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Introduction: Near-fatal asthma (NFA) is a severe condition that can lead to respiratory arrest or high carbon dioxide levels, often requiring mechanical ventilation. Biologics have revolutionized the management of severe asthma, significantly improving symptom severity, reducing the number of exacerbations and hospitalizations, and decreasing the need for oral corticosteroids. However, their effectiveness in acute settings, particularly for ICU patients experiencing severe respiratory failure, is not well-studied. More research is needed to determine if biologics can improve recovery during severe asthma exacerbations., Case Study: We report a case of NFA in a patient with severe allergic eosinophilic asthma, who experienced global respiratory failure necessitating hospitalization, intubation, and veno-venous extracorporeal membrane oxygenation (VV-ECMO). Given the severity of the clinical condition, compassionate administration of Benralizumab, which targets the IL-5 receptor, was attempted., Results: Five days from anti-IL5 receptor treatment start, the patient was extubated and the ECMO stopped. After the stepdown to the respiratory intensive care unit (RICU), the patient was weaned from oxygen therapy and subsequently discharged from hospital., Conclusion: Benralizumab demonstrated rapid effectiveness in improving respiratory failure leading to successful weaning from VV-ECMO and subsequent extubation.

Purpose of Review: To discuss the effectiveness of biologics, some of which comprise the newest class of asthma controller medications, and non-biologics in the treatment of asthma co-existing with obesity., Recent Findings: Our review of recent preliminary and published data from clinical trials revealed that obese asthmatics respond favorably to dupilumab, mepolizumab, omalizumab, and tezepelumab, which are biologics currently indicated as add-on maintenance therapy for severe asthma. Furthermore, clinical trials are ongoing to assess the efficacy of non-biologics in the treatment of obese asthma, including a glucagon-like peptide-1 receptor agonist, a Janus kinase inhibitor, and probiotics. Although many biologics presently indicated as add-on maintenance therapy for severe asthma exhibit efficacy in obese asthmatics, other phenotypes of asthma co-existing with obesity may be refractory to these medications. Thus, to improve quality of life and asthma control, it is imperative to identify therapeutic options for all existing phenotypes of obese asthma., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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.

Background: Patients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD., Methods: QUEST (NCT02414854) data were used in this post hoc analysis. A composite endpoint from validated patient-reported outcomes was developed to identify patients with HSD using sleep-related items from the ACQ-5, Asthma-Related Quality-of-Life Questionnaire, Rhino-Conjunctivitis Quality-of-Life Questionnaire, and Sino-Nasal Outcome Test-22. Impairment in at least 1 item was considered an indication of HSD. Change from baseline to Week 52 in nighttime symptoms, ACQ-5 score, lung function, annualized severe exacerbation rates (AER), and short-acting β-agonists use during treatment was used to assess dupilumab efficacy., Results: In type 2 asthma patients, 64% had HSD at baseline; of those with ACQ-5 ≥2.5 at baseline, 82% had HSD. In this population, dupilumab reduced nighttime symptoms and ACQ-5 score by 0.31 and 0.56 points, respectively, by Week 52 versus placebo, and led to a 66% reduction in AER during QUEST and 0.34 L improvement in pre-bronchodilator (pre-BD) forced expiratory volume in 1 s (FEV 1 ) at Week 52., Conclusion: A majority of patients with moderate-to-severe type 2 asthma with ACQ-5 ≥2.5 at baseline had HSD. Dupilumab reduced nighttime symptoms and exacerbations, and improved lung function, overall asthma control, and quality of life. Further studies are needed to confirm the association between ACQ-5 score ≥2.5 and higher sleep disturbance rates., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Mepolizumab, a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5, has shown improved asthma control and lung function in randomised controlled trials. The aim of this study was to evaluate real-world clinical experience in patients with severe eosinophilic asthma treated with mepolizumab in Slovakia., Methods: A retrospective, non-interventional study based on medical records of all adult asthma patients initiating mepolizumab between November 1, 2017 and January 31, 2019, completing 12 months of treatment. At baseline, general and clinical profile data were recorded 12 months prior to treatment. Primary and secondary endpoints described the results of mepolizumab use at 2, 6, and 12 months after the initiation and compared to baseline. Statistical testing of individual change (in each patient) in selected parameters was performed., Results: The cohort included 17 patients with particularly severe asthma at baseline, with frequent severe exacerbations (SE, median 5 [IQR 4-6]/patient/year), high blood eosinophil counts (median 0.6x10 9 /L), frequent oral corticosteroid (OCS) dependence (82.35%), median dose 15 (IQR 7.5-20) mg/day, impaired lung function, and a spectrum of comorbidities. In a one-year follow-up, the data showed reductions in median SE (0 [IQR 0-1] patient/year, eosinophilia (median 0.175x10 9 /L) and OCS maintenance dose (median 6.25 [IQR 2.5-20] mg/day), all statistically significant after 12 months on mepolizumab. Improved and stabilised lung functions throughout the cohort and a reduced incidence of nasal polyposis were observed., Conclusions: The results provide clinical evidence of mepolizumab efficacy in a real sample of patients with severe asthma when administered in routine care settings in Slovakia., Competing Interests: The authors report no conflicts of interest in this work.

