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Background@#Adverse drug reactions (ADRs) are escalating, and their socioeconomic burden is increasing. However, large-scale prospective studies investigating ADRs during hospitalization are rare in Korea. We prospectively investigated the incidence, characteristics, and economic burden of ADRs in hospitalized patients based on electronic medical records (EMRs). @*Methods@#Among patients admitted to three hospitals from October 2016 to October 2017, 5,000 patients were randomly selected and prospectively observed during hospitalization.Research nurses monitored and detected patients who had symptoms, signs, or laboratory findings suspicious for ADRs using an EMR-based detection protocol. Next, allergy and ADR specialists reviewed the medical records to determine the relationship between adverse reactions and drugs. Cases in which a causal relationship was certain, probable/likely, or possible were included in the ADR cases. Clinically meaningful ADR cases or those leading to prolonged hospitalization were defined as significant ADRs. @*Results@#ADRs occurred in 510 (10.2%) patients. The mean length of hospital stay was approximately 5 days longer in patients with ADRs. Opioids accounted for the highest percentage of total ADRs. Significant ADRs were observed in 148 (3.0%) patients. Antibiotics accounted for the highest percentage of significant ADRs. Drug hypersensitivity reactions (DHRs) occurred in 88 (1.8%) patients. Antibiotics accounted for the highest percentage of DHRs. The average medical expenses for one day of hospitalization per patient were highest in significant ADRs, followed by non-significant ADRs, and non-ADRs. @*Conclusion@#ADRs in hospitalized patients are an important clinical issue, resulting in a substantial socioeconomic burden. EMR-based strategy could be a useful tool for ADR monitoring and early detection.
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Background@#Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics. @*Methods@#Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed. @*Results@#The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2. @*Conclusion@#The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.
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Background/Aims@#Skin (STs) and drug provocation (DPTs) tests are essential for identifying the culprit drugs causing drug hypersensitivity reactions (DHRs). Several protocols have been developed for the identification of some culprit drugs, but they are neither thoroughly validated nor standardized. Furthermore, language barriers may impede the exchange of information necessary for test standardization. @*Methods@#We searched the Korean literature for articles on drug hypersensitivity published from 1933 to 2016 using the KoreaMed search engine and archives of Korean journals. We reviewed and rated all articles according to the description of STs and DPTs. @*Results@#Of the 632 articles obtained in our initial search, 34 had adequate descriptions of 15 STs and 22 DPTs. Up to 27 healthy control subjects in STs were enrolled to determine non-irritating concentrations. The concentrations used for intradermal tests were commonly a 1/10 dilution of those used for skin prick tests. The interpretations of the STs were mostly similar among researchers. For DPTs, most procedures were single-arm open-label tests of various drugs. The initial dose ranged from a quarter dose to a single therapeutic dose, depending on the severity of the original hypersensitivity reaction. The interval between doses was usually 30 to 60 minutes, and a positive reaction usually occurred within twice the time of the original reaction. @*Conclusions@#Efforts to distribute information are necessary to standardize protocols and better understand DHRs.
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Background/Aims@#Recent evidence suggests an association between allergic sensitization and metabolic markers. However, this association has rarely been examined in the elderly. Retinol-binding protein-4 (RBP-4) is a recently identified adipokine that acts on the muscle and liver affecting insulin sensitivity. We evaluated the association between metabolic parameters and allergic sensitization in the elderly. @*Methods@#We analysed the database of the Korean Longitudinal Study on Health and Aging cohort study conducted during 2005 to 2006. Atopy was identified by inhalant allergen skin prick test. Metabolic conditions were assessed using anthropometric indices and serum biomarkers such as fasting glucose, lipid, adiponectin, and RBP-4. @*Results@#Among the 854 elderly subjects, 17.2% had atopy. Plasma RBP-4 levels were significantly higher in the atopic elderly than nonatopic elderly (p = 0.003). When RBP-4 percentiles were categorized as under three groups, the prevalence of atopy and current rhinitis increased significantly with percentiles of RBP-4 levels (p = 0.019 and p = 0.007, respectively). Log RBP-4 was associated with atopy (odds ratio [OR], 4.10; p = 0.009) and current rhinitis (OR, 2.73; p = 0.014), but not with current asthma (OR, 1.17; p = 0.824). Higher RBP-4 level in atopic elderly was also observed in current rhinitis patients. Atopy, but not current rhinitis, showed significant relationships with log RBP-4 levels in multivariate analyses adjusted for other metabolic markers including body mass index. @*Conclusions@#RBP-4 positively associated with atopy in the general elderly population irrespective of other metabolic markers.
