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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.

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.

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.

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.

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.

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".

Objective: The open-label extension TRAVERSE study (NCT02134028) assessed dupilumab long-term safety and efficacy in patients who completed Phase 2/3 dupilumab asthma studies. This post hoc analysis evaluated long-term efficacy in type 2 patients with and without evidence of allergic asthma who enrolled in TRAVERSE from Phase 3 QUEST (NCT02414854) and Phase 2b (NCT01854047) studies. Non-type 2 patients with evidence of allergic asthma were also assessed., Methods: Unadjusted annualized exacerbation rates during parent study and TRAVERSE treatment period, and changes from parent study baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) and in 5-item Asthma Control Questionnaire (ACQ-5) scores were assessed in patients from QUEST and Phase 2b; change from parent study baseline in total IgE level was assessed in patients enrolled from Phase 2b., Results: 2062 patients from Phase 2b and QUEST enrolled in TRAVERSE. Of these, 969 were type 2 with evidence of allergic asthma; 710 were type 2 without evidence of allergic asthma; and 194 were non-type 2 with evidence of allergic asthma at parent study baseline. In these populations, reductions in exacerbation rates observed during parent studies were sustained during TRAVERSE. Type 2 patients who switched from placebo arm to dupilumab in TRAVERSE experienced similar reductions in severe exacerbation rates, and improvements in lung function and asthma control to those patients who already received dupilumab during the parent study., Conclusion: Dupilumab efficacy was sustained for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 inflammatory asthma, with or without evidence of allergic asthma.ClinicalTrials.gov identifier: NCT02134028.

Objective: Acute asthmatic exacerbation is a common condition for pediatric emergency visits. Recently, dexamethasone has increasingly been used as an alternative to prednisone. This study aimed to evaluate the safety and efficacy of dexamethasone (DEX) against prednisone/prednisolone (PRED) in managing pediatric patients with acute asthmatic exacerbation., Data Sources: Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles from their inception to August 2022 by two independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42022353462)., Study Selections: From 316 studies screened, seventeen studies met the eligibility criteria, with 5967 pediatric patients experiencing an asthma exacerbation requiring treatment with either DEX ( n  = 2865) or PRED ( n  = 3102). Baseline patient characteristics (age, sex, PRAM (pediatric respiratory assessment measure), previous corticosteroid and beta-agonist inhaler) were comparable between groups., Results: After treatment administration, the DEX group had fewer vomiting incidents (OR = 0.24, 95% CI: 0.11, 0.51, I 2  = 58%) and reduced noncompliance events (OR = 0.12, 95% CI: 0.04, 0.34, I 2  = 0%) when compared to the PRED group. Regarding emergency-department (ED)-related outcomes, there were no differences in hospital admission rates (OR = 0.83, 95% CI: 0.58, 1.19, I 2  = 15%), time spent in the ED (MD= -0.11 h, 95% CI: -0.52; 0.30, I 2  = 82%) or relapse occurrences (OR = 0.67, 95% CI: 0.30, 1.49, I 2  = 52%) between both groups., Conclusion: Although there were no differences between the DEX and PRED groups in terms of hospital admission rates, time spent in the ED or relapse events, pediatric patients receiving DEX experienced lower noncompliance and vomiting rates.

Objective: While advances in asthma care have been made in Latin America, there is still a large unmet need in patients with uncontrolled asthma. This post hoc analysis of the QUEST study assessed safety and efficacy of dupilumab in the subgroup of patients enrolled in Latin American countries with a type 2 inflammatory asthma phenotype (blood eosinophils ≥ 150cells/µL or FeNO ≥25ppb)., Methods: LIBERTY ASTHMA QUEST (NCT02414854) was a phase 3, multinational, randomized, double-blind, placebo-controlled study in patients with uncontrolled, moderate-to-severe asthma. Eligible patients ≥ 12 years of age were randomized in a 2:2:1:1 ratio to receive 52 weeks of add-on subcutaneous dupilumab 200 or 300 mg every 2 weeks or matched-volume placebos. Pre-specified co-primary efficacy endpoints were the annualized rate of severe exacerbations during the treatment period and the change from baseline in pre-bronchodilator FEV 1 at treatment week 12. Asthma control, changes in asthma biomarker levels, and dupilumab safety were also evaluated., Results: 530 (27.9% of the overall QUEST population; dupilumab: 353, placebo: 177) Latin-American patients were recruited; 420 (79.2%) had a type 2 inflammatory asthma phenotype. Dupilumab vs placebo reduced the annualized rate of severe exacerbations by 52.7% ( P  < 0.001) and increased pre-bronchodilator FEV 1 at week 12 by 0.15 L ( P  < 0.001), in the type 2 population. Safety was consistent with the known dupilumab safety profile., Conclusions: Consistent with the results in the overall population, dupilumab reduced the risk of severe asthma exacerbations and improved lung function in Latin American patients with uncontrolled, moderate-to-severe asthma and a type 2 phenotype.

Background: Severe asthma treatment with oral corticosteroids (OCS) added to inhaled corticosteroids and a long-acting β2-agonist (ICS-LABA) may result in more treatment burden and increased adverse effects., Objective and Methods: This ambispective multicenter observational study aimed at describing the clinical burden in patients with severe asthma on stable high-dose ICS-LABA who received OCS during ≥6 months (maintenance group) or ≥2 cycles in the previous 12 months (bursts group). Data collection comprised a retrospective 12-month baseline period and 2 follow-up visits at 3 and 6 months., Results: Eighty-nine patients were evaluable (30 on maintenance, 59 on bursts). At baseline, mean (SD) daily prednisone equivalent exposure in the total population was 24.6 (14.7) mg: 13.8 (9.4) mg on maintenance and 29.9 (14.3) mg on bursts. During the 6-month follow-up period, mean (SD) daily dose in the total cohort was 22.5 (18.8) mg: 17.2 (18.6) mg on maintenance and 28.4 (20.6) mg on bursts. The overall annual severe exacerbations rate during the 12-month baseline period was 2.05 per patient-year and 1.5 per patient-year over the 6-month follow-up, and frequency of hospitalizations and emergency department visits were similar on both maintenance and bursts use., Conclusions: Results show a suboptimal control of severe asthma despite such high doses of OCS and persistence of disease burden regardless of the prescribing pattern in maintenance or bursts. There is therapeutic inertia to continue using OCS despite the increased risk of adverse effects and the availability of biologics.

