Incidence and Economic Burden of Adverse Drug Reactions in Hospitalization: A Prospective Study in Korea.

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.

Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort.

BACKGROUND: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. OBJECTIVES: We aimed to describe the characteristics of SEA and identify its patient subgroups. METHODS: Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. RESULTS: Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/µL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/µL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/µL), and good treatment response in terms of improved lung function and control status. CONCLUSIONS: Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.

Therapeutic Effects of Mesenchymal Stem Cells on a Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Model.

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.

Longitudinal analysis to better characterize Asthma-COPD overlap syndrome: Findings from an adult asthma cohort in Korea (COREA).

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), which has received much attention, has not been unanimously defined. OBJECTIVE: In this study, we tried to demonstrate that longitudinally defined ACOS is more useful in the real world than blending patients with asthma and COPD. METHODS: The study patients had undergone two consecutive pulmonary function tests measured at least 3 months apart (n = 1889). We selected the patients who had positive bronchodilator response or methacholine provocation tests (n = 959). Next, we defined ACOS as a patient with a persistent airflow obstruction [forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7] that was identified twice consecutively by an interval of at least 3 months (n = 228). RESULTS: The proportions of patients who were older, male and smokers were significantly higher, and baseline lung function was lower in patients with ACOS. In the longitudinal analysis, the mean change in lung function was high, and a greater decline in FEV1 was observed in patients with ACOS. In addition, we compared ACOS and severe asthma, and we also performed a cluster analysis and compared the results with our definition of ACOS. According to our definition, ACOS is an independent subtype with distinctive characteristics. Finally, a genome-wide association study (GWAS) was performed to identify genetic variations associated with ACOS, but no significant single nucleotide polymorphisms were identified. CONCLUSION: Our findings suggest that ACOS should be defined longitudinally and considered as an independent subgroup distinguished by inherited environmental factors rather than as a genetically distinct independent group.

Retinol-binding protein-4 was associated with sensitization to inhalant allergens in the elderly population.

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. CONCLUSION: RBP-4 positively associated with atopy in the general elderly population irrespective of other metabolic markers.

Validation of the Prescreening Intradermal Skin Test for Predicting Hypersensitivity to Iodinated Contrast Media: A Prospective Study with ICM Challenge.

BACKGROUND: The number of hypersensitivity reactions associated with iodinated contrast media (ICM) is increasing with widespread use of radiographic contrast agents. These hypersensitivity reactions are unpredictable and sometimes lead to severe reactions such as anaphylaxis. OBJECTIVE: To investigate the value of intradermal skin test (IDT) as a clinical screening tool for prediction of a hypersensitivity reaction to ICM. METHODS: We performed IDT in the patients scheduled to receive an iodinated contrast agent between September 2015 and April 2017. After IDT, the contrast agent tested was administered intravenously, regardless of the results of skin testing, and the patients were carefully monitored. RESULTS: We recruited 2,918 patients in 2 hospitals, and 2,843 were included in the final analysis. Fifteen (0.5%) of the 2843 patients had a positive IDT result before scheduled computed tomography scan; however, none of these patients experienced a hypersensitivity reaction after the administration of a full dose of ICM. Meanwhile, 19 patients who experienced hypersensitivity reactions after ICM challenge had showed a negative IDT result. The sensitivity and the positive predictive value of IDT for ICM were both 0%. CONCLUSIONS: Routine IDT before the administration of an iodinated contrast agent does not predict hypersensitivity considering its extremely low sensitivity and a low positive predictive value.

Novel Strategy for the Prevention of Recurrent Hypersensitivity Reactions to Radiocontrast Media Based on Skin Testing.

