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).

Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study.

BACKGROUND: Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients. OBJECTIVE: This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use. METHODS: Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines. RESULTS: In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients. CONCLUSION: These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma.

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.

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Different Impacts of Blood and Sputum Eosinophil Counts on Lung Function and Clinical Outcomes in Asthma: Findings from the COREA Cohort.

PURPOSE: Blood (EOS-B) and sputum (EOS-S) eosinophil counts may contribute differently to asthma pathogenesis. We compared the impact of the baseline EOS-B and EOS-S levels on lung function, asthma control, and exacerbation in Korean asthma patients. METHODS: Asthma patients with baseline EOS-B (n = 4257) and EOS-S (n = 1049) levels from a multicenter cohort (COREA) were included. Pulmonary function test (%FEV1 predicted), asthma control test (ACT), and asthma exacerbation incidence were followed-up every 3 months for one year. Linear mixed-effect models and survival analyses were used to examine the association between eosinophilic groups defined by EOS-B or EOS-S and outcomes. RESULTS: High eosinophilic groups were associated with a low baseline value and a high improvement in the %FEV1 predicted and ACT scores over time. The magnitude of group difference in %FEV1 predicted was twofold higher in the EOS-S versus EOS-B classification [mean and 95% CI: 4.7 (0.6-8.8) versus 2.0 (0.2-3.7) for the baseline value and - 1.5 (- 2.3 to - 0.8) versus - 0.8(- 1.1 to -0.4) for the slope of change], whereas it was identical in ACT score. The magnitude of the impact increased linearly with the elevation of the cut-off level for the EOS-B but remained stable for the EOS-S classification. Patients with an elevation of both their EOS-B and EOS-S showed a higher increment in the %FEV1 predicted and ACT over time. Neither the EOS-B nor EOS-S was associated with asthma exacerbation. CONCLUSION: EOS-S and EOS-B contribute differently to the clinical outcomes and should be taken into account independently to improve asthma care.

Variability, Mean, and Baseline Values of Metabolic Parameters in Predicting Risk of Type 2 Diabetes.

CONTEXT: The effect of baseline (B) and alteration of metabolic parameters (MPs), including plasma glucose (PG) testing, insulin resistance surrogates, and lipid profile and their mutual interactions on the development of type 2 diabetes mellitus (T2DM), has not been investigated systematically. OBJECTIVE: To access the association of the past variability (V), past mean (M), and B values of various MPs and their mutual interaction with the risk of T2DM. METHODS: A community-based, longitudinal analysis was conducted using the Korean Genome and Epidemiology Study comprising 3829 nondiabetic participants with completed MPs measurements during 3 biannually visits who were followed over the next 10 years. Outcomes included the incidence of T2DM during follow-up. RESULTS: Among predictors, PG concentrations measured during the oral glucose tolerance test were the most prominent T2DM determinants, in which the M of the average value of fasting PG (FPG), 1-hour, and 2-hour PGs had the strongest discriminative power (hazard ratios and 95% CI for an increment of SD: 3.00 (2.5-3.26), AUC: 0.82). The M values of MPs were superior to their B and V values in predicting T2DM, especially among postload PGs. Various mutual interactions between indices and among MPs were found. The most consistent interactants were the M values of high-density lipoprotein cholesterol and the M and V values of FPG. The findings were similar in normal glucose tolerance participants and were confirmed by sensitivity analyses. CONCLUSION: Postload PG, past alteration of measurements, and mutual interactions among indices of MPs are important risk factors for T2DM development.

Understanding oriental medicine using a systems approach.

Two international meetings, the International Physiome Symposium 2008 and the Workshop on Systems Biology (SB) and Oriental Medicine (OM), were held to discuss the most appropriate scientific tools to research OM. Participants agreed that since OM is holistic medicine it needs a systems approach such as SB. However, SB itself is still a long way from identifying the high-level organization processes in the biological system that might correlate with concepts in OM. As such, a modest goal of launching a project to examine the problems of translation and interpretation of OM concepts would be the first step.

Comparison of sasang constitutional medicine, traditional chinese medicine and ayurveda.

Sasang constitutional medicine (SCM), traditional Chinese medicine (TCM) and Ayurveda are three different forms of Asian traditional medicine. Although these traditions share a lot in common as holistic medicines, the different philosophical foundations found in each confer distinguishing attributes and unique qualities. SCM is based on a constitution-based approach, and is in this way relatively more similar to the Ayurvedic tradition than to the TCM, although many of the basic SCM theories were originally derived from TCM, a syndrome-based medicine. SCM and TCM use the same botanical materials that are distributed mainly in the East Asian region, but the basic principles of usage and the underlying rationale are completely different from each other. Meanwhile, the principles of the Ayurvedic use of botanical resources are very similar to those seen in SCM, but the medicinal herbs used in Ayurveda generally originate from the West Asian region which displays a different spectrum of flora.