Objective: We aim to examine the impact of corticosteroids use on ADHD among children with asthma by administration routes., Methods: A population-based, cross-sectional analysis included pediatric patients ages 5-20 years old from the 2016 and 2019 Kids Inpatient Database (unweighted N  = 111,702). ICD-10-CM codes were used to identify corticosteroids use, asthma, and ADHD cases. Survey logistic regression models with purposeful variable selection algorithms were built to examine the association between corticosteroids use, and ADHD by asthma severity and age. An inverse probability weighting (IPW) approach was used to help further control residual confounding., Results: Among children aged 5-11 years old, the odds of ADHD were significantly higher in children with moderate to severe asthma who used inhaled corticosteroids than nonusers (moderate asthma: adjusted odds ratios [aOR] 1.46, 95% confidence interval [CI] 1.14-2.44; severe asthma: aOR 1.61, 95% CI 1.18-2.21). Although oral corticosteroid use was not independently associated with ADHD in young children, combined use of inhaled and oral corticosteroid had almost 5 times higher odds of use among ADHD in children with severe asthma vs. nonusers (aOR 4.85, 95% CI 2.07 - 11.35). No associations were found between any corticosteroid use and ADHD among asthmatic children aged 12-20 years., Conclusions: In this retrospective analysis, we found inhaled corticosteroids were positively associated with ADHD in younger children with moderate to severe asthma, but not in older children.

Objective: To assess the safety of biological therapy for severe T2 asthma (omalizumab, mepolizumab, benralizumab and reslizumab) under real-life conditions in elderly patients older than 70 years., Methods: Retrospective data collection including clinical characteristics, comorbidities, treatment, disease control and adverse events (AE) of all patients with severe asthma on biological therapy older than 70 years seen in the Severe Asthma Unit of our hospital., Results: Of 147 patients with severe asthma being treated with biologics, 21 patients older than 70 years were included. The median age of these patients was 76.3 years (range 71-86) and the majority were women ( n  = 18, 85.7%). There were 9 patients (42.9%) who experienced an AE related to biological treatment. Four (44.4%) were in treatment with omalizumab, two (22.2%) with mepolizumab, two patients (22.2%) with reslizumab and one (11.1%) with benralizumab. The median FEV 1 (%) was 66%. These patients had a considerably higher body mass index (BMI). No significant differences were found for any other variable. Most of the AE reported were considered mild with the exception of one case of systemic AE (anaphylaxis) associated with omalizumab., Conclusion: This study indicates that the prescription of biological therapy in elderly patients with severe asthma seems to be safe. More evidence is needed in this particular population.

Objective: The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma in randomized controlled trials is well established. Following approval of mepolizumab as add-on therapy for severe eosinophilic asthma in multiple regions worldwide, it is now important to determine its impact in real-world settings in which patients are not subject to stringent eligibility criteria. This systematic literature review assessed published evidence of clinical outcomes, safety, and healthcare resource use among patients with severe asthma receiving mepolizumab in real-world settings., Data Sources: Searches were conducted in Embase, MEDLINE, and MEDLINE In-Process via Ovid., Study Selections: Eligible studies were observational, and enrolled ≥10 patients with asthma who received mepolizumab 100 mg subcutaneously. Data extracted included annualized exacerbation rate, mean daily oral corticosteroid (OCS) dose, proportion of patients using OCS, several measures of lung function, patient-reported asthma control and health-related quality of life (HRQoL), safety, and economic burden., Results: Twenty-three articles (22 unique studies; 2,040 patients with severe asthma on mepolizumab) were identified. Mepolizumab use was associated with a reduction in annualized exacerbation rates (requiring OCS) of 54-97% ( p  < 0.05 in all studies), reduced mean/median daily OCS doses, and OCS discontinuation during follow-up (27-84% of patients). Improvements in lung function, asthma control, and HRQoL were also observed. The most commonly reported adverse events included headache and arthralgia; discontinuation of mepolizumab due to adverse events occurred in 0-10.6% of patients., Conclusion: Findings show that patients with severe asthma consistently demonstrate clinically relevant benefits with mepolizumab treatment in a real-world setting., Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Objective: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions., Methods: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate., Results: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) ( p  < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) ( p  < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) ( p  < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period., Conclusions: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Objective: To improve understanding of real-world asthma treatment and inform physician education, we evaluated regional variation in asthma prevalence and oral corticosteroid (OCS) use across Germany., Methods: We developed a machine learning gradient-boosted tree model with IMS® Disease Analyzer electronic medical records, which cover 3% of German patients. This model had a 91% accuracy in predicting the presence of asthma and chronic obstructive pulmonary disease. We applied the model to the IMS ® Longitudinal Prescription database, with 82% national coverage, to classify patients receiving treatment for airflow obstruction from October 2017-September 2018 in 63 regions in Germany., Results: Of 2.4 million individuals under statutory health insurance predicted to have asthma, 13.7%, 18.7%, 36.5%, 29.4%, and 1.7% received treatment classified as Global Initiative for Asthma (GINA) Steps 1, 2, 3, 4, and 5, respectively. Approximately 7-15% of those at GINA Steps 1-4 and 35% at Step 5 treatment received ≥1 acute OCS prescription (duration <10 days). Of patients receiving GINA Steps 1-4 and Step 5 treatments, 1-3% and 86%, respectively, received ≥1 high-dosage OCS prescription. Cumulative OCS dosage and percentages of patients receiving OCS differed substantially across regions, and regions with lower OCS use had greater use of biologic therapies., Conclusions: Both acute and high OCS use varied regionally across Germany, with overall use suggesting patients are considerable risk of adverse effects and long-term health consequences., Supplemental data for this article can be accessed at publisher's website.

