Pilot study: Unveiling the impact of bisphenol A and phthalate exposure on women with asthma.

Endocrine disruptors are considered estrogenic disruptors, and recent researches suggested that they may have a link to the severity of asthma. We aim to validate the correlation between endocrine disruptors and various clinical measurements of asthma, depending on the menopausal status. A pilot case-control study was performed in female asthmatic patients who visited allergy clinic in SMG-SNU Boramae Medical Center. Medical information and the urinary concentrations of 4 endocrine disruptors on their first visit were collected and analyzed: bisphenol A, mono (2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-oxohexyl) phthalate, and mono-n-butyl phthalate. A total of 35 female participants enrolled in the study, including 20 asthmatic patients and 15 healthy controls. The average concentrations of urinary endocrine disruptors in patient and control group did not demonstrate significant differences. Twenty asthmatic patients were divided into 2 groups according to their menstrual state. Using the Spearman rank correlation test in premenopausal asthmatic patients (n = 7), we found negative correlations between urinary concentration of mono-n-butyl phthalate and asthma control test score, as well as postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (P-value = .007 and .04, respectively). In contrast, it did not show any correlation with asthma control test or postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (P-value = 1.00 and .74, respectively) in postmenopausal group (n = 13). Endocrine disruptors might have an impact on the decline of small airway function and asthma management among premenopausal, but not postmenopausal, female asthmatic patients.

A smartphone-based application for cough counting in patients with acute asthma exacerbation.

Background: While tools exist for objective cough counting in clinical studies, there is no available tool for objective cough measurement in clinical practice. An artificial intelligence (AI)-based cough count system was recently developed that quantifies cough sounds collected through a smartphone application. In this prospective study, this AI-based cough algorithm was applied among real-world patients with an acute exacerbation of asthma. Methods: Patients with an acute asthma exacerbation recorded their cough sounds for 7 days (2 consecutive hours during awake time and 5 consecutive hours during sleep) using CoughyTM smartphone application. During the study period, subjects received systemic corticosteroids and bronchodilator to control asthma. Coughs collected by application were counted by both the AI algorithm and two human experts. Subjects also provided self-measured peak expiratory flow rate (PEFR) and completed other outcome assessments [e.g., cough symptom visual analogue scale (CS-VAS), awake frequency, salbutamol use] to investigate the correlation between cough and other parameters. Results: A total of 1,417.6 h of cough recordings were obtained from 24 asthmatics (median age =39 years). Cough counts by AI were strongly correlated with manual cough counts during sleep time (rho =0.908, P<0.001) and awake time (rho =0.847, P<0.001). Sleep time cough counts were moderately to strongly correlated with CS-VAS (rho =0.339, P<0.001), the frequency of waking up (rho =0.462, P<0.001), and salbutamol use at night (rho =0.243, P<0.001). Weak-to-moderate correlations were found between awake time cough counts and CS-VAS (rho =0.313, P<0.001), the degree of activity limitation (rho =0.169, P=0.005), and salbutamol use at awake time (rho =0.276, P<0.001). Neither awake time nor sleep time cough counts were significantly correlated with PEFR. Conclusions: The strong correlation between cough counts using the AI-based algorithm and human experts, and other indicators of patient health status provides evidence of the validity of this AI algorithm for use in asthma patients experiencing an acute exacerbation. Study findings suggest that CoughyTM could be a novel solution for objectively monitoring cough in a clinical setting.

Development and linguistic validation of the Korean version of the Severe Asthma Questionnaire.

Background: Severe asthma, compared with mild to moderate asthma, has a larger impact on the quality of life (QOL) of the affected patients and their families. These findings underscore the need for patient-reported outcomes that are specific to severe asthma. The Severe Asthma Questionnaire (SAQ) is a validated disease-specific questionnaire that addresses the impact of severe asthma on patients. The present study aimed to develop the Korean language version of the SAQ (SAQ-K), with the translation and linguistic validation. Methods: The development of SAQ-K was achieved through a process of forward translation, reconciliation, back translation, reconciliation, cognitive debriefing involving severe asthmatics, proofreading, and the final report. Results: Two medical personnel who were fluent in Korean and English independently translated the original English version of the SAQ into Korean. After incorporating these translations into a single reconciled version, two other bilingual personnel translated the Korean draft back into English. Discrepancies between the original form and the first Korean translation were then reviewed by the panel. The translated questionnaire was then tested in cognitive debriefing interviews with 15 severe asthma patients. Through this cognitive debriefing process, the second version was verified and finally proofread to check for spelling, grammar, layout, and formatting as the final version. Conclusions: We have generated the SAQ-K to enable clinicians and researchers to assess the health status of severe asthma patients in Korea.

