Montelukast treatment response according to eosinophil-derived neurotoxin level in children with allergic rhinitis.

Eosinophil-derived neurotoxin (EDN) is an important biomarker of eosinophilic inflammation. This study evaluated Montelukast treatment response according to EDN concentration in children with perennial allergic rhinitis (PAR). Fifty-two children with PAR were recruited and took a combination of Montelukast (5mg) and Levocetirizine (5mg) "Mont/Levo Group" or only Montelukast (5mg) "Mont Group" for 4 weeks. All caregivers were instructed to record rhinitis symptoms for 4 weeks. EDN was measured before and after treatment. Daytime nasal symptom scores (DNSS) significantly decreased in both the Mont/Levo (P = 0.0001; n = 20) and Mont Group (P < 0.0001; n = 20), but there were no significant differences between the two groups. EDN concentration also significantly decreased after treatment in both groups (P < 0.0001 and P < 0.001, respectively). For secondary analysis, children with a high initial EDN concentration (EDN ≥ 53 ng/mL) were placed in the "High EDN Group", while those with a lower initial EDN concentration (EDN < 53 ng/mL) were put in the "Low EDN Group". Both groups experienced significant reductions in DNSS after either treatment regimen (P < 0.0001 and P = 0.0027, respectively) but the High EDN Group had greater reductions. EDN concentrations in the High EDN Group decreased significantly from either treatment (P < 0.0001). We found that children with AR and a high serum EDN concentration may respond well to Montelukast treatment. A therapeutic strategy using EDN concentrations in patients with AR to evaluate therapeutic response may help improve quality of care.

Biomarkers in allergen immunotherapy: Focus on eosinophilic inflammation.

Asthma and allergic rhinitis (AR) are 2 of the most common chronic inflammatory disorders and they appear to be on the rise. Current pharmacotherapy effectively controls symptoms but does not alter the underlying pathophysiology. Allergen immunotherapy (AIT) is an evidence-based therapy for asthma and AR and has been recognized as the only therapeutic method that actually modifies the allergic disease process. There is a lack of objective markers that accurately and reliably reflect the therapeutic benefits of AIT. A biomarker indicating patients that would benefit most from AIT would be invaluable. Eosinophilic inflammation is a cardinal feature of many allergic diseases. Biomarkers that accurately reflect this inflammation are needed to better diagnose, treat, and monitor patients with allergic disorders. This review examines the current literature regarding AIT's effects on eosinophilic inflammation and biomarkers that may be used to determine the extent of these effects.

Natural history of eosinophil­derived neurotoxin levels and the onset of allergic airway disease in preschool children.

'Atopic march' is the progression of allergic conditions through infancy and childhood. The present study investigated the association between blood eosinophil-derived neurotoxin (EDN) levels in preschool children with food allergy (FA) or atopic dermatitis (AD) and the onset of allergic airway disease [bronchial asthma (BA), allergic rhinitis (AR)]. A total of 123 children below the age of 1 year were enrolled in the present study, along with controls (n=37). Blood specimens were taken, serum EDN levels were measured and immunoglobulin E was quantified. Finally, a total of 86 subjects were analyzed. EDN values were measured at 3 time-points: before 1 year of age, before 2 years of age and before 3 years of age. The EDN levels were initially similar between those patients who did and those who did not develop allergic airway disease but then markedly diverged at the 2-year time-point (226.6 vs. 65.0 ng/ml; P<0.01) and remained divergent at the 3-year time-point (173.9 vs. 62.7 ng/ml; P<0.01). EDN levels prior to diagnosis were compared between the two groups and they were much higher in the Onset group (n=10) compared to the Non-onset group (n=67) (171.2±34.28 vs. 81.3±10.02 ng/ml; P=0.003), with 4 cases of BA and 6 cases of AR in the Onset group. After diagnosis, EDN levels were compared twice: i) At 1 and 2 years of age; and ii) 1 and 3 years of age. A significant difference was found only in the comparison at 2 years (P=0.001). In conclusion, young children with elevated EDN levels during the FA/AD disease period were more likely to develop allergic airway disease (BA, AR) in their first three years of life. A factor leading to this progression may be increased eosinophil activity.

Eosinophil granule proteins as a biomarker in managing asthma and allergies.

