Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study.

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

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.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

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.

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.

Maternal and paternal effects on hyperuricaemia: a cross-sectional study from the seventh Korean National Health and Nutrition Examination Survey.

OBJECTIVE: As the heritability of hyperuricaemia remains largely unexplained, we analysed the association between parental and offspring hyperuricaemia at the phenotype level. METHODS: This cross-sectional study included data on 2373 offspring and both-parent pairs from the seventh Korean National Health and Nutrition Examination Survey. Logistic regression and generalised estimating equation analysis were used to evaluate the association between offspring and parental hyperuricaemia adjusting for metabolic risk factors and alcohol intake. RESULTS: Both maternal and paternal hyperuricaemia were associated with offspring hyperuricaemia among teenagers, but from the age of 20 years, a strong association was observed between offspring and paternal, rather than, maternal hyperuricaemia, and this could not be explained by metabolic risk factors such as obesity. However, there was a positive interaction between offspring alcohol intake and parental hyperuricaemia, and there was a stronger association between terciles of offspring alcohol intake and hyperuricaemia in the presence of parental hyperuricaemia: T1 (reference), T2 odds ratio (OR) 1.1 (0.3-4.6), and T3 OR 3.3 (1.4-7.9) (P for trend .017) vs. T1 (reference), T2 OR 0.7 (0.3-1.9), and T3 OR 1.1 (0.6-2.2) (P for trend .974). CONCLUSION: These results suggest a gene-environment interaction, especially with respect to alcohol intake for hyperuricaemia in Korean adults.

Implementation of Asthma Management Guidelines and Possible Barriers in Korea.

BACKGROUND: There could be a gap between asthma management guidelines and current practice. We evaluated the awareness of and compliance with asthma management guidelines, and the internal and external barriers to compliance, for the first time in Korea. METHODS: From March to September of 2012, 364 physicians treating asthma patients at primary, secondary, and tertiary teaching hospitals were enrolled. They completed a questionnaire on the awareness of and compliance with asthma management guidelines, and the barriers and alternatives to their implementation. RESULTS: Of the 364 physicians, 79.1% were men and 56.9% were primary care physicians. The mean age was 40.5 ± 11.2 years. Most of them were aware of asthma management guidelines (89.3%). However, only a portion (11.0%) of them complied with the guidelines for asthma. Pulmonary function tests for diagnosis of asthma were performed by 20.1% of all physicians and 9.2% of primary care physicians, and by 9.9% of all physicians and 5.8% of primary care physicians for monitoring. Physicians stated that 'asthma monitoring' was the most difficult part of the guidelines, followed by 'environmental control and risk factors.' Only 39.6% (31.9% of the primary care physicians) prescribed an inhaled corticosteroid (ICS) as the first-line treatment for persistent asthma. The internal barriers were physician's preference for oral medications, difficulty in use even with inhaler training, and concern over ICS side effects. The external barriers were possible rejection of medical reimbursement by health insurance, refusal by the patient, cost, and a poor environment for teaching the patient how to use the inhaler. Alternatives proposed by physicians to implement asthma management guidelines were to improve medical reimbursement policies and the level of awareness of such guidelines. CONCLUSION: Compliance with the asthma management guidelines, including ICS prescription, is low despite the awareness of the guidelines. It is necessary to develop a strategy to overcome the internal and external barriers.

Pisidium coreanum Inhibits Multinucleated Osteoclast Formation and Prevents Estrogen-Deficient Osteoporosis.

