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Inhaled corticosteroids (ICS) suppress eosinophilic airway inflammation in asthma, but patients may not adhere to prescribed use. Mean adherence—averaging total doses taken over prescribed—fails to capture many aspects of adherence. Patients with difficult-to-treat asthma underwent electronic monitoring of ICS, with data collected over 50 days. These were used to calculate entropy (H) a measure of irregular inhaler use over this period, defined in terms of transitional probabilities between different levels of adherence, further partitioned into increasing (Hinc) or decreasing (Hdec) adherence. Mean adherence, time between actuations (Gapmax), and cumulative time- and dose-based variability (area-under-the-curve) were measured. Associations between adherence metrics and 6-month asthma status and attacks were assessed. Only H and Hdec were associated with poor baseline status and 6-month outcomes: H and Hdec correlated negatively with baseline quality of life (H:Spearman rS = − 0·330, p = 0·019, Hdec:rS = − 0·385, p = 0·006) and symptom control (H:rS = − 0·288, p = 0·041, Hdec: rS = − 0·351, p = 0·012). H was associated with subsequent asthma attacks requiring hospitalisation (Wilcoxon Z-statistic = − 2.34, p = 0·019), and Hdec with subsequent asthma attacks of other severities. Significant associations were maintained in multivariable analyses, except when adjusted for blood eosinophils. Entropy analysis may provide insight into adherence behavior, and guide assessment and improvement of adherence in uncontrolled asthma.

SUMMARY OBJECTIVE: A small portion of the asthmatic population (3.6%) has severe asthma (SA), presenting high morbimortality rates and demanding more financial resources than other asthmatic populations. The use of immunobiological therapy is an effective tool in controlling symptoms, decreasing the number of exacerbations, and reducing the use of systemic corticosteroids in these patients. In Brazil, epidemiological data regarding this asthmatic population using immunobiologicals and their evolution are scarce. METHODS: This is an observational, analytical, cross-sectional, and retrospective study. The sample consisted of adult patients with SA in follow-up at the pulmonology service of the Complexo Hospital de Clínicas of the Federal University of Paraná, from January 2011 to August 2019. The analyzed variables were as follows: the number of exacerbations that required hospitalization in the previous year, forced expiratory volume in one second (FEV1), and asthma control test (ACT) scores before and after the start of immunobiological therapy. RESULTS: We studied 20 patients with SA using omalizumab or mepolizumab. We observed an increase in the mean ACT score of 4.8 points, a nonsignificant reduction in the number of exacerbations that required hospitalization, and a slight improvement in the FEV1. Regarding the patients using chronic systemic corticosteroid therapy, 14.2% (n=1) of patients had the medication discontinued and 57% (n=4) of patients had the dose reduced by half. CONCLUSION: The use of omalizumab and mepolizumab as additional therapy in SA provided a significant improvement in the ACT and allowed the dose reduction of systemic corticosteroids, without significant improvement in FEV1 and in the frequency of severe exacerbations.

Objectives Implementation of guidelines into clinical practice is challenging and complex. This study aims to (1) identify the training needs and capacity requirements, and (2) explore the impact on healthcare utilisation and asthma-related quality of life of implementing both spirometry and fraction of exhaled nitric oxide in diagnosis of asthma among children in the UK primary care. Methods Ten UK general practitioner practices and a total of 612 children (5–16 years) with diagnosed or suspected asthma were invited to participate in this prospective observational study. The total times that the trainer and trainee clinical staff spent on developing the training package, providing and receiving, and performing and interpreting the two tests as part of routine child asthma review were collected, and costs were calculated. We compared healthcare utilisation and asthma-related and general health-related quality of life data between the 6 months before and after the asthma review guided by objective tests. Results The average training cost for the 27 primary care clinical members was £1395. The average cost to implement and deliver the test-guided asthma review among the 612 included children was £22. In the 6 months following the tests-guided asthma review, both unplanned primary care attendance, and hospital admissions were reduced, and the asthma-related health status increased significantly. Conclusion This study provides robust cost estimates of the resources needed to implement the National Institute for Health and Care Excellence asthma guideline. It also demonstrates the potential to save healthcare costs and improve health status among asthmatic children by implementing this guideline., Is FeNO testing in primary care cost effective? Yesℏ The average training cost for the 27 primary care clinical members was £1,395. The average cost to implement and deliver the tests-guided asthma review among the 612 included children was £22.

OBJECTIVE New self-management interventions are being developed for older adults who suffer from worse asthma morbidity than their younger counterparts, but high rates of study drop out have hampered these efforts and there is limited literature on what factors may influence retention in behavioral intervention studies with older adults. This study analyzed illness beliefs and patient characteristics that may contribute to retention in an asthma self-management trial for older adults. METHODS This is a secondary analysis of data from a randomized controlled trial of a self-management support intervention for adults 60 years and older with persistent, uncontrolled asthma. Multivariable logistic regression was used to evaluate the association of medication and illness beliefs, and other subject characteristics with study retention, which was defined as completion of the research study interview at 6 and 12 months. RESULTS The randomized trial enrolled 388 individuals; 261 (67.3%) completed the 12-month interview. Higher perceived threat of chronic diseases relative to asthma was associated with higher study retention (OR = 1.11, 95% CI = 1.00-1.24) at 12 months. Other variables including asthma beliefs, age, cognitive function, health literacy, and asthma symptoms were not significantly associated with retention. CONCLUSIONS Concern about non-asthma chronic conditions, but no other illness beliefs, or patient characteristics, were associated with retention in an asthma self-management support intervention. Further research, including qualitative studies, is needed to better understand why patients drop out of asthma behavioral intervention studies.