With increasing rates of asthma in the general population, dental professionals need to be able to recognize the signs and symptoms of poorly controlled asthma and modify dental treatment accordingly. Prevention of an acute asthma exacerbation is key. Patients should be reminded to bring their rescue inhaler with them to every dental appointment. Patients who are using inhaled corticosteroids to manage their asthma are at greater risk of oral candidiasis, xerostomia, and caries. Regular dental visits and good oral hygiene are important among this population., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin. The drug has been tested previously in the phase 3 NAVIGATOR (NCT03347279) and SOURCE (NCT03406078) studies, and was subsequently approved as a treatment for severe asthma. This extension study recruited from NAVIGATOR and SOURCE and aimed to evaluate the long-term safety and efficacy of tezepelumab in individuals with severe, uncontrolled asthma., Methods: DESTINATION was a phase 3, multicentre, randomised, double-blind, placebo-controlled, long-term extension study. The study was done across 182 sites (including hospitals, clinics, medical centres, clinical trial centres, and private practices) in 18 countries. Participants (aged 12-80 years) were required to have good treatment compliance in the parent study. Randomisation was stratified by the parent study and all participants were re-randomised. Those who were previously randomised to receive tezepelumab in either parent study continued treatment of subcutaneous tezepelumab (210 mg every 4 weeks); those who were previously randomised to receive placebo in either parent study were re-randomised 1:1 to receive either subcutaneous tezepelumab (210 mg every 4 weeks) or placebo (every 4 weeks) using a randomisation list prepared by a computerised system. Total treatment duration (including the parent studies) was 104 weeks for all groups. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoints were exposure-adjusted incidence of adverse events and serious adverse events and the secondary endpoint was the annualised asthma exacerbation rate; these were assessed from week 0 of the parent studies to week 104 of DESTINATION in all participants who were randomised and who received at least one dose of tezepelumab or placebo in either of the parent studies. The trial is registered with ClinicalTrials.gov, NCT03706079, and is closed to new participants., Findings: Participants were recruited between Jan 7, 2019, and Oct 15, 2020. For individuals who initially received tezepelumab (n=528) in NAVIGATOR, incidence of adverse events over 104 weeks was 49·62 (95% CI 45·16 to 54·39) per 100 patient-years, compared with 62·66 (56·93 to 68·81) for those receiving placebo (n=531; difference -13·04, 95% CI -17·83 to -8·18). For serious adverse events, incidence was 7·85 (6·14 to 9·89) per 100 patient-years for individuals who initially received tezepelumab and 12·45 (9·97 to 15·35) for those who received placebo (difference -4·59, -7·69 to -1·65). In SOURCE, incidence of adverse events was 47·15 (36·06 to 60·56) per 100 patient-years for those who initially received tezepelumab (n=74) and 69·97 (54·54 to 88·40) for those who received placebo (n=76; difference -22·82, -34·77 to -10·01). For serious adverse events, incidence was 13·14 (7·65 to 21·04) per 100 patient-years for those who initially received tezepelumab and 17·99 (10·66 to 28·44) for those who received placebo (difference -4·85, -14·88 to 4·53). Tezepelumab reduced the annualised asthma exacerbation rate over 104 weeks compared with placebo. In participants initially from NAVIGATOR, the annualised asthma exacerbation rate ratio over 104 weeks was 0·42 (95% CI 0·35 to 0·51); in those initially from SOURCE, the ratio over 104 weeks was 0·61 (0·38 to 0·96)., Interpretation: Tezepelumab treatment was well tolerated for up to 2 years and resulted in sustained, clinically meaningful reductions in asthma exacerbations in individuals with severe, uncontrolled asthma. These findings are consistent with previous randomised, placebo-controlled studies and show the long-term safety and sustained efficacy of tezepelumab in individuals with severe, uncontrolled asthma., Funding: AstraZeneca and Amgen., Competing Interests: Declaration of interests AM-G has attended advisory board meetings for AstraZeneca, GlaxoSmithKline, Novartis, Regeneron, Sanofi, and Teva Pharmaceuticals; has received speaker fees from AstraZeneca, Novartis, Sanofi, and Teva Pharmaceuticals; has participated in research with AstraZeneca, for which his institution has been remunerated; has attended international conferences with Teva Pharmaceuticals; and has consultancy agreements with AstraZeneca and Sanofi. MEW is an employee of National Jewish Health and has received consultancy fees from AstraZeneca, Equillium, Genentech, GlaxoSmithKline, Novartis, Regeneron Pharmaceuticals, resTORbio, Sanofi, and Teva Pharmaceuticals. CEB has received consultancy fees and grants from 4D Pharma, AstraZeneca, Chiesi, Genentech, GlaxoSmithKline, Mologic, Novartis, Regeneron, Roche, and Sanofi. SK has received fees for lectures or advisory board meetings from AstraZeneca, GlaxoSmithKline, Novartis, Roche, Sanofi Aventis, and Teva Pharmaceuticals. JC has received grants and personal fees from AstraZeneca, Genentech, and Vectura and has received grants from Optinose, Sanofi, and Teva Pharmaceuticals. EI has served as a consultant to and received personal fees from 4D Pharma, AB Science, Amgen, AstraZeneca, Avillion, Biometry, Cowen, Equillium, Genentech, GlaxoSmithKline, Merck, Novartis, Pneuma Respiratory, PPS Healthcare, Regeneron Pharmaceuticals, Sanofi, Sienna Biopharmaceuticals, and