Risk factors for asthma-related healthcare use: longitudinal analysis using the NHI claims database in a Korean asthma cohort Lee T, Kim J, Kim S, Kim K, Park Y, Kim Y, Lee YS, Kwon HS, Kim SH, Chang YS, Cho YS, Jang AS, Park JW, Nahm DH, Yoon HJ, Cho SH, Cho YJ, Choi BW, Moon HB, Kim TB; COREA study group PLoS One

link : https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112844 Abstract Background: Though insurance claims data are useful for researching asthma, they have important limitations, such as a diagnostic inaccuracy and a lack of clinical information. To overcome these drawbacks, we used the novel method by merging the clinical data from our asthma cohort with the National Health Insurance (NHI) claims data. Methods and results: Longitudinal analysis of asthma-related healthcare use from the NHI claims database, merged with data of 736 patients registered in a Korean asthma cohort, was conducted for three consecutive years from registration of the cohort. Asthma-related asthma healthcare referred to outpatient and emergency department visits, hospitalizations, and the use of systemic corticosteroids. Univariate and multivariate logistic regression analysis was used to evaluate risk factors for asthma-related healthcare. Over three years after enrollment, many patients changed from tertiary to primary/secondary hospitals with a lack of maintenance of inhaled corticosteroid-based controllers. An independent risk factor for emergency visits was a previous history of asthma exacerbation. In hospitalizations, old age and Asthma Control Test (ACT) score variability were independent risk factors. An independent risk factor for per person cumulative duration of systemic corticosteroids was the FEV1 (Forced expiratory volume in one second)%. The use of systemic corticosteroids was independently associated with being female, the FEV1%, and ACT score variability. Conclusion: We found that old age, being female, long-standing asthma, a low FEV1%, asthma brittleness, asthma drug compliance, and a history of asthma exacerbation were independent risk factors for increased asthma-related healthcare use in Korea.

High Prevalence of Asthma in Elderly Women: Findings From a Korean National Health Database and Adult Asthma Cohort Park SY, Kim JH, Kim HJ, Seo B, Kwon OY, Chang HS, Kwon HS, Kim TB, Kim H, Park CS, Moon HB, Cho YS Allergy Asthma Immunol Res

link : https://e-aair.org/DOIx.php?id=10.4168/aair.2018.10.4.387 Abstract Purpose: The prevalence and burden of asthma is increasing worldwide. In this study, we analyzed 3 different Korean national health survey datasets to determine the general features of adult asthma in Korea and to obtain basic information that would support future strategies for better management of adult asthma. Methods: The surveys used in this study included the Korea National Health and Nutrition Examination Survey (KNHANES), Korea Community Health Survey (KCHS) and National Health Insurance Service-National Sample Cohort (NHIS-NSC). We investigated annual asthma prevalence, evaluating the rate and risk factors of asthma exacerbation by age and sex, and clinical data of 1,832 patients with asthma who were registered in the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) were analyzed to elucidate risk factors for asthma exacerbation. We also analyzed another asthma cohort and added it as replication data. Results: In the KNHANES database, annual asthma prevalence rates varied from 1.2% to 3.1%. In the KCHS database, overall prevalence increased, with significant regional differences (1.6%-2.1%). The NHIS-NSC indicated a gradual increase in annual asthma prevalence from 4.5% to 6.2%. Interestingly, all 3 surveys indicated the highest prevalence of asthma among elderly women. In addition, elderly women with asthma had a significantly higher risk of asthma exacerbation (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.19-2.93; P=0.006). Approximately 11% of patients were classified as having severe asthma. An asthma cohort analysis identified female sex, low baseline pulmonary function, longer treatment duration, high variability in pulmonary function and significant changes in Asthma Control Test scores as risk factors for asthma exacerbation. Conclusions: The prevalence of asthma in Korea is consistently high among elderly and female populations. These results should lay the foundation for strategies for effective asthma prevention and management; elderly female patients with asthma should receive particular attention.