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Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.
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Chronic cough is a common clinical condition with significant impact on quality of life and for which effective therapy remains an unmet clinical need. Over the past decade, there has been a major shift in how we approach this problem, driven by better appreciation of the clinical manifestation of chronic cough and an improved understanding of the associated neurobiology. “Cough hypersensitivity syndrome” has been proposed as a new diagnostic term for chronic cough, encompassing different phenotypes of the condition. Accumulating evidence suggests that this new concept is clinically relevant. However, while it is gaining widespread endorsement within the allergy and respiratory community, raising its profile in routine clinical practice is a priority. Thus, the present paper reviews recent progress in our understanding and management of chronic cough, with focus on mechanistic and clinical studies. It also provides detail on knowledge gaps and future research directions.
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Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are the most severe cutaneous drug hypersensitivity reactions, which are unpredictable adverse drug reactions. SJS/TEN is associated with significant mortality and morbidity; however, effective treatment is difficult. Mesenchymal stem cells (MSCs) are well-known for their anti-inflammatory and tissue regeneration properties. The purpose of the present study was to verify whether MSCs could be applied for the treatment of SJS/TEN. We developed an SJS/TEN mouse model using peripheral blood mononuclear cells from a lamotrigine-induced SJS patient. MSCs were injected into the model to verify the treatment effect. In SJS model mice treated with MSCs, ocular damage rarely occurred, and apoptosis rate was significantly lower. We demonstrated a therapeutic effect of MSCs on SJS/TEN, with these cells presenting a potential novel therapy for the management of this disorder.
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PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm.METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI.RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13–0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction.CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.
Subject(s)
Humans , Alanine , Anti-Bacterial Agents , Bilirubin , Diagnosis , Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Electronic Health Records , Hematologic Tests , Hepatitis , Hospitalization , Hospitals, University , Incidence , Inpatients , Liver , Liver Diseases , Mass Screening , Medical Records , Methotrexate , Pharmacoepidemiology , Retrospective Studies , TransferasesABSTRACT
PURPOSE: Asthma in the elderly (EA; ≥ 65 years of age) is increasing, adding a heavy socioeconomic burden to the healthcare system. However, little is known about risk factors associated with acute exacerbations in EA patients. The objective of this study was to investigate risk factors for acute exacerbation in EA compared to non-elderly asthma (NEA).METHODS: We combined data from 3 adult asthma cohorts under a unified protocol and database. Asthmatic patients with regular follow-up during a 1-year period were selected from the cohorts to identify the risk factors predicting acute exacerbations in EA compared to NEA.RESULTS: We selected a total of 1,086 patients from the merged cohort. During the observation period, 503 and 583 patients were assigned to the EA and NEA groups, respectively. The exacerbation rate was 31.0% in the EA and 33.2% in the NEA group. Multivariate logistic regression analysis revealed fixed airway obstruction, chronic rhinosinusitis (CRS), and male sex as independent risk factors for exacerbation in the EA group. In the NEA group, exacerbation increased along with an increase in eosinophil count. Bayesian analysis of the interactions among clinical factors revealed that forced expiratory volume in 1 second/forced vital capacity was directly related to exacerbation in the EA group, and eosinophil count was related to exacerbation in the NEA group.CONCLUSIONS: We suggest that fixed airway obstruction and CRS as the important clinical factors predicting acute exacerbations in EA, whereas in NEA, eosinophil count was the strong predictor of exacerbation.
