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Objectives: Long-term safety monitoring of mepolizumab is necessary to support real-world use for the treatment of severe asthma. This Long-Term Access Program assessed the safety and benefit:risk of mepolizumab in pediatric, adolescent, and adult patients with severe asthma., Materials and Methods: This was a multicenter, Phase IIIb safety, open-label extension study of multiple prior studies assessing mepolizumab in addition to standard of care (Aug 2015 - Aug 2022). Adults/adolescents (≥12 years of age) received mepolizumab 100 mg subcutaneously (SC) every 4 weeks until mepolizumab was commercialized. Pediatric patients (6-11 years of age) received mepolizumab 40 mg or 100 mg SC (bodyweight <40 or ≥40 kg, respectively) every 4 weeks. Safety was assessed every 4 weeks and benefit:risk every 12 weeks., Results: Of the 514 patients enrolled, 57% were female and the mean age was 51.1 (standard deviation: 14.9) years; 24 (5%) patients were 6-17 years of age. Total cumulative mepolizumab exposure across all mepolizumab studies included in this analysis was 1500.59 patient-years; median exposure was 2.03 (range, 0.08 to 9.97) years. Overall, 37 (7%) patients experienced on-treatment serious adverse events (SAEs): 34/502 (7%) in the 100 mg SC group and 3/7 (43%) in the 40 mg SC pediatric group. Two patients experienced SAEs considered to be treatment-related by the investigator. Infections were the most common SAEs of special interest (9 [2%] patients). Physician-assessed benefit:risk of mepolizumab supported continued treatment over the study period., Conclusions: This long-term safety analysis of mepolizumab was consistent with previous reports, with no emerging safety concerns; most patients had a favorable benefit:risk up to ∼10 years., Clinical Trial Identifier: NCT00244686 (GSK ID 201956).

Background: Some patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients' characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice., Methods: Data of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12 months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV 1 >80% predicted., Results: An improvement in all asthma control parameters was observed after 12 months of treatment and a mean follow-up of 55 months. After 12 months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern., Conclusions: This study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics.

Introduction: Although some factors associated with asthma symptom deterioration and risk of exacerbation have been identified, these are not yet fully characterised. We conducted a clinical modelling and simulation study to understand baseline factors affecting symptom control, reliever use and exacerbation risk in patients with moderate-severe asthma during follow-up on regularly dosed inhaled corticosteroid (ICS) monotherapy, or ICS/long-acting beta 2 -agonist (LABA) combination therapy., Methods: Individual patient data from randomised clinical trials (undertaken between 2001 and 2019) were used to model the time course of symptoms (n = 7593), patterns of reliever medication use (n = 3768) and time-to-first exacerbation (n = 6763), considering patient-specific and extrinsic factors, including treatment. Model validation used standard graphical and statistical criteria. Change in symptom control scores (Asthma Control Questionnaire 5 [ACQ-5]), reduction in reliever use and annualised exacerbation rate were then simulated in patient cohorts with different baseline characteristics and treatment settings., Results: Being a smoker, having higher baseline ACQ-5 and body mass index affected symptom control scores, reliever use and exacerbation risk (p < 0.01). In addition, low forced expiratory volume in 1 s percent predicted, female sex, season and previous exacerbations were found to contribute to a further increase in exacerbation risk (p < 0.01), whereas long asthma history was associated with more frequent reliever use (p < 0.01). These effects were independent from the underlying maintenance therapy. In different scenarios, fluticasone furoate (FF)/vilanterol was associated with greater reductions in reliever use and exacerbation rates compared with FF or fluticasone propionate (FP) alone or budesonide/formoterol, independently from other factors (p < 0.01)., Conclusions: This study provided further insight into the effects of individual baseline characteristics on treatment response and highlighted significant differences in the performance of ICS/LABA combination therapy on symptom control, reliever use and exacerbation risk. These factors should be incorporated into clinical practice as the basis for tailored management of patients with moderate-severe asthma., (© 2024. The Author(s).)

This systematic review and meta-analysis evaluated the safety of montelukast in treating asthma during pregnancy, focusing on maternal and fetal outcomes such as congenital anomalies (CA), preterm delivery, low birthweight, spontaneous abortion, gestational diabetes mellitus, and preeclampsia. A comprehensive literature search was conducted in Google Scholar, PubMed, and the Cochrane Library databases from inception until April 30, 2024. The eligible studies assessed the safety of montelukast for asthma treatment during pregnancy. The review suggests that montelukast use during pregnancy may not significantly increase the risk of major CA. The pooled results yielded risk ratio (RR) for CA was 1.13 [95% CI (0.74, 1.73), p = 0.56, I 2  = 0%]. Montelukast may be associated with preterm delivery and a low birthweight odds ratio (OR) of 1.82 [95% CI (1.35, 2.45), p < 0.001, I 2  = 0%]. No significant risks were found concerning neurodevelopmental outcomes. The associations with spontaneous abortion were inconclusive [OR = 1.03, 95% CI (0.72, 1.5), p = 0.86, I 2  = 73%], highlighting the need for further research. This comprehensive review underscores the importance of further investigating the safety profile of montelukast during pregnancy. While the overall findings indicate a relatively favorable safety profile, especially regarding major CA, careful consideration is needed for the potential risks of preterm delivery and low birthweight., (© 2024 Japanese Teratology Society.)

