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Summary Background No consensus exists on how to reduce oral corticosteroids after the initiation of biologics in severe asthma. The PONENTE trial evaluated the effectiveness and safety of a rapid, individualised steroid-reduction algorithm, including adrenal insufficiency monitoring, after benralizumab initiation. Methods This multicentre, open-label, single-arm study was done at 138 clinical asthma treatment centres across 17 countries. We enrolled adult patients (age ≥18 years) with severe, eosinophilic asthma (blood eosinophil count ≥150 cells per μL at enrolment or ≥300 cells per μL in the previous year) requiring maintenance oral corticosteroids for at least 3 months preceding enrolment. Patients received benralizumab 30 mg (subcutaneous injection) every 4 weeks for three doses, then every 8 weeks thereafter. The oral corticosteroid reduction phase began at week 4 with daily oral corticosteroid dosages reduced by 1–5 mg every 1–4 weeks depending on the starting dosage, asthma control, and adrenal function status. Adrenal function was assessed with an early morning serum cortisol measurement, followed by adrenocorticotropic hormone stimulation when required, once patients achieved a daily oral corticosteroid dosage of 5 mg/day for 4 weeks. Repeat cortisol measurements were taken for patients with evidence of adrenal insufficiency at first testing. Asthma control was assessed with the Asthma Control Questionnaire-6 (ACQ-6) weekly throughout the induction and oral corticosteroid reduction phases. The primary endpoints were the percentage of patients eliminating daily oral corticosteroids, sustained for at least 4 weeks, and the percentage achieving elimination or a daily prednisone or prednisolone dosage of 5 mg or less, for at least 4 weeks, if the reason for no further reduction was adrenal insufficiency. Safety and efficacy analyses included all patients who received at least one dose of benralizumab and were descriptive. We present results after the oral corticosteroid reduction phase; a maintenance phase is ongoing. The trial is registered with ClinicalTrials.gov , NCT03557307 . Findings Between April 1, 2018, and Sept 5, 2020, of 705 patients assessed for eligibility, 598 were recruited and all received at least one dose of benralizumab. Overall, 376 (62·88%, 95% CI 58·86–66·76) of 598 patients eliminated oral corticosteroids and 490 (81·94%, 78·62–84·94) of 598 eliminated use or achieved a dosage of 5 mg or less if the reason for stopping the reduction was adrenal insufficiency. Subgroup analysis showed that dosage reductions were achieved irrespective of baseline eosinophil count, baseline oral corticosteroid dosage, or oral corticosteroid treatment duration. Adrenal insufficiency was detected in 321 (60%) of 533 patients at first assessment and in 205 (38%) of 533 patients 2–3 months later. The safety profile was consistent with previous experience. Most patients (448 [75%] of 598) had no asthma exacerbations during the oral corticosteroid reduction phase with an annualised exacerbation rate of 0·63. Of 598 patients, 38 (6%) experienced a total of 46 exacerbations resulting in emergency department or urgent care visits or hospitalisations. Interpretation Despite a high prevalence of adrenal insufficiency, most patients with eosinophilic asthma treated with benralizumab achieved elimination of oral corticosteroids or maximal possible reduction using a personalised dosage-reduction algorithm. Funding AstraZeneca.

Background Dynamic hyperinflation is highly prevalent in moderate-to-severe asthma, which may significantly impede activities of daily life. We hypothesised that dynamic hyperinflation in asthma is due to inflammation of large and small airways and can be reduced by systemic anti-inflammatory treatment. Therefore, we investigated the effect of systemic glucocorticoids on dynamic hyperinflation in moderate-to-severe asthma patients and explored the relationships between inflammatory markers and changes in dynamic hyperinflation. Methods In this randomised placebo-controlled trial we included 32 asthma patients on inhaled glucocorticoid therapy showing dynamic hyperinflation, defined by a ≥10% reduction in inspiratory capacity measured by standardised metronome-paced tachypnea test. Patients received either triamcinolone (80 mg) or placebo intramuscularly. Before and 2 weeks after treatment, patients completed respiratory health questionnaires, had blood eosinophils and exhaled nitric oxide levels measured, and underwent lung function and dynamic hyperinflation testing. Results After adjustment for potential confounders, dynamic hyperinflation was significantly reduced by 28.1% in the triamcinolone group and increased by 9.4% in the placebo group (p=0.027). In the triamcinolone-treated patients, the reduction in dynamic hyperinflation was greater in patients with higher blood eosinophils at baseline (r=−0.592, p=0.020) and tended to be associated with a reduction in blood eosinophils (r=0.412, p=0.127) and exhaled nitric oxide (r=0.442, p=0.099). Conclusions This exploratory study suggests that dynamic hyperinflation in asthma can be reduced by systemic anti-inflammatory treatment, particularly in patients with elevated blood eosinophils. This supports the hypothesis that dynamic hyperinflation in asthma is due to airway inflammation and should be considered an important target for treatment., Dynamic hyperinflation: a target for treatment in asthma, which can be reduced by systemic anti-inflammatory treatment https://bit.ly/3gfyxYv