İntroduction: Asthma is one of the most common chronic airway disease among reproductive period of women. Chronic inflammation in asthma, eosinophilia, high steroid treatment and uncontrolled asthma may cause infertility by affecting the reproductive organs, menstrual cycle and quality of life. Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids. Mepolizumab (anti-IL-5) is a succesful option of treatment., Cases: First case; 25-year-old female patient has been diagnosed having asthma and rhinitis for 5 years. Even she had desired pregnancy for 3 years, she was unable to have a baby, and had been diagnosed having primary infertility. Second case; 36 years old female had rhinitis for 6 years and asthma for 4 years Although she used the same contraception method (withdrawal,condom) for years, she did not get pregnant until receiving the second dose of mepolizumab treatment., Result: Two women were treated with mepolizumab for eosinophilic severe asthma and they got pregnant., Conclusion: Unexplained infertility in people with severe eosinophilic asthma may be corrected by mepolizumab treatment. However, there is not enough data regarding the use of mepolizumab during pregnancy.

Objective: To assess the efficacy and safety of omalizumab in children with moderate-to-severe asthma., Data Sources: We systematically searched MEDLINE, EMBASE, and Cochrane for randomized controlled trials (RCTs ) (inception to January 2020)., Study Selections: All RCTs which were conducted in childhood and adolescence with asthma and compared the efficacy or safety of omalizumab were adopted., Results: Three studies with four publications including 1380 pediatric patients met our criteria. For children with moderate-to-severe asthma, omalizumab decreased asthma exacerbations rate (OR 0.51, 95% CI: 0.44-0.58, p  < 0.001) compared with placebo with no evidence of heterogeneity. Omalizumab reduced the rate of asthma exacerbations 0.58) with treatment period ≥30 weeks (p for heterogeneity = 0.03). Omalizumab treated patients had an excellent or good response rate of treatment effectiveness assessed by physicians (2.75, 2.45-3.09) and a bigger reduction in the dosage of inhaled corticosteroid (ICS) at the end of follow-up. For children with severe asthma, omalizumab also reduced the likelihood of asthma exacerbations and increased the odd of treatment effectiveness rated as excellent or good. Patients receiving omalizumab had a lower incidence of severe adverse events (0.36, 0.22-0.57)., Conclusions: These findings suggested that omalizumab had beneficial effects on moderate-to-severe asthma in children. Patients may benefit more from long-term use of omalizumab. In addition, omalizumab reduces the rate of serious adverse events requiring hospitalizations.

Objective: This survey aimed to understand the physicians' practice pattern and challenges faced while treating their patients with asthma in five countries-Malaysia, Nepal, Myanmar, Morocco and Lebanon., Methods: Questionnaire-based data was gathered from internal medicine doctors (209), general practitioners (206), chest physicians (152) and pediatricians (58) from 232 locations from across the five countries., Results: Of the 816 physicians, 374 physicians encountered at least 5 asthma patients daily. Approximately, 38% physicians always used spirometry for diagnosis and only 12% physicians always recommended Peak flow meter (PFM) for home-monitoring. Salmeterol/fluticasone (71%) followed by formoterol/budesonide (38%) were the most preferred ICS/long-acting beta 2 -agonists (LABA); Salbutamol (78%) was the most preferred reliever medication. 60% physicians said >40% of their patients were apprehensive to use inhalers. 72% physicians preferred a pressurized metered-dose inhaler (pMDI) to a dry powder inhaler (DPI) with only a third of them using a spacer with the pMDI. 71% physicians believed that using similar device for controller and reliever can be beneficial to patients. Skipping medicines in absence of symptoms (64%), incorrect inhaler technique (48%) and high cost of medication (49%) were considered as major reasons for non-adherence by most physicians. Incorrect inhaler technique (66%) and nonadherence (59%) were considered the most common causes of poor asthma control., Conclusions: There are opportunities to improve the use of diagnostic and monitoring tools for asthma. Non-adherence, incorrect inhaler technique and cost remain a challenge to achieve good asthma control. Asthma education, including correct demonstration of inhaler, can potentially help to improve inhaler adherence.

Objective: This study explored the associations of asthma and long-term asthma control medication with tooth wear among American adolescents and young adults., Methods: Data from 2186 participants of the National Health and Nutrition Examination Survey (NHANES) were used. Asthma and prescribed long-term medication were collected through questionnaires. The number of surfaces with tooth wear was determined during clinical examinations. Associations were tested in Hurdle regression models adjusting for confounders., Results: The prevalence of tooth wear was 58%, with an average of 6.1 (SD: 4.0) surfaces affected among those with the condition. The prevalence of asthma was 10.3%, with 2.9% of participants using long-term medication for asthma control. In the adjusted regression model, asthma was not associated with tooth wear. However, long-term control medication was associated with greater odds of having tooth wear (odds ratio: 3.33; 95%CI: 1.24-8.97), but it was not associated with the number of surfaces with tooth wear among those with the condition (rate ratio: 1.01; 95% CI: 0.58-1.75)., Conclusion: This cross-sectional analysis of national data shows that taking long-term asthma medication was positively associated with having tooth wear.

Objective: Oral corticosteroids (OCS) are frequently used as relievers for acute asthma and controllers for severe asthma. However, the relief offered by OCS is counterbalanced by adverse effects. We aimed to describe how patients perceive OCS treatment benefits and risks, and how this could affect their adherence to the treatment., Methods: Patients aged ≥18 years with asthma registered with Carenity, an online patient community, were invited to respond to a questionnaire containing 35 closed and 3 open questions to assess their asthma and perceptions of OCS., Results: 268/300 respondents were receiving or had received OCS for asthma (58 for long-term use and 107 for short-term use). The mean age at diagnosis was 21.3 years. 66% had uncontrolled asthma (GINA control score 3 or 4). Although 42% perceived OCS to be efficacious, 46% mentioned adverse effects. Respondents were mostly satisfied with OCS (median = 7.0/10), particularly for efficacy (median = 8.0/10). Respondents reported having strategies to avoid OCS, mainly because of adverse effects. 26% of respondents had previously reduced or stopped OCS; this proportion was 22% for short-term OCS users and 36% for long-term users. 15% of the respondents not receiving long-term OCS would take the treatment without doing anything else if long-term OCS were prescribed; 42% would seek an alternative treatment., Conclusions: OCS for asthma is perceived efficient but associated with adverse effects. Patients seek alternative treatment.