Body mass index and facial cues in sasang typology for young and elderly persons.

Facial characteristics may provide reliable information giving an insight into the inner nature of an individual. This study examines the differences in widely used facial metrics, including cheek-to-jaw width ratio (CJWR), width-to-height ratio (WHR), perimeter-to-area ratio (PAR), and facial masculinity indexes across Sasang constitutional types, to investigate the association between these facial cues and body mass index (BMI) and develop a predictive model for Sasang typing. 2D images of 911 participants were analyzed. The results indicated that TaeEum (TE) type generally has a squarer face, with the male TE type having a squarer and wider face than that of both SoYang (SY) and SoEum (SE) types. Male TE type has longer eyes than that of the SE type, and the lower face of the female TE type is longer than that of the SY type. PAR, WHR, CJWR, and eye size had associations with BMI, and the magnitude of correlation of CJWR in Korean men were twofold higher than that of the Caucasian and African men. BMI and facial metrics including PAR, WHR, CJWR, and eye size were good predictors for TE type, and the most parsimonious model for TE typing included BMI and CJWR with high predictive performances.

The mean of fasting, 1-h, and 2-h plasma glucose levels is superior to each separate index in predicting diabetes.

AIMS: The fasting, 1-h, and 2-h plasma glucose (PG) levels during oral glucose tolerance test represent different glucose metabolic functions. We examined whether averaging these PG indices (GLUM0.60.120) results in a better predictor of future type 2 diabetes (T2DM). METHODS: 7533 participants were followed up biannually for 12 years. Hazard ratios (HRs), area under the curve (AUC) of the receiver-operating characteristic, and the net reclassification index (NRI) for T2DM were calculated to compare the discriminative ability of GLUM0.60.120 versus other PG indices. RESULTS: The adjusted HRs and 95% confidence intervals for an increase in SD of GLUM0.60.120 was 2.50 (2.36-2.65) and 1.88 (1.73-2.04) in T2DM-free and normal glucose tolerance (NGT) participants, respectively. The AUC of GLUM0.60.120 was higher than that of fasting PG, 1-h, and 2-h PG values for T2DM-free (0.79 versus 0.67, 0.77, and 0.73) and NGT (0.73 versus 0.65, 0.72, and 0.61). The model using GLUM0.60.120 improved the classification of the models with fasting PG, 1-h, and 2-h PG values (NRI: 0.369, 0.272, and 0.282 for T2DM-free and 0.249, 0.131, and 0.351 for NGT participants with all p < 0.001). CONCLUSIONS: The mean of fasting, 1-h, and 2-h PG levels predicts future T2DM better than each index.

Seasonal effects on resting energy expenditure are dependent on age and percent body fat.

Seasonal variation in resting energy expenditure (REE) is still under debate. This study investigated seasonal changes in REE and relevant factors among Korean adults. A total of 867 healthy volunteers (385 men and 482 women) aged 20-69 years were divided into four seasonal groups and subgroups based on age, body mass index (BMI), and percent body fat (PBF) quartiles. REE, body composition, glucose metabolism, thyroid hormones, and catecholamines were measured. The seasonal factor contributed to REE independent of anthropometric indices, with additional variation decreasing from 6% to 2% among younger and older persons, respectively. The adjusted REE in the winter was 5.4-13.9%, 7.8-14.3%, and 8.6-11.9% higher than that in the summer in the age, BMI, and PBF subgroups, respectively. T3 and log-transformed norepinephrine (NElog) were higher, whereas log-transformed epinephrine (EPIlog) was lower in the winter compared to the summer. The magnitude of the winter-summer difference in REE and T3 and of the summer-winter difference in EPIlog were reduced three-fold between the lowest and highest intervals of age and PBF, whereas the difference in NElog was constant across all age and PBF intervals. There was no obvious change in seasonal differences in REE or its relevant biomarkers across BMI intervals. In summary, season is an independent predictor of REE and its effect is attenuated by the increment of age and PBF but not BMI.

Body weight difference between dual-energy X-ray absorptiometry and multi-frequency bioelectrical impedance analysis attenuates the equivalence of body-composition assessment.