Objective: To evaluate the benefits of combining omalizumab with specific immunotherapy (SCIT) in the treatment of children with bronchial asthma., Methods: In this study, 83 children with asthma were treated at the Allergy Department of Qingdao University from January 2019 to February 2020. Participants were divided into three groups: SCIT, combination (omalizumab + SCIT), and control (standard asthma medications). We assessed Asthma Control Questionnaire (ACQ) scores, Visual Analogue Scale (VAS) scores, and lung function at baseline, 24 wk, and 48 wk. Additionally, asthma medication scores were compared at 24 and 48 wk. Adverse reactions were monitored in both the SCIT and combination groups., Results: The combination group demonstrated lower ACQ scores at both 24 and 48 wk, and improved VAS scores at 48 wk compared to the other groups. Additionally, lung function parameters (FEV1 and FEF50) showed significant improvement in the combination group. Reduced asthma medication scores were noted in the combination group at 24 and 48 wk. Local adverse reactions were fewer in the combination group, and no systemic adverse reactions were reported., Conclusion: Combining omalizumab with SCIT provides quicker asthma control, lowers medication requirements, and enhances lung function with fewer adverse effects, making it a safe and effective treatment for children with bronchial asthma.

The United States Food and Drug Administration (FDA) has been warning about the psychiatric disorders associated with montelukast (MTK) for years. To study the characteristics of the presence of MTK-associated adverse events (AEs), we obtained data from the FDA Adverse Event Reporting System database and used a case (MTK) vs. non-case (all other drugs) analysis to investigate the safety signals in a disproportionality study. 27,507 reported AEs from January 2004 to December 2022 were analyzed. Disproportionality analysis shows that psychiatric, respiratory, thoracic, and mediastinal disorders as well as social circumstances are the most commonly reported AEs. In addition, our study found several unreported AEs, such as increased systolic blood pressure, diastolic dysfunction, hypothyroidism, obesity, bursitis, and polycystic ovaries. The timing of AE occurrence indicates that MTK-associated AEs are mainly acute effects. Most importantly, we found that 60.1% of patients reporting AEs in the category of psychiatric disorders were younger than 18 years. In summary, we revealed an age-preference pattern of psychiatric AEs in patients prescribed MTK. Our study is helpful for physicians and health professionals to better evaluate the value and risk of MTK and to achieve the goal of optimal patient care.

Asthma and cardiovascular disease (CVD) often co-exist. When a patient has both conditions, management requires an approach that addresses the unique challenges of each condition separately, while also considering their potential interactions. However, specific guidance on the management of asthma in patients with CVD and on the management of CVD in patients with asthma is still lacking. Nevertheless, health care providers need to adopt a comprehensive approach that includes both respiratory and CVD health. The management of CVD in patients with asthma requires a delicate balance between controlling respiratory symptoms and minimising potential cardiovascular (CV) risks. In the absence of specific guidelines for the management of patients with both conditions, the most prudent approach would be to follow established guidelines for each condition independently. Careful selection of asthma medications is essential to avoid exacerbation of CV symptoms. In addition, optimal management of CV risk factors is essential. However, close monitoring of these patients is important as there is evidence that some asthma medications may have adverse effects on CVD and, conversely, that some CVD medications may worsen asthma symptoms. On the other hand, there is also increasing evidence of the potential beneficial effects of asthma medications on CVD and, conversely, that some CVD medications may reduce the severity of asthma symptoms. We aim to elucidate the potential risks and benefits associated with the use of asthma medications in patients with CVD, and the potential pulmonary risks and benefits for patients with asthma who are prescribed CVD medications., (© 2024. The Author(s).)

Purpose: Montelukast is used extensively in children and adolescents for allergic rhinitis and asthma. However, concerns have been raised regarding the increased risk of neuropsychiatric adverse events (NPAEs) associated with montelukast use. Therefore, our case-crossover study was conducted to observe whether there is an increased risk of NPAEs associated with montelukast use in children and adolescents., Materials and Methods: A population-based case-crossover study using the customised Health Insurance Review and Assessment (HIRA) dataset was conducted. Paediatric patients aged between 0 and 19 years diagnosed with allergic rhinitis and/or asthma with a history of at least one montelukast prescription between 1 January 2018 and 31 December 2021 were included. Exposure to montelukast was assessed during 3-, 7-, 14-, 28- and 56-day hazard periods prior to each patient's NPAE. Stratified analyses according to age group, gender and season for the risk of NPAEs associated with montelukast use in the previous 7 days and 14 days were performed, respectively. Conditional logistic regression analysis was used to calculate adjusted ORs (aORs) with their corresponding 95% CIs, adjusting for concomitant medications., Results: A total of 161 386 paediatric patients was identified. An increased risk of NPAEs associated with montelukast was found in all time window periods, including 3-day (aOR 1.28, 95% CI 1.24 to 1.32), 7-day (aOR 1.29, 95% CI 1.26 to 1.33), 14-day (aOR 1.34, 95% CI 1.31 to 1.37), 28-day (aOR 1.38, 95% CI 1.36 to 1.41) and 56-day (aOR 1.21, 95% CI 1.19 to 1.22) preceding hazard periods compared with use in the four control periods., Conclusion: Children and adolescents with allergic rhinitis and/or asthma should be prescribed montelukast with caution considering clinical benefits., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Asthma is a chronic disease that often requires medication for control. Polypharmacy remains a major issue to medication adherence; however, its evidence among patients with asthma is limited., Objectives: To evaluate the prevalence and determinants of polypharmacy and its associations with asthma control among adults with asthma in the United States., Methods: Data from the 2005-2020 National Health and Nutrition Examination Survey were used to estimate the weighted prevalence of polypharmacy. Selected variables, including demographics, comorbidities, prescription medications, and asthma-related adverse events, were extracted from the National Health and Nutrition Examination Survey. Multivariable logistic regression was conducted to identify factors associated with polypharmacy. Another two sets of multivariable logistic regression models were employed to further assess the association between polypharmacy and asthma-related adverse events: one for asthma attacks and the other for asthma-related emergency department visits., Results: From 2005 to 2020, polypharmacy prevalence was 34.3% and 14.1% among adults with and without asthma, respectively. Characteristics, including older age (P < 0.01), non-Hispanic Blacks (P < 0.01), health insurance coverage (P < 0.01), number of health care visits (P < 0.01), and multiple comorbidities (P < 0.01), were associated with polypharmacy. Polypharmacy was associated with increased risks of having asthma attacks (odds ratio, 1.38; 95% CI, 1.08-1.76) and asthma-related emergency department visits (odds ratio, 1.46; 95% CI, 1.09-1.94) among adults with asthma. Among patients taking at least one asthma medication, risks of asthma attacks, and asthma-related emergency department visits did not differ between those with and without polypharmacy., Conclusion: Approximately one in three adults with asthma experienced polypharmacy in the United States. Disparities existed in several characteristics, highlighting the necessity for appropriate care and policies among vulnerable populations. Further validation on the impact of polypharmacy on asthma control is required., Competing Interests: Disclosures The author declares no relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objective: Modification of the immune system with biologics raises theoretical concerns about the risk of infections but it is still unclear whether currently routinely used biologics in severe asthma may facilitate the development of pneumonia. Therefore, we aimed to determine whether omalizumab, mepolizumab, benralizumab, and dupilumab are associated with pneumonia in a real-world setting., Methods: A retrospective disproportionality analysis was performed using adverse event (AE) reports submitted to FAERS from January 2020 to September 30, 2023. MedDRA was used to identify infections and infestations and then pneumonia cases. ROR and PRR were used to measure disproportionality., Results: The percentage of reported cases of pneumonia compared to infections and infestations was highest for mepolizumab (36.8%), followed by omalizumab (32.6%), benralizumab (19.2%) and dupilumab (5.7%). We found a moderate or strong signal for increased risk of pneumonia with mepolizumab (ROR = 3.74, 95%CI 3.50-4.00), omalizumab (ROR = 3.26, 95%CI 3.06-3.49) and benralizumab (ROR = 2.65, 95%CI 2.49-2.83)., Conclusions: Mepolizumab, omalizumab and benralizumab, but not dupilumab, were associated with high odds of reporting pneumonia. Our results represent only potential associations between these biologics and pneumonia but not causality. The nature of the FAERS database is such that the cause of the reported events is uncertain. Therefore, we can only roughly estimate the incidence of AEs by the signal strength (ROR value). Nevertheless, although causality could not be assessed, the signal from our study is interesting. We believe it deserves to be further substantiated by real-world studies with robust designs.