Introduction: Severe eosinophilic asthma is an incapacitating disease. Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, proved to be effective as an add-on therapy in patients with severe eosinophilic asthma. However, only data from randomized controlled trials are available and real world data are lacking. Methods: A retrospective observational longitudinal study was conducted in a real world cohort of patients with severe eosinophilic asthma treated with mepolizumab. The primary objective was to determine response rate, based on a global evaluation of treatment effectiveness by the treating pulmonologist. Secondary objectives were to assess exacerbation frequency, systemic maintenance glucocorticoid usage, Asthma Control Questionnaire (ACQ), lung function, and adverse events. Results: Seventy-eight patients were included. Treatment with mepolizumab was considered beneficial and was therefore continued in 75.6% of patients 12 months from the initiation of mepolizumab. The most common reason for drop-out was insufficient response. Secondary objectives: 12 months from the initiation of mepolizumab there was a decrease of 3.2 (CI 2.5-4.1; p  < 0.001) severe asthma exacerbations per year, a decrease of ACQ of 0.80 points (CI 0.49-1.12; p  < 0.001), and an increase of 3.7 (CI 0.3-7.2; p  = 0.034) percent of predicted FEV1 compared to baseline. At baseline 51.3% of patients were treated with systemic glucocorticoid maintenance therapy, compared to 15.4% ( p  < 0.001) of patients 12 months from the initiation of mepolizumab. No serious adverse events considered to be related to mepolizumab were reported. Conclusion: This study confirms that mepolizumab add-on therapy is effective and safe in a real world cohort of patients with severe eosinophilic asthma.

Objective: A high proportion of children and adolescents who have "difficult" or therapy-resistant asthma, are found to have poor adherence to maintenance therapies. Such individuals are thus difficult asthmatics (for reasons of poor adherence) rather than being young people with true difficult asthma. In our centers, once daily ICS/ULABA (Relvar™) is considered if there is an increase in reported interval symptoms, asthma attacks requiring hospital attendance or rescue oral prednisolone, or persistently low lung function despite reported regular use of a twice daily ICS/LABA preparation. In the majority of these young people, a clinical history of overt non-adherence or a clinical suspicion of covert non-adherence will be noted., Methods: The aim of our retrospective cohort study was to assess the clinical effectiveness of Relvar™ in a selected adolescent asthma population., Results: In a pre-selected group of adolescents with likely poor prior adherence to inhaled therapies, a change to Relvar™ (once daily combined ICS/ULABA) led to improvements in asthma control, as assessed by ED attendances and oral steroid burden., Conclusions: A prospective study to verify these findings and also explore the effects on quality of life, asthma control, and adherence is warranted.

Objective: Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year and decreases oral corticosteroid (OCS) use after 28 weeks for patients with severe, uncontrolled eosinophilic asthma. We assessed whether these effects on OCS reduction are sustained for up to an additional year of treatment while maintaining an acceptable safety profile., Methods: Data on OCS maintenance dosage were collected for adult patients with baseline blood eosinophil counts ≥150 cells/μL treated with add-on benralizumab 30 mg (every 4 [Q4W] or 8 weeks [Q8W; first three doses Q4W]) from the 28-week ZONDA study and were integrated with results from the predefined 56-week adult completion phase of the BORA extension study. Efficacy and safety were summarized descriptively., Results: For patients receiving benralizumab Q8W, the median daily OCS dosage reduction of 75% from baseline to end of treatment achieved in ZONDA was sustained at the end of the BORA extension period (median 67% reduction from baseline). This was estimated to result in a median cumulative OCS dosage of 2.98 g over the 1.5-year period for patients receiving benralizumab Q8W compared with 5.74 g if these patients had remained on their baseline OCS dosages prior to benralizumab initiation. All adverse event rates were similar between the BORA extension and ZONDA periods, with no new or unexpected safety findings., Conclusion: This benralizumab 1.5-year integrated analysis demonstrates that OCS reductions and safety were maintained with further follow up and supports long-term use of benralizumab for patients with severe, uncontrolled eosinophilic asthma.

Objective: Patients with severe asthma require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control. Because symptom control remains unsatisfactory in some patients despite these therapies, maintenance therapy with oral corticosteroids (OCS) remains considered a treatment option by physicians. Besides physician-diagnosed exacerbations, many patients intermittently self-medicate with OCS during episodes of worsening symptoms or as a prevention of such episodes. However, long-term OCS use is associated with several comorbidities that may decrease health-related quality of life, worsen prognosis, and should ideally require monitoring and management. In this review, we discuss the adverse effects of OCS use, the OCS-sparing effect of biologics in severe asthma, and the need for optimal referral pathways to ensure the best outcomes for those at-risk asthma patients., Data Sources: PubMed., Study Selection: Studies with results on the OCS-sparing effect of biologics in adult severe asthma were selected., Results: Chronic and intermittent OCS use in asthma is associated with considerable adverse effects in asthma. Omalizumab, mepolizumab, benralizumab, and dupilumab reduce the need for OCS in severe asthma, while also reducing the exacerbation rate and improving several patient-related outcomes., Conclusion: Targeted biologic therapies have revolutionized the treatment of uncontrolled severe asthma by reducing or even eliminating the need for OCS and improving other major outcomes. Novel agents are now rapidly increasing the therapeutic armamentarium, but additional efforts are needed to optimize referral pathways in order to ensure sustainable access to these therapies.

Introduction: Asthma is a common medical condition that can frequently affect pregnancy, and thus optimal management of asthma in pregnancy is important for both mother and baby. This article reviews recent developments of asthma pharmacotherapy and provides emerging data on the safety of asthma controller medications and biological therapies in pregnancy. The authors highlight the clinical outcomes of asthma during pregnancy, and summarize emerging new data related to the influence of sex hormones and fetal sex on asthma severity., Areas Covered: This review of asthma pharmacotherapy during pregnancy examines the recent guidelines and reports the most pertinent publications on safety data and asthma management., Expert Opinion: Asthma management during pregnancy follows the same principles as that of non-pregnant asthma. The available data for most asthma medications are reassuring, however there is a lack of adequate safety data available because pregnant women are generally excluded from clinical trials. More clarity is needed in guidelines regarding the management of asthma in pregnancy, and high-quality randomized control trials are required to strengthen the evidence base and inform future guidelines. In particular, safety studies examining biological therapies in pregnant women with severe asthma are needed.

