Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

The first case of tegoprazan-induced urticaria.

WHAT IS KNOWN AND OBJECTIVE: Tegoprazan induces adverse drug reactions during clinical trials; however, tegoprazan-induced urticaria has not been reported. Here, we describe the first case of this. CASE DESCRIPTION: A 55-year-old woman presented with acute urticaria with pruritus after taking the gastro-oesophageal reflux disease medication, tegoprazan. Urticaria disappeared after tegoprazan discontinuation. In an oral provocation test, after taking 10% of tegoprazan, she developed pruritus, and after taking 30%, she developed urticaria on her back. WHAT IS NEW AND CONCLUSION: This is the first case of urticaria induced by tegoprazan. Physicians should understand the possibility of a tegoprazan-induced hypersensitivity reactions.

Variation of clinical manifestations according to culprit drugs in DRESS syndrome.

PURPOSE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but serious condition that systematically damages various internal organs through T-cell-mediated immunological drug reactions. We aimed to investigate whether clinical manifestations of DRESS syndrome differ according to culprit drugs. METHODS: We retrospectively analyzed data from 123 patients with probable/definite DRESS syndrome based on the RegiSCAR criteria (January 2011 to July 2016). The data were obtained from the Korean Severe Cutaneous Adverse Reaction Registry. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. The culprit drugs were categorized as allopurinol, carbamazepine, anti-tuberculosis drug, vancomycin, cephalosporins, dapsone, and nonsteroidal anti-inflammatory drugs. RESULTS: Differences were observed among culprit drugs regarding the frequencies of hepatitis (P < 0.01), renal dysfunction (P < 0.0001), lymphadenopathy (P < 0.01), and atypical lymphocyte (P < 0.01). Latency period differed among culprit drugs (P < 0.0001), being shorter in vancomycin and cephalosporin. In terms of clinical severity, admission duration (P < 0.01) and treatment duration (P < 0.05) differed among culprit drugs, being longer in vancomycin and anti-tuberculosis drugs, respectively. CONCLUSIONS: Based on the findings, clinical manifestations, including latency period and clinical severity, may differ according to culprit drugs in DRESS syndrome.

Comparison between Newly Developed and Commercial Inhalant Skin Prick Test Reagents Using In Vivo and In Vitro Methods.

BACKGROUND: We developed skin prick test (SPT) reagents for common inhalant allergens that reflected the real exposure in Korea. The study aim was to evaluate diagnostic usefulness and allergen potency of our inhalant SPT reagents in comparison with commercial products. METHODS: We produced eight common inhalant allergen SPT reagents using total extract (Prolagen): Dermatophagoides farinae, Dermatophagoides pteronyssinus, oak, ragweed, mugwort, Humulus japonicus pollens, as well as cat and dog allergens. We compared the newly developed reagents with three commercially available SPT reagents (Allergopharma, Hollister-Stier, Lofarma). We measured total protein concentrations, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), major allergen concentration, and biological allergen potencies measured by immunoglobulin E (IgE) immunoblotting and ImmunoCAP inhibition test. RESULTS: Diagnostic values of these SPT reagents were expressed as positivity rate and concordance rate of the results from ImmunoCAP allergen-specific IgE test in 94 allergic patients. In vitro analysis showed marked differences in protein concentrations, SDS-PAGE features, major allergen concentrations, and biological allergen potencies of four different SPT reagents. In vivo analysis showed that positive rates and concordance rates of Prolagen® SPT reagents were similar compared to the three commercial SPT reagents. CONCLUSION: The newly developed Prolagen® inhalant SPT reagents are not inferior to the commercially available SPT reagents in allergy diagnosis.

Characterization of a Major Allergen from Mongolian Oak, Quercus mongolica, a Dominant Species of Oak in Korea.

