The effect of high-dose fluticasone propionate and budesonide on lung function and asthma exacerbations in patients with severe asthma

AbstractThe purpose of this study was to investigate the comparative efficacy and safety of equal doses of inhaled fluticasone propionate (FP) and inhaled budesonide (BUD) using their respective dry powder inhalers in a population of severe asthmatics requiring high doses of inhaled corticosteroid. This double-blind double-dummy parallel-group study compared the effects of 24 weeks of treatment with FP (2000 μg daily via a Diskhaler® inhaler; Glaxo Wellcome, Evreux, France) and BUD (2000 μg daily via a Turbuhaler® inhaler; Astra Pharmaceuticals, Rijswijka, Netherlands) on lung function and asthma exacerbations in 395 patients with asthma.FP was statistically significantly superior to BUD with respect to the percentage of symptom-free days (P = 0·02), the incidence of days free from rescue bronchodilator usage (P = 0·02) and the distribution of change in peak expiratory flow (PEF) expressed as a percentage of the predicted PEF (P = 0·04). During the treatment period FP was statistically significantly superior to BUD for change in forced expiratory volume in 1 sec (FEV1) at 8, 16 and 24 weeks, change in the median daytime symptom score during weeks 5–16, for incidence of symptomfree days and incidence of days free from rescue bronchodilator usage during weeks 17–24. There was no significant difference between FP and BUD with respect to the number of patients experiencing one or more asthma exacerbation (33·8 and 28·4% of patients, respectively). There was, however, evidence that the exacerbations were clinically less severe in patients treated with FP, in that the time to resolution was quicker (11·0 vs. 14·7 days; P = 0·035), mean duration of all exacerbations (for an individual patient) tended to be shorter (18·5 vs. 23·6 days; P = 0·12), the time off work was reduced (4·2 vs. 7·6 days; P = 0·012) and the lowest PEF recorded during the exacerbation was higher (301 vs. 263 1 min−1; P = 0·07). There were no clinically relevant differences in the safety (serum cortisol levels, markers of bone turnover, adverse events) of FP and BUD at these microgram equivalent doses.The patients recruited into this study, in retrospect, probably had no need for such high doses of inhaled corticosteroid but, irrespective of this, FP at microgram equivalent doses showed evidence of superior efficacy to BUD with respect to lung function and severity of asthma exacerbations without producing any greater adverse systemic effect

A systematic review on diagnostic test accuracy of magnetic resonance neurography versus clinical neurosensory assessment for post-traumatic trigeminal neuropathy in patients reporting neurosensory disturbance

Objectives: To perform a systematic review of published studies on diagnostic accuracy of magnetic resonance neurography (MRN) vs clinical neurosensory testing (NST) for post-traumatic trigeminal neuropathy (PTTN) in patients reporting neurosensory disturbances (NSD). Methods: Human studies except case reports, reviews, systematic reviews and meta-analyses were included. PubMed, Embase, Web of Science and Cochrane Library were consulted. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Predetermined data extraction parameters were noted and summarized. Results: 8 studies met eligibility criteria of which 7 were retrospective, representing 444 subjects. Most studies were at high risk of bias with low applicability concerns. Populations and objectives were divergent with a large variation in timing (3 days-17 years post injury) and parameters (multiple coil designs, fat suppression techniques, additional contrast agent) of MRI acquisition. T-2 weighted 3 T imaging with short echo times (2.2-100 ms) and fat suppression was applied in seven studies, techniques varied. Determination of sensitivity and specificity could not be performed due to the methodological variation between studies and lacking comparative data between index and reference tests. Based on limited data, PTTN correlated reasonably well between clinical assessment, intraoperative findings and MRN abnormalities (k = 0.57). Increased signal intensity correlated with persistency of neurosensory disturbances in one study. Intra- (ICC 0.914-0.927) and interobserver (k = 0.70-0.891) MRN variability was considered good to excellent. One retrospective study showed substantial impact of MRN on clinical decision making in one-third of patients. Conclusion: Currently, there is insufficient scientific knowledge to support or refute the use of MRN. Based on limited data, MRN seems promising and reliable in detection and grading of PTTN. Methodological issues underline the importance for prospective blinded studies with standardization of signal intensity calculation and rigorous reporting of MRI acquisition parameters

Soil settlement and uplift damage to architectural heritage structures in Belgium: country-scale results from an InSAR-based analysis