High ACT score is not sufficient to reduce the risk of asthma exacerbations in asthma with low lung function Kwon JW, Jung H, Kim SH, Chang YS, Cho YS, Nahm DH, Jang AS, Park JW, Yoon HJ, Cho SH, Cho YJ, Choi BW, Moon HB, Kim TB; COREA investigators Respir Med

link : https://www.resmedjournal.com/article/S0954-6111(19)30046-0/fulltext Abstract Background: Low forced expiratory volume in 1 s (FEV1) is a risk factor for asthma exacerbations (AEs). We aimed to determine if asthma control could reduce the future risk of AEs in patients with low FEV1. This study was conducted to evaluate the future risks of AEs within six months according to Asthma Control Test™ (ACT) score and FEV1. Methods: A total of 565 patients with asthma were enrolled from the COREA cohort. The ACT score, lung function test, and number of AEs were assessed at baseline, three-month follow-up, and six-month follow-up with conventional asthma treatments by asthma specialists in real clinical settings. Results: Female sex, low ACT score, low FEV1, low FVC, and AE history in the previous three months were related with increased AEs within six months. AEs during six-month follow-up occurred in 24% of patients with ACT <20 and FEV1 < 60% at baseline. Among patients with an ACT score ≥20, 3.4% of patients with an FEV1 < 2.16 L and 9.8% of patients with FEV1 ≥ 2.16 L had experienced AEs (P = 0.01), although no differences were observed in the presence of AEs within six months according to the predicted FEV1 (FEV1 ≥ 60% vs. FEV1 < 60%, 5.66% vs. 8.51%, P = 0.65). Conclusion: Patient with low FEV1 seemed to show higher risk of AEs than those with near-normal FEV1 despite ACT score ≥20 and asthma treatments. Therefore, treatment strategies that prevent AEs are needed in high-risk asthmatic patients.

Longitudinal analysis to better characterize Asthma-COPD overlap syndrome: Findings from an adult asthma cohort in Korea (COREA) Park SY, Jung H, Kim JH, Seo B, Kwon OY, Choi S, Oh B, Kwon HS, Cho YS, Moon HB, Won S, Park T, Kim TB Clin Exp Allergy

link : https://onlinelibrary.wiley.com/doi/10.1111/cea.13339 Abstract Background: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), which has received much attention, has not been unanimously defined. Objective: In this study, we tried to demonstrate that longitudinally defined ACOS is more useful in the real world than blending patients with asthma and COPD. Methods: The study patients had undergone two consecutive pulmonary function tests measured at least 3 months apart (n = 1889). We selected the patients who had positive bronchodilator response or methacholine provocation tests (n = 959). Next, we defined ACOS as a patient with a persistent airflow obstruction [forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7] that was identified twice consecutively by an interval of at least 3 months (n = 228). Results: The proportions of patients who were older, male and smokers were significantly higher, and baseline lung function was lower in patients with ACOS. In the longitudinal analysis, the mean change in lung function was high, and a greater decline in FEV1 was observed in patients with ACOS. In addition, we compared ACOS and severe asthma, and we also performed a cluster analysis and compared the results with our definition of ACOS. According to our definition, ACOS is an independent subtype with distinctive characteristics. Finally, a genome-wide association study (GWAS) was performed to identify genetic variations associated with ACOS, but no significant single nucleotide polymorphisms were identified. Conclusion: Our findings suggest that ACOS should be defined longitudinally and considered as an independent subgroup distinguished by inherited environmental factors rather than as a genetically distinct independent group.

Novel Trajectories for Identifying Asthma Phenotypes: A Longitudinal Study in Korean Asthma Cohort, COREA Park SY, Jung HW, Lee JM, Shin B, Kim HJ, Kim MH, Song WJ, Kwon HS, Jung JW, Kim SH, Park HW, Jang AS, Chang YS, Cho YS, Cho YJ, Cho SH, Choi BW, Won S, Park T, Moon HB, Kim C, Kim TB; COREA investigators J Allergy Clin Immunol Pract

link : https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S221321981930176X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221321981930176X%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F Abstract Background: Unbiased cluster analysis has identified several asthma phenotypes. However, these phenotypes did not consistently predict disease prognosis and reflect temporal variability in airway inflammation. Objective: We aimed to identify longitudinal trajectories in terms of pulmonary function parameters and investigated whether the trajectories are associated with prognosis. Methods: Data were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). Three-year pulmonary function test results were used to apply finite mixture models for group-based trajectory in 486 patients with eligible data set. Results: Two main sets of longitudinal trajectories were identified in terms of FEV1% predicted, and FEV1 variability. In the 4 trajectories determined with FEV1% predicted, the pulmonary function showed a consistent course in 4 stratified levels during 3 years of follow-up, which was associated with unexpected hospital visits and the use of steroid bursts due to exacerbation. The variability in pulmonary function showed 3 different patterns, and we found that higher blood and sputum eosinophil levels were associated with the higher variability in pulmonary function and more exacerbations. Conclusions: Trajectory analysis is a novel method that provides longitudinal asthma phenotypes and aids in prediction of future risk of exacerbation. Further analysis is needed to validate the usefulness of these trajectories in an independent population.

