating the Euclidian distances between all sample pairs. PERMANOVA revealed that AGS composition differs between social groups, and concentration and complexity in terms of number of measurable VOCs varies between seasons and years. AGS VOC profiles encode individual identity, sex and vary with female reproductive state, indicating an important function in intraspecific communication. Because AGS is excreted together with fecal deposits, we conclude that chemical complexity of AGS enables particularly latrine-using species, such as badgers, to advertise more complex individual-specific information than in feces alone.

Effects of Weather Conditions on Oxidative Stress, Oxidative Damage, and Antioxidant Capacity in a Wild-Living Mammal, the European Badger (Meles meles).

Wild-living animals are subject to weather variability that may cause the generation of reactive oxygen species, resulting in oxidative stress and tissue damage, potentially driving demographic responses. Our 3-yr field study investigated the effects of seasonal weather conditions on biomarkers for oxidative stress, oxidative damage, and antioxidant defense in the European badger (Meles meles). We found age class effects: cubs were more susceptible to oxidative stress and oxidative damage than adults, especially very young cubs in the spring, when they also exhibited lower antioxidant biomarkers than adults. Although previous studies have found that intermediate spring and summer rainfall and warmer temperatures favor cub survival, counterintuitively these conditions were associated with more severe oxidative damage. Oxidative damage was high in cubs even when antioxidant biomarkers were high. In contrast, adult responses accorded with previous survival analyses. Wetter spring and summer conditions were associated with higher oxidative damage, but they were also associated with higher antioxidant biomarkers. Autumnal weather did not vary substantially from normative values, and thus effects were muted. Winter carryover effects were partially evident, with drier and milder conditions associated with greater oxidative damage in the following spring but also with higher antioxidant capacity. Plausibly, warmer conditions promoted more badger activity, with associated metabolic costs at a time of year when food supply is limited. Modeling biomarkers against projected climate change scenarios predicted greater future risks of oxidative damage, although not necessarily exceeding antioxidant capacity. This interdisciplinary approach demonstrates that individual adaptive physiological responses are associated with variation in natural environmental conditions.

Normalizing Gas-Chromatography-Mass Spectrometry Data: Method Choice can Alter Biological Inference.

We demonstrate how different normalization techniques in GC-MS analysis impart unique properties to the data, influencing any biological inference. Using simulations, and empirical data, we compare the most commonly used techniques (Total Sum Normalization 'TSN'; Median Normalization 'MN'; Probabilistic Quotient Normalization 'PQN'; Internal Standard Normalization 'ISN'; External Standard Normalization 'ESN'; and a compositional data approach 'CODA'). When differences between biological classes are pronounced, ESN and ISN provides good results, but are less reliable for more subtly differentiated groups. MN, TSN, and CODA approaches produced variable results dependent on the structure of the data, and are prone to false positive biomarker identification. In contrast, PQN exhibits the lowest false positive rate, though with occasionally poor model performance. Because ESN requires extensive pre-planning, and offers only mixed reliability, and ISN, TSN, MN, and CODA approaches are prone to introducing artefactual differences, we recommend the use of PQN in GC-MS research.

Sexual size dimorphism in musteloids: An anomalous allometric pattern is explained by feeding ecology.

Rensch's rule states that sexual size dimorphism (SSD) increases with body size in taxa where males are larger, and decreases when females are larger. The dominant explanation for the trend is currently that competitive advantage for males is greater in larger individuals, whereas female size is constrained by the energetics of rearing offspring. This rule holds for a variety of vertebrate taxa, and opposing trends are rare. We examine the allometry of SSD within the Musteloidea and demonstrate a hypo-allometry contrary to Rensch's rule, with lower SSD associated with larger body size. We provide evidence that feeding ecology is involved. Where diet promotes group-living, the optimal strategy for the males of larger species is often not to attempt to defend access to multiple females, obviating any competitive advantage of relatively greater size. We conclude that the effect of feeding ecology on mating systems may be a hitherto neglected factor explaining variation in SSD.

Will Trespassers Be Prosecuted or Assessed According to Their Merits? A Consilient Interpretation of Territoriality in a Group-Living Carnivore, the European Badger (Meles meles).