Mollusks have served as important sources of human food and medicine for a long time. Raw Pisidium coreanum, a freshwater bivalve of the phylum Mollusca, is used in traditional therapies in parts of Asia. However, the therapeutic effects of Pisidium coreanum on bone diseases are not known. We investigated the functional roles of Pisidium coreanum in osteoporotic bone diseases. Pisidium coreanum inhibited the differentiation of bone marrow-derived monocytic cells into mature osteoclasts in vitro. The ovariectomized mice that received oral administration of Pisidium coreanum showed improvements in both trabecular and cortical bones. This preventive activity of Pisidium coreanum against bone loss was due to limited osteoclast maturation with reduced osteoclast surface extent in trabecular bone tissue. The formation of large multinucleated osteoclasts in vitro was significantly decreased in response to Pisidium coreanum, consistent with the reduced expression levels of osteoclast markers and fusion-related genes, such as NFATc1, p65, integrin αvß3, DC-STAMP, OC-STAMP, Atp6v0d2, FAK, CD44, and MFR. These data suggest that Pisidium coreanum inhibits osteoclast differentiation by negatively regulating the fusion of mononuclear osteoclast precursors. Thus, our data demonstrate the ability of Pisidium coreanum to effectively prevent estrogen-deficient osteoporosis through inhibition of multinucleated osteoclast formation.

Re-exposure to low osmolar iodinated contrast media in patients with prior moderate-to-severe hypersensitivity reactions: A multicentre retrospective cohort study.

OBJECTIVES: To evaluate the outcomes of re-exposure to low-osmolar iodinated contrast medium (LOCM) in patients with a history of moderate-to-severe hypersensitivity reaction (HSR). METHODS: We retrospectively evaluated a cohort comprising all subjects satisfying the following conditions at 11 centres: (1) experienced a moderate-to-severe HSR to LOCM by December 2014, and (2) underwent contrast-enhanced computed tomography after the initial HSR between January 2014 and December 2014. RESULTS: A total of 150 patients with 328 instances of re-exposure were included; the recurrence rate of HSR was 19.5%. Patients with severe initial HSR exhibited a higher recurrence rate of severe HSR compared to patients with moderate initial HSR, despite more intensive premedication. In the multivariate analysis, the independent risk factors for recurrence of HSR were diabetes, chronic urticaria, drug allergy other than to iodinated contrast media (ICM) and severe initial HSR. The risk of recurrent HSR was 67.1% lower in cases where the implicated ICM was changed to another one (odds ratio: 0.329; P = 0.001). However, steroid premedication did not show protective effects against recurrent HSR. CONCLUSION: In high-risk patients who have previously experienced a moderate-to-severe initial HSR to LOCM, we should consider changing the implicated ICM to reduce recurrence risk. KEY POINTS: • In patients with moderate-to-severe HSR, steroid premedication only shows limited effectiveness. • Changing the implicated ICM can reduce the recurrence of HSR to ICM. • Diabetes, chronic urticaria and drug allergies increase the risk of ICM HSR.

Blocking of the Ubiquitin-Proteasome System Prevents Inflammation-Induced Bone Loss by Accelerating M-CSF Receptor c-Fms Degradation in Osteoclast Differentiation.

Anti-osteoporotic activity of a blocker of the ubiquitin-proteasome system, bortezomib, has known to be achieved by directly opposed action in increased bone formation by osteoblasts and in decreased bone destruction by osteoclasts. However, the mechanisms underlying the proteasome blocker inhibition of osteoclast differentiation and function are not fully understood. Here, we observed that proteasome inhibitors, such as MG132 and bortezomib, in osteoclasts accelerated the degradation of c-Fms, a cognate receptor of macrophage colony-stimulating factor (M-CSF), and did not affect the amount of receptor activator of nuclear factor kappa-B (RANK), a receptor of receptor activator of nuclear factor kappa-B ligand (RANKL). c-Fms degradation induced by proteasome inhibitors was controlled by the activation of p38/tumor necrosis factor-alpha converting enzyme (TACE)-mediated regulated intramembrane proteolysis (RIPping). This was validated through the restoration of c-Fms using specific inhibitors of p38 and TACE, and a stimulation of p38-dependent TACE. In addition, c-Fms degradation by proteasome inhibition completely blocked M-CSF-mediated intrinsic signalling and led to the suppression of osteoclast differentiation and bone resorption. In a mouse model with intraperitoneal administration of lipopolysaccharide (LPS) that stimulates osteoclast formation and leads to bone loss, proteasome blockers prevented LPS-induced inflammatory bone resorption due to a decrease in the number of c-Fms-positive osteoclasts. Our study showed that accelerating c-Fms proteolysis by proteasome inhibitors may be a therapeutic option for inflammation-induced bone loss.