Real-world evidence is important to help unravel unanswered problems in severe asthma and is valuable to better understand the patient experience and common clinical practice. The Severe Heterogeneous Asthma Registry, Patient-centred (SHARP) Clinical Research Collaboration is created as a network of national registries and severe asthma centres that work together to perform registry based real-world research and clinical studies on a pan-European scale. Such collaboration requires a new, innovative design to overcome the many issues that arise with large-scale data collection across national borders. SHARP has developed a platform that offers a federated analysis approach where national registry data are transformed and integrated into a common data model (CDM). The CDM then allows a local analysis of de-identified patient data and subsequent aggregate (meta-)analysis. To facilitate an easily accessible way to set up new registries, SHARP enables new registries to take part in a central database, based on already proven technology. Next to being economical, this linkage ensures data from different SHARP central members to be comparable. Technological advancements lead to an ever-expanding rate of patient data that will be collected; with the collective effort of the pan-European severe asthma research community SHARP hopes to ensure that they are well equipped to enter a new era of medical research, with the ultimate goal to positively impact the lives of patients with severe asthma., SHARP brings together national asthma registries in Europe and enables generation of real-world evidence on severe asthma by using a common data model that aligns data from existing registries and by facilitating the development of new asthma registries https://bit.ly/3a1E42D

IntroductionTreatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown.Materials and methodsThe European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies.ResultsAvailability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity.ConclusionOur study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation.

Rationale: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma targeting airway smooth muscle (ASM). Observational studies have shown ASM mass reduction after BT, but appropriate control groups are lacking. Furthermore, as treatment response is variable, identifying optimal candidates for BT treatment is important. Objectives: First, to assess the effect of BT on ASM mass, and second, to identify patient characteristics that correlate with BT response. Methods: Patients with severe asthma (n = 40) were randomized to immediate (n = 20) or delayed (n = 20) BT treatment. Before randomization, clinical, functional, blood, and airway biopsy data were collected. In the delayed control group, reassessment, including biopsies, was performed after 6 months of standard clinical care, followed by BT. In both groups, post-BT data including biopsies were obtained after 6 months. ASM mass (% positive desmin or a-smooth muscle actin area in the total biopsy) was calculated with automated digital analysis software. Associations between baseline characteristics and Asthma Control Questionnaire and Asthma Quality of Life Questionnaire (AQLQ) improvement were explored. Measurements and Main Results: Median ASM mass decreased by .50% in the immediate BT group (n = 17) versus no change in the delayed control group (n = 19) (P = 0.0004). In the immediate group, Asthma Control Questionnaire scores improved with 20.79 (interquartile range [IQR], 21.61 to 0.02) compared with 0.09 (IQR, 20.25 to 1.17) in the delayed group (P = 0.006). AQLQ scores improved with 0.83 (IQR, 20.15 to 1.69) versus 20.02 (IQR, 20.77 to 0.75) (P = 0.04). Treatment response in the total group (n = 35) was positively associated with serum IgE and eosinophils but not with baseline ASM mass. Conclusions: ASM mass significantly decreases after BT when compared with a randomized non–BT-treated control group. Treatment response was associated with serum IgE and eosinophil levels but not with ASM mass.