Asthma is a heterogeneous lung disease characterized by chronic airway inflammation. It was suggested that patients with mild asthma symptoms could be managed with as-needed short-acting β2-agonists (SABA) in previous years. In 2019, GINA made a radical change and recommended that SABA should not be used as monotherapy in patients with mild asthma, but instead as-needed low-dose inhaled corticosteroid (ICS)-formoterol or "additional low-dose ICS taken whenever SABA is taken" treatments should be commenced to relieve and control symptoms. The approach emerged in the light of the studies that indicate the increased risk of severe exacerbation and asthma-related death due to overuse of SABA. The present article aimed to enlighten the updates in GINA 2019 step 1 and 2 treatment, the grounds for these updates with the supportive studies.

Background and objective Circulating fibrocytes act as precursors of myofibroblasts, contribute to airway remodelling in chronic asthma and migrate to injured tissues by expressing CXCR4 and CCR7. Anti-IgE therapy improves severe allergic asthma (SAA) control and airway remodelling in T2-high SAA. The effects of anti-IgE therapy on fibrocyte activities were investigated in this study. Methods The expression of CCR7, CXCR4, ST2 and α-SMA (α-smooth muscle actin) in both circulating and cultured fibrocytes from all patients with asthma was measured, and was repeated after omalizumab treatment in SAA. Fibrocytes recruitment, proliferation and transformation were also measured in response to anti-IgE therapy. Results Omalizumab effectively improved asthma control and pulmonary function in T2-high SAA, associated with a decline in serum levels of IL-33 and IL-13. Omalizumab down-regulates CXCR4 and CCR7 expression of fibrocytes, which could suppress fibrocyte recruitment into the lungs. Omalizumab also suppressed the increased number of fibrocytes and α-SMA+ fibrocytes within the cultured non-adherent non-T (NANT) cells after 3-7 days of culture. The decrease in serum levels of IL-33 by omalizumab contributed to the effectiveness in inhibiting fibrocyte recruitment, proliferation and myofibroblast transformation through IL-33/ST2 axis. The elevated IL-13 expression in SAA patients potentiated the effects of IL-33 by increasing ST2 expression. Conclusion Omalizumab reduced the number of circulating fibrocytes, cell and number of fibrocytes as well as α-SMA+ fibrocytes after 3-7 days of culture in SAA patients. IL-33 and IL-13 may be implicated in the effectiveness of omalizumab in inhibiting fibrocyte activation contributing partly to the clinical benefits in reducing lamina propria and basement membrane thickening.

BACKGROUND Clinically meaningful improvement in the Sino-Nasal Outcome Test-22 (SNOT-22) was observed in patients with severe, eosinophilic asthma, and nasal polyposis (NP) treated with benralizumab in the ANDHI trial. A post hoc assessment of the effects of benralizumab on SNOT-22 response and asthma efficacy measures in these patients was conducted for further characterization of the efficacy and safety of benralizumab for patients with severe asthma and NP. METHODS Adults with severe, eosinophilic asthma who had experienced ≥2 prior-year exacerbations despite high-dosage inhaled corticosteroid plus additional controller[s] were randomized to 24 weeks of benralizumab or placebo. Patients with physician-diagnosed chronic rhinosinusitis with NP of any severity ongoing at baseline who consented to participate were included in the current ANDHI NP substudy population. Effect on NP symptoms was assessed by the SNOT-22, with an improvement of at least 8.9 defined as clinically significant (responder). Effects on chronic asthma outcomes were assessed by means of annualized asthma exacerbation rate (AER), St. George's Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in one second (FEV1 ), and Asthma Control Questionnaire-6 (ACQ-6). All p-values were nominal. RESULTS Of the ANDHI population (n = 656), 23% (n = 153) participated in the NP substudy (n = 96 benralizumab; n = 57 placebo). Patients were 50% female, with mean age of 53 years, had prior-year AER = 3.3; mean pre-bronchodilator FEV1 = 55% predicted; and median blood eosinophil count ​= 510 cells/µl. For patients with high baseline SNOT-22 scores (>30), benralizumab treatment improved symptoms of NP as measured by SNOT-22 from baseline to Week 24 compared with placebo (Week 24: -10.44 [p = .0176]). Percentage of responders to SNOT-22 was greater for benralizumab vs. placebo (71.3% vs. 45.5%; p = .0036), and effect was enhanced for patients with high baseline SNOT-22 scores (>30). A 69% reduction vs. placebo in annualized AER (0.77 vs. 2.47; p

Background Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p 2(2) = 14.53, p 10 eosinophils/HPF, τb = −8.47, p b = −2.37, p = 0.02). Conclusion Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.

Montelukast, a leukotriene receptor antagonist (LTRA) has been approved for use in Europe since 1998. Indications for use (from the age of 6 months) include mild to moderate asthma, seasonal allergic rhinitis with asthma, and the prevention of exercise-induced asthma episodes. The psychiatric side effects of montelukast have been known for the last 10 years; in the case of such symptoms benefits and risks should be considered. Due to potential life-threatening psychiatric adverse events, particularly suicide, a black box warning was issued. In this statement the Austrian working group of pediatric pulmonology and allergology advises that treatment with montelukast should be started only after critical evaluation. Treatment should be stopped on the occurrence of any neuropsychiatric side effects.

