Search

Transformative capacity (TC) is key for addressing climate change impacts. It refers to urban areas' ability for profound and intentional change to address current challenges and move towards a more desirable and resilient state. However, its varied applications across disciplines can lead to misunderstandings and implementation challenges. Thus, this Semi-Systematic Literature Review (SSLR) on TC within urban studies from 2016 to 2022 aims to overview and synthesise TC literature and its gaps to inform ongoing debates, intersecting it with climate-related research. The results show an increasing interest in TC within two fields of knowledge: resilience studies and transformative research. The review found TC as a catalyst for transformative actions, promoting sustainable pathways, enhancing resilience, and driving fundamental changes in urban climate adaptation. Finally, the prevailing literature gaps concern the TC concept's fragmentation, excessive research on governance features, and lack of joint research about TC and innovation. [ABSTRACT FROM AUTHOR]

Textile‐based shields are one of the most used solutions for electromagnetic interference (EMI) shielding in the radiofrequency range for several applications, such as personal protection, military, and aircraft. Herein, EMI textile shields are produced based on knitted cotton textile substrates (Jersey and American Fleece) coated with industrial‐grade multiwalled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs). An easy and scalable dip‐pad‐dry process is used to fabricate the textile‐based shields. The shielding effectiveness (SE) is evaluated over the frequency range of 5.85–18 GHz. The MWCNT‐coated American Fleece fabric presents the highest EMI shielding, with an average SE of ≈35.6 dB, which corresponds to an excellent classification for general use applications. Additionally, the electrical properties of the carbon nanomaterials and the thickness of the shields reveal to be correlated with an EMI shielding process mostly through radiation absorption mechanism. Numerical simulations are used to further assist in a thorough investigation regarding the influence of the electrical properties of the nanomaterials on the SE of the resulting coated fabrics. [ABSTRACT FROM AUTHOR]

Gold nanoclusters (AuNCs) with fluorescence in the Near Infrared (NIR) by both one- and two-photon electronic excitation were incorporated in mesoporous silica nanoparticles (MSNs) using a novel one-pot synthesis procedure where the condensation polymerization of alkoxysilane monomers in the presence of the AuNCs and a surfactant produced hybrid MSNs of 49 nm diameter. This method was further developed to prepare 30 nm diameter nanocomposite particles with simultaneous NIR fluorescence and superparamagnetic properties, with a core composed of superparamagnetic manganese (II) ferrite nanoparticles (MnFe2O4) coated with a thin silica layer, and a shell of mesoporous silica decorated with AuNCs. The nanocomposite particles feature NIR-photoluminescence with 0.6% quantum yield and large Stokes shift (290 nm), and superparamagnetic response at 300 K, with a saturation magnetization of 13.4 emu g−1. The conjugation of NIR photoluminescence and superparamagnetic properties in the biocompatible nanocomposite has high potential for application in multimodal bioimaging. [ABSTRACT FROM AUTHOR]

Background This study tested the clinical non-inferiority of the fluticasone propionate/salmeterol combination 50/250 μg (FSC) Rotacaps ® /Rotahaler ® system, a single unit dose inhaler, with the multi-dose FSC Diskus ® inhaler in adults with chronic obstructive pulmonary disease (COPD). Methods This multi-centre, randomised, double-blind, double-dummy, two-way cross-over study compared 12 weeks' treatment of FSC administered twice daily using Rotacaps/Rotahaler or Diskus. The primary endpoint was change from baseline in trough morning forced expiratory volume in 1 s (FEV 1 ) at Day 85, and the pre-defined non-inferiority criteria was: the lower limit of the confidence interval (CI) for the treatment difference (Rotacaps/Rotahaler-Diskus) in least squares (LS) mean change from baseline, being greater than −45 mL. Secondary endpoints included change in breathlessness (as measured by transition dyspnoea index (TDI)) and COPD-specific health status measures. Results The LS mean increase from baseline in trough FEV 1 at Day 85 was 116 mL in the Rotacaps/Rotahaler group and 91 mL in the Diskus group (difference in model-adjusted LS mean change: 25 mL (95% CI 2 mL, 47 mL)), the lower limit of the CI for the treatment difference being greater than the protocol-defined criterion for non-inferiority i.e. −45 mL. Data for breathlessness, COPD-specific health status and safety parameters were similar following FSC treatment via either inhaler. Conclusions This study demonstrated the clinical non-inferiority of FSC 50/250 μg when administered using Rotacaps/Rotahaler compared with Diskus in patients with COPD. The risk:benefit profile for the two inhalers was comparable. [ABSTRACT FROM AUTHOR]