BACKGROUND/OBJECTIVES: Low agreement of body-composition analysis (BCA) using dual-energy X-ray absorptiometry (DXA) and multi-frequency bioelectrical impedance analysis (MF-BIA) has been reported. We examined whether this discrepancy is influenced by the precision of body weight (BW) measurement using DXA. SUBJECTS/METHODS: This cross-sectional study enrolled 1353 participants aged 53-83 years. A whole-body DXA scan and an eight-polar tactile-electrode impedance-meter using four electronic frequencies of 5, 50, 250, and 500 kHz were employed for BCA. The level of agreement between BW estimated using DXA and actual BW (WgtA) was calculated. The agreement of BCA parameters using DXA and MF-BIA across WgtA groups was also assessed. RESULTS: DXA incorrectly estimated BW, especially in men. In total, 13.5%, 5.1%, and 5.6% of the participants had BW bias levels of 2%, 3%, and ≥4%, respectively. Correlations of BCA parameters measured using DXA and MF-BIA, including body fat mass, percent body fat, and lean body mass (LBM), were gradually reduced, whereas the root mean square error was increased in accordance with the reduction in WgtA. DXA provided a lower LBM amount compared to MF-BIA and this difference increased significantly across groups with poor WgtA. CONCLUSIONS: Lower WgtA greatly contributed to the difference in BCA measured using DXA and MF-BIA.

Koreans Do Not Have Higher Percent Body Fat than Australians: Implication for the Diagnosis of Obesity in Asians.

OBJECTIVE: It has been assumed that, for a given BMI, Asians have higher percent body fat (PBF) than Caucasians. As a result, it has been suggested that the BMI threshold for diagnosing obesity in Asians be lowered to less than 30 kg/m2 . This study sought to compare PBF between Koreans and Australians. METHODS: Whole-body fat mass and PBF were measured in 1,211 Koreans and 1,006 Australians using dual-energy x-ray absorptiometry (Lunar Prodigy; GE Healthcare, Madison, Wisconsin). The two groups were then matched for age and BMI by the propensity score method. RESULTS: For a given age and BMI, Koreans had lower PBF than Australians, and the difference was statistically significant in women (mean difference: -2.13%; 95% CI: -2.61% to -1.65%) but not in men (difference: -0.54%; 95% CI: -1.22% to 0.14%). Matched-pair analysis (423 pairs of women and 208 pairs of men) also showed that Korean women had statistically lower PBF than their Australian counterparts (P < 0.001). CONCLUSIONS: In individuals aged 60 years and older, Koreans do not have higher PBF than Australians after adjusting for BMI. These results suggest that there is no evidence for lowering the BMI threshold for the diagnosis of obesity in elderly Koreans.

Anthropometry-based estimation of body heat capacity in individuals aged 7-69 years: the Size Korea Survey 2010.

Although our previously developed anthropometry-based calculation of heat capacity (HC) for adults appeared to be precise and valid, its use in children and adolescents may be associated with bias. This study investigated a large dataset from the Size Korea survey, a national anthropometric survey conducted in 2010, to revalidate our previous HC equation and to develop another one that is appropriate for children and adolescents. We enrolled 12,766 participants aged 7-69 years with body composition data measured by multi-frequency bioelectrical impedance analysis. Age was associated with HC in children aged 7-19 years (R2 = 0.58) but not in adults (R2 = 0.007). Linear regression was appropriate to describe the relationship between HC and body surface area (BSA) in adults, whereas the regression in children and adolescent was quadratic. The previously developed HC equation had high reliability (intra-class correlation coefficient = 0.995) and predictive power (accurate prediction rate = 86.1%) in the >20 age group. The model composed of sex, body weight, BSA, and BSA2 was appropriate for the prediction of HC in young individuals aged 7-19 years. In conclusion, anthropometric-based modelling is a simple, reliable, and useful method for the calculation of HC.

Relationship of the Cold-Heat Sensation of the Limbs and Abdomen with Physiological Biomarkers.