Background: Bronchial asthma (BA) is a chronic airway inflammatory disease with reversible airflow limitation as the main clinical manifestations, such as wheezing, cough, shortness of breath, chest tightness, etc., mediated by a variety of inflammatory cells, which can be recurrent. Clinical can improve symptoms, but can not be cured, glucocorticoid is the most important first-line medication. Clinical practice has shown that montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma can improve clinical efficacy and reduce adverse reactions. The purpose of this study is to systematically study the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma. Methods: The Chinese databases (CNKI, VIP, Wanfang, Chinese Biomedical Database) and English databases (PubMed, the Cochrane Library, Embase, Web of Science) were searched by computer, for the randomized controlled clinical studies of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma from establishment of database to October 2020. Two researchers independently extracted the relevant data and evaluated the quality of the literatures, and used RevMan5.3 software to conduct meta-analyze of the included literatures. Results: This study assessed the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma through total effective rate, pulmonary function (FEV1, FVC, PEF, FEV1/FVC), and adverse reactions. Conclusion: this study will provide reliable evidence-based evidence for the clinical application of montelukast sodium combined with fluticasone in the treatment of adult bronchial asthma.

Background: Suboptimal adherence to maintenance medication has been associated with poor outcomes in asthma. This study examined single-inhaler inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) adherence and asthma-related outcomes. Methods: This retrospective observational study of patients with asthma initiating ICS/LABA used data from IQVIA PharMetrics Plus (1 January 2014–31 March 2019). Patients included were ⩾18 years old and had ⩾12 months continuous eligibility before, and ⩾180 days follow-up after, the index date. Adherence was measured as proportion of days covered ([PDC] adherent ⩾ 0.8; non-adherent Results: Overall, 50,037 patients were included (mean age 45.3 years; mean follow-up 23.3 months). Adherent patients were less likely to experience asthma-related overall (adjusted odds ratio [aOR] 95% confidence interval [CI]: 0.942 [0.890, 0.998]; p = 0.041), or severe exacerbations (aOR [95% CI]: 0.778 [0.691, 0.877]; p Conclusion: This real-world study highlights the short-term clinical and economic benefits of ICS/LABA adherence in asthma, particularly in reducing severe exacerbations.

International audience; Metastases are the main cause of death in cancer patients, and platelets are largely known for their contribution in cancer progression. However, targeting platelets is highly challenging given their paramount function in hemostasis. Using a high-throughput screening and platelet-induced breast tumor cell survival (PITCS) assay as endpoint, we identified the widely used anti-asthmatic drugs and cysteinyl leukotriene receptor 1 (CysLT1R) antagonists, zafirlukast and montelukast, as new specific blockers of platelet protumoral action. Here, we show that human MDA-B02 breast cancer cells produce CysLT through mechanisms involving microsomal glutathione-S-transferase 1/2/3 (MGST1/2/3) and that can modulate cancer cell–platelet interactions via platelet–CysLT1R. CysLT1R blockade with zafirlukast decreased platelet aggregation and adhesion on cancer cells and inhibited PITCS, migration, and invasion in vitro. Zafirlukast significantly reduced, by 90%, MDA-B02 cell dissemination to bone in nude mice and reduced by 88% 4T1 spontaneous lung metastasis formation without affecting primary tumor growth. Combined treatment of zafirlukast plus paclitaxel totally inhibited metastasis of 4T1 cells to the lungs. Altogether, our results reveal a novel pathway mediating the crosstalk between cancer cells and platelets and indicate that platelet CysLT1R represents a novel therapeutic target to prevent metastasis without affecting hemostasis.

Interleukin 5 (IL-5) is a major cytokine responsible for eosinophil proliferation, migration and degranulation. Eosinophils play a considerable role in the manifestation of type 2 asthma, and therefore this makes IL-5 a unique and clinically important target for therapeutic intervention. Due to the critical role that IL-5 plays in all areas of eosinophil activity, it has been identified and targeted by three therapeutics, Mepolizumab, Benralizumab and Reslizumab. This review describes the IL-5 pathway and presents the clinical trial history of the three IL-5 inhibitors, to provide insight into the role of IL-5 in clinical asthma presentation. Additionally, this review aims to foster further investigation into the IL-5 pathway by describing current novel therapeutic discovery strategies with monoclonal antibodies.

Oral corticosteroids (OCS) have long been a mainstay of treatment for asthma exacerbations and chronic severe asthma. However, it is increasingly recognized that both long-term and short-term OCS use are directly associated with a wide range of serious adverse effects, and as such OCS-sparing treatment alternatives are now widely recommended for patients with severe asthma. While several international guidelines recommend these treatments, guidance on OCS tapering, and which patients are most likely to tolerate OCS reduction and/or discontinuation, is still lacking. Several biologics have demonstrated efficacy in patients with OCS-dependent asthma. One OCS-sparing treatment is the anti-interleukin-5 monoclonal antibody mepolizumab, which is approved for the treatment of severe eosinophilic asthma. In addition to improved exacerbation rates, asthma control, quality of life, and lung function among patients with severe eosinophilic asthma, mepolizumab also has an OCS-sparing effect, which has been demonstrated in randomized controlled trials and real-world studies. Both physicians and patients express concerns about the adverse effects of OCS, and additional data from the randomized, controlled SIRIUS trial (NCT01691508) highlight the high level of concern among patients regarding OCS-related burden. In this article, we discuss current guidance on OCS-sparing strategies for patients with severe asthma, provide a summary of the available evidence of the OCS-sparing effect of mepolizumab, and highlight patient and physician perspectives on the use of OCS and OCS-sparing treatments in severe asthma.