Urban-rural differences in the prevalence of allergen sensitization and self-reported rhinitis in the elderly population.

BACKGROUND: Urbanization is frequently associated with allergic conditions during childhood; however, the literature lacks studies on the association between allergies and degree of urbanization in the elderly population. OBJECTIVE: To determine how the degree of urbanization affects the prevalence of allergic sensitization and self-reported rhinitis symptoms in elderly community populations. METHODS: The study population consisted of 1,311 elderly subjects identified from 2 community population cohort datasets who were divided into 3 groups according to the degree of urbanization (urban, semirural, and rural) where they resided. Current rhinitis symptoms were assessed using a questionnaire. Sensitization to inhalant allergen was measured using skin prick tests for 9 common allergens. RESULTS: Sensitization to inhalant allergen showed a positive correlation with degree of urbanization (urban 17.2%, semirural 9.8%, rural 6.0%; P for trend <.001), with a significant correlation observed between house dust mite allergens and degree of urbanization. Self-reported rhinitis symptoms were mostly nonallergic, but showed a positive correlation with degree of urbanization (urban 26.8%, semirural 18.2%, rural 11.5%; P for trend <.001). Self-reported rhinoconjunctivitis also correlated with urbanization. Correlations between self-reported allergic conditions and urbanization remained statistically significant in multivariate logistic regression tests. CONCLUSION: The present analyses found significant correlations between degree of urbanization with self-reported rhinitis symptoms and sensitization to inhalant allergen in the elderly population. These findings warrant further investigation of the roles that urban factors play in the development of elderly rhinitis and allergen sensitization.

New scoring system for the differentiation of chronic obstructive pulmonary disease and asthma.

BACKGROUND AND OBJECTIVE: It remains difficult to differentiate between chronic obstructive pulmonary disease (COPD) and asthma in clinical practice, especially in a primary care setting. The purpose of this study was to develop a new scoring system for differentiating between COPD and asthma, and to evaluate its effectiveness. METHODS: First, to identify important variables differentiating COPD from asthma, the data of 197 patients with COPD and 138 patients with asthma were assessed retrospectively. Secondly, a scoring system that was based on these variables was then developed, and its performance was internally validated using a bootstrapping-based method. Thirdly, the scoring system was externally validated using prospectively collected data from patients with COPD (n = 104) or asthma (n = 96). RESULTS: The final scoring system was composed of the four variables: age of onset of breathlessness (<40 years, 0 points; 40-60 years, 2 points; >60 years, 4 points), continuous breathlessness (no, 0 points; yes, 1 point), diurnal variation of breathlessness (yes, 0 points; no, 1 point) and emphysematous change in chest X-ray (no, 0 points; yes, 1 point). The patients were classified by their total score into three categories: 0-2 points, probable asthma; 3-4 points, difficult-to-differentiate; 5-7 points, probable COPD. The new scoring system performed well in the external validation dataset (area under the curve, 0.86; 95% confidence interval: 0.813-0.911; P < 0.001). CONCLUSIONS: The new scoring system that was developed in this study may be a useful tool for differentiating between COPD and asthma in primary care.

Perception of Long-Term Oxygen Therapy for Chronic Lung Diseases May Affect Poor Adherence in Korea.