Purpose: The aim of this study was to evaluate perinatal outcomes between the uncontrolled asthma group and the mild asthma group and to reveal the relationship between disease severity and adverse maternal-fetal outcomes in this study., Methods: This retrospective cohort study analyzed 180 pregnant women diagnosed with asthma, hospitalized, and delivered at our center between September 1, 2019, and December 1, 2021. We compared two groups: 160 with mild asthma and 20 with uncontrolled asthma. Data encompassed maternal characteristics, obstetrical complications, medication use, emergency department admissions for exacerbations, smoking status, and neonatal outcomes., Results: In the uncontrolled asthma group, hospitalization rates, use of inhaled short-acting β-agonist (SABA), and systemic corticosteroids were significantly higher compared to the mild asthma group (p < 0.01). Maternal and fetal complications were more prevalent in the uncontrolled group, including asthma exacerbations (45% vs. 1.2%), anemia (10% vs. 4.4%), prematurity (25% vs. 9.6%), and intrauterine fetal demise (IUFD) (10% vs. 0.6%). Neonatal outcomes in the uncontrolled group showed higher rates of admission to the neonatal intensive care unit (NICU) (50% vs. 25%), respiratory distress syndrome (RDS) (30% vs. 14%), and intraventricular hemorrhage (IVH) (5% vs. 0%) compared to the mild asthma group., Conclusion: Uncontrolled asthma during pregnancy is associated with higher adverse maternal-fetal and neonatal outcomes compared to mild asthma., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: There are no validated decision-making algorithms concerning severe asthma (SA) management. Future risks are crucial factors and can be derived from SA trajectories., Areas Covered: The future severe asthma-decision trees should revisit current knowledge and gaps. A focused literature search has been conducted., Expert Opinion: Asthma severity is currently defined a priori , thereby precluding a role for early interventions aiming to prevent outcomes such as exacerbations (systemic corticosteroids exposure) and lung function decline. Asthma 'at-risk' might represent the ultimate paradigm but merits longitudinal studies considering modern interventions. Real exacerbations, severe airway hyperresponsiveness, excessive T2-related biomarkers, noxious environments and patient behaviors, harms of OCS and high-doses inhaled corticosteroids (ICS), and low adherence-to-effectiveness ratios of ICS-containing inhalers are predictors of future risks. New tools such as imaging, genetic, and epigenetic signatures should be used. Logical and numerical artificial intelligence may be used to generate a consistent risk score. A pragmatic definition of response to treatments will allow development of a validated and applicable algorithm. Biologics have the best potential to minimize the risks, but cost remains an issue. We propose a simplified six-step algorithm for decision-making that is ultimately aiming to achieve asthma remission.