Asthma remains a substantial health burden, despite continued treatment advances. Patients with mild or moderate asthma, even those with intermittent symptoms, are at risk for severe or fatal exacerbations. Use of short-acting beta2-agonist (SABA)-only rescue therapy is associated with an increased risk of exacerbations, beginning at about the second fill annually. Systemic corticosteroids have shortterm and long-term adverse effects, and long-term adverse effects are driven by cumulative lifetime doses starting at 0.5 to 1.0 g. Expert opinion on the use of SABA only for rescue therapy differs, but recent evidence suggests that a fast-acting bronchodilator combined with inhaled corticosteroids (ICS) is more effective at reducing the risk of exacerbations than SABA alone. There is a window of opportunity just prior to an asthma exacerbation during which use of fast-acting bronchodilator + ICS may play a significant role in mitigating the risk of exacerbation. Patients may respond better to a combination inhaler of a fast-acting bronchodilator and an ICS as needed for rescue therapy or as part of a maintenance and rescue therapy paradigm, rather than attempting to use separate inhalers. However, there is currently no fixed-dose, fast-acting bronchodilator + ICS approved in the United States for as-needed use.

Eosinophil-targeted therapy with mepolizumab for severe eosinophilic asthma has significantly improved asthma control and patient quality of life though administration in children had been restricted to health-care provider reconstitution of a lyophilized powder into a solution with in-clinic administration until recently. Here, we profile the newly FDA-approved use of mepolizumab as a prefilled syringe for the treatment of severe eosinophilic asthma in children aged 6-11 years old, allowing for home administration.A literature search was conducted on PubMed using keywords such as mepolizumab, severe asthma, eosinophils, IL-5, anti-IL-5, children, pediatric, prefilled syringe, and home administration in several combinations. Published literature through July 2022 including clinical trials and prescribing information for mepolizumab for severe eosinophilic asthma, particularly for use in children and as administration as a prefilled syringe, is reviewed.Asthma affects a significant number of children worldwide, and having efficacious, tolerable, targeted precision therapies for this population is crucial. Mepolizumab remains the only targeted anti-IL-5 therapy approved for pediatric asthma down to 6 years of age. The innovation of the prefilled syringe will enable home administration, which would decrease the burden of treatment, and could potentially increase adoption of therapy.

Of the patients with asthma, 20% to 25% progress to severe symptoms, resulting in poor quality of life and increased episodes of exacerbation. There is a broad range of drugs used for asthma; the most used medications for severe asthma are inhaled glucocorticoids with or without long-acting β-agonists. Systemic glucocorticoids and other treatments as add-on therapies are also given as needed. Chronic glucocorticoid use is associated with numerous adverse effects, including diabetes mellitus, osteoporosis, anxiety, depression, and cataracts. The occurrence of these side effects has been reduced because of the emergence of new biological therapies. One such treatment is dupilumab, which helps in the reduction of type 2 inflammation involved in the pathophysiology of asthma. We conducted a literature review to assess the efficacy, adverse effects, and pharmacological benefits of dupilumab in glucocorticoid-dependent asthma. In most randomized controlled trials, dupilumab has shown significant efficacy and safety profile in patients with severe asthma with corticosteroid dependence. Associated adverse effects such as injection site reaction and transient eosinophilia have been reported. Our review of the literature indicates that dupilumab has proven to improve lung function, reduce the rate of asthma exacerbations, and reduce the use of corticosteroids.

Background Inhalation corticosteroids (ICS) are prescribed for treatment of asthma in approximately 3% of all children in Denmark. Despite limited evidence, case reports suggest that ICS-related behavioural adverse drug events (ADEs) may be frequent. In general, underreporting of ADEs to official databases is common, and little is known about doctor’s clinical experiences with behavioural ADEs when prescribing ICS for children with asthma. The objective was to investigate the extent of behavioural ADEs in children with asthma treated with ICS by comparing database findings to experiences of specialist doctors. Methods First, databases of the European Medicines Agency (EMA) and the Danish Medicines Agency (DKMA) were searched for reports made by healthcare professionals about behavioural ADEs in children from 2009 to 2018. Second, questionnaire data on behavioural ADEs were collected from eight of the 11 specialist doctors responsible for treating children with asthma at the six paediatric departments in Central Denmark Region and North Denmark Region. Results EMA and DKMA had registered 104 and 3 reports, respectively, on behavioural ADEs during the 10-year study period. In contrast, five of the eight specialist doctors (45.5%) had experienced patients who had developed behavioural changes during ICS treatment. However, none of the five specialist doctors had filed reports on these events to DKMA. Conclusion Behaviour-related ADEs to ICS in children with asthma are likely to be highly underreported in official databases and doctors treating children with ICS should be aware of potential ADEs and consider submitting ADE reports whenever appropriate.

Although short-acting βIn this cross-sectional study in patients (aged ≥12 years) with asthma, data on disease characteristics and asthma treatments were collected from the Middle Eastern cohort of the SABA use IN Asthma (SABINA) III study. Patients were classified by investigator-defined asthma severity and practice type. Multivariable regression models analyzed the association between SABA prescriptions and clinical outcomes.Of 1389 patients (mean age, 46.7 years; female, 69.5%), 85.7% had moderate-to-severe asthma and 88.7% were treated by specialists. Overall, 51.3% of patients experienced ≥1 severe asthma exacerbation in the previous 12 months, with 58.2% having partly controlled or uncontrolled asthma. Notably, 47.1% of patients were prescribed ≥3 SABA canisters (considered overprescription). SABA canisters were purchased over the counter by 15.3% of patients. Higher SABA prescriptions (vs 1-2 canisters), except 3-5 canisters, were associated with increased odds of uncontrolled asthma (p 0.05).SABA overprescription occurred in almost half of all patients in the Middle East, underscoring the need for healthcare providers and policymakers to adhere to the latest evidence-based recommendations to address this public health concern.Asthma is a long-term disease that causes inflammation of the airways in the lungs and affects both adults and children. Despite effective medicines, asthma remains poorly controlled in many patients. Inhaled steroids with anti-inflammatory properties are the most effective controller medications for asthma. However, many patients rely on rescue or reliever medications, including short-acting β

