Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

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.

Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.

Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study.

Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (-117.50 ± 94.38 vs. -115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (-18.62 ± 24.68 vs. -14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (-3.40 ± 10.60 vs. -14.48 ± 24.01 %, P = 0.065), blood eosinophils (-36.47 ± 517.02 vs. -363.22 ± 1294.59, P = 0.013), and exacerbation frequency (-3.07 ± 4.42 vs. -3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

Discovery of Orally Bioavailable Phthalazinone Analogues as an ENPP1 Inhibitor for STING-Mediated Cancer Immunotherapy.

A lack of the T cell-inflamed tumor microenvironment limits the efficacy of immune checkpoint inhibitors (ICIs). Activation of stimulator of interferon genes (STING)-mediated innate immunity has emerged as a novel therapeutic approach in cancer therapy. 2',3'-Cyclic GMP-AMP (cGAMP) is a natural STING agonist; however, cGAMP is subjected to endogenous degradation by ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1). To improve the ICI response rate, we developed 29f, a novel ENPP1 inhibitor with phthalazin-1(2H)-one as the core scaffold. 29f inhibited the cGAMP hydrolysis by ENPP1 in vitro (IC50 = 68 nM) and enhanced the STING-mediated type I interferon response in both immune and tumor cells. 29f demonstrated excellent metabolic stability and bioavailability (F = 65%). Orally administered 29f promoted tumor growth inhibition in a CT26 syngeneic model and increased the anti-PD-L1 response. Furthermore, 29f-induced immunological memory prevented the tumor relapse against tumor rechallenge, suggesting the promising therapeutic potential of 29f.

Pterygium combined with corneal perforation: a case report.

BACKGROUND: Pterygium is a common ocular surface disease. Pterygium combined with corneal perforation is rare. CASE PRESENTATION: A 28-year-old female patient visited our outpatient clinic due to sudden onset of blurred vision and increased tearing in her left eye. The visual acuity was 1.0 OD and intraocular pressure (IOP) of 19.5 mmHg for the right eye with no significant abnormalities found in the anterior and posterior segments. The visual acuity of her left eye was 0.06, and IOP was 6.2 mmHg. A triangular vascular membranous tissue was seen in her left eye below the nose growing into the cornea and the pupil area was not touched. Slit-lamp examination revealed a tiny round corneal perforation in 8 o'clock position of the lesion area. Hospital diagnosis was given as pterygium combined with corneal perforation. The patient was treated with levofloxacin eye drops and autologous serum-based eye drops. CONCLUSIONS: We report a rare case of pterygium combined with corneal perforation. Perforation is a very rare complication of pterygium. This patient received proper treatment and good result was seen. This article aimed to improve clinicians' understanding of pterygium.

Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.

Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation. We find that GHRH-R is not expressed in naïve CD4+ T cells, while its expression is induced throughout Th17 cell differentiation in vitro. Mechanistically, GHRH-R activates the JAK-STAT3 pathway, increases the phosphorylation of STAT3, enhances both non-pathogenic and pathogenic Th17 cell differentiation and promotes the gene expression signatures of pathogenic Th17 cells. Enhancing this signaling by GHRH agonist promotes, while inhibiting this signaling by GHRH antagonist or GHRH-R deficiency reduces, Th17 cell differentiation in vitro and Th17 cell-mediated ocular and neural inflammation in vivo. Thus, GHRH-R signaling functions as a critical factor that regulates Th17 cell differentiation and Th17 cell-mediated autoimmune ocular and neural inflammation.

rTMS ameliorates depression/anxiety-like behaviors in experimental autoimmune encephalitis by inhibiting neurotoxic reactive astrocytes.