Asthma is the most common, long-lasting inflammatory airway disease that affects more than 10% of the world population. It is characterized by bronchial narrowing, airway hyperresponsiveness, vasodilatation, airway edema, and stimulation of sensory nerve endings that lead to recurring events of breathlessness, wheezing, chest tightness, and coughing. It is the main reason for global morbidity and occurs as a result of the weakening of the immune system in response to exposure to allergens or environmental exposure. In asthma condition, it results in the activation of numerous inflammatory cells like the mast and dendritic cells along with the accumulation of activated eosinophils and lymphocytes at the inflammation site. The structural cells such as airway epithelial cells and smooth muscle cells release inflammatory mediators that promote the bronchial inflammation. Long-lasting bronchial inflammation can cause pathological alterations, viz. the improved thickness of the bronchial epithelium and friability of airway epithelial cells, epithelium fibrosis, hyperplasia, and hypertrophy of airway smooth muscle, angiogenesis, and mucus gland hyperplasia. The stimulation of bronchial epithelial cell would result in the release of inflammatory cytokines and chemokines that attract inflammatory cells into bronchial airways and plays an important role in asthma. Asthma patients who do not respond to marketed antiasthmatic drugs needed novel biological medications to regulate the asthmatic situation. The present review enumerates various types of asthma, etiological factors, and in vivo animal models for the induction of asthma. The underlying pathological, immunological mechanism of action, the role of inflammatory mediators, the effect of inflammation on the bronchial airways, newer treatment approaches, and novel biological targets of asthma have been discussed in this review.

Introduction: Asthma is one of the most frequent chronic diseases all over the world. Glucocorticoids (GCs), both inhaled (ICSs) and oral (OCSs), are the most effective treatment in asthma because they control symptoms and prevent exacerbations., Areas Covered: The present article reviews the new therapeutic indications of GCs for the treatment of asthma and focuses on new molecules and safety issues., Expert Opinion: Most patients with asthma benefit from corticosteroid-based treatments. Side effects are mainly due to prolonged use of oral GCs, while they are minor with inhaled GCs. Interesting insights come from the new ICSs, which are characterized by lower oral bioavailability and higher lipophilicity and are more effective with less side effects. Recent trials have shown the efficacy of early use of ICSs in mild asthma. Furthermore, the possibility to prescribe targeted therapies using specific biomarkers in steroid-sensitive asthma can reduce doses and duration of treatment, while biological agents should be reserved for non-responding patients. All this evidence confirm the need to continue on the path toward precision medicine, in which the treatments are based on clinical and molecular traits.

Objective: To evaluate usability of mepolizumab as a liquid drug product self-administered via a single-use prefilled autoinjector (AI) by patients with severe eosinophilic asthma (SEA), or their caregivers, in-clinic and at home. Methods: This open-label, single-arm, Phase IIIa study (NCT03099096; GSK ID: 204959) included patients aged ≥12 years with SEA who were either receiving mepolizumab (100 mg subcutaneously [SC]) every 4 weeks (Q4W) for ≥12 weeks before screening or not receiving mepolizumab but met criteria indicative of SEA. Patients/caregivers self-administered mepolizumab (100 mg SC) via an AI Q4W for 12 weeks. The first (Week 0) and third (Week 8) doses were observed in-clinic; the second dose (Week 4) was administered unobserved at home. Primary and secondary endpoints were the proportion of patients who successfully self-administered their third and second doses, respectively (determined by investigator/site staff). Patient experience, mepolizumab trough concentrations, blood eosinophil count (BEC), and safety were also assessed. Results: Of 159 patients/caregivers who self-administered ≥1 dose of mepolizumab, 157 completed the study. Nearly all patients successfully self-administered their third mepolizumab dose in-clinic and second dose at home (≥98% and ≥96%, respectively); this was further confirmed by mepolizumab trough concentrations/BEC. At study end, ≥88% of patients were "very" or "extremely" confident about using the AI correctly. Incidence of on-treatment drug-related adverse events (AEs) was low (3%); no fatal AEs occurred. Conclusions: Patients/caregivers successfully self-administered mepolizumab via the AI both in-clinic and at home; no new safety concerns were identified.

Objective: Real-world studies on the effectiveness of omalizumab in Egyptian population with asthma are limited. This study aimed to evaluate the real-world effectiveness and safety of omalizumab as an add-on treatment in pediatric and adult patients with severe, persistent allergic asthma in Egypt. Methods: The primary endpoint of this 16-week, prospective, open-label, multicenter, non-interventional study was the reduction in oral corticosteroid (OCS) dose. Secondary endpoints included reduction in exacerbation, improvements in quality of life and global assessment of omalizumab therapy. Results: Of the 59 patients, 53 completed the study. Add-on omalizumab significantly reduced the proportion of patients receiving OCS at Week 16 versus baseline (81.1% at baseline versus 52.8% at Week 16; p  < 0.001). A 55% decrease in the total daily prednisolone-equivalent dose of OCS was observed at the end of the study compared to baseline ( p  < 0.001). No patients reported exacerbations or missed days from work or school after receiving omalizumab for 16 weeks compared to baseline (both p  < 0.001). A statistically significant decrease was observed in asthma control questionnaire-5 scores ( p  < 0.001). Almost all physicians and patients rated omalizumab therapy as 'good,' 'very good' or 'excellent' in tolerability and effectiveness. No new safety signals were observed in the safety analysis of omalizumab as add-on treatment. Conclusions: Outcomes of this real-world study were consistent with previous effectiveness and safety studies of omalizumab. Omalizumab was effective and well tolerated for the management of severe, persistent IgE-mediated asthma in pediatric and adult patients in Egypt.