Teva Pharmaceuticals; has received non-financial support from Circassia, Teva Pharmaceuticals, and Vorso Corp; and has received clinical research grants from AstraZeneca, Avillion, Genentech, Gossamer Bio, Novartis, and Sanofi. GCh has received speaker and consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Teva Pharmaceuticals. AB, SP, GA, MG, KB, and GCo are employees of AstraZeneca and might own stock or stock options in AstraZeneca. SC is an employee of Amgen and owns stock in Amgen. LS is a consultant to AstraZeneca. KL is an employee of Cytel., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose of Review: Three years after the emergence of coronavirus disease 2019 (COVID-19), many studies have examined the association between asthma and COVID-related morbidity and mortality, with most showing that asthma does not increase risk. However, the U.S. Centers for Disease Control (CDC) currently suggests that patients with severe asthma may, nonetheless, be particularly vulnerable to COVID-19-related morbidity., Recent Findings: With respect to poor COVID-19 outcomes, our search yielded nine studies that quantified associations with severe asthma, seven that considered use of monoclonal antibodies (mAB), and 14 that considered inhaled corticosteroids (ICS) use. mAb and ICS use have been used as measures of severe asthma in several studies. Severe asthma was significantly associated with poor COVID-19 outcomes. The results for mAb and ICS were mixed., Summary: An increased risk of poor COVID-19 outcomes in patients with severe asthma is possible. However, these studies remain sparse and suffer from several methodological limitations that hinder their interpretation. Additional evidence is needed to provide clear, cogent guidance for health agencies seeking to inform patients with asthma about potential risks due to COVID-19., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 10 9 /L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Background: It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICSs)., Objective: To determine the effectiveness of stepping up to high-dose ICSs., Methods: A historic cohort study of patients with asthma (≥13 years old), identified from 2 large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICSs were compared with those who stepped up from medium- to high-dose ICSs, whereas patients who stepped up from low- to medium-dose ICSs were compared with those who stepped up from low- to high-dose ICSs. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and the number of exacerbations and antibiotics courses was analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding., Results: The mean follow-up time to first exacerbation was 2.7 ± 2.7 years for those who remained on stable medium-dose ICSs and 2.0 ± 2.2 years for those who stepped up from medium- to high-dose ICSs. A similar pattern was noted for those who stepped up from low- to medium-dose ICSs (2.6 ± 2.5 years) and from low- to high-dose ICSs (2.3 ± 2.5 years). Patients who stepped up from medium- to high-dose ICSs (n = 6879) had a higher risk of exacerbations during follow-up compared with those who remained on medium-dose ICSs (n = 51,737; hazard ratio, 1.17; 95% CI, 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n = 3232) compared with low- to medium-dose (n = 12,659) ICSs (hazard ratio, 1.10; 95% CI, 1.04-1.17). A step-up to high-dose ICSs was also associated with a higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts., Conclusions: We found no evidence that a step-up to high-dose ICSs is effective in preventing future asthma exacerbations., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is a common chronic respiratory disorder associated with significant disease and economic burden. Mepolizumab is an anti-IL-5 mAb approved for use as an add-on treatment in patients with severe eosinophilic asthma., Objective: To assess the impact of mepolizumab initiation on asthma exacerbation frequency, oral corticosteroid (OCS) use, and asthma exacerbation-related costs in a US Medicare population., Methods: This was a retrospective cohort study of mepolizumab claims from patients with asthma in the Centers for Medicare and Medicaid Services Medicare database carried out between January 2016 and December 2018. The index date (first claim for mepolizumab) was required to occur between January and December 2017. The baseline and follow-up periods were the 12 months before and 12 months after the index, respectively. Outcomes included changes in the proportion of patients experiencing exacerbations (primary), OCS use (secondary), and asthma exacerbation-related costs during the baseline and follow-up periods., Results: The study identified 1,278 patients (mean age, 67.9 years; 65% female) with one or more prescription or administration claim for mepolizumab who were eligible for study inclusion. There was a significant relative reduction in the proportion of patients with an asthma exacerbation (27%; P < .0001) in the follow-up versus baseline period. Similarly, a lower proportion of patients received OCS for asthma (16% relative reduction; P < .0001), fewer patients were chronic OCS users (5 mg/day or more; 48% relative reduction; P < .0001), and there was a significant decrease in asthma exacerbation-related costs (total reduction, $888; P = .0002) during the follow-up versus the baseline period., Conclusion: Mepolizumab reduced exacerbations, OCS use, and exacerbation-related healthcare costs in a US Medicare population, confirming its benefits in this specific population with severe asthma., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors certify that none of them have any conflicts of interest.

Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies ( p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 ( p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.

Over 20 years ago, the concept of asthma control was created and appropriate measurement tools were developed and validated. Loss of asthma control can lead to an exacerbation. Years ago, the term "clinically significant asthma exacerbation" was introduced to define when a loss of control is severe enough to declare it an asthma exacerbation. This term is also used by health insurances to determine when an exacerbation is eligible for reimbursement of biologics in clinical practice, however, it sometimes becomes apparent that a clear separation between loss of "asthma control" and an exacerbation is not always possible. In this review, we attempt to justify why exacerbations in early allergic asthma and adult eosinophilic asthma can differ significantly and why this is important in clinical practice as well as when dealing with health insurers., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Mucus plugs are associated with airway obstruction in severe asthma and are involved in the formation of activated eosinophils. Benralizumab, an anti-interleukin-5 receptor antibody, markedly reduces not only peripheral blood eosinophils but also airway eosinophils; however, its effects on mucus plugs have not been clarified. In this study, we examined the efficacy of benralizumab on mucus plugs using computed tomography (CT) imaging., Methods: Twelve patients who were administered benralizumab and underwent CT before and approximately 4 months after the introduction of benralizumab were included in this study, and the number of mucus plugs before and after benralizumab administration was compared. The correlation between the clinical background and treatment effect was also examined., Results: The number of mucus plugs significantly decreased after the introduction of benralizumab. The number of mucus plugs was correlated with sputum eosinophil percentage and eosinophil cationic protein in the sputum supernatants and inversely correlated with forced expiratory volume in 1 s (FEV1). Benralizumab induction resulted in a marked decrease in blood and sputum eosinophil levels and a significant improvement in asthma symptoms, quality of life scores, FEV1, and exacerbation frequency. Furthermore, there was a significant correlation between the reduction in mucus plugs and changes in the symptom score or FEV1., Discussion/conclusion: These data suggest that benralizumab may have the potential to improve symptoms and respiratory function in patients with severe eosinophilic asthma by reducing mucus plugs., (© 2023 S. Karger AG, Basel.)