Background In developing countries, there is a need for access to affordable inhaled respiratory medicines. This study tested the clinical non-inferiority of fluticasone propionate/salmeterol combination (FSC) 50/250 μg Rotacaps ® /Rotahaler ® compared with FSC 50/250 μg Diskus ® . Methods A multi-centre, randomised, double-blind, double-dummy study evaluated 12 weeks, twice daily treatment of FSC 50/250 μg administered using Rotacaps/Rotahaler or Diskus inhaler in a crossover design in patients with asthma (pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) 40%–85% of predicted, FEV 1 reversibility ≥12%, prior stable dose with inhaled corticosteroid (ICS) or ICS/long acting beta-agonist). The primary efficacy endpoint, change from baseline in trough morning FEV 1 at Day 85, was analysed using a model for repeated measures analysis. The pre-defined criterion for non-inferiority was the lower limit of the CI (0.025, one-sided significance level) for the treatment difference (Rotacaps/Rotahaler-Diskus) in least squares (LS) mean change from baseline, being greater than −125 mL. Secondary endpoints included serial FEV 1 measurements, morning peak expiratory flow (PEF), rescue medication use, day- and night-time asthma symptoms, Asthma Control Test (ACT) scores, and serial cortisol measured over 12 h (area under the curve (AUC 0-12 )). Results Treatment with FSC 50/250 μg via Rotacaps/Rotahaler or Diskus resulted in a similar LS mean increase from baseline in trough FEV 1 at Day 85 (231 mL and 203 mL respectively). The difference in the model-adjusted LS mean change was 28 mL (95% CI -24 mL, 80 mL), fulfilling the criterion for non-inferiority. Data for all secondary endpoints were similar for the two treatments, supporting the primary endpoint findings. Both treatments were well tolerated and demonstrated similar safety profiles. Conclusion This study demonstrated the clinical non-inferiority of FSC 50/250 μg when administered using Rotacaps/Rotahaler compared with administration using Diskus in patients with asthma, and suggests there is no difference in the risk:benefit profile between the two FSC inhalers. [ABSTRACT FROM AUTHOR]

Abstract: Phenolic compounds are a sort of common pollutants in water. Phenol index becomes an expedite indicator for the evaluation of the contamination level of water samples, in spite of the knowledge of the individual phenol and its derivatives are also important. In this work, an environmental friendly method for the determination of phenols, using a segmented flow system based on the conventional method''s reactions without the liquid–liquid extraction step, was validated. Three linear dynamic ranges using C6H5OH: 1–10μgl−1, 10–200μgl−1 and 0.2–2.5mgl−1, with a coefficient of variation lower than 2%, were obtained. Several method''s performance parameters were determined: limits of detection, limits of quantification, precision through duplicate analysis and trueness using the reference materials purchased from LGC Promochem, RTC no. QCI-043-2 Lot:P1. Measurement uncertainty was evaluated using an interlaboratory approach based on proficiency testing data. Relative combined uncertainty for phenols in water samples, , of 0.054 were obtained, in according to those imposed by the Portuguese Legislation: target for 1μgl−1 of phenol (surface waters) and target for 500μgl−1 of phenol (wastewaters). A high efficiency reduction and elimination of reagents and wastes, reduction of analysis time and exposition of the analyst were also obtained. [Copyright &y& Elsevier]