Risk factors of anaphylaxis in Korea: Identifying drug-induced anaphylaxis culprits using big data.

Drug-induced anaphylaxis is a fatal medical condition whose incidence has been increasing continuously. Due to differences between genetic backgrounds and health care systems, different populations may be prone to various causative drugs. Using the Health Insurance Service and Assessment Service database, we investigated culprit drugs for drug-induced anaphylaxis and common medication risk factors in the Korean general population. We collected medical prescription histories within 3 days prior to anaphylaxis between January 2011 and December 2019 from the HIRA database. Designed as a case-crossover study, the attributable visits (case visits) were matched to medical visits (control visits) with the drug sets for each visit. We collected a list of medication risk factors for anaphylaxis and calculated the risk ratio of each agent using the chi-square test and conditional logistic regression analysis. A total of 159,473 individuals were listed in the database with a diagnosis of anaphylaxis in the HIRA from 2011 to 2019. After evaluating the suitability of control visits for matching with a case visit, 8168 subjects and 767 drugs were analyzed. The chi-square analysis identified 31 drugs as potential risk factors for drug-induced anaphylaxis in Korea. After applying a conditional logistic regression analysis for each agent, 5 drugs were found to be the common medication risk factors for drug-induced anaphylaxis: cefaclor, iopromide, iohexol, iomeprol, and tolperisone. We found 5 medication risk factors that showed the highest risk of drug-induced anaphylaxis and their degree of risk using an objective methodology in the Korean general population.

Validation of Practical Pathway in Patients With Anaphylaxis to Low Osmolar Contrast Media: A Retrospective Cohort Study.

BACKGROUND: An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis. OBJECTIVES: To validate the practical pathway in patients with anaphylaxis to LOCMs and to compare 2 different doses of challenge testing with skin test-negative LOCM. METHODS: A retrospective cohort study was performed in patients with LOCM-induced anaphylaxis. Patients were challenged with intravenous LOCMs showing negativity in the skin test according to 2 different protocols: low-dose and high-dose (maximum dose 10 and 30 mL, respectively). Challenge-negative LOCMs were selected for use during computed tomography scans, and patients received intravenous pretreatment with 4 mg chlorpheniramine and 40 mg methylprednisolone. RESULTS: Of the 110 challenge tests, there were 4 (3.6%) positive challenges. Among 106 enhanced computed tomography scans performed using challenge-negative LOCMs, breakthrough reactions occurred in 8 (7.6%). Breakthrough reaction rates were not statistically different between the 2 protocols (8.9% and 6.0% in the low-dose challenge and the high-dose challenge, respectively). Compared with the low-dose protocol, the number needed to test of the high-dose challenge test decreased 2.5-fold. Moreover, none of the patients in the high-dose challenge group incurred severe reactions during computed tomography scans with challenge-negative LOCM, whereas 80% of reactions were severe in the low-dose challenge group. CONCLUSIONS: We validated a pathway consisting of a battery of skin testing to LOCMs and challenge with skin test-negative LOCM in patients with LOCM-induced anaphylaxis.

Lung function decline is associated with serum uric acid in Korean health screening individuals.

We performed a retrospective cohort study of 19,237 individuals who underwent at least three health screenings with follow-up periods of over 5 years to find a routinely checked serum marker that predicts lung function decline. Using linear regression models to analyze associations between the rate of decline in the forced expiratory volume in 1 s (FEV1) and the level of 10 serum markers (calcium, phosphorus, uric acid, total cholesterol, total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, creatinine, and C-reactive protein) measured at two different times (at the first and third health screenings), we found that an increased uric acid level was significantly associated with an accelerated FEV1 decline (P = 0.0014 and P = 0.037, respectively) and reduced FEV1 predicted % (P = 0.0074 and P = 8.64 × 10-7, respectively) at both visits only in non-smoking individuals. In addition, we confirmed that accelerated forced vital capacity (FVC) and FEV1/FVC ratio declines were observed in non-smoking individuals with increased serum uric acid levels using linear mixed models. The serum uric acid level thus potentially predicts an acceleration in lung function decline in a non-smoking general population.

