Sex Differences in Severe Asthma: Results From Severe Asthma Network in Italy-SANI

PurposeAfter adolescence, asthma is more frequent in females than in males due to different hormonal, immunologic, and occupational/environmental factors. The higher prevalence and severity of the disease in females have already been reported in international registries. The aim of this study was to explore the difference in terms of clinical, functional, and biological characteristics between male and female patients with severe asthma in a real-life, registry-based setting.MethodsBaseline data from the Severe Asthma Network in Italy registry were analyzed in 1,123 patients with severe asthma, according to sex.ResultsAlmost 2/3 of severe asthmatics were female. Late-onset asthma, obesity and gastro-esophageal reflux were more frequent in females than in males, while previous smoking habits and nasal polyposis were more frequent in males. Females had poor asthma control and a higher number of severe exacerbations leading to hospitalization, in comparison to males. Biomarkers of type 2 inflammation (blood eosinophil, exhaled nitric oxide, and serum immunoglobulin E levels) were significantly higher in males than in females. The type 2 profile (defined by a combination of these 3 biomarkers) was significantly more frequent in males than in females. In multivariate analysis, late-onset asthma and a normal body mass index were only independent variables associated with the type 2 profile, while male sex and age showed only a trend toward the association with the type 2 profile.ConclusionsSignificant differences may be observed between male and female patients with severe asthma, influencing the asthma pheno-endotyping in both sexes.     

Clinical Characteristics and Disease Burden of Severe Asthma According to Oral Corticosteroid Dependence: Real-World Assessment From the Korean Severe Asthma Registry (KoSAR)

PurposeOral corticosteroids (OCS) are commonly used in patients with severe asthma, but they are associated with several adverse events. We estimated the prevalence of patients with OCS-dependent asthma in a large nationwide registry for severe asthma and delineated their clinical characteristics.MethodsThis cross-sectional study analyzed enrollment data of the patients recruited in the Korean Severe Asthma Registry (KoSAR) from 2010 to 2019. The clinical characteristics of patients were compared according to OCS dependency, which was defined as maintenance OCS treatment lasting at least 6 months during the 12 months prior to enrollment.ResultsAmong the 562 patients with severe asthma, 121 (21.5%) patients were defined as having OCS-dependent asthma. Compared with the OCS-independent group, the OCS-dependent group was older at symptom onset and had a higher prevalence of anxiety, worse lung function, and used more medication than the control group. Despite the higher doses of daily ICS and 6-month cumulative OCS, the OCS-dependent group reported greater consumption of relievers and a higher prevalence of unscheduled emergency room visits and repeated OCS bursts. Although anti-interleukin-5 was more commonly prescribed for patients with OCS-dependent asthma, only a limited proportion of patients with severe asthma received biologics.ConclusionsOne-fifth of patients with severe asthma had OCS-dependency, which was associated with a greater disease burden compared to those with OCS-independent asthma. Active intervention including initiation of biologics and regular assessment of OCS-induced morbidities is warranted to reduce the use of OCS and its potential adverse effects.     

Evolving Concept of Severe Asthma: Transition From Diagnosis to Treatable Traits

In recent decades, the concept of severe asthma has evolved from an umbrella term encompassing patients with high-intensity treatment needs to a clinical syndrome with heterogeneous, albeit distinct, pathophysiological processes. Biased and unbiased cluster approaches have been used to identify several clinical phenotypes. In parallel, cellular and molecular approaches allow for the development of biological therapies, especially targeting type 2 (T2) cytokine pathways. Although T2-biologics have significantly improved clinical outcomes for patients with severe asthma in real-world practice, questions on the proper use of biologics remain open. Furthermore, a subset of severe asthma patients remains poorly controlled. The unmet needs require a new approach. The “treatable traits” concept has been suggested to address a diversity of pathophysiological factors in severe asthma and overcome the limitations of existing treatment strategies. With a tailored therapy that targets the treatable traits in individual patients, better personalized medical care and outcomes should be achieved.     