Background: Oral corticosteroids (OCSs) are often used to achieve asthma control. OCS-related comorbidities increase the burden of disease for patients and healthcare providers. Most studies characterizing OCS use and risk of adverse events (AEs) are in non-asthma patients. We sought to systematically review the literature on the burden of OCS use among adults with asthma. Methods: We systematically reviewed the literature including MEDLINE (1946-May 2017), EMBASE (1974-May 2017), and the Cochrane Library (2005-May 2017) to identify studies that considered AEs due to OCS treatment of adults with asthma, their burden on healthcare utilization, and costs. Results: We retrieved 9,589 citations; and 15 studies were included. AEs were significantly higher among OCS-users compared with non-OCS users with pooled adjusted odds ratio (OR) 1.68 (95% CI 1.15-2.46) for diabetes mellitus and 1.34 (95% CI 1.23-1.46) for hypertension. Among high dose OCS-users (>10 mg) compared with non-OCS users, the pooled adjusted ORs for development of any complication was 3.35 (95% CI 2.94-3.82), and bone and muscle complications 2.30 (95% CI 2.18-2.42). The risk of any complication increased with higher doses of OCS, with pooled adjusted OR from 2 studies of 2.26 (95% CI 1.37-3.72), 2.94 (95% CI 2.62-3.29) and 3.35 (95% CI 2.94-3.82) for low dose (<6 mg), medium dose (5-12 mg) and high dose (>10 mg) respectively compared with no OCS use. Conclusions: The use of OCS in the management of asthma is associated with a higher risk of complications. This risk is higher as the OCS dose increases.

Objective: To determine the efficacy and safety of current maintenance therapies consisting of different regimens of long-acting β2-agonists (LABA) with inhaled corticosteroids (ICS) in patients with asthma. Methods: A network meta-analysis (NMA) was conducted after a comprehensive search for relevant studies in the PubMed, Cochrane Library, and Embase databases up to January 1, 2017. Randomized clinical trials comparing LABA combined with ICS in patients with asthma were selected. Results: Seventeen trials were included in the analysis, comprising 10,961 patients and seven treatment regimens. Our NMA revealed that there were no statistically significant differences between agents regarding the frequency of moderate or severe exacerbations. For adverse effects, there were no significant differences between the included studies. Moreover, six of the results showed no statistically significant differences between agents regarding symptom-free days. The heterogeneity and inconsistency analysis of the outcomes showed that there were no differences between the regimens. Conclusions: Our findings have shown that there were no statistically significant differences between the different regimens of LABA + ICS regarding the frequency of moderate or severe exacerbations, adverse events, and symptom-free days.

Objective : Asthma is a common emergency department (ED) presentation. This study examined factors associated with inhaled corticosteroids/long-acting beta-agonist (ICS/LABA) use; and management and outcomes before and after ED presentation. Methods : Secondary analysis of a prospective cohort study; adults treated for acute asthma in Canadian EDs underwent a structured interview before discharge and were followed-up four weeks later. Patients received oral corticosteroids (OCS) at discharge and, at physician discretion, most received ICS or ICS/LABA inhaled agents. Analyses focused on ICS/LABA vs "other" treatment groups at ED presentation. Results : Of 807 enrolled patients, 33% reported receiving ICS/LABA at ED presentation; 62% were female, median age was 31 years. Factors independently associated with ICS/LABA treatment prior to ED presentation were: having an asthma action plan; using an asthma diary/peak flow meter; influenza immunization; not using the ED as usual site for prescriptions; ever using OCS and currently using ICS. Patients were treated similarly in the ED and at discharge; however, relapse was higher in the ICS/LABA group, even after adjustment. Conclusion : One-third of patients presenting to the ED with acute asthma were already receiving ICS/LABA agents; this treatment was independently associated with preventive measures. While ICS/LABA management improves control of chronic asthma, patients using these agents who develop acute asthma reflect higher severity and increased risk of future relapse.

Objective: Our aim is to study the association between bronchial asthma (BA) and periodontitis in Jordan., Methods: A case control study of 260 subjects; 130 with BA and 130 without BA (controls) were recruited at a university hospital in Jordan. BA cases were physician-diagnosed and on anti-asthma medications for 12 months. Periodontitis was defined as the presence of ≥ 4 teeth with ≥ 1 site with probing pocket depth (PPD) ≥ 4 mm and clinical attachment level (CAL) ≥ 3 mm., Results: Mean age of participants was 45.3 years (range, 18-65) and 58.1% were females. Patients with BA had lower education and tended to live in rural areas. Periodontitis was present in 52 (40.0%) patients with BA and 26 (20.0%) in the control group, p < 0.005. Binary logistic regression indicated that patients with BA were more likely to have periodontitis than controls [adjusted odd ratio (OR) = 2.91, 95% CI (1.39-6.11), p = 0.005]. Patients with BA had higher percentage of sites with: PPD ≥ 3 mm, CAL ≥ 3 mm, and CAL ≥ 4 mm than controls, p < 0.05. The risk of periodontitis [OR = 5.27, 95% CI (1.59-17.51)] and CAL ≥ 3 mm were higher in patients on oral corticosteroids compared to inhaled corticosteroids, p < 0.05., Conclusions: Adult Jordanians with bronchial asthma are at higher risk of periodontitis, particularly those on oral corticosteroids. Large and longitudinal studies are needed to better understand this significant association.

Objectives: Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI)., Methods: A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects., Results: There is a statistically significant increase of 0.369 kg/m 2 in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m 2 in the low dose group (p < 0.05). The BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m 2 per year (p < 0.05). Subjects with ≥5 ED visits due to asthma exacerbations had a significantly higher BMI trajectory (p < 0.05)., Conclusions: The potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.

Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.

Electronic clinical summaries are innovations supported by the Electronic Health Record Incentive Program, known as "Meaningful Use" (MU). The MU clinical summary documents the shared understanding of the plan of care for patients and assists families in managing asthma-related health care. The purpose of this analysis was to identify the communicative value of the summaries to patients and families. Readability measurements, content analysis, and descriptive statistics were employed in a review of twenty clinical summaries and compared with provider encounter notes. The average age of the patients from whom we collected clinical summaries was six years old. The average reading level of the summaries was ninth grade. Neither summaries nor health education contained visual images. There was a total of nine different asthma diagnoses. A full list of diagnoses was present in 45% of summaries. The average medications per patient was 5.75, and there were multiple medication changes noted (dosage adjustment, add, discontinued). Allergies, vital signs, and smoking status were reliably reported (99-100%). Provider orders present included medication, follow up, and return to the clinic instructions. The plan of care was replicated on 45% of summaries. There was variable reporting of various asthma guidelines. Opportunities to improve the clinical summary include using plain language to promote readability, action, understanding, and health literacy, training providers to standardize their documentation and include asthma action plans, and configuring EHR settings to ensure diagnoses and plan of care is carried over from provider notes to the summary.