Mesenchymal stem cells (MSCs) possess immunomodulatory properties that have therapeutic potential for the treatment of inflammatory diseases. This study investigates the effects of direct MSC administration on asthmatic airways. Umbilical cord MSCs (ucMSCs) were intratracheally administered to six-week-old female BALB/c mice sensitized and challenged with ovalbumin; airway hyperresponsiveness (AHR), analyses of airway inflammatory cells, lung histology, flow cytometry, and quantitative real-time PCR were performed. Furthermore, ex vivo and in vitro experiments were performed to assess the effects of ucMSC on M2 activation. Intratracheally administered ucMSCs decreased degree of airway resistance and the number of inflammatory cells such as T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), and macrophages in the murine asthma model. Particularly, MHCII and CD86 expression diminished in dendritic cells and alveolar macrophages (AMs) following ucMSC treatment. SiglecF+CD11c+CD11b- AMs show a negative correlation with type II inflammatory cells including Th2 cells, ILC2, and eosinophils in asthmatic mice and were restored following intratracheal ucMSCs treatment. In addition, ucMSCs decreased the macrophage polarization to M2, particularly M2a. The expression levels of markers associated with M2 polarization and Th2 inflammation were also decreased. ucMSC reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla ex vivo. Furthermore, the in vitro study using IL-4 treated macrophages confirmed that both direct and indirect MSC treatment significantly reduced the expression of Il-5 and Il-13. In conclusion, ucMSCs appear to suppress type II inflammation by regulating lung macrophages via soluble mediators.

Asthma is a chronic lung disease that injures and constricts the airways. This study evaluates the effects of agmatine on ovalbumin (OVA)-induced allergic inflammation of the airways.OVA sensitization by intraperitoneal injection was used to induce airway inflammation in mice on days 0 and 7; then the mice were challenged using beclomethasone (150 µg/kg, inhalation), a standard anti-asthmatic drug, from day 14 to day 16. Furthermore, agmatine (200 mg/kg) was intraperitoneally injected on day 0 and then daily for 16 days, followed by OVA challenge. The lung weight ratio, total and differential cell counts, TNF-α, interleukin-5 (IL-5) and IL-13 in bronchoalveolar lavage fluid (BALF), lung nitrite/nitrate (NO), and oxidative parameters were determined. Moreover, histopathological and immunohistochemical staining was employed.Injection of agmatine (200 mg/kg) for 16 days significantly attenuated inflammation of the airways. The levels of BALF inflammatory cells, TNF-α, IL-5, IL-13, lung NO, and malondialdehyde (MDA), significantly decreased with concomitant elevation of superoxide dismutase (SOD) levels. Histological and immunohistochemical analyses of mast cells paralleled to biochemical improvements.Finally, this study illustrated that agmatine attenuates the allergic inflammation of airways caused by OVA by mitigating cytokines release, NO expression, and oxidative stress.

To determine the effect of anti-asthmatic inhalers salbutamol and budesonide on the surface microhardness of bovine tooth enamel.The study was experimental, prospective, longitudinal, and comparative. The sample consisted of permanent mandibular incisors, which were prepared in (It was observed that the enamel surface microhardness decreased after 5 and 10 days, after being in contact with the anti-asthmatic inhalers based on salbutamol and budesonide. In addition, it was evidenced that there is a greater decrease in the superficial microhardness of the enamel when comparing the values at the beginning and after 10 days; likewise, the reduction in the microhardness of enamel exposed to budesonide was greater (120.8 kg/mmThe two anti-asthmatic inhalers studied decreased superficial enamel microhardness, with the budesonide-based inhaler having a greater erosive effect.This research allowed us to know the values of the microhardness of the superficial enamel after being exposed to different anti-asthmatic inhalers that are indicated in daily clinical practice. Therefore, it is important to evaluate this microhardness since the use of different inhalers is very prevalent.

Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders.This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients.In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359).Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab.

For general practitioners there have been important novelties in the treatment of asthma due to recent modifications of the international guidelines from Global Initiative for Asthma (GINA). In Step 1, use of short-acting beta2-agonists (SABA) without concomitant inhaled corticosteroids (ICS) as controller is no longer recommended for lack of efficacy and safety reasons. Instead, low dose ICS-formoterol as needed is recommended. In Step 5, in patients with severe uncontrolled asthma GINA recommends targeted biologic therapies like interleukin antibodies. Asthma patients presenting simultaneously with symptoms of chronic obstructive pulmonary disease (COPD) should receive treatment containing ICS. Independent of the current corona pandemic, GINA recommendations stay in place.Les nouvelles recommandations GINA (Global Initiative for Asthma) modifient radicalement la prise en charge des patients asthmatiques pour le médecin de premier recours. Dans l’asthme léger (palier 1 GINA), les bêta2-agonistes à courte durée d’action (SABA) seuls comme traitement de secours ne sont plus recommandés au profit d’une association de corticostéroïdes inhalés (CSI) faiblement dosés avec un bronchodilatateur à longue durée d’action à début d’action rapide (formotérol). Dans l’asthme sévère non contrôlé (palier 5 GINA), l’objectif est d’éviter la corticothérapie orale au profit de thérapies biologiques ciblées (par exemple, anticorps anti-interleukine). Un traitement contenant des CSI doit être maintenu chez les asthmatiques même si une BPCO est associée. Les recommandations GINA ne sont pas modifiées par les conditions actuelles de pandémie.

