Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Ability of the modified NUTRIC score to predict mortality in patients requiring short-term versus prolonged acute mechanical ventilation: a retrospective cohort study.

BACKGROUND: The modified NUTRIC (nutritional risk in the critically ill) score has been reported to predict clinical outcomes in critically ill patients. However, the applicability of this score may differ between patients undergoing short-term mechanical ventilation (STMV, < 96 h) and those undergoing prolonged acute mechanical ventilation (PAMV, ⩾96 h), as PAMV patients typically experience significantly higher morbidity and mortality. OBJECTIVE: This study aimed to investigate the predictive ability of modified NUTRIC score for predicting 28-day mortality in patients receiving STMV and PAMV. DESIGN: Retrospective single-center cohort study. METHODS: We enrolled patients who received mechanical ventilation (MV) on the day of admission to the intensive care unit (ICU) from 1 December 2015 to 30 November 2020. Modified NUTRIC scores were calculated based on the clinical data of each patient at ICU admission. RESULTS: The study population comprised 464 patients, including 319 (68.8%) men with a mean age of 69.7 years. Among these patients, 132 (28.4%) received STMV and 332 (71.6%) received PAMV. The overall 28-day mortality rate was 26.7%, which was significantly higher in STMV patients than in PAMV patients (37.9% versus 22.3%, p < 0.001). Evaluation of the predictive performance of the modified NUTRIC score for 28-day mortality revealed areas under the receiver operating characteristic curves of 0.672 [95% confidence interval (CI): 0.627-0.714] for total patients, 0.819 (95% CI, 0.742-0.880) for STMV patients, and 0.595 (95% CI, 0.540-0.648) for PAMV patients. The best overall cutoff value was 5 in total, STMV, and PAMV patients. This cutoff value was a significant predictor of 28-day mortality based on the Cox proportional hazard model for total [hazards ratio (HR): 2.681; 95% CI: 1.683-4.269] and STMV (HR: 5.725; 95% CI: 2.057-15.931) patients, but not for PAMV patients. CONCLUSION: The modified NUTRIC score is more effective in predicting 28-day mortality in patients undergoing STMV than in those undergoing PAMV.

Predicting survival: Modified NUTRIC score in short-term vs. prolonged mechanical ventilationIn this study, we examined the scoring system called the Modified NUTRIC (nutritional risk in the critically ill) score to determine whether it could be used to predict 28-day mortality following Intensive Care Unit (ICU) admission. In particular, we wanted to determine whether the score works equally well for patients who need short-term mechanical ventilation (STMV, less than 96 hours) and those who need prolonged acute mechanical ventilation (PAMV, 96 hours or more). PAMV patients tend to have more severe illness and use more medical resources.Here's what we did: We studied 464 patients who were put on a breathing machine (mechanical ventilation) on the same day they were admitted to the ICU between December 1, 2015, and November 30, 2020.We calculated the Modified NUTRIC (m-NUTRIC) scores based on their medical information when they entered the ICU.We found that the overall 28-day mortality was 26.7%, and that it was higher for STMV patients (37.9%) than for PAMV patients (22.3%).When we checked how well the m-NUTRIC score predicted survival, we discovered that it worked better for STMV patients (with an accuracy of 81.9%) than for PAMV patients (with an accuracy of 59.5%).We also found that a m-NUTRIC score of 5 or more points was indicative of a higher mortality in STMV patientsIn conclusion, the m-NUTRIC score is a more reliable predictor of 28-day survival in patients who need short-term mechanical ventilation than in those who need prolonged acute mechanical ventilation.

Development of a Prognostic Scoring System for Tracheostomized Patients Requiring Prolonged Ventilator Care: A Ten-Year Experience in a University-Affiliated Tertiary Hospital.