BACKGROUND: Oaks are the most common trees in Korean forests, and Mongolian oak, Quercus mongolica, is the dominant species. However, no allergen has been characterized from Mongolian oak. In this study, we tried to characterize a major allergen from Mongolian oak. METHODS: A molecule homologous to pathogenesis-related 10 (PR-10)-like protein, Que m 1, was cloned by RT-PCR. Its recombinant protein, along with Que a 1, an allergen from white oak (Q. alba), was produced. The allergenicity and diagnostic value of recombinant Que m 1, Que a 1, and Bet v 1 proteins were compared by ELISA using sera from oak-sensitized subjects. A basophil activation test was also performed using CD63 expression as an activation marker. RESULTS: Que m 1 sequence shares 57.5-96.2% amino acid sequence identity with PR-10-like allergens from various plants. Specific IgE to recombinant Que m 1, Que a 1, and Bet v 1 were detected in 92.0, 74.0, and 38.0% of 50 serum samples from Korean tree pollinosis patients. Recombinant Que m 1 was able to inhibit IgE reactivity to Que a 1 and Bet v 1, indicating its strong cross-reactivity. The activation patterns of basophils from 5 patients were similar in terms of the CD63 expression and protein concentration of challenged Bet v 1 and Que m 1. CONCLUSIONS: A major allergen, Que m 1, was cloned, and its recombinant protein was produced from Mongolian oak, a dominant species in Korea. Recombinant Que m 1 is potentially useful for the diagnosis and treatment of tree pollinosis in Korea.

Adrenal insufficiency associated with long-term use of inhaled steroid in asthma.

BACKGROUND: We previously reported that as many as one third of hospitalized patients with asthma treated with a low to medium daily dose of inhaled steroids (ICSs) for an average of 4.5 years showed adrenal insufficiency (AI). OBJECTIVE: To re-examine this issue in consecutive outpatients with asthma because of possible subject selection bias. METHODS: One hundred twenty-one consecutive adult patients with asthma under ICS treatment for at least 6 months underwent a rapid adrenocorticotrophic hormone stimulation test. AI was defined as a morning serum cortisol level no higher than 3 µg/dL or lower than 18 µg/dL before and after administration of 250 µg of adrenocorticotrophic hormone. RESULTS: The mean durations of ICS use in the short-term (less than the median) and long-term (at least the median) users were 3.8 and 11.5 years, respectively. The proportion of subjects affected by AI tended to increase with the increasing cumulative dose of ICS (short-term users at a low to medium daily dose: mean cumulative dose 502 mg [15 of 34, 44.1%]; short-term users at a high dose of 941 mg [16 of 26, 61.5%]; long-term users at a low to medium dose of 1,077 mg [25 of 41, 61.0%]; long-term users at a high dose of 2,805 mg [13 of 20, 65.0%]), although not significantly. In short-term users, daily and cumulative ICS doses were significantly related to serum cortisol levels 60 minutes after taking adrenocorticotrophic hormone (r = -0.300 and -0.287, respectively; P < .05). CONCLUSION: A large number of patients with asthma might have AI even with low- to medium-dose ICS treatment when ICSs are administered over a long period. Thus, it is essential that patients with asthma under ICS treatment be checked for AI much more frequently.

Roflumilast Ameliorates Airway Hyperresponsiveness Caused by Diet-Induced Obesity in a Murine Model.

Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasone-treated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-α, transforming growth factor-ß, IL-1ß, and IFN-γ increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.

Clinical characteristics of adverse events associated with therapeutic monoclonal antibodies in Korea.