BACKGROUND: Long-term oxygen therapy (LTOT) improves the survival of patients with hypoxemia due to chronic respiratory diseases. The clinical outcomes of LTOT are strongly associated with patient adherence. To improve the adherence of patients, physicians have focused on the efficacy of LTOT. However, poor adherence may stem from patients' perceptions of LTOT. Herein we evaluated patients' perceptions of LTOT affecting adherence. METHODS: We conducted a cross-sectional survey study using descriptive, open, and closed-ended questionnaire. Patients using oxygen therapy (OT) or requiring it but avoiding OT responded to the questionnaires at three university hospitals. RESULTS: Seventy-nine patients responded to the questionnaires. The number of patients using home and portable OT was 69 (93%) and 37 (46.3%), respectively. Patients with good adherence were 22 (30.1%). Among patients with good adherence, 90.9% used oxygen according to physicians' prescriptions whereas only 37.3% of those with poor adherence followed physicians' prescriptions (p<0.01). The reasons for avoiding using home OT were fear of permanent use (50%), unwanted attention (40%), and lack of symptoms (40%). They avoided portable OT because of unwanted attention (39%), heaviness (31.7%), and lack of symptoms (21.6%). CONCLUSION: Patients on LTOT had the perception of the misunderstanding the effects of OT and of psychosocial barriers to initiate or use LTOT. Considering these findings, health professionals need to provide effective education on the purpose of LTOT to improve patient adherence to OT and provide sufficient support for the management of psychosocial barriers in patients using LTOT.

Obstructive sleep apnea is associated with reduced quality of life in adult patients with asthma.

BACKGROUND: Recent data suggest that obstructive sleep apnea (OSA) is an important contributor to severe uncontrolled asthma. OBJECTIVE: To investigate the clinical characteristics, asthma control, and asthma-related quality of life in adult patients with asthma at a high risk for OSA. METHODS: A total of 217 patients with asthma who visited our tertiary-care clinic were randomly recruited. They completed the Berlin questionnaire, which screens for OSA risk, a quality-of-life questionnaire for adult Korean patients with asthma (QLQAKA), and underwent an asthma control test (ACT). Fraction of exhaled nitric oxide (FeNO), lung function, blood lipid profiles, and body composition were evaluated. RESULTS: The mean age was 58.4 ± 15.4, and 91 (41.9%) were male. Eighty-nine subjects (41.0%) were classified as high risk for OSA from the Berlin questionnaire. Patients with a high OSA risk were significantly older, had a higher prevalence of hypertension, higher BMI, non-atopic predisposition, and longer asthma treatment duration in the baseline clinical characteristics. The high OSA risk group had a lower ACT score than the low OSA risk group, but it was not statistically significant (20.9 ± 3.6 vs 21.5 ± 3.3, P = .091). The QLQAKA score was significantly lower in the high OSA risk group compared with the low OSA risk group (64.4 ± 10.9 vs 68.1 ± 11.1, P = .026), especially in the activity-domain (P = .005). The FeNO was not significantly different between the 2 groups. CONCLUSION: Quality of life is significantly decreased in adult patients with asthma with a high risk of OSA. Special consideration is needed for the care and treatment of patients with asthma who have a high risk of OSA.

Rhinitis in a community elderly population: relationships with age, atopy, and asthma.

BACKGROUND: Rhinitis is one of the most frequent medical conditions. However, there is sparse epidemiologic evidence for rhinitis in the elderly population. OBJECTIVE: To investigate the prevalence of rhinitis in elderly adults and its relations to asthma and other comorbidities. METHODS: A cross-sectional analysis was performed using the baseline dataset of the Korean Longitudinal Study on Health and Aging, a community-based elderly population cohort in Korea (≥65 years old). Structured questionnaires were used to define rhinitis, asthma, and comorbidity, and allergen skin prick tests were used to define atopy. Health-related quality of life was assessed by short-form 36 questionnaires. RESULTS: In total, 982 elderly adults (98.2%) were included in the present study. The prevalence of rhinitis was 25.6% and did not decrease until 90 years of age. The prevalence of atopy was 17.2% (18.8% in participants with rhinitis), and atopy did not show a significant association with rhinitis. In multivariate logistic regression analyses, relations between asthma and rhinitis were significant. Among comorbid conditions, none were significantly associated with rhinitis. In the short-form 36 questionnaire analyses, rhinitis was independently related to a decrease in the physical aspects of quality of life. CONCLUSION: The present study found a high prevalence of nonallergic rhinitis in elderly participants, which was significantly related to asthma and quality of life.