Background and Objectives: This study aimed to assess the value of a novel prognostic model, based on clinical variables, comorbidities, and demographic characteristics, to predict long-term prognosis in patients who received mechanical ventilation (MV) for over 14 days and who underwent a tracheostomy during the first 14 days of MV. Materials and Methods: Data were obtained from 278 patients (66.2% male; median age: 71 years) who underwent a tracheostomy within the first 14 days of MV from February 2011 to February 2021. Factors predicting 1-year mortality after the initiation of MV were identified by binary logistic regression analysis. The resulting prognostic model, known as the tracheostomy-ProVent score, was computed by assigning points to variables based on their respective ß-coefficients. Results: The overall 1-year mortality rate was 64.7%. Six factors were identified as prognostic indicators: platelet count < 150 × 103/µL, PaO2/FiO2 < 200 mmHg, body mass index (BMI) < 23.0 kg/m2, albumin concentration < 2.8 g/dL on day 14 of MV, chronic cardiovascular diseases, and immunocompromised status at admission. The tracheostomy-ProVent score exhibited acceptable discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.786 (95% confidence interval: 0.733-0.833, p < 0.001) and acceptable calibration (Hosmer-Lemeshow chi-square: 2.753, df: 8, p = 0.949). Based on the maximum Youden index, the cut-off value for predicting mortality was set at ≥2, with a sensitivity of 67.4% and a specificity of 76.3%. Conclusions: The tracheostomy-ProVent score is a good predictive tool for estimating 1-year mortality in tracheostomized patients undergoing MV for >14 days. This comprehensive model integrates clinical variables and comorbidities, enhancing the precision of long-term prognosis in these patients.

Baseline Cohort Profile of the Korean Chronic Cough Registry: A Multicenter, Prospective, Observational Study.

PURPOSE: The Korean Chronic Cough Registry study was initiated to characterize patients with chronic cough (CC) and investigate their outcomes in real-world clinical practice. This report aims to describe the baseline cohort profile and study protocols. METHODS: This multicenter, prospective observational cohort study included newly referred CC patients and those already being treated for refractory or unexplained chronic cough (RUCC). Cough status was assessed using a visual analog scale, the Leicester Cough Questionnaire (LCQ), and the Cough Hypersensitivity Questionnaire (CHQ). RESULTS: A total of 610 patients (66.9% women; median age 59.0 years) were recruited from 18 centers, with 176 being RUCC patients (28.9%). The median age at CC onset was 50.1 years, and 94.4% had adult-onset CC (≥ 19 years). The median cough duration was 4 years. Compared to newly referred CC patients, RUCC patients had a longer cough duration (6.0 years vs. 3.0 years) but had fewer symptoms and signs suggesting asthma, rhinosinusitis, or gastroesophageal acid reflux disease. Subjects with RUCC had lower LCQ scores (10.3 ± 3.3 vs. 11.6 ± 3.6; P < 0.001) and higher CHQ scores (9.1 ± 3.9 vs. 8.4 ± 4.1; P = 0.024). There were no marked differences in the characteristics of cough between refractory chronic cough and unexplained chronic cough. CONCLUSIONS: Chronic cough typically develops in adulthood, lasting for years. Cough severity and quality of life impairment indicate the presence of unmet clinical needs and insufficient cough control in real-world clinical practice. Longitudinal follow-up is warranted to investigate the natural history and treatment outcomes.

Plasmonic Approach to Fluorescence Enhancement of Mesoporous Silica-Coated Gold Nanorods for Highly Sensitive Influenza A Virus Detection Using Lateral Flow Immunosensor.

Rapid diagnostic tests based on the lateral flow immunoassay (LFI) enable early identification of viral infection, owing to simple interpretation, short turnaround time, and timely isolation of patients to minimize viral transmission among communities. However, the LFI system requires improvement in the detection sensitivity to match the accuracy of nucleic acid amplification tests. Fluorescence-based LFIs are more sensitive and specific than absorption-based LFIs, but their performance is significantly affected by fundamental issues related to the quantum yield and photobleaching of fluorophores. Metal-enhanced fluorescence (MEF), which is a plasmonic effect in the vicinity of metallic nanoparticles, can be an effective strategy to improve the detection sensitivity of fluorescence-based LFIs. The key factors for obtaining a strong plasmonic effect include the distance and spectral overlap of the metal and fluorophore in the MEF system. In this study, MEF probes were designed based on core-shell nanostructures employing a gold nanorod core, mesoporous silica shell, and cyanine 5 fluorophore. To optimize the efficiency of MEF probes incorporated on the LFI platform (MEF-LFI), we experimentally and theoretically investigated the distance dependence of plasmonic coupling between cyanine 5 and gold nanorods by adjusting the shell thickness, resulting in significant fluorescence enhancement. The proposed MEF-LFI enabled highly sensitive detection of influenza A virus (IAV) nucleocapsid protein with a detection limit of 0.52 pg mL-1 within 20 min and showed high specificity and accuracy for determining IAV clinical samples. Overall, our findings demonstrate the potential of this method as an effective tool for molecular diagnosis under emergency conditions.