Background Mepolizumab (100 mg delivered s.c. every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. However, data on the durability of the response to mepolizumab during dosing periods are limited. The aim of this study was to investigate the efficacy profile in patients with severe eosinophilic asthma over the 4-weekly dosing period for various fixed mepolizumab doses. Methods This was a post hoc analysis of data from the phase IIb/III DREAM study. Patients ≥12 years of age with severe eosinophilic asthma were randomised (1:1:1:1) to receive intravenous mepolizumab 75 mg (equivalent to 100 mg s.c.), 250 mg, 750 mg or placebo, plus standard of care, every 4 weeks for 52 weeks. The number of exacerbations and eDiary data (peak expiratory flow, rescue medication use and symptom scores) from two periods in each 4-weekly dosing interval (days 1–14 and 15–28) over the 52-week treatment period were analysed. Findings eDiary data and the proportion of patients experiencing ≥1 exacerbation were similar during the first and second 2 weeks of a dosing period across all mepolizumab doses. Interpretation These results demonstrate that the response to mepolizumab is sustained over the 4-weekly dosing period with no differences across a 10-fold dose range and supports the use of the current mepolizumab dosing regimen in patients with severe eosinophilic asthma., Post hoc analysis of data from DREAM demonstrated a sustained response to mepolizumab across the 4-weekly dosing period, suggesting therapeutic benefit is maintained between each mepolizumab dose following long-term treatment https://bit.ly/3843lH6

Regional and/or national severe asthma registries provide valuable country-specific information. However, they are often limited in scope within the broader definitions of severe asthma, have insufficient statistical power to answer many research questions, lack intraoperability to share lessons learned, and have fundamental differences in data collected, making cross comparisons difficult. What is missing is a worldwide registry which brings all severe asthma data together in a cohesive way, under a single umbrella, based on standardized data collection protocols, permitting data to be shared seamlessly. The International Severe Asthma Registry (ISAR; http://isaregistries.org/) is the first global adult severe asthma registry. It is a joint initiative where national registries (both newly created and preexisting) retain ownership of their own data but open their borders and share data with ISAR for ethically approved research purposes. Its strength comes from collection of patient-level, anonymous, longitudinal, real-life, standardized, high-quality data (using a core set of variables) from countries across the world, combined with organizational structure, database experience, inclusivity/openness, and clinical, academic, and database expertise. This gives ISAR sufficient statistical power to answer important research questions, sufficient data standardization to compare across countries and regions, and the structure and expertise necessary to ensure its continuance and the scientific integrity and clinical applicability of its research. ISAR offers a unique opportunity to implement existing knowledge, generate new knowledge, and identify the unknown, therefore promoting new research. The aim of this commentary is to fully describe how ISAR may improve our understanding of severe asthma.

Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil-reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin-5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add-on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real-world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI-A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.

Background The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use. Methods COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary end-point: time to first clinically significant exacerbation; secondary end-points: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline) and blood eosinophil count ratio to COMET baseline. Safety was assessed. Results Patients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio 1.61, 95% CI 1.17–2.22; p=0.004) and decrease in asthma control (hazard ratio 1.52, 95% CI 1.13–2.02; p=0.005), and higher blood eosinophil counts at week 52 (270 versus 40 cells·µL−1; ratio (stopping versus continuing) 6.19, 95% CI 4.89–7.83; p, This randomised study demonstrates increased exacerbation risk and a decrease in asthma control in patients with severe eosinophilic asthma who stop mepolizumab treatment after long-term use, when compared with those who continue treatment. https://bit.ly/3fsxGV2

Although the pathophysiology of asthma is complex, perturbation of the gut microbiota has been associated with an increased risk of asthma development in childhood.1 Disruption and subsequent dysregulation of gut microbiota-related immunologic processes have also been linked to disease severity and response to treatment.2.

Introduction Breast cancer is the most common malignancy in women around the world. In the Cap Bon, the epidemiological features of breast cancer are unknown. We aim to identify the epidemiological, clinical, and histological characteristics of breast cancer in the Cap Bon. Methods A retrospective study of 130 patients diagnosed with breast cancer from January 2014 to December 2017 and treated in Mohamed Taher Maamouri Hospital of Nabeul, Tunisia. Results Five patients (3.8%) were male. The average age was 55.7 years. The young women (≤35 years) represented 4.6%. Stage T2 was predominantly observed (48.8%). The tumors were classified as N1 in 54.2% of cases. Four patients (3%) had Metastasis. The infiltrating ductal carcinoma was the most common histological type (80%). The average histological size was 27.7 mm. The most common molecular subtype was Luminal B (48%). The nodes were positive in 57.4% of cases. All the patients had breast surgery. It was conservative in 40% of cases. Radiotherapy was performed in 87.3% of cases. The chemotherapy was administrated to 73.8% of patients. The trastuzumab was administered to 76.4% of the patients. Hormonotherapy was administered to 90.3% of patients. Overall survival and progression-free survival at 3 years were 90% and 73.2% respectively. Prognostic factors were the N stage and the lymph node involvement. Conclusion The epidemiological characteristics of breast cancer in the Cap Bon present a number of similarities to the other regions of the country. However, it differs from the high frequency of pejorative histoprognostic factors.