Background: Benralizumab and mepolizumab are interleukin (IL)-5Rα/interleukin-5-targeted monoclonal antibodies indicated as add-on treatments for patients with uncontrolled severe eosinophilic asthma (SEA)., Objective: To evaluate and compare the safety of benralizumab and mepolizumab among patients with SEA treated in MELTEMI and COLUMBA open-label, long-term extension studies, respectively., Methods: MELTEMI was an extension study of benralizumab every 4 weeks (q4w) or every 8 weeks (q8w) for adults (aged 18-75 y) with SEA. MELTEMI participants transitioned from the BORA extension, preceded by participation in 1 of 3 placebo-controlled studies (SIROCCO, CALIMA, or ZONDA). COLUMBA was an extension study of mepolizumab for patients (aged ≥ 12 y) with SEA who transitioned from the dose-ranging DREAM study. Safety endpoints were presented as drug exposure patient-years (MELTEMI, q4w 784.28, q8w 797.03; COLUMBA 1,201) for nonserious adverse events, serious adverse events, and infections; malignancies were counted numerically., Results: This analysis included 446 MELTEMI patients (benralizumab q4w 220; benralizumab q8w 226) and 347 COLUMBA patients (mepolizumab q4w). Viral upper respiratory tract infection was the most common nonserious adverse event in both studies (MELTEMI q8w 46.5%; q4w 47.3%; COLUMBA, 48.7%). Asthma-related events were the most common serious adverse events in both studies: MELTEMI 8.0% (q8w) and 8.6% (q4w) and COLUMBA 9.5%. Serious infections included pneumonia (MELTEMI q8w, 2 [0.9%]; COLUMBA, 6 [1.7%]); cellulitis (MELTEMI q8w, 1 [0.4%]; COLUMBA, 2 [0.6%]); and respiratory tract infections (COLUMBA, 2 [0.6%]). COLUMBA reported 6 malignancies and MELTEMI reported 4 malignancies in each group., Conclusions: This analysis demonstrated generally similar safety events between mepolizumab and benralizumab in patients with SEA., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A male patient in his early 30s was diagnosed with bronchial asthma 3 years previously. He responded well to inhaled corticosteroids and long-acting beta-agonists. Approximately 18 months from the onset, the patient reported worsening symptoms. These symptoms included severe functional limitations, requiring frequent exposure to high-dose prednisolone. Mepolizumab was added to the treatment, leading to optimal control of bronchial asthma. Despite receiving seven doses of mepolizumab at monthly intervals, the patient developed cervical and postauricular lymphadenopathy and subcutaneous swelling of soft tissue. A cervical lymph node biopsy confirmed the diagnosis of Kimura disease. Following treatment with oral glucocorticoids and methotrexate, the patient experienced a complete resolution of symptoms. He has been in remission and off oral prednisolone for the last 13 months. In this case, we highlight the development of Kimura disease in a patient undergoing mepolizumab treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil ® , CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair ® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations., Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks., Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV 1 ) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies., Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters., Clinical Trial Registration: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20)., Competing Interests: Author BG has received educational grants from AstraZeneca, Abidi, and Sanofi. Author MM has received research grants from Koushan Pharmed. Authors HR and DA have received research grants from AstraZeneca. Author MF has received research grants from Abidi. Author AK has received lecture honorarium from AstraZeneca. Author FJ has received research grants from Zist Takhmir and Vitabiotics. Author ST has received travel supports to attend scientific meetings from Novartis, GSK, and AstraZeneca. Author MH has collaborated with Jaber-ebne-hayyan. Author MRF has collaborated with Pooyesh darou. Author HK is the head of the medical department of Orchid Pharmed Company; which is in collaboration with CinnaGen company with respect to conducting clinical trials. Author AS is a member of CinnaGen medical biotechnology research center, which collaborates with universities and researchers all over the world with regards to research and development of medications and health issues. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study was supported by CinnaGen Company by grant number of 701/373. The sponsor also had participated in the conduction of the study., (Copyright © 2024 Ghanei, Ghalebaghi, Sami, Torabizadeh, Mirsadraee, Amra, Tavakol, Raji, Fallahpour, Kiani, Abedini, Jabbari Azad, Mahdaviani, Attaran, Samet, Tavana, Haddadzadeh shoushtari, Nazari, AghaeiMeybodi, Fazlollahi, Ghasemi, Sabzvari, Kafi and Idani.)

Objectives: To investigate community pharmacists' attitudes, confidence, practice, knowledge, and barriers towards the management of oral side effects of asthma medications., Methods: A paper-based questionnaire was developed from previous research, trialled, and validated. Convenience sampling through web search was used to identify pharmacy practices across Cairns, Queensland, Australia. Practices were contacted by email and phone before hand-delivering and collecting questionnaires., Key Findings: Thirty eight community pharmacist responses were descriptively analysed. Community pharmacists surveyed within the Cairns region feel that it is within their role to help manage the side effects of asthma medications. Many feel this is best conveyed during inhaler dispensing and instruction. Current advice is more prompted rather than preventative. Pharmacists routinely advise patients of mouth-rinsing following inhaler use, however the link to preventing side effects is not clearly communicated. Pharmacists are confident in recognizing and managing common side effects such as oral thrush and dry mouth, but fewer are aware of dental decay and gingivitis. Many identify a lack of guidelines as the largest barrier to providing preventive oral health advice., Conclusions: Cairns community pharmacists already self-perceive their role in the management of oral side effects of asthma medications. Advice given to patients is practical but does not clearly convey the causative associations between asthma medications and their potential oral side effects. Patient education is prompted more by enquiry rather than a preventative approach. The development of standardized practice protocols and integration within undergraduate degrees or continuing education may benefit the community-pharmacist delivered care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Background: The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma., Methods: Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides., Results: Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo., Conclusions: Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: People with severe asthma remain at risk of toxicity from maintenance oral corticosteroid (OCS) use and/or frequent OCS burst therapy. Cumulative exposures above 500-1000 mg prednisolone are associated with adverse effects, and recently OCS stewardship principles were promulgated to guide OCS prescription., Aims: To examine real-world registry data to quantify OCS burden, ascertain trends over time in prescription and assess whether opportunities to implement steroid-sparing strategies were utilised., Methods: Participants were enrolled in the Australasian Severe Asthma Registry for the period 2013-2021. Assessments were taken at enrolment and then annual follow-up, which included asthma control and OCS use. Descriptive analyses were performed, and subgroups were compared at baseline and over time., Results: Nine hundred and twenty-four participants were evaluated and 215/924 (23%) were taking maintenance OCS at baseline, with 44% and 32% of participants having exposure to ≥500 or 1000 mg of OCS respectively in the prior year. Twelve months later, an additional 10% and 9% of participants reached cumulative doses of 500 or 1000 mg. People exceeding thresholds had ongoing poor asthma control. At baseline, 240/924 (26%) people were treated with asthma biological therapy. An additional 83 (12%) participants were identified as potentially benefiting from this steroid-sparing medication. Of these patients, only 23% commenced a biologic agent in the next 12 months., Conclusions: A large national asthma registry identifies exposure to toxic cumulative doses of OCS in more than a third of participants, with further subsequent cumulative dose escalation over 2 years. Steroid-sparing strategies were often not employed, highlighting the need for implementation of OCS stewardship initiatives., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS)., Methods: Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps., Results: Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses., Conclusion: Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9.