PURPOSE: The use of monoclonal antibodies (mAbs) is increasing in various clinical fields. Although mAb safety must be demonstrated prior to approval, targeted pharmacovigilance is essential for the recognition and assessment of adverse reactions. The purpose of this study was to identify the major clinical features of adverse reactions to mAbs in Korea. METHODS: Spontaneous reports of adverse reactions attributed to 18 mAbs from January 2005 to December 2014 were extracted from the Korea Adverse Event Reporting System. We analyzed these reports for information relating to patient characteristics and the types of adverse reactions. RESULTS: In total, 11 492 adverse reactions were reported in 7569 patients. Almost 19% of total study population showed suspected hypersensitivity reactions. Leukocyte abnormalities were reported frequently (10.0%), as well as infections (9.5%), drug eruptions (7.5%), and pruritus (5.0%). Furthermore, 3716 of the adverse reactions in 2538 patients were classified as serious; these included severe infections (18.2%), neutropenia (12.1%), visual dysfunctions (6.6%), and anaphylaxis (4.8%). The mAbs with the highest number of adverse reaction reports were rituximab (27.6%), adalimumab (17.5%), cetuximab (11.9%), and infliximab (10.7%). CONCLUSIONS: Hypersensitivity reactions were observed more frequently than expected, although no previously unrecognized reactions were observed. Adverse reactions occurred more frequently in children and in elderly patients. Close monitoring of adverse reactions to therapeutic mAbs is therefore warranted because these can potentially cause serious medical conditions or death. Copyright © 2016 John Wiley & Sons, Ltd.

Occupational contact dermatitis caused by sodium tetradecyl sulfate in a healthcare worker: A case report.

Healthcare workers are known to be at a higher risk of experiencing occupational contact dermatitis and attention should be paid to new materials that cause contact dermatitis. Sodium tetradecyl sulfate is widely used in the treatment of small varicose veins of the legs and venous malformations. We report the case of a 42-year-old woman, a healthcare worker, who presented with contact dermatitis caused by sodium tetradecyl sulfate. The contact dermatitis induced by sodium tetradecyl sulfate resolved completely after sodium tetradecyl sulfate avoidance at the last follow-up. Thus, we recommend increased protective measures when handling this substance.

Relationship of computed tomography-based measurements with symptom perception and quality of life in patients with severe asthma.

BACKGROUND: Symptom perception and quality of life (QOL) are important domains for properly managing severe asthma. This study aimed to assess the relationship between airway structural and parenchymal variables measured using chest computed tomography (CT) and subjective symptom perception and QOL in patients with severe asthma enrolled in the Korean Severe Asthma Registry. METHODS: This study used CT-based objective measurements, including airway wall thickness (WT), hydraulic diameter, functional small airway disease (fSAD), and emphysematous lung (Emph), to assess their association with subjective symptom (cough, dyspnea, wheezing, and sputum) perception measured using the visual analog scale, and QOL measured by the Severe Asthma Questionnaire (SAQ). RESULTS: A total of 94 patients with severe asthma were enrolled in this study. The WT and fSAD% were significantly positively associated with cough and dyspnea, respectively. For QOL, WT and Emph% showed significant negative associations with the SAQ. However, there was no significant association between lung function and symptom perception or between lung function and QOL. CONCLUSION: Overall, WT, fSAD%, and Emph% measured using chest CT were associated with subjective symptom perception and QOL in patients with severe asthma. This study provides a basis for clarifying the clinical correlates of imaging-derived metrics and for understanding the mechanisms of respiratory symptom perception.

Serum MRGPRX2 as a Long-term Biomarker for Iodinated Contrast Media-Induced Anaphylaxis.

The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, P = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 (P = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, P = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.

Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

PURPOSE: Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. METHODS: We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. RESULTS: Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). CONCLUSIONS: SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

Angiotensin Receptor Blockers and the Risk of Suspected Drug-Induced Liver Injury: A Retrospective Cohort Study Using Electronic Health Record-Based Common Data Model in South Korea.

INTRODUCTION: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. OBJECTIVE: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017-31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. METHODS: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. RESULTS: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55-0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28-8.12]). CONCLUSIONS: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice.

Development and Application of an Active Pharmacovigilance Framework Based on Electronic Healthcare Records from Multiple Centers in Korea.