Objective: Evidence of safety issues associated with long-acting beta 2 -agonist (LABA) treatment has led to multiple regulatory activities by the U.S. Food and Drug Administration (FDA) on this class of medications. This study describes the impact of the regulatory activities on incident LABA-containing medication dispensing., Methods: A monthly rolling cohort of asthma patients who were eligible to initiate a LABA-containing product was created in the Mini-Sentinel Distributed Database between January 2005 and June 2011. Cohorts of individuals who initiated LABA were examined for the changes in the proportions of single-ingredient to fixed-dose inhaled corticosteroid (ICS)-LABA initiators, appropriate initiation of LABA-containing products, and use of controller medications. The impact of the 2005 and 2010 FDA regulatory activities associated with LABA-containing products was measured using interrupted time series with segmented regression., Results: LABA-containing product initiation was declining prior to the 2005 regulatory activities and continued to decline over the study period, accompanied by increased initiation of fixed dose ICS-LABA among LABA initiators. While the 2010 regulatory activities had no immediate impact on the proportion of LABA initiation in patients with prior controller medication dispensing and/or poor asthma control, there was an increasing positive trend toward LABA initiation in the appropriate patient population after the regulatory activities., Conclusion: The 2005 and 2010 FDA regulatory activities likely had an impact on communicating the safety concerns of LABA products. However, the impact cannot be viewed independent of scientific publications, guidelines for asthma treatment and other regulatory activities.

Objectives: The first aim of the study (i) assess the current asthma status of general-practitioner-managed patients receiving regular fixed-dose combination inhaled corticosteroid and long-acting beta 2 agonist (FDC ICS/LABA) therapy and (ii) explore patients' perceptions of asthma control and attitudes/behaviors regarding preventer inhaler use., Methods: A cross-sectional observational study of Australian adults with a current physician diagnosis of asthma receiving ≥2 prescriptions of FDC ICS/LABA therapy in the previous year, who were recruited through general practice to receive a structured in-depth asthma review between May 2012 and January 2014. Descriptive statistics and Chi-Square tests for independence were used for associations across asthma control levels., Results: Only 11.5% of the patients had controlled asthma based on guideline-defined criteria. Contrarily, 66.5% of the patients considered their asthma to be well controlled. Incidence of acute asthma exacerbations in the previous year was 26.5% and 45.6% of the patients were without a diagnosis of rhinitis. Asthma medication use and inhaler technique were sub-optimal; only 41.0% of the preventer users reported everyday use. The side effects of medication were common and more frequently reported among uncontrolled and partially controlled patients., Conclusions: The study revealed the extent to which asthma management needs to be improved in this patient cohort and the numerous unmet needs regarding the current state of asthma care. Not only there is a need for continuous education of patients, but also education of health care practitioners to better understand the way in which patient's perceptions impact on asthma management practices, incorporating these findings into clinical decision making.

Objectives: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice., Methods: This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible., Results: The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31-41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7-21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n = 101), 27-37% were omalizumab-eligible and 18% were reslizumab-eligible., Conclusions: Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.

Introduction: Mepolizumab is a humanized monoclonal antibody that binds to and inactivates IL-5. It is available as a subcutaneous preparation. The practical application of mepolizumab is as an add-on therapy in the treatment of severe eosinophilic asthma. Areas covered: This article was created from a comprehensive literature search with information taken from meta-analyses, systematic reviews, and clinical trials of adults. The articles that have been selected evaluate the use of mepolizumab and its role in eosinophilic asthma. Expert opinion: Mepolizumab is significantly more effective than placebo in reducing exacerbations and need for systemic corticosteroids in severe eosinophilic asthma. There is a lack of head to head studies comparing mepolizumab to other monoclonal anti-IL-5 inhibitors in severe eosinophilic asthma. Post marketing surveillance revealed risk of anaphylaxis that is below 1%.

Context: Reslizumab is a humanised anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes programmed cell death., Objective: We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in patients with inadequately controlled, eosinophilic asthma., Data Sources: The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register., Study Selection: A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of reslizumab for the treatment of inadequately controlled, eosinophilic asthma., Data Extraction: Two reviewers independently extracted and verified pre-defined data fields., Results: Four publications including 5 RCTs that compared reslizumab with placebo. For the comparison of reslizumab with placebo, asthma exacerbation (odds ratio (OR) = 0.46, 95% confidence interval (CI) = 0.35 to 0.59, p <0.00001); a forced expiratory volume in 1 s (FEV1) (the standardized mean difference (SMD) = 0.16, 95%CI = 0.10 to 0.23, p <0.00001); Asthma Control Questionnaire (ACQ) score (the SMD = -0.26, 95%CI= -0.36 to -0.16, p <0.00001); blood eosinophil counts (the SMD = -475.62, 95%CI = -528.41 to -422.83, p <0.00001). Safety assessments included the proportion of individuals who withdrawn due to adverse event (AE) (OR = 0.60 95%CI = 0.38 to 1.17, p = 0.16) indicated that reslizumab was well tolerated., Limitations: The article didn't research the safety, efficacy of reslizumab with longer term., Conclusions: This meta-analysis indicates that reslizumab to be an effective and safe treatment for inadequately controlled, eosinophilic asthma.