Introduction: Biologic drugs have been shown to reduce asthma exacerbations, improve lung function and quality of life, reduce oral corticosteroid use in appropriately selected patients. Mepolizumab has been demonstrated to have a safety profile that is similar to placebo, however, when present side effects may lead to treatment discontinuation. Among these, headache is one of the most common., Case Study: We hereby describe the case of a never-smoking male patient with an eosinophilic corticosteroid-dependent severe asthma. He displayed well controlled comorbidities and good adherence to the inhaled therapy. Mepolizumab was started in 2017 with an initial remarkable clinical improvement. After three doses of biologic therapy, he reported a severe orthostatic headache associated with vomiting, unresponsive to analgesic drugs, that required hospitalization. No other cause than treatment with Mepolizumab was found to be plausibly associated with this new-onset headache. The therapeutic regimen was modified by administering Mepolizumab for two consecutive months alternated with a one-month break., Results: The patient did not experience any further episodes of headache, while maintaining a good and stable control of his asthma. We were able to taper oral corticosteroids, and no flares-ups occurred in the following 5 years., Conclusion: Our experience indicates that a tailored strategy for managing severe asthmatic patients, who have experienced side effects from biologic drugs, can be effective in maintaining drug efficacy while minimizing side effects. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes here described are replicable on a larger scale.

Objectives: To review the efficacy of nebulised magnesium sulfate (MgSO 4 ) in acute asthma in children., Methods: The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO 4 as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them., Results: 10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO 4 /placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: -0.09; 95% CI: -0.2 to +0.02, I 2 =21%). Children in the MgSO 4 group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I 2 =0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups., Conclusions: There is low-certainty evidence that nebulised MgSO 4 as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO 4 in paediatric acute asthma management., Prospero Registration Number: CRD42022373692., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aims to evaluate the effect of telephone and short-message follow-ups on compliance and efficacy in asthmatic children treated with inhaled corticosteroids., Methods: A total of 120 children with moderate bronchial asthma who visited the Asthma Outpatient Department of the Affiliated Hospital of Qingdao University were enrolled in the study. They were divided randomly into 3 groups based on the type of follow-up given: a combined telephone and short-message service (Tel + SMS) group, a SMS group, and a control group. After being followed up for 12 weeks, each child's asthma control level was assessed and their lung function was measured., Results: The compliance rates of children in the Tel + SMS group and SMS group were 86.49% and 56.25%, respectively. The total effective rates of these 2 groups (94.59% and 75.0%, respectively) were significantly higher than the rate of the control group (P < .01). The lung function indicators of the children in all 3 groups were better than those before treatment, although only the Tel + SMS group and SMS group improved significantly (P < .05). The lung function indicators of the large and small airways in the Tel + SMS group and the SMS group were also significantly better than those of the control group (P < .01). The results of the study suggest that 1 of the causes of poor compliance in asthmatic children is fear of an adverse reaction to inhaled corticosteroids., Conclusion: Telephone and short-message follow-ups can increase compliance with inhaled corticosteroid treatment and improve the asthma control levels and lung function of asthmatic children., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs., Objective: The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database., Methods: We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3)., Results: Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab., Conclusions: The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation., (© 2024. The Author(s).)

Introduction: Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the development of biomedicines, of which there are currently five available in France, with a safety profile that appears favorable but remains uncertain due to a lack of real-life experience with these new molecules., State of Knowledge: Although relatively benign, the adverse effects of biologics are diverse. Headache, joint pain, skin reactions at the injection site, fever and asthenia are commonly observed during the different treatments. Ophthalmological complications seem restricted to dupilumab, with numerous cases of keratitis and conjunctivitis in patients with atopic dermatitis. Several respiratory complications have also been observed, essentially consisting in pharyngitis and other upper respiratory infections. Hypereosinophilia may occur, mainly with dupilumab, requiring investigation of systemic repercussions or vasculitis. Allergic reactions are uncommon but require careful monitoring during initial injections., Conclusion: Biologics for severe asthma are recent drugs with a favorable safety profile, but with little real-life experience, justifying increased vigilance by prescribing physicians., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration., Competing Interests: Es bestehen keine Interessenkonflikte, (© 2024 Aerzteverlag medinfo AG.)