Background: Infants and young children might be particularly susceptible to the potential side effects from inhaled corticosteroid (ICS) on height and bone mineral content (BMC), but this has rarely been studied in long-term prospective studies., Methods: Children from two Copenhagen Prospective Studies on Asthma in Childhood cohorts were included. ICS use was registered prospectively from birth to age 6 and the cumulative dose was calculated. Primary outcomes were height and BMC from dual-energy X-ray absorptiometry (DXA) scans at age 6., Results: At age 6, a total of 930 children (84%) from the cohorts had a valid height measurement and 792 (71%) had a DXA scan. 291 children (31%) received a cumulated ICS dose equivalent to or above 10 weeks of standard treatment before age 6. We found an inverse association between ICS use and height, -0.26 cm (95% CI: -0.45 to -0.07) per 1 year standard treatment from 0 to 6 years of age, p=0.006. This effect was mainly driven by children with ongoing treatment between age 5 and 6 years (-0.31 cm (95% CI: -0.52 to -0.1), p=0.004), while there was no significant association in children who stopped treatment at least 1 year before age 6 (-0.09 cm (95% CI: -0.46 to 0.28), p=0.64). There was no association between ICS use and BMC at age 6., Conclusions: ICS use in early childhood was associated with reduced height at age 6 years but only in children with continued treatment in the sixth year of life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prostaglandin D 2 receptor 2 (DP 2 ) antagonists inhibit prostaglandin D 2 -induced effects, including recruitment and activation of cells driving asthma pathogenesis. However, challenges identifying target population and end points persist., Research Question: What is the effect of the DP 2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma?, Study Design and Methods: In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count ≥ 250 cells/μL. Patients aged ≥ 18 years to < 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment., Results: A total of 480 patients were treated. The ORs for asthma worsening for GB001 20 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, and GB001 40 mg., Interpretation: Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT03683576; URL: www., Clinicaltrials: gov., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Dupilumab, an anti-IL-4α receptor antibody, is a new treatment for severe or refractory asthma. However, real-world evidence on the efficacy of dupilumab in patients with mild to moderate bronchial asthma is lacking., Methods: We retrospectively evaluated the effects of dupilumab in 62 patients who received dupilumab for eosinophilic sinusitis comorbid with asthma at a single centre in Japan. Type 2 inflammatory markers, ACT, respiratory function tests, and forced oscillation technique (FOT) were analysed before, three months after, and one year after dupilumab administration, mainly in patients with mild to moderate asthma., Results: FEV1, %FEV1, %FVC, treatment steps for asthma and ACT improved significantly after three months of dupilumab treatment. FeNO was markedly decreased, whereas IgE and eosinophil counts showed no significant changes. Pre- and post-treatment respiratory resistance (Rrs) and respiratory reactance (Xrs) correlated significantly with FEV1. Improvement in %FEV1 was associated with higher FeNO and higher serum IgE before dupilumab treatment., Conclusion: Dupilumab treatment for sinusitis may improve respiratory functions, asthma symptoms, and asthma treatment reduction, even if the associated bronchial asthma is not severe., (© 2022. The Author(s).)

Background: Inhaled corticosteroids (ICSs) are important in asthma management, but there are concerns regarding associated risk of pneumonia. While studies in asthmatic adults have shown inconsistent results, this risk in asthmatic children is unclear., Objective: Our aim was to determine the association of ICS use with pneumonia risk in asthmatic children., Methods: A nested case-control study was performed in the Mayo Clinic Birth Cohort. Asthmatic children (<18 years) with a physician diagnosis of asthma were identified from electronic medical records of children born at Mayo Clinic from 1997 to 2016 and followed until 31 December 2017. Pneumonia cases defined by Infectious Disease Society of America were 1:1 matched with controls without pneumonia by age, sex and asthma index date. Exposure was defined as ICS prescription at least 90 days prior to pneumonia. Associations of ICS use, type and dose (low, medium and high) with pneumonia risk were analysed using conditional logistic regression., Results: Of the 2108 asthmatic children eligible for the study (70% mild intermittent and 30% persistent asthma), 312 children developed pneumonia during the study period. ICS use overall was not associated with risk of pneumonia (adjusted OR: 0.94, 95% CI: 0.62 to 1.41). Poorly controlled asthma was significantly associated with the risk of pneumonia (OR: 2.03, 95% CI: 1.35 to 3.05; p<0.001). No ICS type or dose was associated with risk of pneumonia., Conclusion: ICS use in asthmatic children was not associated with risk of pneumonia but poorly controlled asthma was. Future asthma studies may need to include pneumonia as a potential outcome of asthma management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: Although the usefulness of inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) in cough-variant asthma and cough-predominant asthma has been reported, there is no consensus on its starting dose. The aim of this study is to find the optimal dose of ICS/LABA for cough-variant asthma and cough-predominant asthma., Patients and Methods: We analysed 112 patients who visited our clinic from January 2009 to December 2012 with the chief complaint of cough that had continued for more than 3 weeks. Cough-variant asthma (n=30) and cough-predominant asthma (n=7) were treated with ICS/LABA., Results: There was no significant difference in cough duration time from starting ICS/LABA in cough-variant asthma and cough-predominant asthma between medium and high doses (14.3% versus 10.9%, respectively) (p=0.192). Moreover, there was no significant difference in cough duration time from starting ICS/LABA in cough-variant asthma between medium and high doses (13.2% versus 11.5%, respectively) (p=0.433)., Conclusion: The medium starting dose of ICS/LABA is sufficient for treating cough-variant asthma., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Asthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of 'false-negative' T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits., Methods: The STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17-75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m 2 ). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal., Discussion: This study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients. Trial registration Netherlands Trial Register, NL8759, registered 2020-07-06, https://www.trialregister.nl/trial/8759 . Protocol version and date: version 2.1, 20 November 2020., (© 2022. The Author(s).)