BACKGROUND: Hypersensitivity reactions to iodinated contrast media (ICM) is a persistent clinical issue with increased use of computed tomography. With the evidence indicating underlying allergic mechanisms, there have been studies regarding the skin tests using ICM. OBJECTIVE: This study aimed to evaluate the intradermal skin test (IDT) as a tool for preventing recurrent hypersensitivity reactions to ICM in patients with prior reactions to a known culprit agent. METHODS: Sixty-nine patients who had experienced immediate hypersensitivity reactions to ICM were included in the study. All patients underwent IDT with 7 different ICMs, including the causative ICM. We analyzed clinical data from 38 patients who were reexposed to ICMs, grouped by the IDT results to their original culprit ICM. RESULTS: Thirty-eight patients showed positive IDT results to the culprit ICM (CULPRIT+), whereas 31 patients showed negative results (CULPRIT-). Sixteen patients from the CULPRIT+ group and 22 from the CULPRIT- group were subsequently exposed to an ICM. In the CULPRIT+ group, 4 of the 5 patients who were subsequently exposed to an IDT-positive ICM reexperienced hypersensitivity reactions. When patients were exposed to IDT-negative ICM as an alternative, hypersensitivity reactions were not observed. In the CULPRIT- group, IDT-positive ICMs did not provoke hypersensitivity reactions whereas 2 patients using IDT-negative ICMs experienced hypersensitivity reactions. CONCLUSIONS: When the IDT results are positive for the culprit ICM, additional IDTs with other ICMs are needed to select a safe alternative. If the IDT results are negative against the culprit ICM, further IDTs might not play a role in selecting a safe alternative.

High Prevalence of Asthma in Elderly Women: Findings From a Korean National Health Database and Adult Asthma Cohort.

PURPOSE: The prevalence and burden of asthma is increasing worldwide. In this study, we analyzed 3 different Korean national health survey datasets to determine the general features of adult asthma in Korea and to obtain basic information that would support future strategies for better management of adult asthma. METHODS: The surveys used in this study included the Korea National Health and Nutrition Examination Survey (KNHANES), Korea Community Health Survey (KCHS) and National Health Insurance Service-National Sample Cohort (NHIS-NSC). We investigated annual asthma prevalence, evaluating the rate and risk factors of asthma exacerbation by age and sex, and clinical data of 1,832 patients with asthma who were registered in the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) were analyzed to elucidate risk factors for asthma exacerbation. We also analyzed another asthma cohort and added it as replication data. RESULTS: In the KNHANES database, annual asthma prevalence rates varied from 1.2% to 3.1%. In the KCHS database, overall prevalence increased, with significant regional differences (1.6%-2.1%). The NHIS-NSC indicated a gradual increase in annual asthma prevalence from 4.5% to 6.2%. Interestingly, all 3 surveys indicated the highest prevalence of asthma among elderly women. In addition, elderly women with asthma had a significantly higher risk of asthma exacerbation (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.19-2.93; P=0.006). Approximately 11% of patients were classified as having severe asthma. An asthma cohort analysis identified female sex, low baseline pulmonary function, longer treatment duration, high variability in pulmonary function and significant changes in Asthma Control Test scores as risk factors for asthma exacerbation. CONCLUSIONS: The prevalence of asthma in Korea is consistently high among elderly and female populations. These results should lay the foundation for strategies for effective asthma prevention and management; elderly female patients with asthma should receive particular attention.

Case report: A first case of flaxseed-induced anaphylaxis in Korea.

RATIONALE: Anaphylaxis is a serious, generalized allergic reaction typically triggered by drugs, food, and bee venom, which can be life-threatening. Seeds are one of the major food allergens and can cause anaphylaxis as well as systemic hypersensitivity reactions. Flaxseed has been widely used crop for numerous purposes, such as in alternative medicine and as a dietary supplement, hypersensitivity to it has rarely been reported. PATIENT CONCERNS: A 42-year-old female presenting with facial edema, dyspnea and urticaria after ingested half teaspoon of flaxseed flour 30 minutes previously. DIAGNOSES: A skin prick test for heated flaxseed flour extract showed negative responses, but intradermal test showed positivity which suggested an Immunoglobulin E-mediated reaction. INTERVENTIONS: The patient was instructed to avoid future ingestion of flaxseed. OUTCOMES: The patient had no recurrence of symptoms at 1-year follow-up. LESSONS: This is the first case of flaxseed-induced anaphylaxis in Korea, confirmed by an intradermal skin test.