INTRODUCTION: With the availability of retrospective pharmacovigilance data, the common data model (CDM) has been identified as an efficient approach towards anonymized multicenter analysis; however, the establishment of a suitable model for individual medical systems and applications supporting their analysis is a challenge. OBJECTIVE: The aim of this study was to construct a specialized Korean CDM (K-CDM) for pharmacovigilance systems based on a clinical scenario to detect adverse drug reactions (ADRs). METHODS: De-identified patient records (n = 5,402,129) from 13 institutions were converted to the K-CDM. From 2005 to 2017, 37,698,535 visits, 39,910,849 conditions, 259,594,727 drug exposures, and 30,176,929 procedures were recorded. The K-CDM, which comprises three layers, is compatible with existing models and is potentially adaptable to extended clinical research. Local codes for electronic medical records (EMRs), including diagnosis, drug prescriptions, and procedures, were mapped using standard vocabulary. Distributed queries based on clinical scenarios were developed and applied to K-CDM through decentralized or distributed networks. RESULTS: Meta-analysis of drug relative risk ratios from ten institutions revealed that non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of gastrointestinal hemorrhage by twofold compared with aspirin, and non-vitamin K anticoagulants decreased cerebrovascular bleeding risk by 0.18-fold compared with warfarin. CONCLUSION: These results are similar to those from previous studies and are conducive for new research, thereby demonstrating the feasibility of K-CDM for pharmacovigilance. However, the low quality of original EMR data, incomplete mapping, and heterogeneity between institutions reduced the validity of the analysis, thus necessitating continuous calibration among researchers, clinicians, and the government.

Clinical aspects of severe cutaneous adverse reactions caused by beta-lactam antibiotics: A study from the Korea SCAR registry.

Background: Although beta-lactams are 1 of the major causative agents of severe cutaneous adverse reactions (SCAR), their epidemiology and clinical aspects have been poorly studied. This study aimed to investigate the characteristics of SCAR caused by beta-lactams in the Korean SCAR registry. Methods: We retrospectively analyzed beta-lactam-induced SCAR cases collected from 28 tertiary university hospitals in Korea between 2010 and 2015. The SCAR phenotypes included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap, and drug reaction with eosinophilia and systemic symptoms (DRESS). Beta-lactams were classified according to their chemical structures: penicillins, cephalosporins, and carbapenems. The causative beta-lactams, clinical and laboratory features, treatments, and outcomes were evaluated. Results: Among the 275 antibiotic-induced SCAR cases, 170 patients developed SCAR induced by beta-lactams. Beta-lactam antibiotic-induced SCAR showed more frequent SJS/TEN compared to SCAR induced by non-beta-lactam antibiotics (SJS/TEN/SJS-TEN overlap/DRESS: 36.5/11.2/5.9/46.5% vs. 23.8/10.5/2.9/62.9%, P = 0.049). Cephalosporin was the most common culprit drug. Particularly, 91 and 79 patients presented with SJS/TEN and DRESS, respectively. The odds ratio (OR) for poor prognosis, such as sequelae and death, was significantly increased in subjects with SJS-TEN overlap and TEN and carbapenem as culprit drug in the multivariate analysis (OR, 35.61; P = 0.016, OR, 28.07; P = 0.006, OR 30.46; P = 0.027). Conclusion: Among antibiotic-induced SCAR, clinical features were different depending on whether the culprit drug was a beta-lactam antibiotic or SCAR type. The poor prognosis was related to SJS-TEN overlap, TEN type, and carbapenem as the culprit drug.

Efficacy of add-on therapy with intravenous immunoglobulin in steroid hyporesponsive DRESS syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening, delayed, drug-induced hypersensitivity reaction. Immediate withdrawal of the culprit drug and administration of systemic corticosteroids is the most widely accepted treatment. However, it is difficult to manage patients with DRESS syndrome who are not responsive to systemic steroids. We studied the efficacy of intravenous immunoglobulins (IVIGs) in patients with DRESS syndrome unresponsive to systemic steroids. We retrospectively reviewed patients with DRESS syndrome who received IVIG in addition to systemic steroids during 2012-2017 and compared the clinical features and course of DRESS syndrome, before and after IVIG treatment. Eighteen DRESS patients (9 men) were included. The most frequent offending drugs were dapsone in five patients, followed by vancomycin in three patients, and carbamazepine in three patients. Rash, fever, lymphadenopathy, atypical lymphocytes, and hepatic involvement were common clinical findings. IVIG treatment was added within a median time of 7 days from the commencement of systemic steroid therapy. After IVIG treatment (total dosage: 1-2 g/kg), the fever resolved within a median time of 1 day (range, 0-3) and liver enzymes improved substantially within a median time of 13 days (range, 0-27). No severe adverse reactions related to IVIG therapy were observed in this study; however, there was one case of mortality. The addition of IVIG in DRESS syndrome in cases refractory to systemic steroid treatment may be helpful in hastening recovery. However, comparative studies using a placebo group are needed.