Background:\ud Patients with severe asthma may require maintenance oral corticosteroids (mOCS) for disease control as well as systemic corticosteroid (SCS) bursts for clinically significant exacerbations (CSEs); however, mOCS and SCS use are associated with adverse effects, which increases patient disease burden.\ud \ud Objective:\ud To assess the real-world corticosteroid-sparing effect of mepolizumab in patients with severe asthma.\ud \ud Methods:\ud REALITI-A is a 24-month, international, prospective, observational cohort study involving 84 centers across Europe, Canada, and the USA with a 1-year pre- and post-mepolizumab treatment pre-planned interim analysis. 822 adults with a clinical diagnosis of asthma, and a physician decision to initiate mepolizumab (100 mg subcutaneously) treatment were included. Endpoints included: daily mOCS dose at baseline (penultimate 28 days of pre-treatment) and 1-year post-treatment; percentage reduction from baseline in mOCS dose; patients discontinuing mOCS 1-year post-treatment and rate of CSEs (those requiring OCS for ≥3 days/parenteral administration, and/or emergency room visit and/or hospital admission) pre- and post-treatment.\ud \ud Results:\ud 319 patients received mOCS at baseline (median [interquartile range]: 10.0 [5.0, 15.0] mg/day). At 1 year post-treatment, median mOCS dose reduced by 75% (2.5 [0.0, 5.0] mg/day); 64% of patients had a reduction in mOCS dose ≥50% versus baseline and 43% discontinued mOCS. CSEs decreased between pre- and post-treatment (rate ratio [95% confidence interval] 0.29 [0.26, 0.32] P

The single-inhaler extrafine formulation triple combination beclometasone dipropionate (BDP), formoterol fumarate (FF) plus glycopyrronium bromide (GB) is available for asthma management in adults. Its use in adolescents has not yet been evaluated. This study investigated the pharmacokinetic profile of BDP/FF/GB in adults and adolescents, with the aim of ruling out higher plasma exposure in adolescents compared to adults. In this open-label, non-randomized study, patients with asthma aged 12-17 (adolescents) and 18-64 years (adults) self-administered a single dose of BDP/FF/GB 400/24/50 μg via pressurized metered-dose inhaler (pMDI). The primary objective was to rule out higher systemic exposure to beclometasone 17-monopropionate (B17MP; active metabolite of BDP), formoterol, and GB in terms of the area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUC

Herbal drugs offer an alternative approach for the treatment of diseases like asthma due to low cost and comparatively less adverse effects in contrast to synthetic drugs. Leaves of Quercus leucotrichophora are traditionally used for the treatment of asthma. The study was aimed to assess the anti-asthmatic activity of Quercus leucotrichophora (QL) methanolic (QLME) and aqueous extracts (QLAE) in ovalbumin-(OVA) induced asthma and chemical characterization of QL extract by High Performance Liquid Chromatography-Diode array detector (HPLC-DAD). Animals were inoculated with OVA (i.p) on day 1 and 14 followed by intranasal challenge on 27th and 29th day. Both extracts of QL at 600, 300 and 150 mg/kg and dexamethasone (2 mg/kg) l were administered consecutively from days 15-26 via oral gavage. The QL extracts notably reduced (p 0.0001-p 0.05) total and differential leukocyte counts in blood and BALF and serum IgE levels in contrast to disease control. Both extracts and Dex substantially improved activities of superoxide dismutase, catalase, and GSH, while reduced malondialdehyde level in treated mice. Treatment with extracts and Dex caused significant (p 0.0001-p 0.05) downregulation of tumor necrosis factor-α, interleukin-4, - 5, - 13, - 6, - 1β, and NF-κB whereas, increased expression of Aquaporin (AQP) 1 and AQP5 in contrast to disease control. It was inferenced from findings that both extract of QL exhibited notable antiasthmatic potential might be due to presence of Daidzein-glucuronic acid, 3-Hydroxyphloretin 6'-hexoside, Catechin, Quercetin, and Kaemferol.

Assessment of the effect of inhaled therapy with anti-asthmatic medications on the development of caries in children between 3 and 17 years old.Study design: The study involved 208 patients, 114 in the study group and 94 in the control group. Data on general health condition of patients, use of medications, dietary habits and oral hygiene were obtained. Information on the onset of asthma, its severity and type, doses and method of administration of asthma medications were obtained from the available medical records by the paediatrician. Dental examination was performed using the DMFT/dmft and DMFS/dmfs index, ICDAS II classification and Nyvad's criteria for noncavitated white spot lesion differentiation. Additionally, an assessment of salivary S. mutans (SM) and Lactobacillus spp. (LA) was carried out using the CRT Bacteria (Ivoclar Vivadent) test.There is still no clear consensus among the authors as to whether asthma and medications used in its treatment increase the risk of caries. Nowadays, despite better access to various sources of information, there is still a need for increased awareness in patients and medical doctors on the dental care and caries prevention in patients with asthma.