Background: In the 52‐week Phase III SYNAPSE study, mepolizumab given every 4 weeks (100 mg subcutaneously) reduced nasal polyp (NP) size, improved symptoms and quality of life (QoL), and reduced corticosteroid use and number of sinus surgeries in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), versus placebo. Because the durability of mepolizumab's efficacy after discontinuation is poorly understood in CRSwNP, the efficacy of mepolizumab after discontinuation was analyzed in severe CRSwNP, over a 24‐week follow‐up. Methods: Changes from SYNAPSE baseline to end of treatment (week 52) and end of follow‐up (week 76) were assessed for total endoscopic NP score, nasal obstruction and overall symptoms visual analog scale scores, and 22‐item Sino‐Nasal Outcome Test score. Time to first sinus surgery, time to first corticosteroid use, and geometric mean blood eosinophil counts (BECs) were also assessed. Results: Among 134 follow‐up patients, clinical improvements observed with mepolizumab versus placebo were partially evident 24 weeks after discontinuation despite BEC returning to baseline. The mean (95% confidence interval [CI]) change from baseline in NP score (week 52: −1.3 [1.8 to −0.9] vs. −0.3 [−0.6 to 0.1]; week 76: −1.2 [−1.6 to −0.7] vs. −0.1 [−0.5 to 0.3]) and the proportion of patients having sinus surgery (week 52: 4% vs. 25%; week 76: 9% vs. 31%) remained substantially improved with mepolizumab versus placebo. Mepolizumab‐associated improvements in overall symptoms, quality of life, and corticosteroid use versus placebo were partially sustained at week 76. Conclusion: Fifty‐two weeks of mepolizumab treatment is associated with sustained clinical benefits up to 24 weeks after discontinuation in patients with severe CRSwNP, which should be considered by physicians when making treatment decisions. [ABSTRACT FROM AUTHOR]

• Severe asthma patients are at higher risk of anxiety and depression. • Depression in asthma was associated with IL6, MCP1, CCL18 level, and CCL17, whereas anxiety was associated with CCL17 only. • Inflammatory mechanism may underlie this comorbidity. Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition. [ABSTRACT FROM AUTHOR]

Objectives: To characterise the real‐world burden of chronic rhinosinusitis with nasal polyps (CRSwNP) in the UK, stratified by number of surgeries. Design: Retrospective cohort study. Setting: UK Clinical Practice Research Datalink Aurum database with Hospital Episodes Statistics linkage (2007–2019). Participants: Adults ≥18 years of age with a first NP diagnosis (index) and 365 days of baseline and ≥180 days of follow‐up data. Follow‐up continued until disenrollment, death or end of data collection. Main Outcome Measures: Primary: primary care physician prescribed CRSwNP‐related treatments, and all‐cause healthcare resource utilisation (HCRU) in 90 days post‐index, stratified by surgeries during follow‐up. Secondary: rate of surgery and CRSwNP point prevalence. Baseline patient demographics, clinical characteristics and comorbidities were also assessed. Results: Of the 33 107 patients included, 23.5% and 2.2% had ≥1 and ≥2 surgeries during follow‐up, respectively (mean follow‐up: 5.3 years). Patients with more surgeries (≥2/≥1/0) during follow‐up were more likely to be male (67.3%/69.0%/58.0%), have asthma (37.8%/28.2%/20.2%) and have baseline blood eosinophil counts ≥300 cells/μL (68.5%/66.0%/51.5%). During the first 90‐days post‐index as surgery number increased, the proportion of patients using oral corticosteroids (25.8%/20.7%/14.2%) and mean (SD) number of all‐cause healthcare visits (5.9 [4.2]/5.4 [4.0]/4.9 [4.2]) increased. Time between surgeries was shorter among patients with more surgeries. CRSwNP prevalence on 31 December 2018 was 476 cases per 100 000 persons. Conclusion: A small proportion of patients in the UK required multiple surgeries for CRSwNP and this was associated with increasing comorbidity burden, baseline blood eosinophil counts, CRSwNP‐related treatment and HCRU use. [ABSTRACT FROM AUTHOR]

Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in‐depth assessment of surgery endpoints in SYNAPSE. Methods: SYNAPSE was a double‐blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. Results: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan–Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count. Conclusions: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with eosinophilic tissue infiltration linked to type 2 inflammation and characterized by elevated levels of interleukin (IL)‐5 and other type 2 inflammatory mediators. Although distinct and overlapping contributions of eosinophils and IL‐5 to CRSwNP pathology are still being explored, they are both known to play an important role in NP inflammation. Eosinophils secrete numerous type 2 inflammatory mediators including granule proteins, enzymes, cytokines, chemokines, growth factors, lipids, and oxidative products. IL‐5 is critical for the differentiation, migration, activation, and survival of eosinophils but is also implicated in the biological functions of mast cells, basophils, innate lymphoid cells, B cells, and epithelial cells. Results from clinical trials of therapeutics that target type 2 inflammatory mediators (including but not limited to anti‐IL‐5, anti‐immunoglobulin‐E, and anti‐IL‐4/13) may provide further evidence of how eosinophils and IL‐5 contribute to CRSwNP. Finally, the association between eosinophilia/elevated IL‐5 and greater rates of NP recurrence after endoscopic sinus surgery (ESS) suggests that these mediators may have utility as biomarkers of NP recurrence in diagnosing and assessing the severity of CRSwNP. This review provides an overview of eosinophil and IL‐5 biology and explores the literature regarding the role of these mediators in CRSwNP pathogenesis and NP recurrence following ESS. Based on current published evidence, we suggest that although eosinophils play a key role in CRSwNP pathophysiology, IL‐5, a cytokine that activates these cells, also represents a pertinent and effective treatment target in patients with CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Patients with asthma who have aspirin sensitivity have greater cysteinyl leukotriene production and greater airway hyperresponsiveness to the effects of inhaled cysteinyl leukotrienes than their aspirin-tolerant counterparts. We hypothesized that the latter effect reflects elevated expression of the cysteinyl leukotriene receptor CysLT1 on inflammatory cells in the target organ and that its expression is down-regulated by aspirin desensitization. Methods: We obtained nasal-biopsy specimens from 22 aspirin-sensitive and 12 non–aspirin-sensitive patients with chronic rhinosinusitis and nasal polyps. Additional specimens were then obtained from subgroups of the aspirin-sensitive patients after intranasal application of lysine aspirin or placebo for two weeks (five and four patients, respectively) or for six months (five and four patients, respectively). The numbers of leukocytes expressing the CysLT1 and leukotriene B4 (LTB4) receptors per unit area of sections of the nasal submucosa were determined by immunohistochemistry. Results: The absolute number of cells expressing the CysLT1 receptor was significantly higher in the aspirin-sensitive patients than in the non–aspirin-sensitive patients (median, 542 cells per square millimeter [range, 148 to 1390] vs. 116 cells per square millimeter [range, 40 to 259]; P<0.001). The percentage of CD45+ leukocytes expressing the CysLT1 receptor was also higher in the aspirin-sensitive subjects (25 percent of CD45+ leukocytes [range, 4 to 50] vs. 5 percent of CD45+ leukocytes [range, 2 to 11]; P<0.001); the percentage of CD45+ leukocytes expressing the LTB4 receptor did not differ significantly between these two groups. Desensitization was associated with a decrease in the numbers of inflammatory cells expressing CysLT1. Conclusions: The elevated numbers of nasal inflammatory leukocytes expressing the CysLT1 receptor in aspirin-sensitive patients with chronic rhinosinusitis as compared with their non–aspirin-sensitive counterparts and the down-regulation of receptor expression after desensitization to aspirin are probably fundamental in the pathogenesis of aspirin sensitivity and in the mechanism of aspirin desensitization. (N Engl J Med 2002;347:1493-9.) [ABSTRACT FROM AUTHOR]

Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high.Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity?Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry.Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels.Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. Objective: Within the U‐BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. Methods: Bronchial biopsies were collected from two severe asthma groups, one non‐smoker (SAn, n = 28) and one current/ex‐smoker (SAs/ex, n = 13), and a mild‐moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. Results: The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18–20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups. Conclusion: These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma. [ABSTRACT FROM AUTHOR]

Keywords: asthma; bioinformatics; endotypes; precision medicine; systems biology EN asthma bioinformatics endotypes precision medicine systems biology 380 383 4 01/09/21 20210101 NES 210101 I To the Editor, i Asthma is a complex heterogeneous disease that presents with varying degrees of severity. We identified four optimal clusters (TAC*1, TAC*2, TAC*3a and TAC*3b) (Figure S3), in agreement with our previous clustering1 where TAC*3a and TAC*3b were combined. Asthma, bioinformatics, endotypes, precision medicine, systems biology. [Extracted from the article]

Objectives: To qualitatively explore patient experiences of severe, recurrent, bilateral nasal polyps (NP).Methods: A targeted literature review of published qualitative studies and online blogs describing patient experiences of NP was conducted. Semistructured concept elicitation interviews were conducted in the United States and Germany with participants ≥18 years with severe, recurrent, bilateral NP to explore their symptom experience and impacts on health-related quality of life (HRQoL; NCT03221192). A subset of 10 participants reported symptoms and impacts using a smartphone or tablet application (app) over a 10-day period.Results: A paucity of qualitative evidence regarding patient experience of NP was identified from the literature or blog review. Twenty-seven participant interviews were conducted. Thirty-six symptoms were identified, including 7 primary symptoms (nasal congestion [n = 27 of 27], breathing difficulties [n = 27 of 27], postnasal drip [n = 25 of 27], runny nose [n = 24 of 27], head/facial pressure [n = 23 of 27], loss of smell [n = 23 of 27], loss of taste [n = 22 of 27]) and 29 secondary symptoms (the most common were mucus/catarrh and nose bleeds [both n = 20 of 27]). Most symptoms were reported to vary both within and between days. Sixty impacts of severe NP were reported, including impacts on sleep (n = 22 of 27), physical functioning (n = 21 of 27), activities of daily living (n = 21 of 27), emotional well-being (n = 27 of 27), treatment (n = 23 of 27), social life (n = 26 of 27), and work (n = 19 of 27). Symptoms/impacts reported using the app were consistent with interview findings, although new symptoms were identified (ear pain, throat pain, nasal scabs, and nasal burning). These results supported the development of a conceptual model outlining concepts related to symptoms, impacts, and treatment of NP.Conclusions: Severe, recurrent, bilateral NP are associated with a range of symptoms that have significant detrimental impact on HRQoL. [ABSTRACT FROM AUTHOR]

The article offers information on the Treatable Traits, a precision medicine approach for the diagnosis and management of chronic airway diseases. It mentions the prevalence of treatable traits, both pulmonary and nonpulmonary, was higher in severe asthma compared to mild and moderate asthma; mentions the label‐free, precision medicine approach provided by the treatable traits construct allowed for the identification of multiple treatment opportunities for patients with asthma.