The present study explored the relationship between the regional Cold-Heat sensation, the key indicator of the Cold-Heat patterns in traditional East Asian medicine (TEAM), and various biomarkers in Korean population. 734 apparently healthy volunteers aged 20 years and older were enrolled. Three scale self-report questions on the general thermal feel in hands, legs, and abdomen were examined. We found that 65% of women tended to perceive their body, particularly their hands and legs, to be cold, versus 25% of men. Energy expenditure and temperature load at resting state were lower in women, independently of body mass index (BMI). Those with warm hands and warm legs had a 0.74 and 0.52 kg/m2 higher BMI than those with cold hands and cold legs, respectively, regardless of age, gender, and body weight. Norepinephrine was higher, whereas the dynamic changes in glucose and insulin during an oral glucose tolerance test were lower in those with cold extremities, particularly hands. No consistent differences in biomarkers were found for the abdominal dimension. These results suggest that gender, BMI, the sympathetic nervous system, and glucose metabolism are potential determinants of the Cold-Heat sensation in the hands and legs, but not the abdomen.

Body temperature regulation: Sasang typology-based perspective.

Global warming induces a dramatic elevation of heat-related morbidity and mortality worldwide. Individual variation of heat stress vulnerability depends on various factors such as age, gender, living area and conditions, health status, and individual innate characteristics. Sasang typology is a unique form of Korean traditional medicine, which is based on the hypothesis that constitution-specific traits of an individual determine the particular distinctive tendency in various aspects, including responses to the external environment. Recent scientific evidence shows that Sasang types differ in body composition, metabolic profile, susceptibility to certain disease patterns, and perspiration. This review aims to interpret these findings under the context of heat balance consisting of heat production (Hprod), heat loss (Hloss), and heat load (Hload). Based on the published data, at a given body mass, the TaeEum type tended to have a lower Hprod at rest and at the exhaustion state, which may indicate the lower metabolic efficiency of this type. Meanwhile, the surface-to-mass ratio and heat capacity of the TaeEum type appear to be lower, implying a lower heat dissipation capacity and heat storage tolerance. Thus, because of these characteristics, the TaeEum type seems to be more vulnerable to heat stress than the other constitutions. Differences in temperature regulation across constitutional types should be taken into account in daily physical activity, health management, and medical research.

Thermoregulatory Responses to Graded Exercise Differ among Sasang Types.

We compared sweat rate and variables such as workload (W e ), metabolic heat production (H prod), and temperature increment load (T inc) across Sasang types. 304 apparently healthy participants aged 20-49 years with their Sasang type determined were enrolled. Local sweat rates on the chest (LSRchest) and back (LSRback) were measured using a perspiration meter during a maximum treadmill exercise test. Oxygen uptake was measured continuously using a breath-by-breath mode indirect calorimeter. The TaeEum (TE) type had a larger body size, a higher percent body fat, and a lower body area surface area (BSA) to body mass compared with the other Sasang types, particularly the SoEum (SE) type. The TE type tended to have a shorter exercise time to exhaustion and lower maximal oxygen uptake (mL·kg(-1)·min(-1)) than the other types. LSRchest in TE types was greater than that of the SE and SoYang (SY) types in men, whereas LSRback was higher in the TE type than that of the other types in women. After normalizing LSR for W e , H prod, T inc, and BSA, this tendency still remained. Our findings suggest that the thermoregulatory response to graded exercise may differ across Sasang types such that the TE type was the most susceptible to heat stress.

Novel Anthropometry-Based Calculation of the Body Heat Capacity in the Korean Population.

Heat capacity (HC) has an important role in the temperature regulation process, particularly in dealing with the heat load. The actual measurement of the body HC is complicated and is generally estimated by body-composition-specific data. This study compared the previously known HC estimating equations and sought how to define HC using simple anthropometric indices such as weight and body surface area (BSA) in the Korean population. Six hundred participants were randomly selected from a pool of 902 healthy volunteers aged 20 to 70 years for the training set. The remaining 302 participants were used for the test set. Body composition analysis using multi-frequency bioelectrical impedance analysis was used to access body components including body fat, water, protein, and mineral mass. Four different HCs were calculated and compared using a weight-based HC (HC_Eq1), two HCs estimated from fat and fat-free mass (HC_Eq2 and HC_Eq3), and an HC calculated from fat, protein, water, and mineral mass (HC_Eq4). HC_Eq1 generally produced a larger HC than the other HC equations and had a poorer correlation with the other HC equations. HC equations using body composition data were well-correlated to each other. If HC estimated with HC_Eq4 was regarded as a standard, interestingly, the BSA and weight independently contributed to the variation of HC. The model composed of weight, BSA, and gender was able to predict more than a 99% variation of HC_Eq4. Validation analysis on the test set showed a very high satisfactory level of the predictive model. In conclusion, our results suggest that gender, BSA, and weight are the independent factors for calculating HC. For the first time, a predictive equation based on anthropometry data was developed and this equation could be useful for estimating HC in the general Korean population without body-composition measurement.