Background: Magnesium sulfate (MgSO4) is considered to be a well-tolerated, inexpensive, and effective medication for severe asthma exacerbations. We surveyed physicians who treat patients with asthma to evaluate the current knowledge and usage of MgSO4., Methods: A self-administered questionnaire was e-mailed to members of the Turkish National Society of Allergy and Clinical Immunology and was distributed to participants of its annual congress., Results: Of the 456 respondents (mean age: 36.53 ± 9.11 years), 42.3% reported to use MgSO4 in asthma exacerbations in their practice, and 48.7% agreed that MgSO4 was included in asthma guidelines. The best known indication was that it was useful only in patients refractory to bronchodilators and systemic corticosteroids (67.7%). The two most common reasons to use MgSO4 were to shorten hospital stay (94.7%), and prevent admission to intensive care unit (80.3%). The respondents mostly used MgSO4 in the treatment of severe or life-threatening exacerbations. Thirty-nine percent believed that MgSO4 had no effect on discharge period, and 29% of them marked minor side effects. The most common reason for not using MgSO4 was inexperience (36.5%). Having an academic affiliation (OR = 3.20, p < 0.001), the number of asthmatic outpatients seen per month (OR = 1.82, p = 0.007), and more recent graduation from medical school (≤1991) (OR = 0.23, p < 0.001) were associated with the use of MgSO4 in the multivariate analysis., Conclusion: Even though the effect of MgSO4 in acute severe asthma is well known, only half of the physicians dealing with asthma patients have used it in their practice. Education and encouragement in this regard are necessary.

Background: Information on ethnic diversity of adverse drug reactions (ADRs) to asthma medications is rare despite evidence suggesting higher risk for African Americans when using β2-adrenergic receptor agonists. The objectives are to investigate how ethnic background was involved in ADR assessment and to examine the relationship between ethnic background and ADRs to asthma medications., Methods: MEDLINE was searched until March 2014. All types of studies reporting ADRs to asthma medications involving more than one ethnic group were included. Extracted information includes study designs, ethnic backgrounds, intervention, and types and severities of ADRs., Results: Among the selected 15 randomised clinical trials, six pooled analyses of randomized clinical trials, and five prospective observational studies, only six studies compared ADRs across different ethnic groups. The majority of the comparisons were either statistically insignificant or inconclusive., Conclusions: Ethnicity was largely overlooked. Most studies neglected to report ADRs by ethnicity. Lack of consistency in defining ethnicities complicated further pooled analyses. Despite the higher prevalence of asthma among specific ethnic minority groups, few studies disaggregated information by ethnic background, and reports of ADRs to asthma medications in different ethnic groups were rare. We suggest that the inclusion of ADR analysis by different ethnic backgrounds is desirable.

Introduction: Pregnancy may be complicated by new onset or pre-existing asthma. This article reviews the recognition and management of asthma during pregnancy, paying close attention to the general principles of asthma medication use during pregnancy. Asthma is one of the most common potentially serious medical problems to complicate pregnancy, and asthma may adversely affect both maternal quality of life and perinatal outcomes. Therefore, optimal management of asthma during pregnancy is important for both mother and baby. This article reviews asthma pharmacotherapy during pregnancy, with an emphasis on gestational safety of commonly used medications., Areas Covered: In this review of asthma pharmacotherapy during pregnancy, the most pertinent recent publications are reported. Electronic databases such as PubMed were searched for terms pregnan* or perinat* or obstet* and asthma or wheeze and treatment., Expert Opinion: Although retrospective data have been reassuring, since pregnant women are generally excluded from clinical trials, there is a lack of adequate safety information for most medications taken during pregnancy. One of the most important needs for the future is the availability of further safety information for asthma medications used during pregnancy that can also account for asthma control.

Introduction: Long-acting β2-agonists are an effective class of drugs, when combined with inhaled corticosteroids, for reducing symptoms and exacerbations in patients with asthma that is not adequately controlled by inhaled corticosteroids alone. However, because this class of drugs has been associated with severe adverse events, including hospitalization and death in small numbers of patients, efforts to identify a pharmacogenetic profile for patients at risk has been diligently investigated., Areas Covered: The PubMed search engine of the National Library of Medicine was used to identify English-language and non-English language articles published from 1947 to March 2015 pertinent to asthma, pharmacogenomics, and long-acting β2-agonists. Keywords and topics included: asthma, asthma control, long-acting β2-agonists, salmeterol, formoterol, pharmacogenetics, and pharmacogenomics. This strategy was also used for the Cochrane Library Database and CINAHL. Reference types were randomized controlled trials, reviews, and editorials. Additional publications were culled from reference lists. The publications were reviewed by the authors and those most relevant were used to support the topics covered in this review., Expert Opinion: Children, who carry the ADRB2 Arg16Arg genotype, may be at greater risk than adults for severe adverse events. Rare ADRB2 variants appear to provide better clues for identifying the at-risk population of asthmatics.

Background: Long-term subcutaneous or intravenous infusion of terbutaline has been used to stabilize asthma in patients enduring frequent hospital admissions due to severe asthma despite maximum therapy. However, this treatment is not supported by significant body of evidence., Aim: To study long-term efficacy and safety of using continuous infusions of terbutaline in unstable severe asthma., Methods: The available medical records of all patients received terbutaline infusions at a severe asthma unit between 1982 and 2008 were retrospectively studied. We retrieved data on treatment indication, asthma subtype, patient demographics, pre-treatment terbutaline trial outcome, duration of treatment, effect on lung function, hospital admissions, oral corticosteroids (OCSs) requirement, safety and side effects., Results: Forty-two patients with adequate medical information were studied (31 females, mean age 43.6 years, 88% had type 1 brittle asthma and 12% had other severe asthma). This group of patients had a mean body mass index of 30.8 kg/m2, mean oral prednisolone or equivalent of 26.6 mg and mean predicted FEV1 of 66.8%. The mean treatment duration was 86.7 months (range 7-216). Long-term continuous terbutaline infusion significantly reduced hospital admissions (mean pre-treatment = 6.7 (95% CI 0.96-12.4) per annum, and mean annualized on-treatment admission = 3.3 (95% CI 0.63-6.9, p = 0.045). We observed overall reduction in OCSs use in 59% of patients with available data, but there was no significant change in lung function. Side effects related to terbutaline or the method of its infusion were common and some were serious especially when central venous access device were used., Conclusion: Continuous terbutaline infusion could be a treatment option for severe unstable asthma and may reduce hospital admissions. However, the treatment was associated with significant side effects and its use should be limited to centers possessing necessary expertise.