In the past few decades, biomarkers have been successfully used for the diagnosis, treatment, and monitoring of disease. Taking together clinical, genetic, lifestyle, and information on relevant biomarkers, the therapy of diseases can be personalized to an individual. Several novel biomarkers have been recently reported for allergic diseases. However, to interpret the validity of biomarker data, the validation of their reliability, precision, and reproducibility is imperative. Once validated, they can be used in therapeutic product development and in clinical practice. Eosinophils are multifunctional leukocytes and major effector cells that play a crucial role in the immunological mechanisms of allergic disease. Measuring eosinophils has been the gold standard for treating and monitoring eosinophil-related diseases such as asthma, atopic dermatitis, and allergic rhinitis. However, eosinophil numbers/percentages yield little information about eosinophil activity. Eosinophil activation leads to the extracellular release of 4 granule proteins, with the most promising biomarker of the 4 being eosinophil-derived neurotoxin (EDN). EDN is more easily recovered from measuring instruments and cell surfaces than other eosinophil biomarkers because of its weaker electrical charge. EDN is known to be released from eosinophils at a greater efficiency, adding to its recoverability. It also has antiviral activity in respiratory infections associated with allergic disease development in early life (eg, respiratory syncytial virus and human rhinovirus infections in early childhood). EDN can be measured in several body fluids, including blood, urine, sputum, nasal secretions, and bronchoalveolar lavage. EDN is a stable biomarker utilized to precisely diagnose, treat, and monitor many eosinophil-related allergic diseases. This eosinophil granule protein may prove useful in precision medicine approaches and should always be considered as a useful tool for the clinician to give the best patient care possible.

Clinical characteristics of pediatric patients infected with SARS-CoV-2 versus common human coronaviruses: a national multicenter study.

BACKGROUND: Human coronaviruses (HCoV) cause mild upper respiratory infections; however, in 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, causing an acute respiratory disease pandemic. Coronaviruses exhibit marked epidemiological and clinical differences. PURPOSE: This study compared the clinical, laboratory, and radiographic findings of children infected with SARS-CoV-2 versus HCoV. METHODS: SARS-CoV-2 data were obtained from the Korea Disease Control and Prevention Agency (KDCA) registry and 4 dedicated coronavirus disease 2019 (COVID-19) hospitals. Medical records of children admitted with a single HCoV infection from January 2015 to March 2020 were collected from 10 secondary/tertiary hospitals. Clinical data included age, sex, underlying disease, symptoms, test results, imaging findings, treatment, and length of hospital stay. RESULTS: We compared the clinical characteristics of children infected with HCoV (n=475) to those of children infected with SARS-CoV-2 (272 from KDCA, 218 from COVID-19 hospitals). HCoV patients were younger than KDCA patients (older than 9 years:3.6% vs. 75.7%; P<0.001) and patients at COVID-19 hospitals (2.0±2.9 vs 11.3±5.3; P<0.001). Patients with SARS-CoV-2 infection had a lower rate of fever (26.6% vs. 66.7%; P<0.001) and fewer respiratory symptoms than those with HCoV infection. Clinical severity, as determined by oxygen therapy and medication usage, was worse in children with HCoV infection. Children and adolescents with SARS-CoV-2 had less severe symptoms. CONCLUSION: Children and adolescents with COVID-19 had a milder clinical course and less severe disease than those with HCoV in terms of symptoms at admission, examination findings, and laboratory and radiology results.

Clinical Potential of Eosinophil-Derived Neurotoxin in Asthma Management.

The assessment and management of patients with asthma is challenging because of the complexity of the underlying inflammatory mechanisms and heterogeneity of their clinical presentation. Optimizing disease management requires therapy individualization that should rely on reliable biomarkers to unravel the phenotypes and endotypes of asthma. The secretory activity and turnover of eosinophils, as assessed by measuring eosinophil-derived proteins, may provide an accurate and complementary tool that mirrors the eosinophil activation status. Emerging evidence suggests that eosinophil-derived neurotoxin has considerable potential as a precision medicine biomarker. In this review, we explore the suitability of eosinophil-derived neurotoxin as a biomarker in asthma management, with particular emphasis on its clinical significance in the management of both pediatric and adult populations.