Vitamin D deficiency and lung function decline in healthy individuals: A large longitudinal observation study.

AIM: A reliable evidence from a comprehensive large-scale study supporting associations between serum vitamin D (25-hydroxyvitamin D) level (SVDL) and lung function decline (LFD) in healthy individuals has been unavailable. Using a well-established health screening database, we assessed the associations between SVDL and LFDs, measured as the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. METHODS: Serial SVDL and lung function data were analyzed using linear mixed models, which were performed in smokers and non-smokers, separately. Vitamin D-deficient individuals (VDDs) were defined when their SVDLs were consistently lower than 20 ng/mL at all measurements. RESULTS: A total of 1371 individuals were analyzed. The mean FEV1 decline rates of VDDs and vitamin D-normal individuals (VDNs) in smokers were -33.35 mL/year (95% CI: 39.44 to -27.26 mL/year) and -15.61 mL/year (95% CI: 27.29 to -4.21 mL/year) respectively, over a mean of 6.29 years of observation with statistical significance (P < 0.001). However, there was no significant differences observed between decline rates of FEV1 in non-smokers. Similarly, FVC decline rates of VDDs were significantly greater than those of VDNs only in smokers (P < 0.001). However, FEV1/FVC ratio decline rates showed no significant difference between VDDs and VDNs regardless of their smoking status. CONCLUSIONS: Consistently low SVDLs predicted more rapid FEV1 and FVC declines in smokers. However, FEV1/FVC decline rate was not associated with SVDL. SVDL may be used to identify healthy smoking individuals at high risk for accelerated LFD.

Incidence rates of severe cutaneous adverse reactions due to antiseizure medication: A nationwide study using health claims data in Korea.

OBJECTIVE: Antiseizure medications (ASMs) can rarely result in severe, sometimes fatal, cutaneous adverse reactions. To date, few studies have reported on the incidence rates (IRs) of severe cutaneous adverse reactions (SCARs) due to ASM use. This study aimed to determine the IRs of SCAR resulting from the use of seven commonly prescribed ASMs, carbamazepine (CBZ), phenytoin (PHT), oxcarbazepine (OXC), lamotrigine (LMT), zonisamide (ZNS), levetiracetam (LVT), and topiramate (TPM), and to compare the associated risks among the drugs. METHODS: Using a nationwide health claims database, we selected all the patients prescribed with one of the target ASMs. We defined a SCAR case as the first hospitalization with one of three specific codes provided by the International Classification of Diseases, 10th revision (L511, L512, and L27). We then calculated the IR of SCARs according to each target ASM. RESULTS: The IR of SCARs for each ASM was as follows: 870/1 000 000 person-years (PYs) for CBZ, 5750/1 000 000 PYs for PHT, 1490/1 000 000 PYs for OXC, 3860/1 000 000 PYs for LMT, 1540/1 000 000 PYs for ZNS, 830/1 000 000 PYs for LVT, and 400/1 000 000 PYs for TPM. Concomitant use of antibiotics and nonsteroidal anti-inflammatory drugs significantly increased the risk of SCARs with OXC, LVT, or TPM use. Comorbid skin disease was associated with a significantly higher IR of SCARs from CBZ, PHT, OXC, LMT, or LVT use. SIGNIFICANCE: This is the first study in Asia to determine the IRs of SCARs for various ASMs and compare the rates across drugs using a large dataset. The results from this study should help clinicians select safer ASMs in practice.

Blood Eosinophil Count as a Predictor of Lung Function Decline in Healthy Individuals.