Subject(s)
Adult , Aged , Humans , Male , Airway Obstruction , Asthma , Bayes Theorem , Cohort Studies , Delivery of Health Care , Eosinophils , Follow-Up Studies , Forced Expiratory Volume , Logistic Models , Risk Factors , Vital CapacityABSTRACT
PURPOSE: Reduction-oxidation reaction homeostasis is vital for regulating inflammatory conditions and its dysregulation may affect the pathogenesis of chronic airway inflammatory diseases such as asthma. Peroxiredoxin-6, an important intracellular anti-oxidant molecule, is reported to be highly expressed in the airways and lungs. The aim of this study was to analyze the expression pattern of peroxiredoxin-6 in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients and in bronchial epithelial cells (BECs).METHODS: The expression levels and modifications of peroxiredoxin-6 were evaluated in PBMCs from 22 asthmatic patients. Phosphorylated and acetylated peroxiredoxin-6 in hydrogen peroxide-treated human BECs was detected using immunoprecipitation analysis. The expression level of peroxiredoxin-6 was also investigated in BECs treated with hydrogen peroxide. Cycloheximide and proteasome inhibitors were used to determine whether peroxiredoxin-6 is degraded by proteasomes.RESULTS: Peroxiredoxin-6 expression was significantly reduced in the PBMCs of asthmatic patients compared to control subjects. Distinct modification patterns for peroxiredoxin-6 were observed in the PBMCs of asthmatic patients using 2-dimensional-electrophoresis. The levels of phosphorylated serine and acetylated lysine in peroxiredoxin-6 were significantly increased in the BECs following hydrogen peroxide treatment. The level of peroxiredoxin-6 expression was reduced in hydrogen peroxide-stimulated BECs, presumably due to proteasomes.CONCLUSIONS: The expression of peroxiredoxin-6, which is down-regulated in the immune cells of asthmatic patients and BECs, can be modified by oxidative stress. This phenomenon may have an effect on asthmatic airway inflammation.
Subject(s)
Humans , Asthma , Cycloheximide , Epithelial Cells , Homeostasis , Hydrogen , Hydrogen Peroxide , Immunoprecipitation , Inflammation , Lung , Lysine , Oxidative Stress , Proteasome Inhibitors , Protein Processing, Post-Translational , SerineABSTRACT
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
ABSTRACT
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
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PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.
Subject(s)
Adult , Humans , Male , Adrenal Cortex Hormones , Allergy and Immunology , Aspirin , Asthma , Cohort Studies , Comorbidity , Demography , Forced Expiratory Volume , Hospitals, University , Hypersensitivity , Korea , Leukotriene Antagonists , Mortality , Nebulizers and Vaporizers , Prospective Studies , Quality of Life , Respiratory Function Tests , Rhinitis, Allergic , Skin , Vital CapacityABSTRACT
The cough reflex is a vital protective mechanism for the lower airways against aspiration, but when dysregulated, it becomes a clinical problem. Indeed, chronic cough is an important clinical issue as it is common in the general population and causes considerable morbidity. Anatomic diagnostic protocols were the first breakthrough in the management of patients with chronic cough; however, as systematic approaches are not always successful, a new paradigm of cough hypersensitivity syndrome has been proposed. The introduction of this paradigm has provided new opportunities for managing chronic cough, including development of new cough assessment tools and effective cough control therapies. However, it also warranted re-appraisal of existing clinical evidence and refinement of our clinical pathways. Against this background, international and domestic evidence-based practice guidelines based on a strict methodology have been published recently. In this review, we introduce clinical approaches based on the concept of cough hypersensitivity syndrome and discuss key aspects of recently published guidelines for chronic cough in adults.
