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Novel approach of asthma includes personalised therapy involving specific immune pathways. We describe here a case of T2-high asthma in a 66-year-old woman treated with maximal inhaled therapy and inappropriate usage of oral corticosteroids showing poor symptoms control. Both anti-IgE and (omalizumab) and anti-interleukin (IL)-5 (mepolizumab) monoclonal antibodies treatments were prescribed without significant benefit. Add-on subcutaneous dupilumab, a monoclonal antibody directed against the IL-4 receptor subunit alpha, inhibiting signalling from both IL-4 and IL-13, proved to be an effective and safe medication to obtain rapid asthma control. Considering the previous lack of response to both anti-IgE and anti-eosinophilic strategies, we hypothesise that dupilumab upstream activity could exert different and more relevant effects than the simple inhibition of the two single downstream pathways. The current case highlights the need for a deeper analysis of biomolecular interactions in the framework of different asthma endotypes, to identify peculiar profiles associated with specific treatment responses.

Poorly controlled asthma can affect neonatal outcomes including congenital anomalies, which can be reduced with appropriate asthma care during pregnancy. Although there is a concern regarding the safety of asthma medication use during pregnancy and congenital anomalies, the risk of uncontrolled asthma outweighs any potential risks of controller and reliever medication use. Patient education before and during pregnancy is critical to ensure good compliance to therapy and reduce the risk of poor asthma control.

Prescribing inhalers without imparting adequate education regarding proper technique of their usage may result in suboptimal clinical improvement and wastage of medication. Training interventions using a standard check-list may help improve faulty techniques and enhance drug efficacy.Patients using metered dose inhaler (MDI) were included in the study. Inhaler technique was first evaluated at baseline using a standard check-list of recommended steps (National Institute of Health guidelines; see Table) and scores were given for each step correctly performed. Those who could not perform all steps correctly were given training intervention. The patients were assigned to two methods of educational intervention; one group was trained by providing written material giving step-wise instructions while the other group was given an actual physical demonstration using a placebo device. The technique was re-evaluated and scored following each educational session, and continued till the patient achieved a full score, or for a maximum of 3 sessions, whichever occurred earlier. Median score was calculated after each session and was compared between the two groups. Each patient was followed up after two months and the re-evaluated the same way.One hundred and seventeen subjects were enrolled in the study (59 in the written group and 57 in the practical demonstration group). At baseline, only 1 of the 117 subjects could perform all the steps of inhaler usage correctly. This patient was, therefore, not provided the inhaler technique education. The overall median (range) score of the whole group was 3 (range 1-8). This score rose to 6, 7 and 8 after each of the three subsequent educational intervention sessions. At one-month follow-up, the median score dropped to 7 and improved with a repeat educational session as previously done. A significant difference was observed in the median score improvement achieved in the practical demonstration group compared with the written instruction group (3.0 versus 2.0 respectively, p0.001).Inhalation technique of patients improves after imparting systematic educational intervention. A practical demonstration of all the steps proved more effective than simple verbal/written advice. In view of increasing errors being committed over a period of time, repeated demonstration of the proper technique using a standard check-list significantly improves the errors committed during inhaler use.

Bronchial asthma is a serious global health problem. Depression, the most common mood disorder, is often found to be higher among people with chronic health conditions like bronchial asthma.Patients with newly diagnosed to have bronchial asthma (n = 100) who fulfilled the study criteria were evaluated for depression with Beck Depression Inventory (BDI) score. Severity and level of bronchial asthma control were determined as per Global Initiative for Asthma (GINA) guidelines. Subjective asthma severity was assessed by Perceived Control of Asthma Questionnaire. Follow-up evaluation was done after three months of asthma management with the same study tools.In our study population, 65% asthma patients showed depression on first visit (95% Confidence interval [CI] 55.65-74.35). Correlation coefficient between subjective asthma severity and severity of depression was -0.945 (p0.001) while correlation coefficient between objective asthma severity and depression severity was 0.066 (p = 0.515). In follow-up visit after asthma management 63% patients still had depression (95% CI 53.54-72.46). Correlation coefficient between objective asthma control and depression severity was 0.1 (p = 0.320). Correlation coefficient between subjective asthma severity and severity of depression was -0.979 (p0.001).Our observational study suggests that depression is highly prevalent in asthma patients. There is a high inverse correlation between depression and patient's perception of asthma control. However, no significant correlation could be observed between objective measures of asthma severity and depression.