Introduction: Appropriate timing for dual bronchodilator therapy initiation in chronic obstructive pulmonary disease (COPD) management is uncertain. Combination therapy is recommended as step-up from monotherapy or first-line treatment in patients with persistent symptoms. In this setting, umeclidinium/vilanterol (UMEC/VI) demonstrated improved lung function and reduced rescue medication use over tiotropium/olodaterol (TIO/OLO). This subgroup analysis explored efficacy differences between these combinations in patients naïve to COPD maintenance therapy before study entry.Methods: Post hoc analysis of an 8-week, randomized, open-label, assessor-blind, two-period crossover study (204990; NCT02799784) comparing UMEC/VI 62.5/25 mcg and TIO/OLO 5/5 mcg, focused on maintenance-naïve (MN) patients with moderate COPD and persistent symptoms (modified Medical Research Council dyspnea score ≥ 2). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), percentage of FEV1 responders (CFB ≥ 100 ml), rescue medication use and safety were evaluated.Results: The MN population comprised 63% of the intent-to-treat (ITT) population (148/236 patients) and had similar baseline demographics. At week 8, adjusted mean (standard error) improvements in trough FEV1 from baseline were clinically meaningful for both combinations (UMEC/VI: 167 [17] ml; TIO/OLO 110 [18] ml; adjusted mean difference [95% confidence interval (CI)]: 57 [23-92] ml; p = 0.001; %CFB: 11 vs. 8%). Proportion of FEV1 responders was greater with UMEC/VI versus TIO/OLO at week 8 (60 vs. 42%; odds ratio [95% CI] 1.90 [1.12-3.22]; p = 0.018). Reduction in rescue medication use was 0.20 (95% CI 0.07-0.34) puffs/day greater with UMEC/VI versus TIO/OLO over weeks 1-8 (p = 0.003). Adverse events incidence was similar (UMEC/VI: 24%; TIO/OLO: 29%).Conclusions: These results highlight that the efficacy difference between UMEC/VI and TIO/OLO demonstrated in the ITT population is maintained in MN patients. Greater lung function improvements with UMEC/VI versus TIO/OLO were accompanied by symptom improvements, as reflected in a significantly lower need for supplemental rescue medication.Funding: GSK.Trial registration: NCT02799784 [ABSTRACT FROM AUTHOR]

O01 Serum IL-1RL1-A levels predict an eosinophilic subtype of asthma in preschool wheezing ch... M. E. Ketelaar 1, K. Van De Kant 2, F. N. Dijk 1, E. M. M. Klaassen 3, N. Grotenboer 4,... 1 University Medical Center Groningen, Beatrix Children's Hospital, Groningen Research Instit... B Correspondence b : Maria Elizabeth Ketelaar - m.e.ketelaar@student.rug.nl I Clinical and Translational Allergy i 2017, B 7(Suppl 2) b :O01 B Introduction b : Respiratory symptoms are common in preschool children. The children were divided into four groups - 10 children with scoliosis without asthma (Sc),10 children with scoliosis and asthma (AS), 10 children with moderate asthma (BA), 10 children with severe asthma (SA) and 10 healthy children (HC). B Keywords b : Preschool Wheezing, Respiratory Viruses, Asthma Exacerbation, Severity P09 Tele-monitoring decreases unscheduled outpatient visits in pediatric patients with severe... Mihai Craiu, Iustina Violeta Stan INSMC Alessandrescu-Rusescu, Bucharest, Romania B Correspondence b : Mihai Craiu - mcraiu@yahoo.com I Clinical and Translational Allergy i 2017, B 7(Suppl 2) b :P09 B Introduction b : Pediatric asthma patients originating from poor-resource areas experience a significant increase of unscheduled and emergency department visits and most of medical care for them is delivered in such a facility. [Extracted from the article]