Subject(s)
Adult , Humans , Cough , Critical Pathways , Evidence-Based Practice , Hypersensitivity , ReflexABSTRACT
PURPOSE: The purpose of this study was to investigate the effects of short-term and very short-term exposure to particulate matter (PM) exceeding the daily average environmental standards for Korea (≤100 µg/m³ for PM₁₀ and ≤50 µg/m³ for PM(2.5)) on on asthma-related hospital visits. MATERIALS AND METHODS: This was a population-based, case-crossover study using National Health Insurance and air pollution data between January 1, 2014 and December 31, 2016. The event day was defined as a day when PM exceeded the daily average environmental standard (short-term exposure) or daily average environmental standard for 2 hours (very short-term exposure). The control day was defined as the same day of the week at 1 week prior to the event day. RESULTS: Compared with control days, asthma-related hospital visits on the 24-hr event days and 2-hr event days increased by 4.10% and 3.45% for PM₁₀ and 5.66% and 3.74% for PM(2.5), respectively. Asthma-related hospital visits increased from the 24-hr event day for PM₁₀ to 4 days after the event day, peaking on the third day after the event day (1.26, 95% confidence interval, 1.22–1.30). Hospitalizations also increased on the third day after the event. While there was a difference in magnitude, PM(2.5) exposure showed similar trends to PM₁₀ exposure. CONCLUSION: We found a significant association between short-term and very short-term PM exposure exceeding the current daily average environmental standards of Korea and asthma-related hospital visits. These results are expected to aid in establishing appropriate environmental standards and relevant policies for PM.
Subject(s)
Humans , Air Pollution , Asthma , Hospitalization , Korea , National Health Programs , Outpatients , Particulate MatterABSTRACT
Cough is a physiological defense reflex for protecting the airways from aspiration and irritation. Thus, roles of environmental triggers are postulated in the pathogenesis of chronic cough. There are several lines of epidemiological evidence demonstrating the relationships between environmental irritant and pollutant exposure and chronic cough. However, positive findings from cross-sectional studies just reflect the protective nature of cough but may not properly address the true impact of environmental triggers. If harmful inhalation is repeated, cough may be seen as chronic but indeed is protective in nature. Therefore, long-term residual outcomes would be the key for understanding the effects of environmental triggers on chronic cough. The present review aims to summarize the associations between chronic cough and environmental pollutants or irritant exposure, with a focus on the long-term residual effects of (1) chronic persistent exposure and (2) acute high-intensity exposure on chronic cough, and also to examine (3) whether childhood irritant/pollutant exposure may increase the risk of chronic cough in adulthood.
Subject(s)
Cough , Cross-Sectional Studies , Environmental Pollutants , Epidemiology , Hypersensitivity , Inflammation , Inhalation , ReflexABSTRACT
Subject(s)
Humans , Anti-Bacterial Agents , Cefazolin , Drug Hypersensitivity , Electronic Health Records , Hypersensitivity , Hypersensitivity, Immediate , Intradermal Tests , Mass Screening , Medical Records , Prospective Studies , Seoul , Skin Tests , Skin , SpecializationABSTRACT
The cough reflex is a vital protective mechanism for the lower airways against aspiration, but when dysregulated, it becomes a clinical problem. Indeed, chronic cough is an important clinical issue as it is common in the general population and causes considerable morbidity. Anatomic diagnostic protocols were the first breakthrough in the management of patients with chronic cough; however, as systematic approaches are not always successful, a new paradigm of cough hypersensitivity syndrome has been proposed. The introduction of this paradigm has provided new opportunities for managing chronic cough, including development of new cough assessment tools and effective cough control therapies. However, it also warranted re-appraisal of existing clinical evidence and refinement of our clinical pathways. Against this background, international and domestic evidence-based practice guidelines based on a strict methodology have been published recently. In this review, we introduce clinical approaches based on the concept of cough hypersensitivity syndrome and discuss key aspects of recently published guidelines for chronic cough in adults.
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A major burden of severe asthma is the future risk of adverse health outcomes. Patients with severe asthma are prone to serious exacerbation and deterioration of lung function and may experience side effects of medications such as oral corticosteroids (OCSs). However, such future risk is not easily measurable in daily clinical practice. In particular, currently available tools to measure asthma control and asthma-related quality of life incompletely predict the future risk of medication-related morbidity. This is a significant issue in asthma management. This review summarizes the current evidence of future risk in patients with severe asthma. As future risk is poorly perceived by controlled asthmatics, our review focuses on the risk in patients with ‘controlled’ severe asthma. Of note, it is likely that long-term OCS therapy may not prevent future asthma progression, including lung function decline. In addition, the risk of drug side effects increases even during low-dose OCS therapy. Thus, novel treatments are highly desirable for reducing future risks without any loss of asthma control.