Changes in Type 2 Biomarkers After Anti-IL5 Treatment in Patients With Severe Eosinophilic Asthma

Patients with severe eosinophilic asthma (SEA) suffer from frequent asthma exacerbations, where eosinophils are major effector cells in airway inflammation, and anti-interleukin (IL)-5 becomes an effective treatment modality to control eosinophilic inflammation of SEA. Fifteen patients with SEA who had been treated with anti-IL5 (reslizumab, 100 mg monthly intravenously) for 6 months at Ajou University Hospital (Suwon, Korea) were enrolled in this study. Clinical parameters, including total blood eosinophil count (TEC), FEV1%, fractional exhaled nitric oxide (FeNO) levels, and serum biomarkers such as eosinophil-derived neurotoxin (EDN), periostin (PON), and transforming growth factor-β1 (TGF-β1), were analyzed. EDN levels and TEC decreased significantly after 1 month of treatment (P < 0.05 for both), while no changes were noted in FeNO/PON/TGF-β1 levels. FEV1% increased after 2 months of treatment (P < 0.05). A positive correlation was observed between TEC and EDN levels (r = 0.60, P = 0.02). Significant negative correlations were noted between age and TEC/EDN levels (r = −0.57, P = 0.02 and r = −0.56, P = 0.03, respectively). Baseline TEC was higher in the EDN-responder group (≥75% decrease) than in the non-responder group (P = 0.06) with a positive correlation between %reduction in EDN and TEC (r = 0.67, P = 0.01). The onset age was younger and asthma duration was longer in the FEV1%-non-responder group (<12% increase) than in the FEV1%-responder group (P = 0.07 and P = 0.007, respectively). In conclusion, changes in the serum EDN level may be a potential biomarker for monitoring eosinophilic inflammation after anti-IL5 treatment in SEA, which is affected by onset age and asthma duration.     

Severe asthma in childhood: assessed in 10 year olds in a birth cohort study

Background:  Limited information is available regarding the prevalence of severe asthma in children. The present study aimed at investigating the prevalence of severe asthma in an urban child population; secondarily evaluating the applicability of the chosen definition by clinical characteristics. Methods:  Children enrolled in the prospective birth cohort; the Environment and Childhood Asthma Study in Oslo; were reinvestigated at the age of 10 years (n = 1019). A representative population based cohort of 616 children [mean age 10.9 (SD 0.9) years] with lung function measurements at birth was used for prevalence estimates, whereas all 1019 children (154 with current asthma) attending the 10‐year follow‐up were included for verification of the definition of severe asthma. Clinical investigations included spirometry, tests of bronchial hyperresponsiveness, skin prick tests and exhaled nitric oxide. Severe asthma was defined as poorly controlled asthma despite treatment with ≥ 800 μg budesonide or equivalent; assessed by a detailed structured interview. Results:  The population point prevalence at age 10 years of current severe asthma was 0.5% (three of 616) and among children with current asthma 4.5% (three of 67). The 10/154 children identified as suffering from severe asthma more often had severe bronchial hyperresponsiveness (PD₂₀ methacholine <1 μmol) (60%vs 22%, P = 0.015), lower median forced expiratory volume in 1 s/forced vital capacity ratio (93%vs 99%, P = 0.04) and higher body mass index (mean BMI 22.3 vs 18.3, P < 0.001) than nonsevere current asthmatics. Conclusions:  The prevalence of severe asthma was 0.5% in all 10‐year olds, and 4.5% among current asthmatics. The severe asthma definition applied in this study is supported by results of clinical investigations.     

Association Between Clinical Burden and Blood Eosinophil Counts in Asthma: Findings From a Korean Adult Asthma Cohort

BackgroundSome reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort.MethodsClinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated.ResultsIn total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266–23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083–11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL.ConclusionThe baseline blood eosinophil count may predict the future clinical burden of asthma.     

Specialist Perception of Severe Asthma in Korea: A Questionnaire Survey

The Working Group on Severe Asthma of the Korean Academy of Allergy and Clinical Immunology recently published an expert opinion paper on the management of severe asthma in Korea. When developing a consensus, the working group encountered several diagnostic and treatment issues and decided to perform a questionnaire survey of Korean specialists with regard to severe asthma. An e-mail with a uniform resource locator link to the questionnaire was sent to 121 asthma specialists, of whom 44.6% responded. The most commonly accepted definitions of severe asthma were a history of fatal exacerbation or an asthma-triggered need for mechanical ventilation, 3–4 oral corticosteroid (OCS) bursts/year, and maintenance of OCS therapy for 3–6 months per year. Before diagnosing severe asthma, most physicians contemplate chest computed tomography, seek to control chronic rhinosinusitis, and consider poor inhaler compliance. For patients with uncontrolled severe asthma accompanied by type 2 (T2)-high inflammation, most biologics available in Korea were considered appropriate, but gaps were apparent in terms of T2-low asthma treatments. These findings about specialist perception of diagnosis and treatment of severe asthma will inform the use of emerging new drugs and facilitate personalized therapy.     