One third of patients with multiple sclerosis (MS) suffered from depressive symptoms. The pathogenesis of depression in MS patients has been related to innate immune activation in certain regions of the brain such as hippocampus. However, pharmacotherapy lacks sufficient evidence for beneficial effects on depression in MS patients, urging for a novel treatment modality for this mental disorder. Treatment effects of rTMS on depression/anxiety-like behaviors in mice with experimental autoimmune encephalomyelitis (EAE) were assessed by behavioral tests. The role of innate immune response was examined by RNA sequencing, quantitative RT-PCR, and immunofluorescence techniques. Depressive symptom severity and astroglial activation in patients with MS were assessed by Beck Depression Inventory and serum glial fibrillary acidic protein (GFAP), respectively. EAE mice displayed depression/anxiety-like behaviors, which were ameliorated by rTMS. Transcriptome and gene-specific expression analysis of the hippocampus showed significant reduction in transcript levels associated with neurotoxic reactive astrocytes in EAE mice after rTMS treatment. This was confirmed by immunofluorescence studies. Complement component 3d, a marker of neurotoxic reactive astrocytes, was highly expressed in EAE hippocampus, but was reduced to a basal level after rTMS treatment. In patients with MS, astroglial activation, indicated by serum GFAP levels, was significantly elevated in those with moderate or major depressive symptoms. These findings support that the suppression of neurotoxic reactive astrocytes might be a potential target for treatment of depression in patients with MS, and suggest the potential of using rTMS as a potential therapeutic treatment for this disorder.

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

Idiopathic Hypereosinophilia: A Multicenter Retrospective Analysis.

Purpose: Physicians can sometimes encounter idiopathic hypereosinophilia (HE), but little is known about it. In this multicenter study, we analyzed the clinical characteristics, treatment, and outcomes of patients with idiopathic HE. Patients and Methods: Patients diagnosed with idiopathic HE (idiopathic hypereosinophilic syndrome: iHES or hypereosinophilia with undetermined significance: HEus) at six tertiary hospitals between January 2010 and June 2021 were included in this retrospective observational study. Demographics, clinical and laboratory data, and treatment responses were obtained from the electronic medical records of the study subjects. Results: A total of 73 patients with idiopathic HE (45 with iHES and 28 with HEus) were included in the present study. Overall, 12 (26.7%) and 5 (17.9%) were women, and mean age of patients at diagnosis was 51.84 ± 17.29 years and 60.21 ± 18.01 years in iHES and HEus groups, respectively. Forty-three (95.6%) patients of iHES and 15 (53.6%) patients of HEus received corticosteroids as 1st-line treatment. Treatment response to corticosteroids in patients with iHES was generally good: complete response (n=25, 58.1%), partial response (n=12, 27.9%), no response (n=6, 14.0%). Treatment response to corticosteroids in HEus was complete response (n=7, 46.7%), partial response (n=6, 40.0%), and no response (n=2, 13.3%). There were 13 patients (46.4%) with HEus who were not treated. Conclusion: Corticosteroid treatment is generally effective and well tolerated by patients with iHES. Some patients with HEus are treated with corticosteroids in clinical practice. Extensive research is needed to establish a standardized management guidelines for iHES and determine whether treatment for HEus is required.

Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: From multicenter real-world cohort data in Korea.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. Methods: We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. Results: The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6-47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8-161.5, P = 0.024], and 3) initial ACT score <20 [OR = 24.1, 95% CI: 5.45-158.8, P < 0.001] for ACT responders. FEV1 responders also showed a longer exacerbation-free period than those with no FEV1 increase (P = 0.014), yielding a hazard ratio for the first asthma exacerbation of 0.5 (95% CI: 0.3-0.9, P = 0.016). Conclusions: The results of this study suggest that tiotropium add-on for uncontrolled asthma with ICS-LABA would be more effective in patients with positive BDR or ACO. Additionally, an increase in FEV1 following tiotropium may predict a lower risk of asthma exacerbation.

Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors.

In an effort to discover novel scaffolds of non-nucleotide-derived Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors to stimulate the Stimulator of Interferon Genes (STING) pathway, we designed and synthesised pyrrolopyrimidine and pyrrolopyridine derivatives and performed structure-activity relationship (SAR) study. We found 18p possessed high potency (IC50 = 25.0 nM) against ENPP1, and activated STING pathway in a concentration dependent manner. Also, in response to STING pathway activation, cytokines such as IFN-ß and IP-10 were induced by 18p in a concentration dependent manner. Finally, we discovered that 18p causes inhibition of tumour growth in 4T1 syngeneic mouse model. This study provides new insight into the designing of novel ENPP1 inhibitors and warrants further development of small molecule immune modulators for cancer immunotherapy.

Discovery of 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one and 3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one derivatives as novel ENPP1 inhibitors.

Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) negatively regulates the anti-cancer Stimulator of Interferon Genes (STING) pathway. We discovered that 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one and 3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one derivatives possessed inhibitory activities on ENPP1. A structure-activity relationship (SAR) study led to the identification of 46 and 23 as potent ENPP1 inhibitors. Also, compounds 46 and 23 possessed high microsomal stabilities in human, rat, and mouse liver microsome. Additionally, CYPs (1A2, 2C9, 2C19, 2D6, and 3A4) were not inhibited by 46 and 23. Molecular dynamics simulations provided an insight of binding modes between ENPP1 and compounds (46 and 23).

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

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

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.

Intradermal testing increases the accuracy of an immediate-type cefaclor hypersensitivity diagnosis.

Background: Hypersensitivity reactions to cefaclor have increased in accordance with its frequent use. However, only limited data are available on the diagnostic value of skin tests for these conditions, particularly intradermal tests (IDTs). Objective: To evaluate the clinical usefulness of IDT compared to the ImmunoCAP test in patients with cefaclor-induced immediate-type hypersensitivity. Methods: We conducted a retrospective chart review from January 2010 to June 2020 of adult subjects from 2 tertiary hospitals in Korea with a history of suspected immediate-type hypersensitivity to cefaclor, and who had undergone ImmunoCAP and IDT. Results: Overall, 131 subjects diagnosed with cefaclor hypersensitivity were included in the analysis. Fifty-nine patients (59/131, 45.04%) were positive in both IDT and ImmunoCAP. Fifty-four (54/131, 41.22%) and 6 (6/131, 4.58%) subjects showed positive results only with IDT or the ImmunoCAP test, respectively. Twelve subjects (12/131, 9.16%) were negative by both tests but reacted positively in a drug provocation test. The frequency of IDT positivity was similar regardless of the severity of reactions. However, positivity of ImmunoCAP was lower in subjects with mild reactions compared to those with anaphylaxis. Regarding the diagnosis of cefaclor hypersensitivity, the overall sensitivity of IDT and ImmunoCAP was 0.863 and 0.496, respectively while the specificity was 1. The combination of IDT and ImmunoCAP further increased this sensitivity to 0.908. Conclusion: IDT was more sensitive than ImmunoCAP for the diagnosis of cefaclor allergy, regardless of the severity of the hypersensitivity reaction. Therefore, we recommend a combination of IDT and ImmunoCAP for the diagnosis of cefaclor hypersensitivity.

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

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

Need for sensitization on serious threats of second-hand smoke: Findings from a national study in Mauritius, a small island developing state in the Indian Ocean.

This study had the following objectives: To assess the level of knowledge of Mauritians aged ≥ 20 years on the health effects of Second Hand Smoke (SHS), to investigate their behaviour when exposed to SHS and to look for any association between SHS-related knowledge and behaviour towards exposure. A national cross-sectional online survey was conducted. With the total population of Mauritians above the age of 20 years being 941,719, the calculated sample size was 400. A validated questionnaire was used to collect data among respondents from all 9 districts of the island of Mauritius, with representative district-wise samples. Data analysis was carried out using SPSS version 19.0. Considering the findings of the study, there were 408 respondents: Two-thirds of participants showed good knowledge of the harmful effects of SHS. Participants were aware of the link of SHS to respiratory diseases, nonetheless, they were not aware of its causes for non-respiratory diseases. One out of four participants (25.5%) were not aware that maternal passive smoking causes preterm delivery. More than one-third of the participants (37.3%) did not know that passive smoking causes sudden infant death syndrome. Inadequate levels of knowledge were also revealed by authors in other developing countries. We thus recommend bold sensitization campaigns about the serious threats of SHS. We highlight the pertinence of longitudinal cohort studies with assessment of SHS-related knowledge/behaviour before and after health education campaigns, in Mauritius and other developing countries.

ELEVATED LEVEL OF URIC ACID, BUT NOT GLUCOSE, IN AQUEOUS HUMOR AS A RISK FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES.

PURPOSE: To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes. METHODS: Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls. RESULTS: A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P < 0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (<2.46 mg/dL) and aqueous glucose (<6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME. CONCLUSION: Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.