High ACT score is not sufficient to reduce the risk of asthma exacerbations in asthma with low lung function Kwon JW, Jung H, Kim SH, Chang YS, Cho YS, Nahm DH, Jang AS, Park JW, Yoon HJ, Cho SH, Cho YJ, Choi BW, Moon HB, Kim TB; COREA investigators Respir Med

link : https://www.sciencedirect.com/science/article/pii/S0954611119300460?via%3Dihub Abstract Background: Low forced expiratory volume in 1 s (FEV1) is a risk factor for asthma exacerbations (AEs). We aimed to determine if asthma control could reduce the future risk of AEs in patients with low FEV1. This study was conducted to evaluate the future risks of AEs within six months according to Asthma Control Test™ (ACT) score and FEV1. Methods: A total of 565 patients with asthma were enrolled from the COREA cohort. The ACT score, lung function test, and number of AEs were assessed at baseline, three-month follow-up, and six-month follow-up with conventional asthma treatments by asthma specialists in real clinical settings. Results: Female sex, low ACT score, low FEV1, low FVC, and AE history in the previous three months were related with increased AEs within six months. AEs during six-month follow-up occurred in 24% of patients with ACT <20 and FEV1 < 60% at baseline. Among patients with an ACT score ≥20, 3.4% of patients with an FEV1 < 2.16 L and 9.8% of patients with FEV1 ≥ 2.16 L had experienced AEs (P = 0.01), although no differences were observed in the presence of AEs within six months according to the predicted FEV1 (FEV1 ≥ 60% vs. FEV1 < 60%, 5.66% vs. 8.51%, P = 0.65). Conclusion: Patient with low FEV1 seemed to show higher risk of AEs than those with near-normal FEV1 despite ACT score ≥20 and asthma treatments. Therefore, treatment strategies that prevent AEs are needed in high-risk asthmatic patients.

Relationship between age and bronchodilator response at diagnosis in adult-onset asthma Tommola M, Won HK, Ilmarinen P, Jung H, Tuomisto LE, Lehtimäki L, Niemelä O, Kim TB, Kankaanranta H Respir Res

link : https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-020-01441-w Abstract Background: Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like reversibility in asthma-COPD overlap (ACO). Methods: A total of 1030 patients with adult-onset asthma were included; 245 from SAAS (Seinäjoki Adult Asthma Study, Finland) and 785 from COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) cohorts. BDR in FEV1 at the diagnosis of asthma was assessed. Patients were divided into groups based on age at asthma diagnosis: < 40, 40-59.9, and ≥ 60 years. The cohorts were analyzed separately. Results: BDR % in FEV1 did not differ between the groups of different age at asthma diagnosis and no correlation between BDR and age was found. Of patients aged ≥40 years, only 18% (SAAS-cohort) and 5% (COREA-cohort) reached the 400 mL BDR in FEV1. After exclusion of possible ACO patients, the results remained similar. Conclusion: By using two large cohorts of steroid-naive patients with asthma, we have shown that BDR at diagnosis of asthma is constant over large age span range, and the limit of 400 mL in BDR in FEV1 is rarely reached.

Association between obesity and lung function changes by sex and age in adults with asthma Kim M, Cho SH, Jung JW, Choi BW, Kim SH, Park HK, Jang AS, Jin HJ, Shin YS, Kim MH, Lee JH, Park JW, Kwon JW, Lee T, Kim S, Kim TB, Choi JH; COREA investigators J Asthma

link: https://www.tandfonline.com/doi/abs/10.1080/02770903.2020.1839904?journalCode=ijas20 Abstract Objective: The lung function changes presenting before and after asthma treatment in obese people remain largely unknown. This study aimed to investigate the association between obesity and lung function changes before and after treatment in adults with asthma. Methods: We enrolled 937 newly diagnosed asthma patients from Cohort for Reality and Evolution of Adult Asthma in Korea cohort in 2015-2017, who performed follow-up spirometry after three months of asthma treatment. The percentage changes (Δ) between the spirometry results before and after treatment were calculated. Patients were categorized into four body mass index (BMI) groups; underweight (<18.5), normal (18.5-22.9), overweight (23.0-24.9), and obese (≥25.0). Association between percent change of pulmonary function and BMI was analyzed according to sex and/or age (< 45 yrs, 45-65 yrs, ≥ 65 yrs), which were statistically corrected for age, sex, smoking status, and medication history. Results: There was no consistent correlation between BMI and each lung function parameter. However, there were significant differences between BMI and ΔFEV1/FVC before and after 3 months of controller treatment. The obese asthmatics showed significantly lower ΔFEV1/FVC (6.0 ± 13.5%) than the underweight (12.6 ± 21.4%, P = 0.044) or normal weight (9.1 ± 14.6%, P = 0.031). Middle-aged women had higher BMI (24.11 ± 3.60 vs. 22.39 ± 3.52) and lower ΔFEV1/FVC (5.7 ± 11.9% vs. 8.9 ± 14.3%, P = 0.012) than young women. Conclusions: Obesity is negatively correlated with the ΔFEV1/FVC before and after controller treatment. Sex and age differentially contribute to lung function changes in response to asthma medications in adult asthmatics, showing a significant decrease in the ΔFEV1/FVC in middle-aged women.