Background: Adequate management is crucial to reduce symptoms, hospitalization, and relapses in patients with asthma. Hospitals often struggle to meet treatment guidelines, and no recent data for Switzerland are available. Objectives: The aim of the study was to audit the asthma exacerbation management in the Cantonal Hospital of Baselland in order to evaluate the level of compliance with guidelines in a narrative discussion. Method: The study design is a retrospective observational cohort study. We evaluated all adult patients presenting to the hospital with a physician-diagnosed asthma exacerbation in 2018 and 2019. The asthma management patients received was compared to the Swiss guidelines and the international GINA guidelines. Results: 160 patients were included (mean age: 50 years old, 57.5% female). SpO2 and heart rate were assessed at presentation in nearly all patients. Peak expiratory flow (PEF) was measured in only 14%. Adequate management of asthma exacerbation with inhaled bronchodilator medication in a combination of short-acting beta-agonists and short-acting anticholinergics was administered to 96% of the patients. Patients with severe symptoms received systemic glucocorticosteroids within 6 h in 55%. At discharge, a reliever medication was prescribed for 64% of the patients and 55% received a new or increased controller therapy with inhaled glucocorticosteroid (ICS). 49% of the patients had no follow-up organized. Conclusion: To increase the guideline conformity and quality of asthma exacerbation management, the severity should be better assessed, especially by routinely performing PEF measurements. Treatment needs to be intensified; in particular, the ICS dose should be increased significantly and systemic glucocorticosteroids should be given with a lower threshold.

To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents.A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease.Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%).The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Rationale: The past 25 years have seen huge progress in understanding of the pathobiology of type-2 (T2) asthma, identification of measurable biomarkers, and the emergence of novel monoclonal antibody treatments. Although present in a minority of patients with severe asthma, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. Objectives: The objective of this study was to explore the differences between study exacerbators and nonexacerbators, to describe physiological changes at exacerbation in those who are T2 HIGH and T2 LOW at the time of exacerbation, and to evaluate the stability of inflammatory phenotypes when stable and at exacerbation. Methods: Exacerbation assessment was a prespecified secondary analysis of data from a 48-week, multicenter, randomized controlled clinical study comparing the use of biomarkers and symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2 LOW (fractional exhaled nitric oxide < 20 ppb and blood eosinophil count < 150 cells/ml) or T2 HIGH (fractional exhaled nitric oxide. 20 or blood eosinophil count. 150) at study enrollment and at each exacerbation. Here, we report the findings of the exacerbation analyses, including comparison of exacerbators and nonexacerbators, the physiological changes at exacerbation in those who had evidence of T2 biology at exacerbation versus those that did not, and the stability of inflammatory phenotypes when stable and at exacerbation.Measurements and Main Results: Of the 301 participants, 60.8% (183) had one or more self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher body mass index, and have more exacerbations requiring oral corticosteroid and unscheduled primary care attendances for exacerbations. At enrollment, 23.6% (71) were T2 LOW and 76.4% (230) T2 HIGH. The T2 LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU (high dependency unit)/ICU and to be receiving maintenance oral corticosteroids. At exacerbation, the T2 LOW events were indistinguishable from T2 HIGH exacerbations in terms of lung function (mean fall in T2 LOW FEV 1, 200 [400] ml vs. T2 HIGH 200 [300] ml; P = 0.93) and symptom increase (ACQ5: T2 LOW, 1.4 [0.8] vs. T2 HIGH, 1.3 [0.8]; P = 0.72), with no increase in T2 biomarkers from stable to exacerbation state in the T2 LOW exacerbations. The inflammatory phenotype within individual patients was dynamic; inflammatory phenotype at study entry did not have a significant association with exacerbation phenotype. Conclusions: Asthma exacerbations demonstrating a T2 LOW phenotype were physiologically and symptomatically similar to T2 HIGH exacerbations. T2 LOW asthma was an unstable phenotype, suggesting that exacerbation phenotyping should occur at the time of exacerbation. The clinically significant exacerbations in participants without evidence of T2 biology at the time of exacerbation highlight the unmet and pressing need to further understand the mechanisms at play in non-T2 asthma.

Background Asthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of ‘false-negative’ T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits. Methods The STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17–75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m2). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal. Discussion This study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients. Trial registration Netherlands Trial Register, NL8759, registered 2020–07-06, https://www.trialregister.nl/trial/8759. Protocol version and date: version 2.1, 20 November 2020.