Purpose of Review: Severe asthma patients suffer from decreased quality of life, and increased asthma symptoms, exacerbations, hospitalizations, and risk of death. Biologics have revolutionized treatment for severe asthma. However, with multiple biologic agents now available, clinicians must consider initial selection the long-term effectiveness of biologics. Additionally, patients have overlapping eligibilities and clinicians may consider switching between biologics for improved response. Finally, careful assessment of biologics cessation is needed for severe asthma patients who depend on these add-on therapies for asthma control., Recent Findings: Evidence for long-term durability and safety varies by biologic agent. In general, initial benefits noted from these agents (ex. exacerbation reduction) is, at minimum, sustained with long term use. Rates of adverse events and serious adverse events, including those requiring cessation of a biologics are low with long term use. Further studies are needed to understand the development of antidrug antibodies but currently their prevalence rates are low. Adverse events and insufficient efficacy are common reasons for biologic cessation or switching. Discontinuation maybe associated with waning of benefits but can be considered in certain situations. Biologic switching can be associated with improved asthma control., Summary: Biologics are safe and effective long-term therapies for the management of asthma. Discontinuation must be carefully considered and if possible avoided. Reasons for insufficient efficacy must be evaluated and if needed, biologic switching should be considered., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to investigate asthma medication reduction in the periconceptional period as it relates to asthma status and adverse outcomes in pregnancy., Study Design: In a prospective cohort study, self-reported current and past asthma medications were collected and analyzes compared measures of asthma status in women who discontinued asthma medication in the 6 months prior to enrollment ("step-down") versus those who did not ("no change"). Evaluation of asthma was done at three study visits (one per trimester) and by daily diaries, including measures of lung function (percent predicted forced expiratory volume in 1 and 6 s [%FEV1, %FEV6], peak expiratory flow [%PEF], forced vital capacity [%FVC], FEV1 to FVC ratio [FEV1/FVC]), lung inflammation (fractional exhaled nitric oxide [FeNO], ppb), rate of asthma symptoms (activity limitation, night symptoms, rescue inhaler use, wheeze, shortness of breath, cough, chest tightness, chest pain), and rate of asthma exacerbations. Adverse pregnancy outcomes were also evaluated. Adjusted regression analyses examined whether adverse outcomes differed by periconceptional asthma medication changes., Results: Of 279 participants included in analyses, 135 (48.4%) did not change asthma medication in the periconceptional period, whereas 144 (51.6%) reported a step down in medication. Those in the step-down group were more likely to have milder disease (88 [61.1%] in the step-down vs. 74 [54.8%] in the no change group), exhibited less activity limitation (rate ratio [RR]: 0.68, 95% confidence interval [CI]: 0.47-0.98), and experienced fewer asthma attacks (RR: 0.53, 95% CI: 0.34-0.84) during pregnancy. The step-down group had a nonsignificant increase in overall odds of experiencing an adverse pregnancy outcome (odds ratio: 1.62, 95% CI: 0.97-2.72)., Conclusion: Over half of women with asthma reduce asthma medication in the periconceptional period. Although these women typically have milder disease, a step down in medication may be associated with an increased risk of adverse pregnancy outcomes., Key Points: · Many women reduce their asthma medication in pregnancy.. · Reduction is more common among those with mild disease.. · Medication reduction may lead to adverse pregnancy outcomes.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab., Methods: We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety., Results: 48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51-0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27-0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09-0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI -0.46--0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26-0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile., Conclusions: This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation., Competing Interests: Conflict of interest: A. Gogali has received consulting fees from Boehringer Ingelheim and Chiesi; and payment or honoraria for lectures, presentations or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK and Novartis. K. Kostikas has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis, Pfizer and Sanofi Genzyme; and payment or honoraria for lectures, presentations or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis, Pfizer and Sanofi Genzyme. K. Kostikas is a member of the GOLD Assembly. C. Kyriakopoulos and G. Markozannes declare no competing interests., (Copyright ©The authors 2024.)

Aim: To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up., Materials and Methods: We recruited 129 adult outpatients (29% males) aged 18-81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3-6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab - 9 pts, мepolizumab - 8 pts, benralizumab - 11 pts, dupilumab - 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ., Results: The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma ( p <0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%., Conclusion: Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.

Introduction: The data on the use of dual biologics are scant, but a topic of current interest., Case Study: In this report, the treatment regimen of a patient with two T helper 2 pathway-related comorbidities, severe asthma, and chronic spontaneous urticaria, was presented., Results: Both urticaria and asthma symptoms of the patient could not be controlled entirely with monotherapy while both diseases could be controlled after omalizumab-mepolizumab dual treatment. No adverse events were observed after 6 months of dual biologics use., Conclusion: This report supports other publications in the literature involving the use of dual biologics and provides a summary of the literature.

Introduction: The prevalence of asthma in adults >65 years old is approximately 12-14%, and 10% have severe asthma. A higher mortality rate is observed in subjects with asthma >65 years old and especially >80 years old., Objective: To analyze the effectiveness and safety of at least three doses of benralizumab in a subgroup of elderly subjects (>65 years old) with uncontrolled severe eosinophilic asthma in real-life conditions., Methods: This was a retrospective multicenter study (AUTOBENRA study) conducted in 9 hospitals that included 72 patients aged >18 years old with uncontrolled severe asthma based on the Spanish Asthma Guidelines who were treated with at least three doses of benralizumab, self-administered at home since before April 30, 2021. The recruitment period ended on October 1, 2021. Written consent was obtained before the study commencement. In this subanalysis, we compared the results between patients >65 years old and patients <65 years old., Results: A total of 72 subjects with severe asthma were screened, and 54 were included ( MD : 57.3 ± 10 years old). There were 12 subjects aged >65 years old [ MD : 69.8 ± 4.3 years old (minimum: 65 years old; maximum: 83 years old)]. Subjects >65 years old experienced statistically significant improvement in lung function, ACT and mini-AQLQ with benralizumab. Additionally, 9 patients (75%) experienced no asthma exacerbation ( p  = 0.0047), half (3/6) were able to stop OCS ( p  = 0.08), and no adverse effects with benralizumab were reported during the 20 months of follow-up., Conclusions: In patients aged >65 years old, benralizumab was an effective and safe therapy for severe eosinophilic asthma in our study, with no significant differences from the younger subgroup. This is especially important since they are a group with numerous comorbidities, medications and worse quality of life.