Increase in eosinophil-derived neurotoxin level in school children with allergic disease.

Background: Eosinophils are major effector cells of allergic disease and excellent markers of eosinophilic inflammation. Accurate and reliable biomarkers are helpful in the diagnosis, treatment, and control of allergic disease. Objective: This study aimed to investigate an alternate marker of eosinophilic inflammation, eosinophil-derived neurotoxin (EDN), in a number of allergic diseases. Methods: Three hundred ninety-six elementary school-age children with various allergic conditions were recruited for this study. Subgroups included food allergies (FAs), atopic dermatitis (AD), bronchial asthma (BA), and allergic rhinitis (AR). EDN levels in these groups were compared to those in 93 healthy controls (HC). Results: All subjects with allergic disease had elevated levels of serum EDN (median [interquartile range]: FA, 124.2 ng/mL [59.13-160.5 ng/mL]; AD, 110.8 ng/mL [57.52-167.9 ng/mL]; BA, 131.5 ng/mL [60.60-171.0 ng/mL]; AR, 91.32 ng/mL [46.16-145.0 ng/mL]) compared to HC (38.38 ng/mL [32.40-55.62 ng/mL]) (p < 0.0001). These elevated levels were consistent throughout the age range (6-12 years) of the healthy study subjects (p = 0.0679). EDN levels also correlated well with total immunoglobulin E (Rs = 0.5599, p < 0.0001). Looking at all individuals with an allergic disease, the area under the curve was 0.790. Conclusions: Direct measures of eosinophilic inflammation are needed for accurate diagnosis, treatment, and monitoring of allergic diseases. EDN may be a worthy biomarker of eosinophil activity and a useful screening tool for allergic diseases including FA, AD, BA, and AR.

Eosinophil-derived neurotoxin: An asthma exacerbation biomarker in children.

Background: Asthma is a heterogeneous disease, characterized by chronic airway inflammation. Asthma exacerbations (AE) are episodes characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing, or chest tightness with a decrease in lung function. There have been previous studies that examined the role of eosinophil-derived neurotoxin (EDN) in asthma, but there have been no studies of the role of EDN in children experiencing AE. Objective: In this study, we aimed to examine the association of EDN with lung function and prognosis in children admitted for severe AE. Methods: We enrolled 82 children who were admitted for severe AE at two different university hospitals in South Korea between January 2018 and December 2019. Blood tests, including white blood cell count, myeloperoxidase (MPO), total eosinophil count, EDN, C-reactive protein (CRP) level, and interleukin (IL) 4, IL-5, IL-10 values, and lung function were measured on admission and at discharge in each patient. Results: We observed significant decreases in the levels of MPO, EDN, CRP, and IL-4, with significant improvement in lung function after treatment. We then classified the subjects into two groups of different clinical phenotypes: eosinophilic asthma exacerbation (EAE) group and non-EAE group. EDN levels were higher and lung functions were lower in the EAE group. Also, we found that the EDN level was a significant biomarker useful for predicting the number of days for hospital stay. Conclusion: We found that EDN can act as a biomarker that reflects lung function, and that EDN could act as a prognostic biomarker, which demonstrated the complex role of EDN in children experiencing AE.

Clinical Characteristics of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Korean Children: A Multicenter Retrospective Study.

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Allergen Immunotherapy management during vaccinations: An international survey.

Vaccination against viral and bacterial pathogens represents a challenging issue in allergic subjects, mainly concerning patients undergoing allergen immunotherapy (AIT). For this reason, an international survey has been performed involving a panel of experts who responded to a series of questions, also concerning the COVID-19 impact on allergen immunotherapy and vaccinations. The results showed that co-administration of vaccines and AIT requires caution, mainly during the pandemic era. Moreover, the choice of AIT product should be oriented considering also the safety profile.

Efficacy of subcutaneous immunotherapy for patients with asthma and allergic rhinitis in Korea: effect on eosinophilic inflammation.