Clinical outcomes of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe for peripheral lung lesions - A prospective pilot study.

OBJECTIVES: Transbronchial cryobiopsy (TBCB) is a novel technique for the diagnosis of peripheral lung lesions (PLLs). We aim to evaluate the clinical outcomes of TBCB using a new 1.1-mm diameter cryoprobe for the diagnosis of PLLs. MATERIALS AND METHODS: We performed a prospective observational pilot study on the diagnosis of PLLs (diameter ≤30 mm) by TBCB, using a 1.1-mm diameter cryoprobe with radial endobronchial ultrasound (RP-EBUS), virtual bronchoscopic navigation and fluoroscopy from December 2021 to July 2022. Primary outcome was the pathological diagnostic yield of TBCB, and secondary outcome was adverse event. RESULTS: A total of 50 patients were enrolled (mean lesion size, 21 mm). TBCB was performed in 49 patients up to three times except for the one with "invisible" finding on RP-EBUS. The overall diagnostic yield of TBCB was 90% (45/50). There was no difference in the diagnostic yield between size (20 mm vs. 20-30 mm; 88% [22/25] vs. 92% [23/25]; P = 1.000), RP-EBUS findings (concentric vs. others; 97% [28/29] vs. 81% [17/21]; P = 0.148), and acute angle location (apical segment of both upper lobes vs. others; 92% [12/13] vs. 89% [33/37]; P = 1.000). The cumulative diagnostic yields of the first, second, and third TBCB were 82% (41/50), 88% (44/50), and 90% (45/50), respectively. Mild bleeding was developed in 56% (28/50), and moderate bleeding was found in 26% (13/50). CONCLUSION: TBCB using a 1.1-mm diameter cryoprobe is an effective, reasonable method for the diagnosis of PLLs regardless of its size, RP-EBUS finding, and anatomical location without serious complication. TRIAL REGISTRATION: Clinical Trials.Gov (NCT05046093).

The prevalence of multiple chronic conditions and medical burden in asthma patients.

BACKGROUND: The prevalence of multiple chronic conditions (MCC), defined as several coexisting chronic conditions, has increased with the aging of society. MCC is associated with poor outcomes, but most comorbid diseases in asthma patients have been evaluated as asthma-associated diseases. We investigated the morbidity of coexisting chronic diseases in asthma patients and their medical burdens. METHODS: We analyzed data from the National Health Insurance Service-National Sample Cohort for 2002-2013. We defined MCC with asthma as a group of one or more chronic diseases in addition to asthma. We analyzed 20 chronic conditions, including asthma. Age was categorized into groups 1-5 (< 10, 10-29, 30-44, 45-64, and ≥ 65 years, respectively). The frequency of medical system use and associated costs were analyzed to determine the asthma-related medical burden in patients with MCC. RESULTS: The prevalence of asthma was 13.01%, and the prevalence of MCC in asthmatic patients was 36.55%. The prevalence of MCC with asthma was higher in females than males and increased with age. The significant comorbidities were hypertension, dyslipidemia, arthritis, and diabetes. Dyslipidemia, arthritis, depression, and osteoporosis were more common in females than males. Hypertension, diabetes, COPD, coronary artery disease, cancer, and hepatitis were more prevalent in males than females. According to age, the most prevalent chronic condition in groups 1 and 2 was depression, dyslipidemia in group 3, and hypertension in groups 4 and 5. Older age, low income, and severe disability were independent risk factors for MCC in patients with asthma. The frequency of asthma-related medical system use and asthma-associated costs increased with increasing numbers of coexisting chronic diseases. CONCLUSION: Comorbid chronic diseases in asthma patients differed according to age and sex. The asthma-related-medical burdens were highest in patients with five or more chronic conditions and groups 1 and 5.

Association between Participation in a Rehabilitation Program and 1-Year Survival in Patients Requiring Prolonged Mechanical Ventilation.