Background: Patients with severe eosinophilic asthma may respond differently to various anti-IL-5 biologics. Many patients experience residual disease manifestations, causing physicians to switch between these biologics. Insight into these residual disease manifestations could increase our understanding of mechanisms of severe asthma and reveal unmet therapeutic needs in these patients. Aim: We aimed to: (1) assess the frequency and reasons for switching between anti-IL-5 biologics, and; (2) evaluate whether residual disease manifestations still exist after 2 years anti-IL-5 treatment in patients with severe eosinophilic asthma. Methods: In this real world cohort study, severe asthma patients were included who had been treated with an anti-IL-5 biologic (mepolizumab, reslizumab, benralizumab) ≥2yr (n=95). Data on disease manifestations (asthma control, exacerbations, FEV1, blood eosinophils, exhaled NO, symptoms of sinonasal disease, atopy and adrenal insufficiency) and medication history, were collected at baseline and after 2 years of anti-IL-5 treatment. Results: Switches between anti-IL-5 biologics occurred in 41% of patients, mainly because of insufficient clinical response. After 2 years anti-IL-5 treatment 79 patients (83%) experienced residual disease manifestations: uncontrolled sinonasal symptoms (49%), impaired lung function (48%) and uncontrolled asthma (41%). 26% were still OCS dependent (8% adrenal insufficient). Conclusion: Despite significant clinical improvements, the majority of severe eosinophilic asthma patients showed residual disease manifestations after 2 years anti-IL-5 treatment. This suggests that non-IL-5 driven inflammatory pathways may be activated.

Background: Blood eosinophil count (bEOS) is an important biomarker in obstructive lung disease. NOVELTY (NCT02760329) is a global, prospective, observational study with potential to identify obstructive lung disease phenotypes associated with differential outcomes, using biomarkers and clinical features. Objective: To evaluate factors associated with bEOS in patients with either physician-assigned asthma or COPD in NOVELTY. Methods: A cross-sectional analysis of associations between a single bEOS measurement and other baseline characteristics was performed using univariate and multivariate regression models. Results: Of 4,538 patients with data, the geometric mean (SE) bEOS was 0.16 (0.002) x109/L. Of these, 864 (19%) had EOS ≥300 cells/µL (23% asthma; 14% COPD). High bEOS was positively associated with male sex, ≥2 symptom worsenings in prior 3 months, FeNO, FEV1 reversibility, obesity and frequent mucoid cough, in both asthma and COPD (Figure). For asthma, positive associations with higher bEOS were observed for reduced lung function and physician-assessed severity; for COPD, positive associations were observed with current/former smokers. Associations with FeNO and frequent mucoid cough persisted in multivariate models for both diagnoses. Conclusions: Higher bEOS was independently associated with higher FeNO and presence of frequent mucoid cough regardless of physician-assigned asthma or COPD.

Background: The long-term efficacy and safety of mepolizumab in severe eosinophilic asthma (SEA) have been shown. Aims: To assess the impact of stopping versus continuing long-term mepolizumab on asthma worsening. Methods: COMET (NCT02555371) was a randomised, double-blind, placebo-controlled study. Patients had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692), had continuous mepolizumab for ≥3 years (mean 46.6 months), and stayed on asthma controller therapy. Randomisation was 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg for 52 weeks. Composite endpoint: time to first asthma worsening (defined in Table). Daily eDiary data were analysed using Kaplan–Meier estimates and a Cox proportional hazards model adjusted for covariates. Results: Treatment differences for those who stopped versus continued mepolizumab emerged by Week 4 (8 weeks post last open-label mepolizumab dose). For those who stopped mepolizumab, 51.7% reported asthma worsening by Week 52 versus 35.0% who continued mepolizumab (Table), leading to a significantly shorter time to first asthma worsening in those who stopped mepolizumab. Conclusion: Stopping mepolizumab in patients with SEA led to an increased risk of asthma worsening with a significantly shorter time to first asthma worsening versus those continuing long-term mepolizumab. Funding: GSK [201810/NCT02555371].