PURPOSE: We quantified the magnitude of exercise-induced bronchodilation in adult asthmatics under conditions of narrowed and dilated airways. We then assessed the effect of the bronchodilation on ventilatory capacity and the extent of ventilatory limitation during exercise. METHODS: Eleven asthmatics completed three exercise bouts on a cycle ergometer. Exercise was preceded by no treatment (trial(CON)), inhaled β(2)-agonist (trial(BD)), or a eucapnic voluntary hyperpnea challenge (trial(BC)). Maximal expiratory flow-volume maneuvers (MEFV) were performed before and within 40 seconds of exercise cessation. Exercise tidal flow-volume loops were placed within the pre- and post-exercise MEFV curve and used to determine expiratory flow-limitation (EFL) and maximum ventilatory capacity ([Formula: see text]). RESULTS: Pre-exercise airway function was different among the trials (forced expiratory volume 1 second [FEV(1)] during trial(CON), trial(BD), and trial(BC) = 3.3 ± 0.8, 3.8 ± 0.8, and 2.9 ± 0.8 L, respectively; P

Background: MIDD0301 is an oral asthma drug candidate that binds GABAA receptors on airway smooth muscle and immune cells. Objective: The objective of this study is to identify and quantify MIDD0301 metabolites in vitro and in vivo and determine the pharmacokinetics of oral, IP, and IV administered MIDD0301. Methods: In vitro conversion of MIDD0301 was performed using liver and kidney microsomes/S9 fractions followed by quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A LC-MS/MS method was developed using synthesized standards to quantify MIDD0301 and its metabolites in urine and feces. Blood, lung, and brain were harvested from animals that received MIDD0301 by oral, IP, and IV administration, followed by LCMS/ MS quantification. Imaging mass spectrometry was used to demonstrate the presence of MIDD0301 in the lung after oral administration. Results: MIDD0301 is stable in the presence of liver and kidney microsomes and S9 fractions for at least two hours. MIDD0301 undergoes conversion to the corresponding glucuronide and glucoside in the presence of conjugating cofactors. For IP and IV administration, unconjugated MIDD0301 together with significant amounts of MIDD0301 glucoside and MIDD0301 taurine were found in urine and feces. Less conjugation was observed following oral administration, with MIDD0301 glucuronide being the main metabolite. Pharmacokinetic quantification of MIDD0301 in blood, lung, and brain showed very low levels of MIDD0301 in the brain after oral, IV, or IP administration. The drug half-life in these tissues ranged between 4-6 hours for IP and oral and 1-2 hours for IV administration. Imaging mass spectrometry demonstrated that orally administered MIDD0301 distributes uniformly in the lung parenchyma. Conclusion: MIDD0301 undergoes no phase I and moderate phase II metabolism.

Patients with life-threatening asthma typically experience recurrent exacerbations, are dependent on oral corticosteroids (OCSs), and have considerable asthma-related health care costs. Data on the impact of mepolizumab on exacerbations and OCS use in patients with life-threatening asthma in real-world clinical practice are limited. This study assessed the impact of mepolizumab on exacerbation rates and OCS use in patients with life-threatening asthma in a real-word setting.This retrospective study utilized data from US administrative claims from patients with life-threatening asthma. Eligible patients were treated between November 1, 2015, and December 31, 2017; were ≥12 years of age upon mepolizumab initiation (index date); and had undergone at least two mepolizumab administrations during the 6 months postindex. Data from the 12 months before (baseline) and after (follow-up) index were collected, with each patient serving as his or her own control. Life-threatening asthma was defined as at least three exacerbations and/or at least one asthma-related hospitalization during baseline, and/or a history of endotracheal intubation. Asthma exacerbation frequency and OCS use were assessed.The analysis included 327 patients who received a mean (SD) of 10.6 (4.3) mepolizumab doses during follow-up. The percentage of patients experiencing at least one exacerbation and the mean exacerbation rate were significantly reduced from baseline to follow-up with mepolizumab, from 94.5% to 67.9% (P0.001), and from 3.2 to 1.5 events per patient per year, corresponding to a 53.1% relative reduction (P0.001). The percentage of patients with OCS claims was reduced by 12.6%, from 99.1% to 86.5% (P0.001). Of the patients who had a reduction in mean daily OCS use, most (57.9%, 140/242) had a reduction in mean daily OCS use of at least 50%.These data from patients with life-threatening asthma in clinical practice demonstrated that asthma exacerbation and OCS use were significantly reduced with mepolizumab treatment.

Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed. Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. The efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma are unclear.In a phase 2 trial, we randomly assigned, in a 1:1:1:1 ratio, adults with moderate-to-severe asthma receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) to receive subcutaneous itepekimab (at a dose of 300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. After randomization, LABA was discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary end point was an event indicating a loss of asthma control, assessed in the itepekimab group and the combination group, as compared with the placebo group. Secondary and other end points included lung function, asthma control, quality of life, type 2 biomarkers, and safety.A total of 296 patients underwent randomization. By 12 weeks, an event indicating a loss of asthma control occurred in 22% of the patients in the itepekimab group, 27% of those in the combination group, and 19% of those in the dupilumab group, as compared with 41% of those in the placebo group; the corresponding odds ratios as compared with placebo were as follows: in the itepekimab group, 0.42 (95% confidence interval [CI], 0.20 to 0.88; P = 0.02); in the combination group, 0.52 (95% CI, 0.26 to 1.06; P = 0.07); and in the dupilumab group, 0.33 (95% CI, 0.15 to 0.70). As compared with placebo, the forced expiratory volume in 1 second before bronchodilator use increased with the itepekimab and dupilumab monotherapies but not with the combination therapy. Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in the mean blood eosinophil count. The incidence of adverse events was similar in all four trial groups.Interleukin-33 blockade with itepekimab led to a lower incidence of events indicating a loss of asthma control than placebo and improved lung function in patients with moderate-to-severe asthma. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03387852.).

Interleukin-23 has been implicated in airway inflammation that is mediated by type 2 and type 17 cytokines. Whether targeting interleukin-23 in the treatment of asthma improves disease control and reduces airway inflammation is unclear.We conducted a phase 2a, multicenter, randomized, double-blind, placebo-controlled, 24-week, parallel-group trial to assess the efficacy and safety of risankizumab, an anti-interleukin-23p19 monoclonal antibody, in adults with severe asthma. Patients were assigned to receive 90 mg of risankizumab or placebo, administered subcutaneously once every 4 weeks. The primary end point was the time to the first asthma worsening. Asthma worsening was defined as deterioration from baseline on 2 or more consecutive days; deterioration was considered to be a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in the number of puffs of rescue medication in a 24-hour period (equating to at least four additional puffs), a severe asthma exacerbation, or an increase of 0.75 or more points on the 5-item Asthma Control Questionnaire (ACQ-5; scores range from 0 to 6, with higher scores indicating less control). Secondary end points were the annualized rate of asthma worsening, the annualized rate of severe exacerbations, the ACQ-5 score, and the forced expiratory volume in 1 second. Exploratory end points were assessed with the use of sputum cytologic analysis and gene expression analysis, and safety was assessed.A total of 105 patients received risankizumab and 109 received placebo. The clinical characteristics of the patients were similar in the two groups. The time to the first asthma worsening was shorter with risankizumab than with placebo (median, 40 days vs. 86 days; hazard ratio, 1.46; 95% confidence interval [CI], 1.05 to 2.04; P = 0.03). The rate ratio for annualized asthma worsening with risankizumab as compared with placebo was 1.49 (95% CI, 1.12 to 1.99), and the rate ratio for severe exacerbations was 1.13 (95% CI, 0.75 to 1.70). Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of the type 1 helper T and type 17 helper T transcription factors were down-regulated by risankizumab. No safety concerns were associated with risankizumab therapy.Risankizumab treatment was not beneficial in severe asthma. The time to the first asthma worsening was shorter and the annualized rate of asthma worsening was higher with risankizumab than with placebo. (Funded by AbbVie and Boehringer Ingelheim; ClinicalTrials.gov number, NCT02443298.).

Rationale: Infants and young children might be particularly likely to experience the potential clinical side effects of inhaled corticosteroids (ICSs) on body mass index (BMI), adiposity rebound (A...