Severe asthma is a heterogenous disease characterized by multiple phenotypes. Targeted biologic therapies have revolutionarily changed the management of severe asthma by affecting various clinical outcomes, mainly by reducing exacerbations and the use of maintenance corticosteroids, but also by improving lung function and patient quality of life.Randomized controlled trials have convincingly demonstrated the efficacy of different biologics in improving the above outcomes. However, no head-to-head studies exist to compare their efficacy and many patients with severe asthma are eligible for more than one biologic agent. In this review, we present the effect of various biologics in the various outcomes as shown in randomized controlled trials and discuss their similarities and differences.Both the initial choice of a biologic as well as the option of switching to another give the clinician an interesting but also difficult decision when choosing a biologic therapy for patients with severe asthma. This decision is mainly based on the individual characteristics of the patient, especially rate of exacerbations and use of systemic corticosteroids, but is also influenced by the presence of comorbidities and lung function impairment. No safety concerns have been raised around the use of these biologics.

Background Asthma is a significant health issue in primary care. We examined the journeys of patients with asthma exacerbations requiring urgent therapy at a primary care clinic in Singapore. Methods Face-to-face semi-structured interviews were conducted with patients who received urgent therapy for asthma exacerbation at a primary care clinic. Data collected was used to construct themes. Results Fifteen multi-ethnic adult patients were recruited. Participants cited treatment cost, underuse of preventer medication, difficulties attending routine asthma care due to work, and stigma as barriers to asthma control. Reasons for delay in seeking urgent care for asthma were: inability to access medical care out of hours, competing priorities, perception that an exacerbation was ‘not serious enough’, difficulty recognizing symptoms of asthma exacerbation, and being tired or despondent. Participants were triggered to seek care due to failure of reliever inhalers, duration of symptoms, sleep disturbance, inability to work, or advice from others. During an exacerbation, participants often initiated other self-management measures besides using reliever medication. This included over-the-counter medications and non-pharmacological interventions (e.g. drinking water). Of the 15 patients interviewed, only one stepped up preventer inhaler adequately, according to their Asthma Action Plan (AAP). Conclusions In caring for patients with asthma, primary care providers should address patients’ asthma self-management skills, such as recognizing symptoms of asthma exacerbations and regular preventer use, and provide clear instructions on how to respond to asthma symptoms (AAP). Minimizing direct (medication and consultation fees) and indirect costs (loss of earnings and adverse impact on employment prospects) are also important considerations.

Background While inhaled corticosteroids (ICS) are considered the essential foundation of most asthma therapy, ICS inhaler nonadherence is a notoriously common problem and a significant cause of asthma-related morbidity. Partially acknowledging the problem of nonadherence, international organizations recently made paradigm-shifting recommendations that all patients with mild-to-moderate persistent asthma be considered for symptom-driven ICS-containing inhalers rather than relying on adherence to traditional maintenance ICS inhalers and symptom-driven short-acting beta-agonists (SABA). With this new approach, asthma patients are at least exposed to the important anti-inflammatory effects of ICS-containing inhalers when their symptom reliever inhaler is deployed due to acute symptoms. Methods This study will (Part 1) complete a pragmatic randomized controlled trial to evaluate if an inhaler strategy that utilizes symptom-driven ICS inhalers is particularly beneficial in maintenance ICS inhaler non-adherent asthma patients, and (Part 2) use a dissemination and implementation (D&I) science conceptual framework to better understand patients’ and providers’ views of inhaler nonadherence. This study, which will have an option of taking place entirely remotely, will use a Food and Drug Administration (FDA)-approved electronic sensor (Hailie® sensor) to monitor inhaler adherence and includes semi-structured interviews guided by the Consolidated Framework for Implementation Research (CFIR). Discussion This study is assessing the problem of nonadherence using a D&I implementation science research lens while testing a new inhaler approach to potentially ameliorate the detrimental consequences of maintenance inhaler nonadherence. We hypothesize that the use of a symptom-driven ICS/LABA management strategy, as compared to traditional maintenance ICS treatment and symptom-driven SABA, will lead to improved adherence to an asthma treatment strategy, decreased asthma-related morbidity, less cumulative ICS exposure, and greater patient satisfaction with an inhaler approach. Trial registration ClinicalTrials.gov NCT05111262. Registered on November 8, 2021.

Anti-asthmatic medication makes the oral habitat susceptible to opportunistic infections like

To evaluate the effectiveness and practicality of single maintenance and reliever therapy (SMART) in the treatment of asthma exacerbation.PubMed, MEDLINE, Cochrane, and Clinical Trial databases using the keywords SMART therapy, maintenance and reliever therapy, and budesonide and formoterol.Articles were selected based on their relevance and applicability to this topic.Multiple studies have evaluated the efficacy of SMART in reducing asthma exacerbations in comparison to standard inhaled corticosteroid maintenance and short-acting beta-agonist rescue therapy. Most of the randomized trials demonstrated a reduction in asthma exacerbation with open-label studies revealing similar effectiveness in reducing asthma exacerbation. Previously, concerns have been raised regarding the administration of increased doses of long-acting beta-agonist that may potentially mask symptoms and delay appropriate medical attention. However, studies have not demonstrated an increase in morbidity or mortality. The primary concern regarding many of these trials is that they have been sponsored by pharmaceutical companies.Although not all studies demonstrated the effectiveness of SMART, most revealed a substantial reduction in asthma exacerbation frequency and severity.

ObjectiveTo identify risk factors for asthma attacks and poor asthma control in children aged 5–16 years.MethodsProspective observational cohort study of 460 children with asthma or suspected asthma from 10 UK general practices.Gender, age, ethnicity, body mass index, practice deprivation decile, spirometry and fraction of exhaled nitric oxide (FeNO) were recorded at baseline. Asthma control scores, asthma medication ratio (AMR) and the number of asthma attacks were recorded at baseline and at 6 months.The above independent variables were included in binary multiple logistic regression analyses for the dependent variables of: (1) poor symptom control and (2) asthma attacks during follow-up.ResultsPoor symptom control at baseline predicted poor symptom control at 6 months (OR 4.4, p=0.001), while an increase in deprivation decile (less deprived) was negatively associated with poor symptom control at 6 months (OR 0.79, p=0.003). Higher FeNO levels (OR 1.02, pA decrease in AMR was also associated with an increased OR for future asthma attacks (OR 2.99, p=0.003) when included as an independent variable.ConclusionsWe identified risk factors for poor symptom control and asthma attacks in children. Routine assessment of these factors should form part of the asthma review to identify children at an increased risk of adverse asthma-related events.