Background: Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody approved as an add-on maintenance treatment for patients with uncontrolled severe asthma. Prior Phase 3 studies have evaluated benralizumab in patients aged ≥12 years with severe uncontrolled asthma. The TATE study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab treatment in children., Methods: TATE was an open-label, Phase 3 study of benralizumab in children aged 6-11 years from the United States and Japan (plus participants aged 12-14 years from Japan) with severe eosinophilic asthma. Participants received benralizumab 10/30 mg according to weight (<35/≥35 kg). Primary endpoints included maximum serum concentration (C max ), clearance, half-life (t 1/2 ), and blood eosinophil count. Clearance and t 1/2 were derived from a population PK (popPK) analysis. Safety and tolerability were also assessed., Results: Twenty-eight children aged 6-11 years were included, with an additional two participants from Japan aged 12-14 years also included in the popPK analysis. Mean C max was 1901.2 and 3118.7 ng/mL in the 10 mg/<35 kg and 30 mg/≥35 kg groups, respectively. Clearance was 0.257, and mean t 1/2 was 14.5 days. Near-complete depletion of blood eosinophils was shown across dose/weight groups. Exploratory efficacy analyses found numerical improvements in mean FEV 1 , mean ACQ-IA, patient/clinician global impression of change, and exacerbation rates. Adverse events occurred in 22/28 (78.6%) of participants; none led to discontinuation/death., Conclusion: PK, PD, and safety data support long-term benralizumab in children with severe eosinophilic asthma, and were similar to findings in adolescents and adults., Trial Registration: ClinicalTrials.gov-ID: NCT04305405., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The goal of asthma guideline therapy is to achieve disease control, by minimizing impairment and decreasing the risk of exacerbations and adverse effects of the disease and its treatment. The primary objective of most clinical trials of biologics for severe asthma is a reduction in exacerbation rate. Recently, studies with patients at the lower guideline steps have also selected exacerbation reduction as a primary objective. These trials in patients with milder disease frequently demonstrate statistically significantly fewer exacerbations, but their power calculations reflect larger sample size and smaller effect size. Exacerbations have a precise consensus definition, although a minimal clinically important difference has not been established. Reduction of exacerbations in severe asthma is commonly 10-fold greater than in mild disease. Further, reduction in exacerbations is not always associated with reduced impairment. If superior control is the objective, both domains should demonstrate consistent and parallel improvement. The disconnect may reflect the need for alternative tools for measurement of impairment or, possibly, different therapeutic mechanisms of action. Determining response to biologics or discussion of disease remission requires assessing symptoms that may occur daily rather than focusing on exacerbations that occur once or twice a year for patients at the highest steps of care according to the guidelines., Competing Interests: Disclosure statement Disclosure of potential conflict of interest: S. J. Szefler has been a consultant for AstraZeneca, Eli Lilly, GlaxoSmithKline, Moderna, OM Pharma, Propeller Health, Regeneron, and Sanofi. D. A. Stempel is a former employee of Propeller Health and GlaxoSmithKline., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to clarify comprehensively the safety profiles of anti-IL-5 drugs and pinpoint potential safety concerns that may arise in their post-marketing phase., Methods: Two researchers conducted comprehensive searches of PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to September 2022. Additionally, we investigated the FDA AE Reporting System for post-marketing adverse event (AE) reports related to anti-IL-5 drugs. The outcomes fulfilled the proportional reporting rate criteria and the Bayesian confidence propagation neural network., Results: We included 24 published studies in our analysis. The anti-IL-5 treatment group showed an incidence of AEs comparable to the placebo group, and it exhibited a significantly lower frequency of serious AEs. Common AEs were asthma, nasopharyngitis, headache, upper respiratory tract infection (URTI), and bronchitis. The post-marketing data included 28,478 case reports associated with the suspect drugs and 75 suspect safety observations affecting 16 system organ classes. New suspect observations included incomplete therapeutic product effect, URTIs, and pulmonary mass in reports related to mepolizumab. Reports associated with mepolizumab and benralizumab also indicated issues with incorrect technique in device usage and product issues., Conclusions: Individual anti-IL-5 drugs' safety profiles largely matched their product inserts. We identified issues like improper device usage, product issue, and URTIs as potential concerns for mepolizumab and benralizumab. Additionally, all anti-IL-5 drugs showed signs of incomplete therapeutic effects., (© 2024. The Author(s).)

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is heterogeneous in both phenotypes and endotypes. Due to insufficient head-to-head comparison studies, it is hard to decide which biological to initiate. This study aimed to compare the efficacy of omalizumab and mepolizumab which can be used in the treatment of patients with severe eosinophilic asthma diagnosed with N-ERD., Methods: The population of this observational, cross-sectional study comprised of N-ERD patients who received omalizumab or mepolizumab for at least 6 months for severe asthma. Outcomes included the asthma control test (ACT), and sino-nasal outcome test scores (SNOT-22), blood eosinophil counts at initiation of biological treatment (T0, baseline) and at the end of 6th months (T6). Adverse effects related to biological treatment and changes of oral corticosteroids dose was recorded., Results: The study included a total of 22 patients, of whom 11 received mepolizumab and 11 received omalizumab. The change in ACT, SNOT-22, eosinophil counts, and adverse effects related to biologicals were similar at T6 (p = 0.606, p = 0.168, p = 0.05, p = 0.053, respectively). However, when examining the SNOT-22 and ACT based on the cumulative distribution curve (SUCRA), mepolizumab (SUCRA value: 0.61, 0.72, respectively) demonstrated greater efficacy compared to omalizumab (SUCRA value: 0.19, 0.35, respectively). The oral corticosteroids discontinuation rate was similar between the two groups (p = 0.05)., Conclusion: We found both omalizumab and mepolizumab to be effective in treatment; however, we determined that mepolizumab may have a potential superiority in efficacy., (© 2024 S. Karger AG, Basel.)