BACKGROUND: Atopic asthma (AA) and allergic rhinitis (AR) are often seen as comorbidities and specific immunotherapy (SIT) is considered evidence-based treatment for them both. OBJECTIVE: The purpose of this study was to evaluate the efficacy of multiallergen subcutaneous SIT (SCIT) in reducing nasal and sputum eosinophilia, symptom scores, and impaired lung function in Korean pediatric patients with AR and AA. METHODS: Children aged 6-15 years with a documented history of bronchial asthma and seasonal/perennial AR were recruited then randomly selected to 1 of 2 groups: "immunotherapy group" (inhaled corticosteroids [ICS] and short-acting beta2-agonist [SABA] + subcutaneous injection of standardized extracts of up to 4 allergens [n = 53]) or "drug only group" (ICS and SABA only [n = 19]). All data were collected retrospectively. RESULTS: Comparing the 2 treatment groups, the immunotherapy group showed a significantly (p = 0.006) greater reduction in nasal eosinophilia over the 3-year treatment period. Only the immunotherapy group exhibited a significant reduction in sputum eosinophilia over the 3-year treatment period (p = 0.003). Fifty-one point one percent of patients in the immunotherapy group showed significant improvement in the methacholine challenge test negative conversion rate compared to only 17.65% in the drug only group (p = 0.0168). There were significantly greater improvements in symptom scores in the immunotherapy group compared to the drug only group. For all allergens tested, only house dust mite reactivity changed significantly over the treatment period and only in the immunotherapy group (Dermatophagoides pteronyssinus [p < 0.0001] and Dermatophagoides farina [p = 0.035]). CONCLUSION: SCIT was associated with greater improvements in lung function and bronchial hyperresponsiveness and reductions in nasal and sputum eosinophilia and allergen reactivity. Changes in symptom scores were also much greater in patients receiving SCIT when compared to those who did not receive it. Korean children with AA and AR respond well to long-term multiallergen SCIT.

Changes in Type 2 Biomarkers After Anti-IL5 Treatment in Patients With Severe Eosinophilic Asthma.

Patients with severe eosinophilic asthma (SEA) suffer from frequent asthma exacerbations, where eosinophils are major effector cells in airway inflammation, and anti-interleukin (IL)-5 becomes an effective treatment modality to control eosinophilic inflammation of SEA. Fifteen patients with SEA who had been treated with anti-IL5 (reslizumab, 100 mg monthly intravenously) for 6 months at Ajou University Hospital (Suwon, Korea) were enrolled in this study. Clinical parameters, including total blood eosinophil count (TEC), FEV1%, fractional exhaled nitric oxide (FeNO) levels, and serum biomarkers such as eosinophil-derived neurotoxin (EDN), periostin (PON), and transforming growth factor-ß1 (TGF-ß1), were analyzed. EDN levels and TEC decreased significantly after 1 month of treatment (P < 0.05 for both), while no changes were noted in FeNO/PON/TGF-ß1 levels. FEV1% increased after 2 months of treatment (P < 0.05). A positive correlation was observed between TEC and EDN levels (r = 0.60, P = 0.02). Significant negative correlations were noted between age and TEC/EDN levels (r = -0.57, P = 0.02 and r = -0.56, P = 0.03, respectively). Baseline TEC was higher in the EDN-responder group (≥75% decrease) than in the non-responder group (P = 0.06) with a positive correlation between %reduction in EDN and TEC (r = 0.67, P = 0.01). The onset age was younger and asthma duration was longer in the FEV1%-non-responder group (<12% increase) than in the FEV1%-responder group (P = 0.07 and P = 0.007, respectively). In conclusion, changes in the serum EDN level may be a potential biomarker for monitoring eosinophilic inflammation after anti-IL5 treatment in SEA, which is affected by onset age and asthma duration.

Low immunoglobulin G4 subclass level is associated with recurrent wheezing in young children.