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.

Biological disease-modifying agents have increasingly become available for the effective treatment of both cutaneous and non-cutaneous inflammatory conditions. We report a case of a woman treated successfully for psoriasis and psoriatic arthritis with the IL-17 inhibitor secukinumab whilst simultaneously being treated for severe asthma and nasal polyps, initially with the IL-5 inhibitor benralizumab, followed by dupilumab, a monoclonal antibody that targets the IL-4 receptor alpha subunit which blocks signalling from both IL-4 and IL-13., (© 2021 The Australasian College of Dermatologists.)

The Global initiative against asthma (GINA) 2020 strategy has been released with some changes and updates. GINA recommends the continuation of medications, avoidance of nebulization and spirometry, and ensuring a written asthma action plan in COVID-19 times. GINA 2020 specifies which step of management is to be followed according to the patient's symptoms in an easy flowchart. Clinicians need to be aware of the changes and the evidence behind them.

Rationale: Infants and young children might be particularly likely to experience the potential clinical side effects of inhaled corticosteroids (ICSs) on body mass index (BMI), adiposity rebound (AR), and body composition, but this has rarely been studied in long-term studies in this age group. Objectives: To determine the association between ICS exposure in the first 6 years of life and the BMI, AR, body composition, and blood lipid concentrations. Methods: Children from the two mother-child cohorts of the COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) were included. ICS use was registered prospectively to age 6 years, and the cumulative dose was calculated. Multiple linear regression models were used for analysis. Measurements and Main Results: A total of 932 (84%) of the 1,111 children from the COPSAC cohorts had BMI data, 786 (71%) had dual-energy X-ray absorptiometry scan data at the age of 6 years, and 815 (73%) had an AR age calculated. Two hundred ninety-one children (31%) received a cumulative ICS dose higher than that from 10 weeks of standard treatment before the age of 6. ICS treatment during 0-6 years of age was associated with an increased BMI z -score (0.05 [95% confidence interval, 0.005 to 0.09] SDs per each year of standard treatment; P  = 0.03) an earlier age at AR (-0.18 [95% confidence interval, -0.28 to -0.08] yr; P  = 0.0006), and a 2% increased geometric mean android fat percentage ( P  = 0.05). ICS exposure and dual-energy X-ray absorptiometry scan data were not associated. Conclusions: ICS use in early childhood was associated with an increased BMI z -score at age 6, an earlier AR, and a trend of association with an increased android body fat percentage.

Introduction: Only little is known about COVID-19 in patients with asthma. There is no data on COVID-19 in patients with severe asthma or patients with asthma who are treated with monoclonal antibodies., Case Study: Here, we present the case of a severe eosinophilic asthmatic in whom benralizumab treatment, an anti-IL-5R monoclonal antibody, was initiated 2 years ago. Prior to benralizumab treatment, every viral infection had resulted in a prolonged course of oral corticosteroids (OCS). Since initiation of benralizumab, the patient has had good asthma control. Mid-March 2020, the patient developed high fever., Results: A SARS-CoV-2-PCR (nasopharyngeal swab) was positive. The patient's symptoms subsided after few days. No OCS was needed. The asthma control questionnaire 6-item scale worsened moderately in the week of the infection and returned to normal levels thereafter. The asthma control test, measuring longer term asthma control, showed no decline., Conclusion: The course of COVID-19 was very mild in this particular patient with severe eosinophilic asthma. So far, there is no evidence that would suggest a more severe course of COVID-19 in patients with asthma. It is worth noting, that prior to the initiation of benralizumab this patient had multiple exacerbations per year triggered by viral infections (4/year), which all required OCS. Whilst only anecdotal, this case study provides the first evidence to support the current recommendation of continuing monoclonal antibodies in patients with severe asthma during the COVID-19 pandemic.

Objectives/hypotheses: The primary objective of this study was to determine whether the diagnosis and treatment of pediatric Paradoxical Vocal Fold Motion Disorder (PVFMD) leads to decreased asthma medication use. Our secondary objective was to determine dyspnea outcomes following diagnosis and treatment for PVFMD., Study Design: Prospective observational study., Methods: Patients with newly diagnosed PVFMD between the ages of 11 and 17 were recruited at a single pediatric institution. A medication questionnaire and Dyspnea Index (DI) were completed at the initial visit, at the first return visit, and at greater than 6 months post-diagnosis and therapy. Laryngeal Control Therapy (LCT) consisted of teaching breathing techniques and identifying emotional, physical, and environmental contributing factors and strategies to reduce them., Results: Twenty-six patients were recruited to the study. There were 19/26 (73%) patients diagnosed with asthma prior to a diagnosis of PVFMD, and 26/26 (100%) patients were using an inhaler prior to the enrollment visit. Twenty-two (85%) patients completed follow-up questionnaires. Five patients participated in no therapy, seven patients in partial therapy, and 14 patients in full therapy. Significant reduction in asthma medication use was seen in the full therapy group (P < .05) and in those with exercise as their only trigger (P < .05). Furthermore, symptoms as scored by the DI decreased overall from 25.5 to 18.8 (P < .001)., Conclusions: Diagnosis and treatment of pediatric PVFMD leads to a decline in asthma medication use in those patients who participate in at least two LCT sessions and in those with exercise-induced PVFMD. LCT for pediatric PVFMD leads to a significant decrease in symptoms as measured by the DI., Level of Evidence: 4 Laryngoscope, 131:1639-1646, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

A 13-year-old male asthmatic presented to the general paediatric clinic with papilloedema identified following a check-up with his optician due to blurred vision. His asthma was well controlled on a moderate dose of inhaled corticosteroid and there had been no recent increase or decrease in the dose. A diagnosis of benign intracranial hypertension (BIH) was made based on a raised cerebrospinal fluid opening pressure, papilloedema, a normal neurological examination and normal neuroimaging. The only associated risk factor was his inhaled corticosteroids. He was commenced on acetazolamide and the inhaled corticosteroid dose was reduced, resulting in resolution of his papilloedema. This case serves to highlight that steroid side effects including BIH may occur at moderate doses of inhaled corticosteroids and that inhaled corticosteroid dose should be regularly reviewed and decreased to the lowest dose that maintains asthma control., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Severe asthma is very difficult to manage in many individuals, and systemic corticosteroids are often used to prevent or manage acute exacerbations. Furthermore, comorbid allergic conditions may render standard therapies inadequate. A 51-year-old man presented with severe eosinophilic asthma requiring nearly constant oral corticosteroid usage despite using high-dose inhaled corticosteroids and secondary asthma controllers. His condition was complicated by aspirin-exacerbated respiratory disease, including severe nasal polyposis, chronic rhinosinusitis, as well as chronic idiopathic urticaria. Mepolizumab was initiated and led to dramatic improvement of asthma over 6 months. However, he continued to experience exacerbations of chronic idiopathic urticaria not responsive to H1-antihistamines. Omalizumab was added, and the patient's urticaria attained marked improvement with only an occasional breakthrough rash. Dual biologic therapies can be a unique and useful steroid-sparing treatment option for patients with uncontrolled severe asthma and chronic idiopathic urticaria., Competing Interests: Competing interests: DK reports speaker bureau fees from GSK outside the submitted work. JRC reports no conflicts of interest., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients' health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03-0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005-0.08), and number of lost working days (Δ = - 7.9, 95% CI - 11.2 to - 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI - 1588-2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (- €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide rapidly. However, the effects of asthma, asthma medication and asthma severity on the clinical outcomes of COVID-19 have not yet been established., Methods: The study included 7590 de-identified patients, who were confirmed to have COVID-19 using the severe acute respiratory syndrome coronavirus 2 RNA-PCR tests conducted up to May 15, 2020; we used the linked-medical claims data provided by the Health Insurance Review and Assessment Service. Asthma and asthma severity (steps suggested by the Global Initiative for Asthma) were defined using the diagnostic code and history of asthma medication usage., Results: Among 7590 COVID-19 patients, 218 (2.9%) had underlying asthma. The total medical cost associated with COVID-19 patients with underlying asthma was significantly higher than that of other patients. Mortality rate for COVID-19 patients with underlying asthma (7.8%) was significantly higher than that of other patients (2.8%; p<0.001). However, asthma was not an independent risk factor for the clinical outcomes of COVID-19 after adjustment, nor did asthma medication use and asthma severity affect the clinical outcomes of COVID-19. However, use of oral short-acting β 2 -agonists was an independent factor to increase the total medical cost burden. Patients with step 5 asthma showed significant prolonged duration of admission compared to those with step 1 asthma in both univariate and multivariate analysis., Conclusions: Asthma led to poor outcomes of COVID-19; however, underlying asthma, use of asthma medication and asthma severity were not independent factors for poor clinical outcomes of COVID-19, generally., Competing Interests: Conflict of interest: Y.J. Choi has nothing to disclose. Conflict of interest: J-Y. Park has nothing to disclose. Conflict of interest: H.S. Lee has nothing to disclose. Conflict of interest: J. Suh has nothing to disclose. Conflict of interest: J.Y. Song has nothing to disclose. Conflict of interest: M.K. Byun has nothing to disclose. Conflict of interest: J.H. Cho has nothing to disclose. Conflict of interest: H.J. Kim has nothing to disclose. Conflict of interest: J-H. Lee has nothing to disclose. Conflict of interest: J-W. Park has nothing to disclose. Conflict of interest: H.J. Park has nothing to disclose., (Copyright ©ERS 2021.)

Background: Obesity is a common comorbidity in asthma and associated with poorer asthma control, more frequent/severe exacerbations, and reduced response to asthma pharmacotherapy., Objective: This review aims to compare use of all classes of asthma medications in obese (body mass index (BMI) ≤30 kg·m -2 ) versus healthy-weight (BMI <25 kg·m -2 ) subjects with asthma., Design: Databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, Embase and MEDLINE were searched up to July 2019 for English-language studies that recorded medication use or dose in obese and healthy-weight adults with asthma. A critical appraisal checklist was utilised for scrutinising methodological quality of eligible studies. Meta-analysis was performed and heterogeneity was examined with the use of the Chi-squared test. This review was conducted based on a published protocol (www.crd.york.ac.uk/PROSPERO CRD42020148671)., Results: Meta-analysis showed that obese subjects are more likely to use asthma medications, including short-acting β 2 -agonists (OR 1.75, 95% CI 1.17-2.60; p=0.006, I 2 =41%) and maintenance oral corticosteroids (OR 1.86, 95% CI 1.49-2.31; p<0.001, I 2 =0%) compared to healthy-weight subjects. Inhaled corticosteroid (ICS) dose (µg·day -1 ) was significantly higher in obese subjects (mean difference 208.14, 95% CI 107.01-309.27; p<0.001, I 2 =74%). Forced expiratory volume in 1 s (FEV 1 ) % predicted was significantly lower in obese subjects (mean difference -5.32%, 95% CI -6.75--3.89; p<0.001, I 2 =42%); however, no significant differences were observed in FEV 1 /forced vital capacity (FVC) ratio between groups., Conclusions: We found that obese subjects with asthma have higher use of all included asthma medication classes and higher ICS doses than healthy-weight asthma subjects, despite lower FEV 1 and a similar FEV 1 /FVC %. A better understanding of the factors driving increased medication use is required to improve outcomes in this subgroup of asthmatics., Competing Interests: Conflict of interest: C.A. Thompson has nothing to disclose. Conflict of interest: S.R. Eslick has nothing to disclose. Conflict of interest: B.S. Berthon has nothing to disclose. Conflict of interest: L.G. Wood has nothing to disclose., (Copyright ©ERS 2021.)

Introduction: Children with food allergy are at increased risk for asthma and asthma morbidity. Since leukotrienes are implicated in the pathogenesis of both asthma and probably in food allergies, we hypothesized that asthmatic children with concomitant food allergy may have a favorable response to antileukotriene treatment., Methods: Asthmatic children aged 6-18 years with and without food allergy were treated with montelukast and placebo in a double-blind, placebo-controlled cross-over parallel-group study. The primary outcome of the study was improvement in FEV1%. Asthma control tests, spirometry and methacholine challenges were performed as well as Fractional Exhaled Nitric Oxide (FeNO) levels. PGD2, CystLT, and lipoxin levels were measured in exhaled breath condensate (EBC)., Results: A total of 113 children were enrolled and 87 completed the study in accordance with the protocol. At baseline, children with food allergy and asthma (FAA) had higher levels of PGD2 and CysLT levels in the EBC than children with asthma alone (AA) (p < 0.001 for each). In the montelukast arm, although FEV1% was significantly higher in the FAA group compared to AA (p = 0.005), this effect was linked to the baseline difference of FEV1% between both arms. Montelukast treatment failed to improve FEV1% in both groups compared to the placebo. No effect of montelukast was observed in the remaining study parameters., Conclusion: Although children with FAA do not show a more favorable response to montelukast treatment compared to AA, a significant difference between baseline PGD2 and CystLT levels between FAA and AA groups may point to a different endotype of childhood asthma., (© 2021 S. Karger AG, Basel.)