Despite near-universal health care and timely updates to treatment guidelines in Saudi Arabia, asthma control remains suboptimal, warranting deeper exploration of its management practices. This study describes asthma characteristics and prescription patterns of short-acting β

Objectives: The SABINA CHINA study aimed to determine prescription data for asthma medication with a focus on SABA and ICS in a representative population of patients with asthma in China. Methods: SABINA China was a multicentre, observational, cross-sectional study with data collected retrospectively from a convenience sample of 25 tertiary centres across China. Patients (age ⩾ 12 years) with ⩾3 consultations/year were enrolled. Data were collected on clinical characteristics, asthma severity, and symptom control (as per GINA 2017), treatment and history of severe exacerbations over the past year. SABA over-prescription was defined as ⩾3 SABA canisters/year. Descriptive statistics are presented. Results: Between March and August 2020, 498 patients were included in the outcome analysis. Mean (SD) age was 48.7 (15.0) years, 57.9% were female and 91% had moderate-to-severe asthma ( n = 453). Overall, 12.5% ( n = 62) and 26.4% ( n = 131) of patients had uncontrolled and partly controlled asthma, respectively. SABA add-on was prescribed to 20.3% ( n = 101) of patients; one patient with moderate-to-severe asthma was prescribed SABA-alone. SABA over-prescription in the overall population was 4.0% ( n = 20; all with moderate-to-severe asthma) and 19.8% (20/101) among those prescribed SABA add-on. In the mild asthma group, 50% ( n = 22) were prescribed ICS/LABA and 43.2% ( n = 19) were prescribed LTRA. Among those with moderate-to-severe asthma, 97.4% ( n = 441) were prescribed ICS/LABA and 55.0% ( n = 249) were prescribed LTRA. Approximately 30% of patients ( n = 149) experienced ⩾1% and 6.6% ( n = 33) ⩾3 severe exacerbations in the preceding year; mean annual number of severe exacerbation/patient was 0.6 (1.2). Among those prescribed SABA add-on, ICS/LABA and LTRA (non-mutually exclusive groups due to overlapping prescriptions), 54.5%, 29.9%, and 35.3% had ⩾1 severe exacerbations, respectively. Conclusion: Among patients with predominantly moderate-to-severe asthma managed in tertiary care and were prescribed SABA, 1 in 5 received ⩾3 canisters/year. Fewer patients who received ICS/LABA prescriptions experienced annual exacerbations than those prescribed SABA add-on.

Asthma can manifest in a variety of clinical phenotypes like cough variant asthma, chest tightness variant asthma (CTVA), and masked asthma. Patients with CTVA usually have a singular or primary complaint of chest tightness, which is often overlooked or misdiagnosed due to the lack of characteristic asthma symptoms. We hereby report a case of CTVA managed by omalizumab.A 15-year-old female patient reported to us with repeated coughing persisting for 3 weeks. Initial treatment with standard asthma drugs had minimal effect. Later during the disease, chest tightness became the primary symptom, and she was managed with steroids, β2 receptor agonists, and leukotriene receptor agonists but without complete relief. Based on clinical signs and symptoms, the response to baseline drugs, and results of bronchial provocation test, the diagnosis was revised to CTVA, and the patient was started on Omalizumab in addition to baseline drugs, which significantly improved her condition.CTVA is difficult to diagnose due to its insidious symptoms and poor characteristics. Improper treatment can lead to uncontrolled disease, negative psychological issues, and reduced quality of life. Comprehensive assessment of children's airway inflammation level, lung function, bronchial provocation test, and responsiveness to drug therapy should be performed for accurate diagnosis. Omalizumab in combination with standard drugs can significantly improve the outcomes of CTVA.

OBJECTIVE Pharmacological treatment plays a key role in the management of asthma, but medication adherence is generally low. Our aim was to assess factors associated with dispensing patterns of, and adherence to, asthma medication in young adults with asthma. METHODS The study included young adults (age 22-24 years) from the Swedish population-based birth cohort BAMSE (n = 3,064) with linkage to register data on dispensed asthma medications and recorded diagnosis. Dispensing information was collected in January 2014-June 2019 (the study period) to cover the period of questionnaire data. Adherence to asthma medication was defined as refilling a prescription within 18 months. RESULTS In total, 234 individuals (7.6%) had asthma (doctor's diagnosis of asthma in combination with respiratory symptoms) and had been dispensed at least one prescription of asthma medication during the study period. Among them, 77% were dispensed a controller medication. The mean number of prescriptions dispensed per individual was higher in males than females (11.0 vs. 7.2; p