Background: Determinates of how physicians assign severity in asthma or COPD are poorly understood. The NOVEL observational longiTudinal studY NOVELTY (NCT02760329) is a global, prospective, 3-year observational study of patients with a physician-assigned diagnosis or suspected diagnosis of asthma, asthma+COPD or COPD. Objective: To identify factors associated with physician-assigned severity of either asthma or COPD in the NOVELTY population. Methods: Ordinal regression analysis was used to identify factors associated with higher physician-assigned severity (severe vs mild or moderate; moderate vs mild) at baseline in patients with asthma (n=4,361) or COPD (n=2,931). Results: Factors associated with higher levels of physician-assigned severity are shown in the figure. Clinical features including exacerbation history in the past year, lower post-bronchodilator FEV1 % predicted, or FEV1/FVC ratio, reversibility and higher mMRC dyspnoea score were associated with greater severity for both diagnoses. Presence of allergic or non-allergic rhinitis or nasal polyps were notable factors in asthma, as was emphysema in COPD. Conclusions: Greater physician-assigned severity was associated with worse respiratory symptoms, lower lung function and exacerbation history in patients with asthma or COPD in NOVELTY; associations between greater severity and some diagnosis-related features and comorbidities varied between asthma and COPD.

Background In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. Objective We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. Methods We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. Results Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). Conclusion FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.

Asthma is managed using “step-wise” adjustment of corticosteroid therapy to achieve asthma control. When corticosteroid treatment is adjusted using sputum eosinophil count or exhaled nitric oxide fraction, exacerbations are reduced [1, 2]; however, implementation in clinical care has been slow. In parallel, airway transcriptomic analysis has demonstrated that type 2 eosinophilic inflammation is absent in many patients with minimal response to corticosteroid treatment [3–5]. The UK Refractory Asthma Stratification Programme (RASP-UK) (http://rasp.org.uk/) is exploring non-sputum biomarker-based strategies to target corticosteroid treatment in severe asthma [6, 7], and sought to determine clinician and patient views on clinically relevant reductions in corticosteroid treatment., UK asthma physicians are supportive of biomarker-based steroid adjustment, but European physicians need more evidence http://ow.ly/sTrf30my3jw

ZnO and SnO2 thin films were deposited on glass and Polyetherimide (PEI) flexible substrates by spray pyrolysis deposition at low temperature (250 °C). The structural characterization by X-ray diffraction (XRD) reveals that PEI promotes the crystallization of ZnO and SnO2 thin films while the films deposited on glass substrate are amorphous. The physical investigations show that ZnO/PEI and SnO2/PEI have a good crystalline quality and high transparency in visible range (T>80%). Their gap energies are calculated from absorbance data (3.3 eV for ZnO and 3.72 eV for SnO2). Furthermore, the surface properties are investigated by atomic force microscopy and contact angle measurements. It is found that the ZnO/PEI film has a higher surface roughness (RMS = 20.20 nm ± 0.62 nm) compared to SnO2/PEI (RMS = 5.41 nm ± 0.16 nm). The metal oxides (ZnO and SnO2) catalysts exhibit excellent photodegradation activities under UV irradiation up to 80%. The highest activity was observed for ZnO thin films because it exhibits smaller gap energy. Furthermore, both samples show excellent photocatalytic stability.

Introduction: The complexity and heterogeneous nature of asthma and chronic obstructive pulmonary disease (COPD) results in difficulties in diagnosing and treating patients. Biomarkers that can identify underlying mechanisms, identify patient phenotypes and to predict treatment response could be of great value for adequate treatment. Areas covered: Biomarkers play an important role for the development of novel targeted therapies in airways disease. Blood biomarkers are relatively non-invasive, easy to obtain and easy to apply in routine care. Several blood biomarkers are being used to diagnose and monitor chronic airways diseases, as well as to predict response to treatment and long-term prognosis. Blood eosinophils are the best studied biomarker, the most applied in clinical practice, and until now the most promising of all blood biomarkers. Other blood biomarkers, including serum periostin, IgE and ECP and plasma fibrinogen are less studied and less relevant in clinical practice. Recent developments include the use of antibody assays of many different cytokines at the same time, and ‘omics’ techniques and systems medicine. Expert commentary: With the exception of blood eosinophils, the use of blood biomarkers in asthma and COPD has been rather disappointing. Future research using new technologies like big-data analysis of blood samples from real-life patient cohorts will probably gain better insight into underlying mechanisms of different disease phenotypes. Identification of specific molecular pathways and associated biomarkers will then allow the development of new targets for precision medicine.

Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait. These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant and timapiprant). Although these novel biologic agents have shown promising results in many patients with asthma and COPD who have eosinophilic airway inflammation, it is evident that not all patients respond equally well, despite similar clinical, functional, and inflammatory characteristics. This heterogeneity in treatment response is probably related to different molecular pathways or endotypes leading to eosinophilic airway inflammation, including adaptive immune pathways mediated by T helper 2 cells and innate immune pathways mediated by innate lymphoid cells. The relative contribution of these pathways in asthma and COPD is not yet clarified, and there are currently no reliable biomarkers that represent the various pathways. Therefore, there is an urgent need for easily measurable and reproducible biomarkers that are linked to underlying pathophysiologic disease mechanisms and can predict and monitor responses to novel biologic agents.

A successful deposition of undoped and Fluorine doped tin oxide (TO and FTO) nano films at relatively low temperature 250 °C on flexible substrate (Polyethyerimide) was obtained using the spray pyrolysis technique. The Fluorine doping effects on the structural, morphological and optical properties were investigated. XRD measurements permit textural characterization, and show that the films have a tetragonal polycrystalline structure. The increase of crystalline size and reduction of defects and strain with Fluorine doping improve the crystalline quality. This is may be due to the substitution of O −2 by F - . Furthermore, the structural changes of the films affected the surface roughness which became rough with the Fluorine. This was confirmed by wettability measurements. Moreover, the gap energy exhibits a slight red-shift with F-doping. The photoluminescence spectra showed that Fluorine doping increased the radiative centers, which is confirmed by structural results. The photocatalytic performance of TO and FTO nanofilms were investigated by degradation of crystal violet dye under UV radiations. Results showed that TO and FTO exhibit high photocatalytic activities, which can be enhanced by H 2 O 2 addition.

Background: Asthma patients using high doses of oral corticosteroids are exposed to serious adverse effects. It is therefore important to know the prevalence and characteristics of these patients, as this may help physicians to find appropriate measures and therapies to reduce the use of these harmful drugs. Aim: We assessed the prevalence of asthma patients using high-dose oral corticosteroids, to investigate whether this use was justified, and to estimate the proportion of patients eligible for steroid-sparing biologics. Methods: A pharmacy database containing data from 500,500 Dutch inhabitants was used to select patients using high dose inhaled corticosteroids (≥500 mcg/day) plus longacting β-agonists (GINA 4-5). 5002 of these patients were sent questionnaires, 2312 were returned and analyzed. In patients in whom asthma diagnosis was confirmed oral corticosteroid use was calculated, and adherence to treatment and inhaler technique were assessed. The proportions of cases from this analysis were applied to the Dutch population. Results: 29% of asthma patients using high-dose inhaled corticosteroids were exposed to harmful doses of oral corticosteroids (≥420 mg/yr). 78% of these patients showed either poor adherence to treatment or incorrect inhalation technique. The remaining patients could be candidates for biologics, but currently, in the Netherlands, only 46% are receiving these drugs. Conclusion: One third of GINA 4-5 patients use harmful doses of oral corticosteroids. In the majority a potential cause for overuse can be identified, and only a small proportion is receiving steroid-sparing biologics. Taking this into account, oral corticosteroid overuse could be substantially reduced.

Insight into the criteria that physicians use to classify asthma and COPD severity is crucial to understand treatment decision-making, identify distinct patient phenotypes and drive personalised care. The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, study of >11,000 adult patients with physician-assigned asthma and/or COPD, stratified by physician-assigned severity, from primary and specialist care. NOVELTY aims to enhance our understanding of obstructive lung disease, including current treatment patterns and disease burden. Here we describe the baseline characteristics of the patients included in NOVELTY by physician-assigned disease severity. By March 2018, 11,308 patients from 19 countries were enrolled (11,289 included in baseline analysis; 47% from primary care and 74% Caucasian); recruitment in China is ongoing. Across all diagnoses, spirometry results and patient-reported outcomes were worse and exacerbations rates higher [Table 1] with increasing disease severity. From preliminary unadjusted data, blood neutrophil counts increased with severity across diagnoses. Physician-assigned severity was associated with more patient-reported symptoms, lower lung function, more exacerbations and higher blood neutrophil counts. Future analyses will explore which features are the strongest determinants of physician-assigned severity, and any variations by diagnosis.