BACKGROUND: The present study evaluated the association between participation in a rehabilitation program during a hospital stay and 1-year survival of patients requiring at least 21 days of mechanical ventilation (prolonged mechanical ventilation [PMV]) with various respiratory diseases as their main diagnoses that led to mechanical ventilation. METHODS: Retrospective data of 105 patients (71.4% male, mean age 70.1±11.3 years) who received PMV in the past 5 years were analyzed. Rehabilitation included physiotherapy, physical rehabilitation, and dysphagia treatment program that was individually provided by physiatrists. RESULTS: The main diagnosis leading to mechanical ventilation was pneumonia (n=101, 96.2%) and the 1-year survival rate was 33.3% (n=35). One-year survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score (20.2±5.8 vs. 24.2±7.5, p=0.006) and Sequential Organ Failure Assessment score (6.7±5.6 vs. 8.5±2.7, p=0.001) on the day of intubation than non-survivors. More survivors participated in a rehabilitation program during their hospital stays (88.6% vs. 57.1%, p=0.001). The rehabilitation program was an independent factor for 1-year survival based on the Cox proportional hazard model (hazard ratio, 3.513; 95% confidence interval, 1.785 to 6.930; p<0.001) in patients with APACHE II scores ≤23 (a cutoff value based on Youden's index). CONCLUSION: Our study showed that participation in a rehabilitation program during hospital stay was associated with an improvement of 1-year survival of PMV patients who had less severe illness on the day of intubation.

Health-Related Quality of Life and Its Determinants in Chronic Cough: The Korean Chronic Cough Registry Study.

PURPOSE: Chronic cough (CC) is associated with health-related quality of life (HRQoL) impairment. However, the determinants of HRQoL are under-investigated. METHODS: Patients aged 19-80 years with CC were prospectively recruited from 10 referral clinics. Comparisons were made with age- and sex-matched controls (1:4 ratio) selected from a Korean general population survey database; 1) a group without current cough (non-cough controls) and 2) another group without major chronic illnesses (healthy controls). HRQoL was assessed using the EuroQoL 5-dimension (EQ-5D) index. In CC patients, cough-specific patient-reported outcomes (PROs) were additionally measured. Cross-sectional analyses were performed to evaluate demographic and clinical parameters associated with the EQ-5D index of CC patients. RESULTS: A total of 200 CC patients (137 newly referred with CC and 63 refractory or unexplained CC [RUCC] patients), 800 non-cough controls, and 799 healthy controls were analyzed. The EQ-5D index of CC patients was significantly lower than that of non-cough controls or healthy controls (0.82 ± 0.14 vs 0.92 ± 0.14/0.96 ± 0.08; P < 0.001, respectively). The index was also associated with older age (≥ 60 years), female sex, and comorbidities such as asthma or depression. Among the patients with CC, the index was significantly lower in patients with RUCC than in those with newly referred CC, being treated with codeine or cough neuromodulators, or with cough-related fatigue. In Spearman analyses, the EQ-5D index correlated with cough-specific quality of life and cough severity scores, not with throat sensation or cough trigger scores. CONCLUSIONS: The HRQoL impairment of CC patients was associated with older age, female sex, and comorbidities but it was also affected by cough severity, complications, treatments, and treatment responses. Longitudinal studies are warranted to further understand and improve the HRQoL of CC patients.

Real-world evaluation of atezolizumab and etoposide-carboplatin as a first-line treatment for extensive-stage small cell lung cancer.

BACKGROUND/AIMS: Despite the obvious benefits of adding immune checkpoint inhibitors to platinum-etoposide chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC), real-world data remain scarce. METHODS: This retrospective study included 89 patients with ES-SCLC treated with platinum-etoposide chemotherapy alone (chemo-only group; n = 48) or in combination with atezolizumab (atezolizumab group; n = 41) and compared the survival outcomes between these two groups. RESULTS: Overall survival (OS) was significantly longer in the atezolizumab group than in the chemo-only group (15.2 months vs. 8.5 months; p = 0.047), whereas the median progression-free survival was almost the same (5.1 months vs. 5.0 months) in both groups (p = 0.754). Subsequent multivariate analysis revealed that thoracic radiation (hazard ratio [HR], 0.223; 95% confidence interval [CI], 0.092-0.537; p = 0.001) and atezolizumab administration (HR, 0.350; 95% CI, 0.184-0.668; p = 0.001) were favorable prognostic factors for OS. In the thoracic radiation subgroup, patients who received atezolizumab demonstrated favorable survival outcomes and no grade 3-4 adverse events (AEs). CONCLUSION: The addition of atezolizumab to platinum-etoposide resulted in favorable outcomes in this real-world study. Thoracic radiation was associated with improved OS and acceptable AE risk in combination with immunotherapy in patients with ES-SCLC.