Prescription Patterns of Oral Corticosteroids for Asthma Treatment and Related Asthma Phenotypes in University Hospitals in Korea.

PURPOSE: Oral corticosteroids (OCSs) are frequently prescribed for asthma management despite their adverse effects. An understanding of the pattern of OCS treatment is required to optimize asthma treatment and reduce OCS usage. This study evaluated the prescription patterns of OCSs in patients with asthma. METHODS: This is a retrospective multicenter observational study. We enrolled adult (≥18 years) patients with asthma who had been followed up by asthma specialists in 13 university hospitals for ≥3 years. Lung function tests, the number of asthma exacerbations, and prescription data, including the days of supply and OCS dosage, were collected. The clinical characteristics of OCS-dependent and exacerbation-prone asthmatic patients were evaluated. RESULTS: Of the 2,386 enrolled patients with asthma, 27.7% (n = 660) were OCS users (the median daily dose of OCS was 20 mg/day prednisolone equivalent to a median of 14 days/year). OCS users were more likely to be female, to be treated at higher asthma treatment steps, and to show poorer lung function and more frequent exacerbations in the previous year than non-OCS users. A total of 88.0% of OCS users were treated with OCS burst with a mean dose of 21.6 ± 10.2 mg per day prednisolone equivalent to 7.8 ± 3.2 days per event and 2.4 times per year. There were 2.1% (51/2,386) of patients with OCS-dependent asthma and 9.5% (227/2,386) with exacerbation-prone asthma. These asthma phenotypes were consistent over the 3 consecutive years in 47.1% of OCS-dependent asthmatic patients and 34.4% of exacerbation-prone asthmatic patients when assessed annually over the 3-year study period. CONCLUSIONS: We used real-world data from university hospitals in Korea to describe the OCS prescription patterns and relievers in asthma. Novel strategies are required to reduce the burden of OCS use in patients with asthma.

Fixed drug eruption and anaphylaxis induced concurrently by erdosteine: a case report.

BACKGROUND: Erdosteine is used as a mucolytic agent and has a low incidence of adverse drug reactions, most of which are gastrointestinal and mild. Moreover, drug antigens rarely induce multiple simultaneous immunologic reactions. Only one previous case report has demonstrated hypersensitivity reaction induced by erdosteine. Here, we report a case of fixed drug eruption and anaphylaxis, which were concurrently induced by erdosteine. The association between the symptoms and erdosteine was proven by a drug provocation test. CASE PRESENTATION: A 35-year-old woman presented with recurrent angioedema and pruritic rash on the hands, which developed within 2 h following the administration of drugs, including erdosteine, for acute upper respiratory infection. Her rash was characterized by well-defined erythematous plaques, which recurred at the same site following the administration of the medications. She also experienced angioedema of the lips. Fixed drug eruption was considered after excluding other possible causes for the presented skin lesions. A drug provocation test confirmed that fixed drug eruption on both hands had occurred after administration of erdosteine, suggesting that erdosteine was the cause of the allergic reaction. However, she also experienced angioedema, isolated wheal, and laryngeal edema; thus, IgE-mediated type I hypersensitivity could also be concurrently occurring with the fixed drug eruption. CONCLUSIONS: We report about a patient who was diagnosed with two different hypersensitivity reactions concurrently induced by erdosteine. We also demonstrate that patients may exhibit multiple simultaneous symptoms that usually arise from overlapping of different hypersensitivity mechanisms. Physicians should be aware of the possibility that some patients who are allergic to certain drugs could exhibit several symptoms caused by different mechanisms of hypersensitivity reactions simultaneously.