Clinical value of radiocontrast media skin tests as a prescreening and diagnostic tool in hypersensitivity reactions.

BACKGROUND: Some radiocontrast media (RCM) hypersensitivity reactions may have underlying IgE- or T-cell-mediated mechanisms. RCM skin testing may be useful for predicting future reactions. OBJECTIVE: To investigate the clinical value of RCM skin testing before computed tomography and after RCM hypersensitivity reactions. METHODS: Patients who underwent RCM skin testing were a prospective sample of convenience at a single medical center and were tested just before their pending nonionic RCM-enhanced computed tomogram. In addition, skin test data of patients who were referred to the allergy clinic because of their previous RCM hypersensitivity reactions were reviewed retrospectively. RESULTS: A total of 1048 patients enrolled in the study prospectively. Of these, 672 (64.1%) had never been exposed to RCM. Of the 376 previously exposed to RCM, 61 (16.2%) had a history of at least one mild RCM-associated reaction, 56 (91.8%) had immediate reactions, and 5 had no-immediate reactions. There was only 1 positive immediate hypersensitivity RCM skin test result (0.09%). There were 51 mild immediate reactions (4.9%), 1 moderate immediate reaction (0.09%), 8 mild nonimmediate reactions (0.76%), and 1 moderate nonimmediate reaction (0.09%). There was only 1 positive delayed hypersensitivity skin test result (0.09%), retrospectively determined, in 1 (11.1%) of the nonimmediate RCM-associated reactions. Sensitivity of RCM skin testing was significantly higher with severe immediate reactions (57.1%) than mild reactions (12.9%) and moderate reactions (25.0%) in the retrospective review of diagnostic skin test data (P = .03). CONCLUSION: RCM skin testing for screening is of no clinical utility in predicting hypersensitivity reactions. RCM skin testing may have modest utility in retrospectively evaluating severe adverse reactions.

Association between knee osteoarthritis and mortality: a serial propensity score-matched cohort study.

BACKGROUND/AIMS: The association between symptomatic knee osteoarthritis (OA) and higher cardiovascular disease (CVD) mortality is established; however, findings from studies that utilized regression analysis were limited, attributed to the strong association between OA and metabolic risk factors. This study aimed to evaluate the association between knee OA and mortality through propensity score matching. METHODS: This was a cohort study including Korean National Health and Nutrition Examination Survey (2010-2013) participants aged ≥ 50 years. By linking the survey data to cause of death data (through 2019) from Statistics Korea, mortality and cause-specific mortality data were obtained. Radiographic knee OA (ROA) was defined as bilateral Kellgren-Lawrence grade ≥ 2. Propensity score matching (1:1) was conducted between asymptomatic ROA, knee pain, and symptomatic ROA groups and normal groups, balancing the confounding factors. Time to death was analyzed using Cox proportional hazard modeling. RESULTS: A higher CVD mortality was observed in the symptomatic ROA group, but not in others; the risk estimates were asymptomatic ROA (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.77-1.65), knee pain (HR 0.61; 95% CI 0.27-1.38), and symptomatic ROA (HR 1.39; 95% CI 0.89-2.17). No association was found between the all-cause/cancer mortality and other groups. CONCLUSION: When propensity score matching controls metabolic risk factor imbalances, the association between symptomatic knee OA and higher CVD mortality was weaker compared to results of prior studies that used regression adjustment. The results may be more precise estimates of the total risk of knee OA for mortality in Koreans.

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.

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.