Socio-spatial interactions of Carnivores have traditionally been described using the vocabulary of territoriality and aggression, with scent marks interpreted as 'scent fences'. Here, we investigate the role of olfactory signals in assumed territorial marking of group-living solitary foragers using European badgers Meles meles as a model. We presented anal gland secretions (n = 351) from known individuals to identifiable recipients (n = 187), to assess response-variation according to familiarity (own-group, neighbours, strangers) and spatial context (in-context: at a shared border; out-of-context: at an unshared border/ the main sett). Sniffing and over-marking (with subcaudal gland secretion) responses were strongest to anal gland secretions from strangers, intermediate to neighbouring-group and weakest to own-group members. Secretions from both, strangers and neighbours, were sniffed for longer than were own-group samples, although neighbour-secretion presented out-of-context evoked no greater interest than in-context. On an individual level, responses were further moderated by the relevance of individual-specific donor information encoded in the secretion, as it related to the physiological state of the responder. There was a trend bordering on significance for males to sniff for longer than did females, but without sex-related differences in the frequency of subcaudal over-marking responses, and males over-marked oestrous female secretions more than non-oestrous females. There were no age-class related differences in sniff-duration or in over-marking. Evaluating these results in the context of the Familiarity hypothesis, the Threat-level hypothesis, and the Individual advertisement hypothesis evidences that interpretations of territorial scent-marks depicting rigid and potentially agonistic discrimination between own- and foreign-group conspecifics are overly simplistic. We use our findings to advance conceptual understanding of badger socio-spatial ecology, and the general context of territoriality and group-range dynamics.

Avoiding verisimilitude when modelling ecological responses to climate change: the influence of weather conditions on trapping efficiency in European badgers (Meles meles).

The signal for climate change effects can be abstruse; consequently, interpretations of evidence must avoid verisimilitude, or else misattribution of causality could compromise policy decisions. Examining climatic effects on wild animal population dynamics requires ability to trap, observe or photograph and to recapture study individuals consistently. In this regard, we use 19 years of data (1994-2012), detailing the life histories on 1179 individual European badgers over 3288 (re-) trapping events, to test whether trapping efficiency was associated with season, weather variables (both contemporaneous and time lagged), body-condition index (BCI) and trapping efficiency (TE). PCA factor loadings demonstrated that TE was affected significantly by temperature and precipitation, as well as time lags in these variables. From multi-model inference, BCI was the principal driver of TE, where badgers in good condition were less likely to be trapped. Our analyses exposed that this was enacted mechanistically via weather variables driving BCI, affecting TE. Notably, the very conditions that militated for poor trapping success have been associated with actual survival and population abundance benefits in badgers. Using these findings to parameterize simulations, projecting best-/worst-case scenario weather conditions and BCI resulted in 8.6% ± 4.9 SD difference in seasonal TE, leading to a potential 55.0% population abundance under-estimation under the worst-case scenario; 38.6% over-estimation under the best case. Interestingly, simulations revealed that while any single trapping session might prove misrepresentative of the true population abundance, due to weather effects, prolonging capture-mark-recapture studies under sub-optimal conditions decreased the accuracy of population estimates significantly. We also use these projection scenarios to explore how weather could impact government-led trapping of badgers in the UK, in relation to TB management. We conclude that population monitoring must be calibrated against the likelihood that weather conditions could be altering trap success directly, and therefore biasing model design.

Climate and the individual: inter-annual variation in the autumnal activity of the European badger (Meles meles).

We establish intra-individual and inter-annual variability in European badger (Meles meles) autumnal nightly activity in relation to fine-scale climatic variables, using tri-axial accelerometry. This contributes further to understanding of causality in the established interaction between weather conditions and population dynamics in this species. Modelling found that measures of daylight, rain/humidity, and soil temperature were the most supported predictors of ACTIVITY, in both years studied. In 2010, the drier year, the most supported model included the SOLAR*RH interaction, RAIN, and 30cmTEMP (w = 0.557), while in 2012, a wetter year, the most supported model included the SOLAR*RH interaction, and the RAIN*10cmTEMP (w = 0.999). ACTIVITY also differed significantly between individuals. In the 2012 autumn study period, badgers with the longest per noctem activity subsequently exhibited higher Body Condition Indices (BCI) when recaptured. In contrast, under drier 2010 conditions, badgers in good BCI engaged in less per noctem activity, while badgers with poor BCI were the most active. When compared on the same calendar dates, to control for night length, duration of mean badger nightly activity was longer (9.5 hrs ±3.3 SE) in 2010 than in 2012 (8.3 hrs ±1.9 SE). In the wetter year, increasing nightly activity was associated with net-positive energetic gains (from BCI), likely due to better foraging conditions. In a drier year, with greater potential for net-negative energy returns, individual nutritional state proved crucial in modifying activity regimes; thus we emphasise how a 'one size fits all' approach should not be applied to ecological responses.

Once- vs twice-daily budesonide/formoterol in 6- to 15-year-old patients with stable asthma.

OBJECTIVE: To assess efficacy/tolerability of once-daily budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide pMDI (primary) and twice-daily budesonide/formoterol (secondary) in children/adolescents with asthma stabilized with twice-daily budesonide/formoterol. METHODS: This 12-week multicenter, double-blind randomized controlled study (www.clinicaltrials.gov identifier NCT00646321) included 521 patients aged 6 to 15 years with mild/moderate persistent asthma. Patients stabilized during a 4- to 5-week run-in with twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily) received twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily), once-daily budesonide/formoterol pMDI 80/4.5 microgx2 inhalations (160/9 microg daily; evening), or once-daily budesonide pMDI 80 microgx2 inhalations (160 microg daily; evening). RESULTS: Once- or twice-daily budesonide/formoterol was more effective than budesonide for evening peak expiratory flow (primary variable) at the end of the 24-hour once-daily dosing interval (P

Treatment of persistent asthma with Symbicort (budesonide/formoterol inhalation aerosol): an inhaled corticosteroid and long-acting beta2-adrenergic agonist in one pressurized metered-dose inhaler.