Soil movement may be induced by a wide variety of natural and anthropogenic causes, which are detectable in the local scale, but may influence the movement of the soil over vast geographical expanses. Space borne interferometric synthetic aperture radar (InSAR) measurements of ground movement provide a method for the remote sensing of soil settlement and uplift over wide geographic areas. Based on this settlement and uplift evaluation, the assessment of the potential damage to architectural heritage structures is possible. In this paper an interdisciplinary monitoring and analysis method is presented that processes satellite, cadastral, patrimonial and building geometry data, used for the calculation of settlement and uplift damage to architectural heritage structures in Belgium. It uses processed InSAR data for the determination of the soil movement profile around each case study, of which the typology is determined from patrimonial information databases and the geometry is calculated from digital elevation models. The impact on the historic structures is calculated from the determined soil movement profile based on various soil-structure interaction models for buildings. The Declercqresulting damage is presented in terms of a numerical index illustrating its severity according to different criteria. In this way the potential soil movement damage is quantified in a large number of buildings in an easily interpretable and user-friendly fashion. The processing of InSAR data collected over the previous 3 decades allows the determination of the progress of settlement- and uplift-induced damage in this time period. With the integration of newly acquired and more accurate data, the methodology will continue to produce results in the coming years, both for the evaluation of soil settlement and uplift in Belgium as for introducing related damage risk data for existing architectural heritage buildings. Results of the analysis chain are presented in terms of potential current damage for selected areas and buildings.The authors wish to acknowledge the funding received by BRAIN.be, BelSPO in support of the GEPATAR research project (“GEotechnical and Patrimonial Archives Toolbox for ARchitectural conservation in Belgium” BR/132/A6/Gepatar)Peer ReviewedPostprint (published version

Advanced processing of remotely sensed big data for cultural heritage conservation

Damage assessment, protection and preservation of built patrimony are a priority at national and local levels due to their importance to many cultural and economic aspects. This paper presents a methodology to estimate the potential damage caused by ground settlement for cultural heritage buildings using remotely sensed big data. Specifically, it presents a framework to assess the potential damage caused by ground settlement for masonry, infilled and bare frames structures using Persistent Scatterer Interferometric (PSI) measurements. The proposed solution advances the state-of-the-art by integrating big Earth observation (EO), environmental, architectural and historical data, for estimating the settlement induced damage to hundreds thousands of buildings. The fully automatic scheme was created within cloud computing environment for accelerating data transfer, processing and modeling and for improving the visualization of image-derived products.Peer ReviewedPostprint (author's final draft

Soil Settlement and Uplift Damage to Architectural Heritage Structures in Belgium: Country-Scale Results from an InSAR-Based Analysis

Soil movement may be induced by a wide variety of natural and anthropogenic causes, which are detectable in the local scale, but may influence the movement of the soil over vast geographical expanses. Space borne interferometric synthetic aperture radar (InSAR) measurements of ground movement provide a method for the remote sensing of soil settlement and uplift over wide geographic areas. Based on this settlement and uplift evaluation, the assessment of the potential damage to architectural heritage structures is possible. In this paper an interdisciplinary monitoring and analysis method is presented that processes satellite, cadastral, patrimonial and building geometry data, used for the calculation of settlement and uplift damage to architectural heritage structures in Belgium. It uses processed InSAR data for the determination of the soil movement profile around each case study, of which the typology is determined from patrimonial information databases and the geometry is calculated from digital elevation models. The impact on the historic structures is calculated from the determined soil movement profile based on various soilstructure interaction models for buildings. The resulting damage is presented in terms of a numerical index illustrating its severity according to different criteria. In this way the potential soil movement damage is quantified in a large number of buildings in an easily interpretable and user-friendly fashion. The processing of InSAR data collected over the previous 3 decades allows the determination of the progress of settlement- and uplift-induced damage in this time period. With the integration of newly acquired and more accurate data, the methodology will continue to produce results in the coming years, both for the evaluation of soil settlement and uplift in Belgium as for introducing related damage risk data for existing architectural heritage buildings. Results of the analysis chain are presented in terms of potential current damage for selected areas and buildings

The Pressure Is On – Epiphyte Water-Relations Altered Under Elevated CO2

Vascular epiphytes are a major biomass component of forests across the globe and they contribute to 9% of global vascular plant diversity. To improve our understanding of the whole-plant response of epiphytes to future climate change, we investigated for the first time both individual and combined effects of elevated CO2 (560 ppm) and light on the physiology and growth of two epiphyte species [Tillandsia brachycaulos (CAM) and Phlebodium aureum (C3)] grown for 272 days under controlled conditions. We found that under elevated CO2 the difference in water loss between the light (650 μmol m-2s-1) and shade (130 μmol m-2s-1) treatment was strongly reduced. Stomatal conductance (gs) decreased under elevated CO2, resulting in an approximate 40–45% reduction in water loss over a 24 h day/night period under high light and high CO2 conditions. Under lower light conditions water loss was reduced by approximately 20% for the CAM bromeliad under elevated CO2 and increased by approximately 126% for the C3 fern. Diurnal changes in leaf turgor and water loss rates correlated strong positively under ambient CO2 (400 ppm) and high light conditions. Future predicted increases in atmospheric CO2 are likely to alter plant water-relations in epiphytes, thus reducing the canopy cooling potential of epiphytes to future increases in temperature

Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis

We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ−IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls. Moreover, higher expression of IL10 in TH17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory TH17 cells, which can be used to both identify pathogenic TH17 cells and to measure the effect of treatment on TH17 cells in human autoimmune diseases

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients