Recurrent Asthma Exacerbations Research Articles

TNF Superfamily and ILC2 Activation in Asthma.

Eosinophilic asthma is the most prevalent and well-defined phenotype of asthma. Despite a majority of patients responding to corticosteroid therapy and T2 biologics, there remains a subset that have recurrent asthma exacerbations, highlighting a need for additional therapies to fully ameliorate airway eosinophilia. Group 2 innate lymphoid cells (ILC2) are considered key players in the pathogenesis of eosinophilic asthma through the production of copious amounts of type 2 cytokines, namely IL-5 and IL-13. ILC2 numbers are increased in the airways of asthmatics and with the greatest numbers of activated ILC2 detected in sputa from severe prednisone-dependent asthma with uncontrolled eosinophilia. Although epithelial-derived cytokines are important mediators of ILC2 activation, emerging evidence suggests that additional pathways stimulate ILC2 function. The tumor necrosis factor super family (TNFSF) and its receptors (TNFRSF) promote ILC2 activity. In this review, we discuss evidence supporting a relationship between ILC2 and TNFSF/TNFRSF axis in eosinophilic asthma and the role of this relationship in severe asthma with airway autoimmune responses.

Unveiling the complexity of right middle lobe syndrome: a case series highlighting the association with asthma.

Right middle lobe syndrome (MLS) is a rare lung disorder primarily affecting children with a history of asthma or atopy. It encompasses a range of pathological and clinical conditions, from recurrent collapses of the middle lobe to bronchiectasis. In this study, the authors present a case series featuring four individuals with MLS associated with asthma, aiming to deepen our understanding of this uncommon condition. Four paediatric patients with right MLS exhibited symptoms of persistent cough, dyspnoea, and recurrent asthma exacerbations. Radiographic evaluations confirmed features consistent with right MLS, and bronchoscopy revealed mucus plugs and oedematous airways obstructing the right middle lobe bronchus. Treatment with bronchodilators, antibiotics, and corticosteroids led to symptom improvement and resolution of atelectasis. MLS is a rare condition characterized by chronic collapse of the right middle lobe and bronchiectasis. It is challenging to diagnose MLS, but computed tomography (CT) scans provide detailed lung images for confirmation. Treatment focuses on addressing the underlying cause, such as infections or mucus obstruction. Lobectomy may be considered in severe cases. This case series emphasizes the need for further research on MLS, as its rarity and characteristics remain unclear. These cases exhibited obstructive MLS with and without asthma. Accurate diagnosis is challenging, requiring imaging techniques. MLS has clinical implications, particularly in asthma patients. Future studies should focus on understanding the aetiology of non-obstructive MLS.

Socioeconomic status, diet, and recurrent severe asthma exacerbations in Puerto Rican youth

Why Puerto Rican youths have higher rates of severe asthma exacerbations (SAEs) than their non-Hispanic White peers is unclear. We aimed to identify risk factors associated with recurrent SAEs in Puerto Rican youths with asthma. We performed cross-sectional and longitudinal analyses of recurrent SAEs in 209 Puerto Rican youths with asthma who participated in 2 cross-sectional studies approximately 5.2 years apart: the Puerto Rico Genetics of Asthma and Lifestyle study (visit 1, participants aged 6-14 years) and the Epigenetic Variation and Childhood Asthma in Puerto Ricans study (visit 2, participants aged 9-20 years). Recurrent SAEs were defined as at least 2 SAEs in the previous year. Of the youths in our study, there were 80 (38.3%) and 47 (22.4%) with recurrent SAEs at visit 1 and visit 2, respectively, and 31 participants (14.8%) had persistent recurrent SAEs (ie, recurrent SAEs at both visits). In multivariable analyses, low household income was significantly associated with 2.4 to 12.3 times increased odds of recurrent SAEs in all analyses, with stronger longitudinal associations. Low parental education level, nonprivate or employer-based health insurance, overweight or obesity, residential proximity to a major road, and low or moderate level of outdoor activity were each significantly associated with recurrent SAEs in at least 1 analysis. Further, persistence of low parental numeracy level, low household income, and an unhealthy diet were each associated with persistent recurrent SAEs. In this study of Puerto Rican youths with asthma, persistence of low parental numeracy level, a low household income, and an unhealthy diet were associated with persistent recurrent SAEs. Our findings support policies promoting equity and healthy lifestyles for Puerto Rican children and their families.

PENGARUH EDUKASI FARMASI TERHADAP TINGKAT KONTROL ASMA DI POLI PARU RUMAH SAKIT BHAYANGKARA KEDIRI

Asthma control level is one of the indicators to assess the success of asthma therapy. The provision of pharmaceutical education is crucial in changing respondents' attitudes in controlling and preventing recurrent asthma exacerbations. The type of research used is pre-experimental (One group pre-post-test design) which will be conducted through pre-testing first, then giving the intervention, and then providing a post-test to determine the changes that occur before and after the intervention. Data collection is done through interviews and filling out the Asthma Control Test questionnaire. In this study, a sample of 35 respondents was used. The research analysis was conducted using the Wilcoxon test. The demographic data results showed that the majority of respondents were female, 21 respondents (60%), aged 36-45 years, 14 respondents (40%), with high school education, 14 respondents (40%), occupation as a homemaker, 13 respondents (37.1%), and a history of asthma for more than 10 years, 13 respondents (37.1%). Out of 35 respondents, before receiving pharmaceutical education, there were 7 respondents (20%) well-controlled, 13 respondents (37.1%) partially controlled, and 15 respondents (42.9%) uncontrolled. The questionnaire results after providing education showed 12 respondents (34.3%) well-controlled, 17 respondents (48.6%) partially controlled, and 6 respondents (17.1%) uncontrolled. The statistical test results showed that there is an influence of pharmaceutical education on asthma control level with a significance value of 0.003.

Comparison of the clinical outcomes of patients with NSAID-exacerbated respiratory disease receiving aspirin or biologicals

Objective NSAID-exacerbated respiratory disease (NERD) is characterized by exacerbation of respiratory symptoms after NSAID intake. While research for specific treatment options continues in patients who cannot tolerate or are unresponsive to aspirin treatment after aspirin desensitization (ATAD), biologicals have emerged as a new therapeutic option in NERD patients. The aim of this study was to compare the quality of life, and the sinonasal and respiratory outcomes of NERD patients treated with ATAD or biologicals. Methods Patients who have been followed up at a tertiary care allergy center and who have been receiving at least one of ATAD, mepolizumab or omalizumab for at least six months were included. Evaluations were made using sinonasal outcome test (SNOT-22), asthma control test (ACT), short form-36 (SF-36), blood eosinophil counts, need for recurrent functional endoscopic sinus surgeries (FESS), and asthma or rhinitis exacerbations requiring oral corticosteroids (OCS). Results A total of 59 patients comprised of 35 (59%) females and 24 (41%) males with a mean age of 46.1 (min-max, 20–70) years were included. The baseline blood eosinophil count was higher, and a significant decrease in blood eosinophil counts was observed in the mepolizumab group compared to ATAD group (p = 0.001, p < 0.001, respectively). At follow-up, the rate of recurrent FESS was lower in the group that received mepolizumab (p = 0.02). Conclusions In NERD patients, mepolizumab significantly decreased blood eosinophil counts and recurrent FESS. There was no significant difference between the patients receiving ATAD or mepolizumab regarding other clinical parameters.

Biomarker underuse contributes to an inability to phenotype patients with severe uncontrolled asthma.

Background: Biomarker measurements improve the phenotyping of patients with severe uncontrolled asthma (SUA) and predict therapeutic responses. The use of biomarkers in asthma, however, remains underused. Objective: To test the hypothesis that biomarker measurements of patients with SUA remain markedly underused and contributes to asthma morbidity and oral corticosteroid use. Methods: Leveraging claims data linked to electronic health record data, we calculated biomarker use by providers treating patients with SUA from January 2017 to August 2020. Results: From 3.6 million clients, 3817 had a primary diagnosis of asthma; most were between 50 and 60 years old. Also, 63.2% were female patients; those under ages 10 years were primarily boys. Of the 728 patients who reported race, 69.9% were white and 21.8% were African American. Of the 840 who reported ethnicity, 14% were Latinx. A predetermined definition of SUA identified 348 patients with SUA. In a nested sample of 151 patients with SUA, 43% were managed by primary care physicians (PCP), 4% by specialists, and 49.7% by both. Of this sample, 61.5% had a measurement of serum eosinophils, 9.9% total immunoglobulin E values, and 9.3% radioallergosorbent skin tests; 38% received no tests, whereas 9.9% had more than one. Specialists ordered a biomarker test 4.6 times more often than did PCPs, whereas PCPs ordered 70% of the prednisone prescriptions for recurrent asthma exacerbations. Conclusion: Specialists were more likely to order biomarkers than were PCPs. Patients managed exclusively by PCPs were more likely prescribed oral prednisone. Real-world evidence shows that biomarkers are infrequently used to characterize patients with SUA, especially among patients exclusively managed by PCPs. Programs that encouraged biomarker use may improve SUA management and oral corticosteroid burden.

A territory-wide study on the factors associated with recurrent asthma exacerbations requiring hospitalization in Hong Kong.

BackgroundThe real‐world relationships between the demographic and clinical characteristics of asthma patients, their prehospitalization management and the frequency of hospitalization due to asthma exacerbation is poorly established.ObjectiveTo determine the risk factors of recurrent asthma exacerbations requiring hospitalizations and evaluate the standard of baseline asthma care.MethodsA territory‐wide, multicentre retrospective study in Hong Kong was performed. Medical records of patients aged ≥18 years admitted to 11 acute general hospitals from January 1 to December 31, 2016 for asthma exacerbations were reviewed.ResultsThere were 2280 patients with 3154 admissions (36.7% male, median age 66.0 [interquartile range: 48.0–81.0] years, 519 had ≥2 admissions). Among them, 1830 (80.3%) had at least one asthma‐associated comorbidity, 1060 (46.5%) and 885 (38.9%) of patients had Accident and Emergency Department (AED) attendance and hospitalization in the preceding year, respectively. Patients with advancing age (incidence rate ratio [IRR]: 1.003 for every year increment), a history of AED visits or hospitalization (IRR: 1.018 and 1.070 for every additional episode, respectively) for asthma exacerbation in the preceding year, the presence of neuropsychiatric (IRR: 1.142) and gastrointestinal (IRR: 1.154) comorbidities were risk factors for an increasing number of admissions for asthma exacerbation. For patients with ≥2 admissions, 17.1% were not prescribed inhaled corticosteroid and only 44.6% had spirometry checked before the index admission. Asthma phenotyping was often incomplete, as assessment of atopy (total serum immunoglobulin E level and senitization to aeroallergens) was only performed in 30 (5.8%) patients with ≥2 admissions.Conclusions and Clinical RelevanceImproving asthma care, especially in elderly patients with a prior history of urgent healthcare utilization and comorbidities, may help reduce healthcare burden. Suboptimal management before the index admission was common in patients hospitalized for asthma exacerbations. Early identification of patients at risk and enhancement of baseline asthma management may help to prevent recurrent asthma exacerbation and subsequent hospitalization.

Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians\u2019 prescription habits

BackgroundA national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians’ ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis.MethodsFrom the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies.ResultsOne thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged.ConclusionsPediatricians’ ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians’ work settings and geographical distribution.

Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial

IntroductionPreschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the...

Inhaled corticosteroids prescriptions increased in the ED for recurrent asthma exacerbations by automated electronic reminders in the ED

Objective: The objective of this study was to evaluate the impact of an electronic alert on the prescription rate of inhaled corticosteroids (ICS) by ED providers for poorly controlled persistent asthmatic children.Methods: Study subjects included asthmatic patients age 4–18 presenting to the ED at Phenix Children’s Hospital between February 9, 2018 and December 4, 2018, with a history of at least two previous ED visits for acute exacerbation of asthma within 365 days, no active ICS prescription within 90 days, and free from developmental delay, bronchopulmonary dysplasia due to prematurity, cystic fibrosis, sickle cell disease, and/or interstitial ling disease. Patients meeting these criteria triggered an electronic alert prompting the medical provider to prescribe ICS or indicate reason for not prescribing. Instruction on the alert was provided to ED attending physicians and residents by email and through several educational sessions held prior to the implementation.Results: Among 62 patients without prior ICS who were discharged home from the ED, ICS was prescribed for 48 (77%). No statistically significant differences were detected in baseline characteristics between patients discharged home from the ED with and without ICS prescription. While ICS was prescribed by a larger proportion of physicians (56%) compared to residents (42%), statistical significance was not reached. For the 14 (33%) patients who were discharged home without ICS, no reason was provided to indicate why ICS were not prescribed.Conclusion: An electronic alert incorporated into the ED workflow to populate a discharge order set is effective to initiate asthma controller medication for poorly controlled pediatric patients. Additional data describing reasons for not prescribing ICS can further refine recommendations for ICS prescriptions, and provide a comprehensive strategy to support clinical decision for pediatric asthma control in acute care settings.

Recurrent asthma exacerbations: What else could it be?

Recurrent asthma exacerbations: What else could it be?

Impact of Environmental Factors on Recurrent Asthma Exacerbations among Inner-CIty Schoolchildren from the Pittsburgh Region

Impact of Environmental Factors on Recurrent Asthma Exacerbations among Inner-CIty Schoolchildren from the Pittsburgh Region

Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study

PurposePatients with severe eosinophilic asthma often experience recurrent asthma exacerbations despite intensive inhaled corticosteroid therapy. In 2 previous double-blind studies (MENSA [NCT01691521] and SIRIUS [NCT01691508]), treatment with intravenous or subcutaneous mepolizumab was associated with significantly reduced annualized exacerbation rates and oral corticosteroid (OCS) requirements compared with placebo. The purpose of this study was to assess the long-term safety and efficacy of subcutaneous mepolizumab treatment in patients with severe eosinophilic asthma. MethodsCOSMOS was a 52-week, open-label extension study in patients who received mepolizumab or placebo in MENSA or SIRIUS. Patients received subcutaneous mepolizumab regardless of prior treatment allocation and continued to receive appropriate standard-of-care asthma therapy throughout. The primary objective was to assess the long-term safety of mepolizumab; end points included adverse events (AEs) and serious AEs (SAEs). Efficacy assessments included the annualized exacerbation rate and durability of response (defined as the exacerbation rate and OCS dose reduction when combined with MENSA and SIRIUS data, respectively). FindingsIn total, 558 (86%; previous mepolizumab: 358; previous placebo: 200) and 94 (14%; previous mepolizumab: 58, previous placebo: 36) patients experienced on-treatment AEs and SAEs, respectively. No fatal AEs were reported. Totals of 13 (2%) and 29 (4%) patients experienced systemic and local site reactions, respectively. There were no reports of mepolizumab-related anaphylaxis. Mepolizumab treatment was shown to exert a durable response, with patients who previously received mepolizumab in MENSA or SIRIUS maintaining reductions in exacerbation rate and OCS dosing throughout COSMOS. Patients who previously received placebo in MENSA or SIRIUS demonstrated improvements in these end points following treatment with mepolizumab in COSMOS. ImplicationsThese data demonstrate a favorable safety profile of mepolizumab and indicate a durable and stable effect over time, supporting long-term treatment in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT01842607.

Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation.

Genetic associations of the response to inhaled corticosteroids (ICSs) during an asthma exacerbation are unknown. To evaluate the role of genetic variants in the therapeutic response to high-dose ICS in children with moderate-to-severe asthma exacerbations. Eighty-two children (56 boys/26 girls, mean age 9.6 ± 3.2 years) with moderate-severe asthma exacerbation were genotyped for eight single-nucleotide polymorphisms that were a priori associated with ICS response in chronic asthma treatment: glucocorticosteroid receptor (NR3C1) rs41423247; corticotrophin-releasing hormone receptor1 (CRHR1) rs242939, rs242941, and rs1876828; T-box 21 (TBX21) rs2240017; glucocorticoid-induced transcript 1 (GLCCl1); and T gene rs3099266 and rs2305089. Children were treated with a single high-dose (4000 μg) fluticasone propionate given by a nebulizer followed by 1000 μg/day of inhaled fluticasone propionate for 6 days. Primary outcome measure was the improvement in FEV1 at 4 h. Mean FEV1 was 71.7 ± 14.2% at presentation. Overall, fluticasone treatment resulted in a significant improvement in asthma score and FEV1 (p < 0.0001 for both). Children with the GG genotype at NR3C1 rs41423247 (n = 26) had a higher improvement in FEV1 [24.2% (interquartile range 11.5-36.3)] compared to those with CG+CC (n = 19), [7.9% (interquartile range 6.1-24.6) (p = 0.006)]. Homozygosity for the G allele at rs41423247 of the glucocorticosteroid receptor (NR3C1) gene is associated with a higher improvement in FEV1 at 4 h in children with moderate-to-severe asthma exacerbation treated with high-dose ICS. This observation may have important clinical implications especially for children who use systemic steroids frequently for recurrent asthma exacerbations.

Intravenous immunoglobulin therapy in a selective IgG3 deficient patient with recurrent respiratory infections and asthma attacks

The IgG subclass deficiency is defined as a significant decrease in the serum concentrations of one or more subclasses of IgG in a patient whose total IgG concentration is normal. IgG subclass deficiency can predispose to recurrent sinopulmonary infections. A 29-year-old female patient with a 4-year history of bronchial asthma presented with cough, sputum, dyspnea, and recurrent respiratory infections. She had frequently been treated with antibiotics and systemic steroids for recurrent respiratory infections and acute asthma exacerbations. Chest X-ray and computed tomography showed pectus excavatum and bronchial wall thickening without lung parenchymal abnormalities. On immunological evaluation, she was found to have a low serum IgG3, with normal total IgG concentration. Under diagnosis of selective IgG3 deficiency, she was started on monthly infusions of intravenous immunoglobulin (IVIG) therapy. The frequency and severity of respiratory infections and acute asthma exacerbations were markedly decreased during 3 years of IVIG therapy. Our case report suggests that a patient who has underlying selective IgG3 deficiency and asthma may benefit from IVIG therapy as this can significantly reduce the incidence and severity of recurrent respiratory infections and acute asthma exacerbations. (Allergy Asthma Respir Dis 2016;4:225-229)

Mepolizumab: First Global Approval.

Mepolizumab (Nucala(®)) is a fully humanized monoclonal antibody against interleukin-5 (IL-5) that is being developed by GlaxoSmithKline. Subcutaneous mepolizumab is approved in the USA for the add-on maintenance treatment of patients aged ≥12 years with severe asthma and an eosinophilic phenotype, and is awaiting approval in the EU. Mepolizumab blocks IL-5 and reduces blood and sputum eosinophil counts in patients with asthma. In the phase III MENSA trial in patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high-dose inhaled glucocorticoid therapy, mepolizumab significantly reduced the annualized exacerbation rate. In the phase III SIRIUS trial, mepolizumab had an oral glucocorticoid-sparing effect in patients with severe eosinophilic asthma requiring systemic glucocorticoid maintenance therapy. This article summarizes the milestones in the development of mepolizumab leading to this first approval for severe asthma with an eosinophilic phenotype.

Children with severe asthma can start allergen immunotherapy after controlling asthma with omalizumab: a case series from Poland.

Children with severe asthma can start allergen immunotherapy after controlling asthma with omalizumab: a case series from Poland.

Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma

BackgroundSome 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.MethodsIn this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory volume in 1 second (FEV1) and scores on the St. George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed.ResultsThe rate of exacerbations was reduced by 47% (95% confidence interval [CI], 28 to 60) among patients receiving intravenous mepolizumab and by 53% (95% CI, 36 to 65) among those receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both comparisons). Exacerbations necessitating an emergency department visit or hospitalization were reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in those receiving placebo (P=0.02) and 98 ml greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03). The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo.ConclusionsMepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.)

Chinese expert consensus on bronchial asthma control.

Chinese and international guidelines for prevention and treatment of bronchial asthma (hereinafter referred to as asthma) indicate: the goal of asthma management is to achieve and maintain symptom control; treatment protocols need to be adjusted according to asthma control levels during asthma management; asthma management is a long-term process which incorporates three essential aspects—evaluation, treatment, and monitoring (1,2). These guidelines highlight that asthma control as the goal of treatment can be achieved by medication in the majority of patients, particularly with effective asthma management (1,2). The 2009 updates on the Global Initiative for Asthma (GINA) proposed a new conception of “overall asthma control”, which expanded the previous understanding of asthma control to emphasize the equal importance of achieving current asthma control and reducing future risk (3). However, a number of surveys in China and other countries have revealed that the rate of asthma control in the real world is far below as proposed by the guidelines (4-9). Poorly controlled asthma was shown to seriously affect the daily life, work and school of patients, and was associated with recurrent asthma exacerbations, unscheduled hospital visits and stay, and impaired lung functions, which eventually lead to increased treatment cost, lost productivity, as well as heavy social and economic burden (4-9). Therefore, with the updated understanding, efforts to improve the current pattern of asthma management and to reinforce the treatment strategies will have a long way to go for better outcomes of overall asthma control. In this regard, the Asthma Workgroup of Chinese Thoracic Society convened a panel meeting of experts in the related fields, which formed the following consensus. In order to guide clinical practicing, the present consensus was developed with reference to related guidelines and consensus documents published elsewhere, in particular, the important papers on asthma control that appeared in the recent years.

The role of mepolizumab in atopic and nonatopic severe asthma with persistent eosinophilia

To the Editor: Atopy is a common finding in asthma, but at least one third of severe asthmatics have no evidence of atopy (so-called “intrinsic” asthma) [1]–[4]. Despite the uncertainty of the mechanisms leading to nonatopic asthma, these patients have no history of allergic respiratory disease, no detectable specific IgE to common aeroallergens, and no positive skin-prick test. One hypothesis suggests that differences in the phenotypes might be driven by the local, and not by the systemic, production of IgE [5]. Eosinophils are involved in diverse inflammatory responses irrespective of atopy. Eosinophilic inflammation and IgE production are promoted by T-helper cell (Th)2 cytokines, such as interleukin (IL)-5, IL-4 and IL-13. IL-4/IL-13 are major factors involved in Th2 differentiation and IgE class switching [6], while IL-5 is involved primarily in eosinophil growth, survival, activation, and in mediating inflammation. Recurrent asthma exacerbations are a major problem in some patients and can predominate in a subgroup of asthmatics with elevated eosinophils, irrespective of their atopic status [2], [7]. Mepolizumab, a humanised monoclonal antibody against IL-5, selectively inhibits eosinophilic airway inflammation and has been shown to be associated with a significant reduction in severe asthma exacerbations irrespective of the baseline IgE levels or radioallergosorbent test (RAST) status in the Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) trial [7]. In this post hoc analysis of the DREAM trial, we aimed to: examine and discuss the effect of treatment with mepolizumab on the frequency of exacerbations in the atopic and nonatopic subgroups; to present the analyses of seasonal patterns of response by subgroup; and to evaluate changes in lung function and exhaled nitric oxide fraction ( F eNO) according to subgroup. Specific details …