BACKGROUND: The most important infectious trigger of asthma is the virus and patients with immunoglobulin deficiencies are prone to recurrent respiratory infections. OBJECTIVE: We investigated the relationship between immunoglobulin G subclass and recurrent respiratory symptom exacerbation and explored possible therapeutic effects of intravenous immunoglobulin administration. METHODS: Twenty-eight infants less than 24 months old with 2 or more recurrent wheezing episodes (infantile wheezer group) and 29 asthmatic children aged 24 months to 15 years (bronchial asthma [B-asthma] group) visited our hospital from October 2010 to January 2018. Serum immunoglobulin G, A, M, E, G1, G2, G3, and G4 were measured in each group and compared. In both groups, serum immunoglobulin and symptoms were compared before and after intravenous immunoglobulin administration. RESULTS: The 2 study groups exhibited several statistically significant differences when comparing respiratory virus infection rate (p < 0.001), coinfection rate (p < 0.0001), most commonly found viral infection (human bocavirus vs. human rhinovirus), and immunoglobulin A (p < 0.001), E (p = 0.008), G2 (p < 0.001), and G4 (p = 0.011) levels. In the infantile wheezer group, there was an inverse correlation between immunoglobulin G4 levels and wheezing numbers (R = -0.5538, P = 0.0022). Both groups showed significant changes in immunoglobulin levels and respiratory symptom exacerbations (recurrent wheezing, shortness of breath, chest tightness, cough, and fever) over 1 year after intravenous immunoglobulin administration. CONCLUSION: There was an association between recurrent wheezing and specific immunoglobulin G deficiencies. We suggest that intravenous immunoglobulin therapy significantly elevates specific immunoglobulin G levels though it lasts only for short term and might be associated with decreased respiratory symptoms. Therefore, low IgG4 levels among infants with recurrent wheezing may be indicative for intravenous immunoglobulin therapy.

The role of alanine glyoxylate transaminase-2 (agxt2) in ß-alanine and carnosine metabolism of healthy mice and humans.

PURPOSE: Chronic ß-alanine supplementation leads to increased levels of muscle histidine-containing dipeptides. However, the majority of ingested ß-alanine is, most likely, degraded by two transaminases: GABA-T and AGXT2. In contrast to GABA-T, the in vivo role of AGXT2 with respect to ß-alanine metabolism is unknown. The purpose of the present work is to investigate if AGXT2 is functionally involved in ß-alanine homeostasis. METHODS: Muscle histidine-containing dipeptides levels were determined in AGXT2 overexpressing or knock-out mice and in human subjects with different rs37369 genotypes which is known to affect AGXT2 activity. Further, plasma ß-alanine kinetic was measured and urine was obtained from subjects with different rs37369 genotypes following ingestion of 1400 mg ß-alanine. RESULT: Overexpression of AGXT2 decreased circulating and muscle histidine-containing dipeptides (> 70% decrease; p < 0.05), while AGXT2 KO did not result in altered histidine-containing dipeptides levels. In both models, ß-alanine remained unaffected in the circulation and in muscle (p > 0.05). In humans, the results support the evidence that decreased AGXT2 activity is not associated with altered histidine-containing dipeptides levels (p > 0.05). Additionally, following an acute dose of ß-alanine, no differences in pharmacokinetic response were measured between subjects with different rs37369 genotypes (p > 0.05). Interestingly, urinary ß-alanine excretion was 103% higher in subjects associated with lower AGXT2 activity, compared to subjects associated with normal AGXT2 activity (p < 0.05). CONCLUSION: The data suggest that in vivo, ß-alanine is a substrate of AGXT2; however, its importance in the metabolism of ß-alanine and histidine-containing dipeptides seems small.

Serum Eosinophil-Derived Neurotoxin Better Reflect Asthma Control Status Than Blood Eosinophil Counts.

BACKGROUND: Although several biomarkers have been proposed for eosinophilic asthma, biomarkers for reflecting asthma control status remain controversial. Eosinophil-derived neurotoxin (EDN), a degranulated eosinophil protein, is an emerging biomarker in asthmatic patients. OBJECTIVE: This study analyzed serum EDN concentrations in asthmatics and compared its performance with that of blood eosinophil count as an indicator of asthma control status. METHODS: We enrolled 75 uncontrolled asthmatics, 56 controlled asthmatics, and 43 healthy controls from Asan Medical Center. Serum EDN levels (ng/mL) were measured using an enzyme-linked immunosorbent assay kit. The predictability of EDN for asthma control status was analyzed by univariate and multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was conducted to compare the performances of a serum EDN level and blood eosinophil count as indicators of uncontrolled asthma status. RESULTS: The mean serum EDN level in the uncontrolled asthma group was higher than that in the controlled asthma and healthy groups (103.2 ± 60.2 vs 60.8 ± 49.7 vs 49.6 ± 28.3 ng/mL, P < .001). Serum EDN level was the significant parameter related to asthma control status in univariate and multivariable analysis (both P < .001). Serum EDN levels correlated with blood eosinophil counts (r = 0.510, P < .001). However, in the ROC analysis, serum EDN level showed a significantly better performance for predicting uncontrolled asthma status (area under the curve, 0.726 vs 0.628, P = .024). CONCLUSIONS: Serum EDN levels significantly differed between patients with controlled and uncontrolled status in adult asthmatics. To our knowledge, this is the first study to identify EDN as a better indicator of asthma control status than blood eosinophil count.