The introduction of biological drugs for the treatment of severe allergic asthma in children, almost twenty years ago, had a substantial impact on both the pathology's clinical course and the quality of life of the patients who receive treatment. Over the years, several molecules have been developed that inhibit molecular targets involved in the pathogenesis of the asthmatic disease. Biological drugs demonstrate a significant improvement in several key clinical parameters in patients with severe asthma. In this review, we provide a concise summary of the evidence on biological therapy for children and adolescents with severe asthma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Asthma is a disease characterized by chronic airway inflammation, however one-third of asthmatic cases did not respond adequately. Inhaled magnesium has been proposed as a treatment for unresponsive asthma cases. However, its role remains controversial. This review evaluates the effectiveness and safety of nebulized magnesium compared to standard therapy (Beta Agonist, Anticholinergic, Corticosteroid) in adults with acute asthma attacks., Methods: The protocol has been registered in PROSPERO. A literature search was conducted through PubMed/MEDLINE, Cochrane, ProQuest, and Google Scholar, and using the keywords "inhaled magnesium" and "asthma". Manual searches were carried out through data portals. Journal articles included are randomized controlled trials. The assessment risk of bias was performed using Version 2 of the Cochrane risk-of-bias tool for randomized trials., Results: There are five articles included in this review. There is no significant difference in readmission rate and oxygen saturation in the magnesium group compared to control (RR 1; 95% CI 0.92 to 1,08; p= 0,96 and MD 1,82; 95% CI -0.89 to 4.53; p= 0.19, respectively). There is a significant reduction of respiratory rate and clinical severity in magnesium (MD -1,72; 95% CI -3,1 to 0.35; p= 0.01, RR 0.29; 95% CI 0.17 to 0.69; p <0.001, respectively). There was a higher risk of side effects in the magnesium group (HR 1.56; 95%CI 1.05 to 2.32; p= 0.03). However, the side effects are relatively mild such as hypotension and nausea., Conclusion: Inhaled magnesium improves the outcome of asthmatic patients, especially in lung function, clinical severity, and respiratory rate. Moreover, inhaled magnesium is safe to be given.

Introduction: Asthma is a chronic inflammatory disease that can lead to airways remodeling. Despite their well-known side-effects, oral corticosteroids (OCS) continue to be used to reduce exacerbations and control asthma symptoms in many patients., Case Study: We describe two cases of uncontrolled severe asthma characterized by systemic clinical consequences of prolonged OCS use, such as diabetes, weight gain, and osteoporosis., Results: Both patients were treated with Dupilumab. During follow-up both patients showed an improvement in asthma control and were able to gradually taper the OCS dose, thus reducing the clinical burden associated with hypercortisolism., Conclusion: Dupilumab was able to control both the inflammatory-induced "airway remodeling" as well as the OCS-induced "patient remodeling".

Background/aims: Despite short-acting β2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study., Methods: This study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms., Results: Data from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation., Conclusion: SABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.

Purpose: This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children., Methods: Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran's Q test and I 2 statistics, followed by sensitivity analysis and publication bias evaluation., Results: Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The cough remission and disappearance times in the Mon + Flu group were significantly lower than those in the Flu group. FEV1% recovery in the Mon + Flu group was significantly better than that in the Flu group., Conclusion: Mon + Flu is effective and safe for the treatment of CVA in children., (© 2023. The Author(s).)

Background: A multistakeholder core outcome set created for asthma trials showed that asthma-specific quality of life (QoL) was a critically meaningful outcome. However, the definition and measurement methods were undetermined. The adverse effects (AEs) of corticosteroids may be a vital clinical trial outcome. Nevertheless, the AE burden from the patient perspective has not yet been elucidated in an asthma population., Objective: To characterize patient burden of AEs in oral (OCS) and inhaled corticosteroids (ICS) and how this relates to QoL within an asthma population., Methods: We used a convergent parallel mixed-methods design with quantitative surveys of known ICS and OCS AEs that were distributed through the Allergy & Asthma Network database, social channels, and the Asthma UK newsletter. Participants rated the AEs that were (1) most burdensome and (2) most desired to be eliminated. Qualitative interviews and focus groups were performed to better understand patient views on barriers reported in the quantitative data, and to identify patient-important barriers that were not a part of the quantitative survey., Results: The 3 most burdensome AEs for OCS were bone mineral density, infectious complications, and weight gain, whereas weight gain was the most desired to be eliminated. The 3 most burdensome AEs for ICS were pneumonia, hoarse voice, and oral thrush, with concordant results for the most desired to be eliminated. In the focus groups, OCS AEs were concordant with quantitative findings. Focus groups identified unmeasured psychosocial effects, such as embarrassment., Conclusion: The most burdensome AEs may not be those that would cause patients to stop therapy. Furthermore, qualitative focus groups suggest a psychosocial burden associated with ICS, which needs further investigation., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning., Objective: To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast., Methods: This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting β2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group)., Results: There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls., Conclusions: We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period., (Copyright © 2023. Published by Elsevier Inc.)

Purpose of Review: A modified Delphi process was undertaken to provide a US expert-led consensus to guide clinical action on short-acting beta 2 -agonist (SABA) use. This comprised an online survey (Phase 1), forum discussion and statement development (Phase 2), and statement adjudication (Phase 3)., Recent Findings: In Phase 1 (n = 100 clinicians), 12% routinely provided patients with ≥4 SABA prescriptions/year, 73% solicited SABA use frequency at every patient visit, and 21% did not consult asthma guidelines/expert reports. Phase 3 experts (n = 8) reached consensus (median Likert score, interquartile range) that use of ≥3 SABA canisters/year is associated with increased risk of exacerbation and asthma-related death (5, 4.75-5); SABA use history should be solicited at every patient visit (5, 4.75-5); usage patterns over time, not absolute thresholds, should guide response to SABA overuse (5, 4.5-5). Future asthma guidelines should include clear recommendations regarding SABA usage, using expert-led thresholds for action., (© 2023. The Author(s).)