To investigate the pharmacokinetics and effects on the hypothalamic-pituitary-adrenal (HPA) axis of mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Study 1 : Fourteen healthy participants received inhaled and intravenous MF (inhaled dose via Twisthaler) and FP (inhaled dose via Diskus), both given at 400 μg, using a randomised, single-dose, four-way crossover design. Study 2: Twenty-seven participants with mild to moderate asthma, who discontinued their corticosteroid medication for 5 days to obtain a baseline 24 h serum cortisol, received inhaled MF Twisthaler and FP Diskus, both given at 400 μg twice daily (BID), using a randomised, 14-day repeat dose, two-way crossover design. Study 3: Forty-four healthy participants were randomised to a double-blind, placebo-controlled, five-period crossover study where the following treatments were administered via the inhaled route for 7 days: FP Diskus (250, 500, 1000 μg BID), FF Diskus (100, 200, 400, 800, 1600 μg once daily [QD]) or placebo Diskus. In each study, 24-h serial blood samples were collected and assayed to assess concentrations of MF, 6β-hydroxy mometasone, mometasone, FP, FF and cortisol. Pharmacokinetic and serum cortisol parameters were estimated as geometric means and 95% confidence intervals (CI). Study 1 : For intravenous MF and FP, respectively: absolute bioavailability was 11.4% (95% CI: 7.5, 17.6) and 7.8% (6.3, 9.6); plasma clearance was 47 L/h (41, 52) and 60 L/h (52, 69); half-life was 7.4 h (6.9, 8.0) and 7.2 h (6.5, 8.0); and volume of distribution was 499 L (439, 567) and 623 L (557, 698). Inhalation of single dose MF or FP did not significantly affect serum cortisol (<10% reduction from baseline), whereas intravenous administration of MF or FP each changed serum cortisol by approximately −50% from baseline. Study 2 : For MF and FP, respectively: area under the curve up to the last measurable concentration on Day 1 was 421 pg h/mL (270, 659) and 248 pg h/mL (154, 400), and on Day 14 was 1092 pg h/mL (939, 1269) and 591 pg h/mL (501, 696); absolute bioavailability was 12.8% (11.2, 14.2) and 8.9% (7.7, 10.2). On Day 14, 24-h serum cortisol change from baseline was −35% (−44%, −26%) and −18% (−28%, −5%) for MF and FP, respectively; the reduction was significantly greater for MF than FP (ratio for geometric adjusted mean serum cortisol concentration: 1.28 [1.04, 1.56]). Low plasma concentrations of 6β-hydroxy mometasone were detected after intravenous dosing (Study 1) and after multiple inhaled dosing (Study 2); mometasone was not detected in any samples. Study 3 : Inhaled FP and FF had similar systemic bioavailability estimates (12.0% [11.0, 13.2] and 15.0% [12.0, 17.3], respectively), but a differential effect on the HPA axis which was in agreement with the known 1.7-fold higher glucocorticoid receptor-binding affinity of FF versus FP. However, for FP 250 μg BID and FF 100, 200 and 400 μg QD, reduction in serum cortisol was not significantly different from placebo. For higher doses, FP 500 and 1000 μg BID, and FF 800 and 1600 μg QD, changes in serum cortisol concentration relative to placebo were −30%, −70%, −41% and −90%, respectively. Repeat inhaled dosing of FP 1000 μg/day (within the therapeutic dose range) resulted in comparable cortisol suppression to MF in the therapeutic range (30% reduction); whereas for FF this occurred at more than 3-fold above the therapeutic dose range (644 μg/day). Single inhaled and intravenous doses of MF and FP (400 μg) resulted in similar bioavailability and reductions in serum cortisol. Repeat dosing of inhaled MF and FP in the therapeutic range (800 μg/day) resulted in greater systemic exposure for MF, and a 35% reduction in serum cortisol that was 2-fold greater than for FP. The higher glucocorticoid receptor-binding affinity and bioavailability, lower clearance and the presence of active metabolites may contribute to the greater systemic exposure and effect on cortisol for MF. Repeat dosing of inhaled FP and FF resulted in similar systemic bioavailability but differed in terms of the dose required for comparable cortisol suppression to MF in the therapeutic range. Unlike FP and FF, MF has active metabolites that may contribute to its systemic effects, while device/formulation performance differences also exist between MF-containing products. • PK profiles of FP and FF are similar; MF has active metabolites and lower clearance. • Cortisol suppression for FP and FF is mainly related to differences in potency. • Higher systemic exposure and cortisol suppression are seen with MF versus FP. • FP and FF mono and combo products have matching nominal doses and systemic activity. • MF mono and combo products have different nominal doses but same systemic activity. [ABSTRACT FROM AUTHOR]

Background: Lung epithelial lining fluid (ELF)—sampled through sputum induction—is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood.Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.Methods: Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes.Results: The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender.Conclusions: We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism. [ABSTRACT FROM AUTHOR]