Adaptive responses of histone modifications to resistance exercise in human skeletal muscle.

Exercise training causes epigenetic changes in skeletal muscle, although it is unclear how resistance exercise (RE) affects histone modifications. The present study was carried out to investigate the effects of acute RE and RE training on gene expression profiles and histone modifications in human skeletal muscle. Healthy male adults were assigned to acute RE (n = 9, age = 20.5±4.3yr, BMI = 28.0±6.8kg/m2) or RE training (n = 21, age = 23.7±2.5yr, BMI = 24.2±2.7kg/m2) groups. Biopsy samples were obtained from the vastus lateralis muscle before and three hours after a single bout of acute RE, or 3-days after 10 weeks of RE training. RNA sequencing analysis revealed that 153 genes with GO terms including muscle development, stress response, metabolism, cell death, and transcription factor were significantly up-regulated (+291% vs. pre-acute RE) upon acute RE. Expressions of these genes were also greater (+9.6% vs. pre-RE training, p<0.05) in RE trained subjects. Significant up-regulation of acetylated histone 3 (H3) (+235%) and H3 mono-methylated at lysine 4 (+290%) and tri-methylated at lysine 27 (+849%), whereas down-regulation of H3.3 variant (-39%) distributions relative to total H3 were observed at transcriptionally activated loci after acute RE compared to pre-acute RE levels. Interestingly, the distribution of acetylated H3 was found to be up-regulated as compared to the level of total H3 after RE training (+40%, p<0.05). These results indicate that a single bout of RE drastically alters both gene expressions and histone modifications in human skeletal muscle. It is also suggested that enhanced histone acetylation is closely related to up-regulation of gene expressions after RE training.

Prevalence of and associations between metabolic syndrome and the constitutions defined by Korean Eight Constitution Medicine.

Eight Constitution Medicine (ECM) is a Korean constitutional medicine system that classifies people into 8 types: Pulmotonia (PUL), Colonotonia (COL), Renotonia (REN), Vesicotonia (VES), Pancreotonia (PAN), Gastrotonia (GAS), Hepatonia (HEP), and Cholecystonia (CHO). Metabolic syndrome (MS) is a major public health problem worldwide. We assessed the prevalence of and associations between ECM and MS. Cross-sectional convenience sample of 245 adults was used at a medical check-up center in Seoul, South Korea, from 2010 to 2015. Adults were classified into 1 of 8 constitutions by an ECM specialist. MS was diagnosed on the basis of National Cholesterol Education Program Adult Treatment Panel III and Asian Pacific Criteria for abdominal obesity. We also computed the prevalence by percentage and calculated odds ratios (ORs) for MS among 6 constitutions with PUL as the reference.Among 245 adults, 20 (8.2%) were diagnosed with PUL, 43 (17.6%) with COL, 35(14.3%) with REN, 4 (1.6%) with VES, 71 (29.0%) with PAN, 0 (0.0%) with GAS, 54 (22.0%) with HEP, and 18 (7.3%) with CHO. The prevalence of MS in the constitutions was significantly different: CHO, 38.9%; HEP, 35.2%; PAN, 18.3%; COL, 11.6%; PUL, 5.0%; REN, 2.9% (P = .001). We observed higher ORs for HEP and CHO (OR = 13.03, 95% confidence interval [CI] = 1.61-105.70; and OR = 13.19, 95% CI = 1.39-125.46, respectively) than for the other constitutions.People with HEP and CHO constitutions could be at higher risk for MS. Therefore, ECM-based diagnosis may be useful for preventing and managing MS.