BACKGROUND: Little is known about the effect of blood eosinophil count (BEC) on a decline in lung function in healthy individuals. OBJECTIVE: Using a well-established health screening database, we assessed the associations between BEC and a decline in lung function, measured as the forced expiratory volume in 1 second (FEV1). METHODS: Serial BEC and FEV1 data were analyzed using linear mixed models adjusted for gender, height, and smoking status. The association between BEC consistency and a decline in FEV1 was evaluated in subpopulation analyses. RESULTS: A total of 4634 individuals were enrolled. The mean number of health screenings was 7.49 over an average of 11.74 years of observation. A higher log2-transformed BEC was significantly associated with a greater decline in FEV1 that was stronger in nonsmokers (P = 8.56 × 10-8) than in smokers (P = 1.52 × 10-3). In subpopulation analyses of 2018 individuals with consistent BECs, those with BECs consistently ≥100/µL (P = 4.58 × 10-6), ≥200/µL (P = 3.53 × 10-7), and ≥300/µL (P = 1.12 × 10-3) had a significantly higher dose-dependent FEV1 decline than those with BECs consistently <100/µL. A BEC threshold of 100/µL in nonsmokers and 200/µL in smokers may predict an accelerated decline in FEV1. CONCLUSIONS: BEC is associated with a decline in FEV1, and a consistently high BEC is an independent risk factor for an accelerated decline in FEV1. These results suggest the use of the BEC to identify healthy individuals at high risk for developing chronic lung disease, which in turn may enable a tailored preventive strategy.

Usefulness of routine blood test-driven clusters for predicting acute exacerbation in patients with asthma.

AIM: Acute exacerbation (AE) is a significant burden in the management of asthma. In this study we aimed to investigate whether routine blood test results predicted AE in asthmatics. METHODS: We applied k-means cluster to routine blood test results which included eosinophil counts, total calcium, phosphorus, uric acid (UA), total cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, aspartate transaminase (AST), alanine transferase (ALT), gamma-glutamyltransferase, blood urea nitrogen, creatinine, and high-sensitive C-reactive protein (hsCRP) obtained from 590 asthmatics. AEs collected over the prospective follow-up of one-year were used to evaluate clinical trajectories of these clusters. RESULTS: Three blood clusters were identified. The essential features of each cluster can be characterized as follows: (i) high eosinophil count, UA, total cholesterol, AST, ALT, and hsCRP levels (Cluster 1); (ii) intermediate features (Cluster 2); (iii) low UA, total cholesterol and total bilirubin levels (Cluster 3). Kaplan-Meier analysis confirmed that clusters were strongly predictive of time to the first AE (log-rank P = 0.001). Hazard ratio for each group was as follows: Cluster 2 = 1, Cluster 1 = 2.67 (1 vs. 2, P = 4.68 × 10-4), and Cluster 3 = 1.69 (2 vs. 3, P = 0.021). CONCLUSIONS: We defined three blood clusters in asthmatics. These blood clusters are easily identifiable from routine test results and may help clinicians to predict the future risk of AE in asthmatics.

Past, present, and future of pharmacovigilance in Korea.

As an essential part of patient safety, pharmacovigilance is of worldwide interest and should expand its scope and focus on new emerging issues. South Korea has been making continuous efforts in the field of pharmacovigilance for the last 3 decades since voluntary adverse drug reaction (ADR) reporting system was first launched in 1988. Korea joined the World Health Organization Program for International Drug Monitoring in 1992, and the activities of Pharmacovigilance Research Network, Korean Society for Pharmacoepidemiology and Risk Management, and Regional Pharmacovigilance Center (RPVC) have contributed to the remarkable progress in the pharmacovigilance area and global status. RPVCs have played pivotal roles in establishment of pharmacovigilance system in Korea by monitoring voluntary ADR reports. RPVCs started with 3 hospitals in 2006 and have now expanded to 27 hospitals nationwide. The Korea Institute of Drug Safety & Risk Management was established in 2012 and in charge of operating the decentralized national pharmacovigilance system. The voluntary report of ADR, which is the basis of current pharmacovigilance system, has various limitations and an active surveillance system can be the overarching alternative. This change in pharmacovigilance paradigm is a global trend and Korea has excellent infrastructure such as broad distribution of electronic medical recording systems and a nationwide single healthcare insurance. As a result, the pharmacovigilance in Korea is now expected to progress to a new active surveillance system from traditional spontaneous reporting system.