The Additive Impact of Transbronchial Cryobiopsy Using a 1.1-mm Diameter Cryoprobe on Conventional Biopsy for Peripheral Lung Nodules.

PURPOSE: The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs). Materials and Methods: From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022. RESULTS: The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm2) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm2, p < 0.001) and 1.9-mm forceps (3.7 mm2, p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications. CONCLUSION: Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

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.

Absorption-Modulated SiO2@Au Core-Satellite Nanoparticles for Highly Sensitive Detection of SARS-CoV-2 Nucleocapsid Protein in Lateral Flow Immunosensors.

The worldwide spread of coronavirus disease 2019 (COVID-19) highlights the need for rapid, simple, and accurate tests to detect various variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antigen test, based on the lateral flow immunoassay (LFI), is a suitable "first line of defense" test that enables early identification and timely isolation of patients to minimize viral transmission among communities. However, it is generally less accurate than nucleic acid testing, and its sensitivity needs improvement. Here, a novel rapid detection method is designed to sensitively detect SARS-CoV-2 using isolated gold nanoparticle (AuNP)-assembled SiO2 core-satellite nanoparticles (SiO2@Au CSNPs). Well-grown AuNP satellites in the synthesis of SiO2@Au CSNPs significantly enhanced their light absorption, increased the detection sensitivity, and lowered the detection limit by 2 orders of magnitude relative to conventional gold colloids. The proposed system enabled highly sensitive detection of the SARS-CoV-2 nucleocapsid protein with a detection limit of 0.24 pg mL-1 within 20 min. This is the first study to develop a highly sensitive antigen test using the absorption-modulated SiO2@Au CSNPs. Our findings demonstrate the capacity of this platform to serve as an effective sensing strategy for managing pandemic conditions and preventing the spread of viral infections.

The First Case of Erythritol-Induced Anaphylaxis in Korea.

Erythritol is a natural sugar alcohol found in some fruits and fermented foods, which is used as a dietary sweetener because it has few calories. Here, we describe a 36-year-old woman who experienced anaphylaxis upon ingestion of an erythritol-containing drink. She presented to the emergency department with dyspnea and angioedema after drinking a peach-containing diet beverage. Her blood pressure dropped to 70/40 mmHg and the symptoms improved after administration of an antihistamine, glucocorticoid, and epinephrine. After 10 days, she drank another peach-containing diet beverage and experienced urticaria. No serum-specific immunoglobulin E findings were observed, including against peach components. A skin prick test (SPT) was performed using a peach, the two ingested diet beverages, and another peach-containing beverage. The SPT results for the peach and the peach-containing product were negative, but the wheal sizes for the two diet beverages were > 3 mm. The diet beverages contained erythritol as a food additive. The SPT result was positive for erythritol. The patient was diagnosed with anaphylaxis to erythritol and was instructed to avoid foods containing erythritol. She was prescribed a self-injectable epinephrine pen. To our knowledge, this is the first case of erythritol-induced anaphylaxis in Korea. Physicians should be aware of the possibility of allergic reactions to food additives, and additives should be evaluated to prevent the recurrence of symptoms.

Wafer-Scale LSPR Substrate: Oblique Deposition of Gold on a Patterned Sapphire Substrate.

Label-free detection of biomolecules using localized surface plasmon resonance (LSPR) substrates is a highly attractive method for point-of-care (POC) testing. One of the remaining challenges to developing LSPR-based POC devices is to fabricate the LSPR substrates with large-scale, reproducible, and high-throughput. Herein, a fabrication strategy for wafer-scale LSPR substrates is demonstrated using reproducible, high-throughput techniques, such as nanoimprint lithography, wet-etching, and thin film deposition. A transparent sapphire wafer, on which SiO2-nanodot hard masks were formed via nanoimprint lithography, was anisotropically etched by a mixed solution of H2SO4 and H3PO4, resulting in a patterned sapphire substrate (PSS). An LSPR substrate was finally fabricated by oblique deposition of Au onto the PSS, which was then applied to label-free detection of the binding events of biomolecules. To the best of our knowledge, this paper is the first report on the application of the PSS used as an LSPR template by obliquely depositing a metal.