Predicting Factors of Severe COVID-19 in Patients With Asthma: A Korean National Cohort Study

As there are limited data on the disease course of and factors predicting severe coronavirus disease 19 (COVID-19) in patients with asthma, this study aims to perform a detailed analysis of the clinical course of asthmatic patients with COVID-19 and evaluate factors related to severe infection. Of the 5,628 patients confirmed with COVID-19, 128 (2.3%) had asthma. Among the 128 asthmatic patients, 32 (25%) had severe COVID-19 and 96 (75%) had non-severe COVID-19. Among asthmatic patients, those with severe COVID-19 were significantly older and had more dyspnea and fever, more comorbidities, and lower lymphocyte and platelet counts than those with non-severe COVID-19. In multivariable logistic regression analysis, chronic obstructive pulmonary disease (adjusted odds ratio [aOR], 6.49; 95% confidence interval [CI], 1.18–41.81), low lymphocyte proportion (aOR, 0.91; 95% CI, 0.86–0.97), and low platelet count (aOR, 0.99; 95% CI, 0.98–0.99) were independently associated with severe COVID-19.     

Advances in pediatric asthma in 2010: addressing the major issues

Last year's "Advances in pediatric asthma" concluded with the following statement: "If we can close these [remaining] gaps through better communication, improvements in the health care system and new insights into treatment, we will move closer to better methods to intervene early in the course of the disease and induce clinical remission as quickly as possible in most children." This year's summary will focus on recent advances in pediatric asthma that take steps moving forward as reported in Journal of Allergy and Clinical Immunology publications in 2010. Some of these recent reports show us how to improve asthma management through steps to better understand the natural history of asthma, individualize asthma care, reduce asthma exacerbations, and manage inner-city asthma and some potential new ways to use available medications to improve asthma control. It is clear that we have made many significant gains in managing asthma in children, but we have a ways to go to prevent asthma exacerbations, alter the natural history of the disease, and reduce health disparities in asthma care. Perhaps new directions in personalized medicine and improved health care access and communication will help maintain steady progress in alleviating the burden of this disease in children, especially young children.     

Global Initiative for Asthma (GINA) guidelines: 15 years of application

The Global Initiative for Asthma (GINA), founded in 1993, embodies a network of public health organizations and medical societies, as well as other individuals concerned with asthma. Its first report, published in 1995 and entitled ‘A Global Strategy for Asthma Management and Prevention’, has been widely adopted, providing the foundation for asthma guidelines in many nations across the world. To this effect, the report has not only been translated into several languages but has also been frequently updated. Since its establishment 15 years ago, GINA has undergone two major paradigm shifts. The first was the change in the late 1990s from an opinion- to an evidence-based approach for the management of asthma severity. The second, an even more radical shift, was seen in 2006, when the revised GINA guidelines involved the classification of asthma severity according to the level of control as a guide to treatment. In order to classify asthma control, elements such as the significance of the partnership between the patient and caregiver, patient education, guided self-management and treatment goals were introduced. In addition to compiling guidelines and reports for the management of asthma, GINA is actively involved in organizing and coordinating the World Asthma Day, regional initiatives and GINA symposia. On the whole, during the 15 years since their original publication in 1995, the GINA guidelines have provided the basis for many national asthma strategies around the world. This course is most likely to continue in the future. In this paper, the history of the development of the guidelines and other issues regarding the GINA project will be addressed.     

Advances in pediatric asthma in 2011: moving forward

Last year's "Advances in pediatric asthma" concluded with the following statement: "Perhaps new directions in personalized medicine and improved health care access and communication will help maintain steady progress in alleviating the burden of this disease in children, especially young children." This year's summary will focus on recent advances in pediatric asthma that show significant accomplishments in reducing asthma morbidity and mortality over the last 10 years and discuss some pathways to further reduce asthma burden, as indicated in Journal of Allergy and Clinical Immunology publications in 2011. Some of the recent reports continue to shed light on methods to improve asthma management through steps to reduce asthma exacerbations, identify features of the disease in early childhood, alter asthma progression, intervene with nutrition, and more effectively implement the asthma guidelines. As new information evolves, it is also time to consider a revision of the asthma guidelines based on key studies that affect our management of the disease since the last revision in 2007. Now is also the time to use information recorded in electronic medical records to develop innovative disease management plans that will track asthma over time and enable timely decisions on interventions to maintain control that can lead to disease remission and prevention.