BACKGROUND: Despite guidelines recommending inhalation therapy as the preferred choice, oral therapy is still widely used in the treatment of asthma in India. However, data about the level of asthma control and healthcare use in patients on oral anti-asthma medications are scarce.METHODS: A retrospective study was conducted to assess the level of asthma control and healthcare use in patients taking oral anti-asthma medications.RESULTS: The study population consisted of 381 adults randomly selected from health screening programmes. All subjects were already receiving oral anti-asthma medications; however, up to 72% had not been diagnosed with asthma by their treating doctors prior to the screening programmes. The cohort had a mean age of 48.26 ± 13.83 years (70% males) and mean peak expiratory flow of 245 ± 78.93 mL/sec. The mean Asthma Control Questionnaire 5 (ACQ-5) score was 2.53 ± 1.15, with respectively 33%, 49.3% and 32.6% reporting at least one episode of breathlessness, one emergency doctor visit and one hospitalisation due to asthma or its symptoms in the past year.CONCLUSION: Underdiagnosis and inappropriate management, as indicated by the poor asthma control and increased hospitalisations seen in this study, is probably a key contributor to the increased burden of the disease in India.

Background The anti–immunoglobulin E therapy, omalizumab, improves asthma control and reduces exacerbations in patients with moderate-to-severe allergic asthma. However, it has been suggested that omalizumab should be reserved for highly allergic patients with multiple allergen sensitivities or perennial-only sensitivities. Objective To examine impact of allergy burden, including number and type of allergen sensitivities, on omalizumab response in a real-world setting. Methods This post hoc analysis evaluated a subset of omalizumab-treated patients from the Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (NCT01922037) who had completed 13 allergen assessments (N=478). Patients were classified by allergen burden (nonsensitized, 1, 2-4, or ≥5 allergen sensitivities) and type of allergen (nonsensitized, seasonal, perennial, or both). Outcome measures included exacerbation rate vs previous year and improvements in lung function and Asthma Quality of Life Questionnaire (AQLQ). Results Comparable adjusted exacerbation rates were observed after omalizumab initiation, regardless of number or type of allergen sensitizations (0.56-0.85/y). Improvements in forced expiratory volume in 1 second from baseline at months 6 (0.03-0.09 L) and 12 (–0.08 to 0.08 L) were also similar across subgroups. Least squares mean change in AQLQ from baseline at months 6 (1.0-1.2) and 12 (1.1-1.4) was comparable across patient subgroups, and similar percentages of patients achieved AQLQ minimal clinically important difference of at least a 0.5-point improvement at month 6 (71%-75%), which was maintained or improved to month 12 (71%-89%). In all analyses, 95% confidence intervals overlapped. Conclusion Overall findings suggest that patients with allergic asthma achieved comparable improvements across distinct outcome measures after omalizumab therapy in a real-world setting, regardless of number and type of allergen sensitizations. Trial Registration ClinicalTrials.gov Identifier: NCT01922037.

Introduction: Asthma is one of the most common conditions that afflict pregnant women. Because uncontrolled asthma in pregnancy affects both maternal and offspring outcomes, careful attention to ma...

Background Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory diseases, presenting overlapping prevalence with age. Mepolizumab is a humanized monoclonal antibody targeting interleukin-5. In major randomized clinical trials, this antibody reportedly reduced the circulating eosinophil count, exacerbation rate, and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data regarding the efficacy of mepolizumab in elderly patients with asthma and overlapping COPD are limited. Methods This was a single-center, retrospective, observational study. Elderly patients (age ≥65 years) administered mepolizumab between August 2016 and March 2019 were enrolled and the effects of mepolizumab on the eosinophil level, exacerbation numbers, OCS dosage, and lung functions were assessed. We compared treatment responses in patients with asthma and COPD overlap (ACO) with responses observed in patients with severe asthma alone. Adverse events were also evaluated. Results Twenty patients (10 men and 10 women), with a mean age of 77.5 ± 1.3 years, were included. Mepolizumab significantly reduced the blood eosinophil count, as well as significantly decreased clinically significant exacerbation, in both populations. The OCS dosage was significantly reduced in patients treated receiving maintenance OCS therapy. However, mepolizumab did not improve lung function in either population, and no significant difference was observed in treatment responses between patients with asthma alone and ACO. Conclusions Mepolizumab may be effective in elderly patients with eosinophilic asthma and ACO.

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.

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.

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.

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.

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.

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