International audience; BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell–derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment.METHODS: We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (12 to 80 years of age) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV1) and scores on the Asthma Control Questionnaire–6 (ACQ-6; range, 0 [no impairment] to 6 [maximum impairment]), Asthma Quality of Life Questionnaire (AQLQ; range, 1 [maximum impairment] to 7 [no impairment]), and Asthma Symptom Diary (ASD; range, 0 [no symptoms] to 4 [worst possible symptoms]).RESULTS: Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P

Background and Objective Clinical evidence suggests no clinically relevant pharmacokinetic interactions between indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF). A population pharmacokinetic (popPK) analysis was conducted to identify structural models describing systemic pharmacokinetic profiles of IND, GLY and MF, and estimate the effect of covariates on their pharmacokinetics following inhalation as IND/GLY/MF. Methods Pharmacokinetic data from 698 patients with asthma were pooled from two Phase III studies that evaluated IND/MF medium- (150/160 µg) and high-dose (150/320 µg), IND/GLY/MF medium- (150/50/80 μg) and high-dose (150/50/160 μg), and a device bridging Phase II study with MF. One popPK model was developed each for IND, GLY and MF using a nonlinear mixed-effect modelling approach. Maximal and trough plasma concentrations were compared across formulations and studies, including data for IND/GLY from chronic obstructive pulmonary disease (COPD) patients. The effect of predefined covariates on the pharmacokinetics of components was evaluated using a full covariate modelling approach. Results The final pharmacokinetic models were two-compartment disposition models with first-order elimination and sequential zero-order/first-order absorption (IND), with bolus administration and first-order elimination (GLY), and with mixed zero-order/first-order absorption and first-order elimination (MF). All model parameters were estimated with good precision (% relative standard error: IND and MF ≤25%; GLY

This study aims to investigate the prevalence of short-acting β2-agonist (SABA) overuse in asthma and the associated risk of acute exacerbation and mortality in Taiwan. We used the Taiwanese pay-for-performance asthma program database, which included patients aged between 12 and 100 years who were enrolled in the program between 2001 and 2015. Among a total of 218,039 patients, 34,641 (15.9%) patients are classified as SABA over-users. Compared with patients who did not receive inhaled corticosteroids (ICS) and collected ≤2 canisters, SABA over-users had a higher risk of severe exacerbations. SABA over-users had a higher risk of all-cause mortality compared with patients who did not receive ICS and collected ≤2 canisters. The overall prevalence of SABA overuse in Taiwan is 15.9%, and this is even higher in concomitant ICS users. In addition, the overuse of SABA is associated with an increased risk of severe exacerbation and death.

Qing Ye,1,* Qiqiang Zhang,1,* Huijuan Yao,1,* Ajing Xu,1 Yan Liu,1 Jia Qi,1 Hai Zhang,2 Jian Zhang1 1Department of Pharmacy, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Pharmacy, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian ZhangDepartment of Pharmacy, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, People’s Republic of ChinaTel/Fax +86 21-25077150Email zhangjian@xinhuamed.com.cnHai ZhangDepartment of Pharmacy, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 2699 High Tech West Road, Pudong New Area, Shanghai, 201204, People’s Republic of ChinaTel/Fax +86 21-20261401Email zhxdks2005@126.comBackground: Shegan Mixture (SGM) is a traditional Chinese medicine that has anti-inflammatory and therapeutic effects on asthma. However, its active ingredients and combined action mechanism have not been fully elucidated so far. The purpose of this study was to screen the effective ingredients and targets and elucidate the synergistic action mechanism of SGM in asthma mice using the network pharmacological approach.Methods: A mouse model of asthma model was used in this study. Mice were orally administered SGM at three doses for 4 weeks and the effect of SGM on asthma was evaluated. The active ingredients and their targets of SGM were identified by searching databases, such as Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). The main active ingredients were selected with parameters OB and DL. The synergistic action mechanisms of SGM in asthma were studied through key active ingredient-target interaction network and verified using surface plasmon resonance assay (SPR).Results: SGM exerts anti-asthmatic effects by reducing lung tissue damage and inflammatory factors (IFN-γ, IL-4, IL-5, and IL-13) in asthmatic mice. Twenty ingredients and 45 related proteins were selected as potential nodes using enrichment analysis and network analysis. Inflammation and smooth muscle regulation-related pathways were considered to be the main pharmacological mechanisms of SGM in the treatment of asthma. Especially, 5 molecule-target pairs (including 3 ingredients and 4 proteins) were well docked with each other and the SPR assay revealed that glabridin-PTGS2 had good binding with 44.5 μM Kd value.Conclusion: SGM exerts the synergistic anti-asthma effects by virtue of reducing lung-tissue damage and inflammatory factors in asthmatic mice, which explains the theoretical basis for the traditional Chinese medicine, SGM, to treat asthma. Our study thus sheds light on a variety of options including Chinese medicine that could potentially be used in the clinical treatment of asthma.Keywords: Shegan mixture, asthma, network pharmacology, surface plasmon resonance, traditional Chinese medicine