OBJECTIVE: Budesonide/formoterol inhalation aerosol (Symbicort AstraZeneca, Wilmington, Delaware) is an inhaled corticosteroid (ICS) and long-acting beta(2)-adrenergic agonist (LABA) combination administered twice daily via one hydrofluoroalkane pressurized metered-dose inhaler (pMDI) approved in the United States for the long-term maintenance treatment of persistent asthma in patients >or=12 years of age whose asthma cannot be controlled by an ICS alone. The objective was to review efficacy, safety, and pharmacogenetic data on budesonide/formoterol pMDI in the treatment of persistent asthma. METHODS: The authors searched PubMed and respiratory meeting databases to identify asthma studies of budesonide/formoterol pMDI. Studies involving traditional and patient-reported outcomes, safety, tolerability, or pharmacogenetics were included. RESULTS: In two 12-week pivotal trials in adolescents and adults, treatment with budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations (320/9 microg) twice daily for moderate to severe persistent asthma or 80/4.5 microg x 2 inhalations (160/9 microg) twice daily for mild to moderate persistent asthma, demonstrated greater efficacy and similar tolerability compared with placebo and the same nominal dose of its monocomponents. Comparisons with formoterol dry powder inhaler (DPI) for predose forced expiratory volume in one second (FEV(1)) and with budesonide pMDI for 12-hour mean postdose FEV(1) demonstrated the anti-inflammatory and bronchodilatory contributions of budesonide and formoterol, respectively. Evaluations of patient-reported outcomes, including asthma-specific quality of life and treatment satisfaction, further supported the clinical benefits of budesonide/formoterol pMDI. In a 52-week tolerability study of patients aged >or=12 years, budesonide/formoterol pMDI was delivered at up to double the maximum dose (640/18 microg twice daily) and demonstrated a safety profile similar to that of budesonide (640 microg twice daily), with no unexpected pattern of abnormalities. Additional studies reported that budesonide/formoterol pMDI 320/9 microg twice daily and fluticasone propionate/salmeterol DPI 250/50 microg twice daily have similar efficacy and tolerability, with significantly more patients achieving >or=15% improvement in FEV(1) within 15 minutes with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI. Moreover, inheritance of the Gly16Arg polymorphism of the beta(2)-adrenergic receptor does not appear to affect clinical outcomes with budesonide/formoterol pMDI. CONCLUSION: Budesonide/formoterol pMDI administered twice daily is effective and generally well tolerated in patients whose asthma is not well controlled on ICS alone.

Effects of mometasone furoate given once daily in the evening on lung function and symptom control in persistent asthma.

BACKGROUND: The chronobiology of asthma suggests that, for once-daily dosing, an evening dose may be the most effective treatment paradigm. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate dry powder inhaler (MF-DPI) administered once daily in the evening or twice daily in patients with asthma previously maintained on twice-daily regimens of inhaled corticosteroids. METHODS: In this 12-week, multicenter, placebo-controlled trial, 268 subjects > or =12 years of age with inhaled corticosteroid-dependent asthma and baseline forced expiratory volume in 1 second (FEV(1)) between 50% and 85% of predicted were randomized to receive treatment with MF-DPI 400 mug once daily in the evening, MF-DPI 200 mug twice daily, or placebo. The primary efficacy variable was mean change in FEV(1) from baseline to endpoint. Other lung function measures, asthma symptoms, quality of life, and rescue medication use also were assessed. RESULTS: At endpoint, mean FEV(1) was significantly improved with both MF-DPI doses compared with placebo (p < 0.001). The 2 active treatment groups were statistically indistinguishable from each other. Secondary efficacy variables, including nocturnal awakenings, asthma worsenings, quality of life, and rescue medication use, were also significantly improved for both MF-DPI treatments compared with placebo. Both dosages were well tolerated; no clinically meaningful changes in laboratory values or vital signs were observed. CONCLUSIONS: MF-DPI 400 mug once daily in the evening was as effective as MF-DPI 200 mug twice daily in improving pulmonary function, asthma symptoms, and quality of life compared with placebo in subjects previously using twice-daily regimens of an inhaled corticosteroid.

Fluticasone propionate HFA-134a pressurized metered-dose inhaler in adolescents and adults with moderate to severe asthma.

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 microg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV1) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 microg bid; 9.8%, 220 microg bid; 11.2%, 440 microg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.