Objective: A liquid mepolizumab formulation in a single-use prefilled syringe (PFS) is under development. We evaluated the usability of mepolizumab self-injected via PFS by patients with severe eosinophilic asthma (SEA), or their caregivers, in clinic and at home. Methods: This open-label, single-arm, Phase IIIa study included patients with SEA, aged ≥12 years, and receiving mepolizumab (100 mg subcutaneously) every 4 weeks for ≥12 weeks prior to screening. Patients with SEA not receiving mepolizumab at screening who met additional criteria were also included. Patients/caregivers self-administered mepolizumab (100 mg subcutaneously) via PFS every 4 weeks for 12 weeks. The first (Week 0) and third (Week 8) dose were observed in clinic; the second dose (Week 4) was unobserved at home. Primary and secondary endpoints were the proportion of patients who successfully self-administered their third and second doses, respectively. Injection success was determined by investigator/site staff. Patient experience, mepolizumab trough concentrations, blood eosinophil counts, and safety were also assessed. Results: Of the 56 patients/caregivers who self-administered ≥1 dose of mepolizumab, 55 completed the study. All patients were reported to have successfully self-administered their third mepolizumab dose in clinic (N = 55, 100%); this was further evidenced by trough concentrations/blood eosinophil counts. Most patients/caregivers found the PFS easy and convenient to use with 75% (n = 42) expressing little/no anxiety about using the device at home. Incidence of on-treatment drug-related adverse events was low (4%); none were fatal. Conclusions: Patients/caregivers successfully self-administered mepolizumab via the PFS both in clinic and at home, with no new safety concerns identified.

Purpose The goal of this study was to assess the long-term safety and efficacy of mepolizumab in patients with the most severe eosinophilic asthma. Methods This multicenter, open-label, long-term, Phase IIIb study (COSMEX [COSMOS Extension]; 201312/NCT02135692) enrolled patients from the 52-week, open-label extension study COSMOS (A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects) that previously enrolled patients from the double-blinded, placebo-controlled Phase III studies MENSA (Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma) and SIRIUS (Steroid Reduction with Mepolizumab Study). To enter COSMEX, patients had to have life-threatening/seriously debilitating asthma before entering MENSA or SIRIUS and to have completed these previous studies with demonstrated improvement while receiving mepolizumab. In COSMEX, patients received mepolizumab 100 mg subcutaneously every 4 weeks as add-on therapy for up to 172 weeks. Primary endpoints were adverse event frequency and exacerbation rate per year; also assessed were forced expiratory volume in 1 s, Asthma Control Questionnaire-5 score, and daily oral corticosteroid (OCS) use. Findings Of the 340 patients enrolled, 339 received mepolizumab; median treatment duration within this extension study was 2.2 years, equating to 718 patient-years of additional exposure. No new safety signals were identified. Patients receiving mepolizumab throughout this study and previous studies had lasting reductions in exacerbation rate and daily OCS use and improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire-5 score. In COSMEX, the on-treatment exacerbation rate (95% CI) was 0.93 (0.81–1.06) event/year for clinically significant exacerbations, 0.13 (0.10–0.18) event/year for exacerbations requiring hospitalization/emergency department visit, and 0.07 (0.05–0.10) event/year for exacerbations requiring hospitalization. In patients requiring systemic/oral corticosteroids with ≥128 weeks of continuous enrollment across SIRIUS, COSMOS, and COSMEX, mepolizumab maintained the median daily OCS dose at 1.3–2.8 mg during COSMEX, with additional patients no longer requiring OCS after extended mepolizumab treatment. Implications This study indicates that long-term mepolizumab treatment is well tolerated and associated with sustained clinical benefits in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT02135692.

BackgroundThe long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.MethodsCOMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary end-point: time to first clinically significant exacerbation; secondary end-points: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline) and blood eosinophil count ratio to COMET baseline. Safety was assessed.ResultsPatients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio 1.61, 95% CI 1.17–2.22; p=0.004) and decrease in asthma control (hazard ratio 1.52, 95% CI 1.13–2.02; p=0.005), and higher blood eosinophil counts at week 52 (270 versus 40 cells·µL−1; ratio (stopping versus continuing) 6.19, 95% CI 4.89–7.83; pConclusionPatients who stopped mepolizumab had an increase in exacerbations and reduced asthma control versus those who continued.