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.

Comparison of murine retroorbital plexus and facial vein blood collection to mitigate animal ethics issues.

BACKGROUND: Blood collection is an important procedure used in animal experiments. Blood collection methods that reduce pain, injury, and stress in experimental animals are important with regard to animal ethics. Various comparative studies of blood collection methods have been reported; however, there are no comparative studies on serial blood collection considering animal ethics. To suggest simple methods that minimize pain during serial blood collection, we compared the retroorbital plexus (RP) and facial vein (FV) blood collection methods performed by both experienced and novice groups. The experienced and novice groups collected up to 0.4 mL of blood via the RP and FV methods every second day for 2 weeks. After blood collection, all mice were evaluated by corticosterone concentrations for stress, hematological, immunological, and histological analyses. RESULTS: We found that the FV methods reduced the collection time, pain, distress, tissue damage and lasting harms without anesthesia. Corticosterone concentrations in the peripheral blood were decreased in mice subjected FV methods compare with those subjected to RP methods. The proportion of granulocytes and monocytes, such as macrophages in the peripheral blood and spleen, was decreased in mice subjected to FV methods compared with that in mice subjected to RP methods in both experienced and novice groups. White blood cells were infiltrated in RP areas with severe tissue damage and inflammation. CONCLUSIONS: With respect to animal ethics, we suggest that the FV method, a simple and fast technique that can easily be performed by both experienced and novice researchers, is suitable for serial blood collection.

Electrochemiluminescence-Incorporated Lateral Flow Immunosensors Using Ru(bpy)32+-Labeled Gold Nanoparticles for the Full-Range Detection of Physiological C-Reactive Protein Levels.

C-reactive protein (CRP) is used as a general biomarker for inflammation and infection. During stroke and myocardial infarction, CRP increases and is present in a broad concentration range of 1-500 µg/mL. Therefore, full-range CRP detection is crucial to identify patients who need close follow-up or intensive treatment after a heart attack. Here, we report the first attempt to develop an electrochemiluminescent lateral flow immunosensor (ECL-LFI) that allows full-range CRP detection. Ru(bpy)32+-labeled gold nanoparticles (AuNPs) are used as a CRP-targeting probe and a signal generator; they form sandwich immunocomplexes at the test line of the strip and generate strong ECL emission via a Ru(bpy)32+/tripropylamine system. The ECL-LFI shows high sensitivity in detecting CRP in spiked serum, with a limit of detection of 4.6 pg/mL within 15 min, and a broad detection range of 0.01-1000 ng/mL, which is 2 orders of magnitude broader than that of conventional colorimetric LFI. The clinical usability of the ECL-LFI was evaluated using 30 clinical serum samples (200 ng/mL to 5 mg/mL), which showed a good linear correlation (R2 = 0.9896), with a clinical chemistry analyzer. The results suggest that the ECL-LFI holds great potential for CRP detection in point-of-care diagnostics.

Patterns of medical care utilization according to environmental factors in asthma and chronic obstructive pulmonary disease patients.

BACKGROUND/AIMS: Weather and air pollution are associated with the exacerbation of respiratory diseases. We investigated patterns of medical care use according to meteorological factors and air pollution in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: We analyzed the medical care utilization patterns of patients with asthma or COPD registered in the Korea Health Insurance Review and Assessment database for the period 2007 to 2013. The patterns were divided into hospitalization and emergency department (ED) use. RESULTS: The medical care use of patients with asthma or COPD increased when the mean temperature and relative humidity were lower, and the temperature difference and atmospheric pressure were greater. Medical care use increased with the concentrations of particulate matter and ozone. Among age groups, sensitivity to pollutants was greatest in patients aged ≥ 65 years. The effect of being elderly was greater for asthma than for COPD, with a higher hospitalization rate. ED utilization affected by environmental factors was significantly greater for females and hospitalization was significantly more common for males. CONCLUSION: Meteorological factors and air pollutants were shown to contribute to increased medical care utilization by patients with asthma and COPD, particularly elderly patients. The overall effect was greater for COPD, but the effect in elderly patients was greater for asthma. In addition, the patterns of change in medical care use due to environmental factors differed according to sex.