A Randomized, Noninferiority Trial Comparing ICS + LABA with ICS + LABA + LAMA in Asthma-COPD Overlap (ACO) Treatment: The ACO Treatment with Optimal Medications (ATOMIC) Study Park SY, Kim S, Kim JH, Kim SH, Lee T, Yoon SY, Kim MH, Moon JY, Yang MS, Jung JW, Kim JH, Choi JH, Park CS, Kim S, Lee J, Kwon JW, Hur GY, Kim SH, Kim HK, Shin YS, Kim SH, Nam YH, Jang AS, Park SY, Kim TB; Cohort for Reality and Evolution of Adult Asthma J Allergy Clin Immunol Pract

link : https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S221321982031120X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221321982031120X%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F Abstract Background: Current guidelines for the treatment of asthma and chronic obstructive pulmonary disease overlap (ACO) recommend initial treatment using inhaled corticosteroids (ICSs) plus 1 or more bronchodilators. Objective: To clarify which therapeutic effect is better between the ICS + long-acting β2 agonist (LABA) and ICS + LABA + long-acting muscarinic antagonist (LAMA) treatment in patients with ACO. Methods: We conducted a multicenter, 48-week, randomized, noninferiority trial. Patients with ACO were enrolled if they were treated with a moderate to high dose of ICS + LABA. In total, 303 patients were involved in the present trial, with 149 receiving ICS + LABA + LAMA. The primary end point was the time to first exacerbation. Secondary outcomes included changes in FEV1, forced vital capacity, FEV1/forced vital capacity ratio, asthma control, blood eosinophil count, and fractional exhaled nitric oxide. Results: In the ICS + LABA treatment group, 29 of 154 patients (18.83%) experienced exacerbation, whereas 28 of 149 patients (18.79%) experienced exacerbation in the ICS + LABA + LAMA treatment group. The results of this noninferiority study were ultimately inconclusive (hazard ratio, 1.1; 95% CI, 0.66-1.84). However, the patients treated with the addition of LAMA showed significant improvements in FEV1 and forced vital capacity (P < .001). Asthma control did not improve in either group. Conclusions: Although this study was unable to conclude that ICS + LABA treatment is not inferior to ICS + LABA + LAMA in terms of exacerbation, it is obvious that the ICS + LABA + LAMA treatment group had improved lung function in ACO.

Pragmatic Randomized Controlled Trial for Stepping Down Asthma Controller Treatment in Patients Controlled with Low-Dose Inhaled Corticosteroid and Long-Acting β2-Agonist: Step-Down of Intervention and Grade in Moderate Asthma Study Kim SH, Lee T, Jang AS, Park CS, Jung JW, Kim MH, Kwon JW, Moon JY, Yang MS, Lee J, Choi JH, Shin YS, Kim HK, Kim S, Kim JH, Lee SY, Nam YH, Kim SH, Kim TB; Cohort for Reality and Evolution of Adult Asthma (COREA) Study Group J Allergy Clin Immunol Pract

link : https://linkinghub.elsevier.com/retrieve/pii/S2213219821005043 Abstract Background: Current asthma guidelines recommend stepping down controller treatment when the condition is well-controlled for a certain time. However, the optimal step-down strategy for well-controlled patients receiving a low-dose inhaled corticosteroid (ICS) with a long-acting β2-agonist (LABA) remains unclear. Objective: This study was a randomized, open-label, three-arm, parallel pragmatic trial comparing two kinds of step-down approaches for maintaining treatment. Methods: Adults with asthma who were aged 18 years or older, and who had been stable with low-dose ICS/LABA for at least 3 months, were enrolled. Subjects (n = 225) were randomly allocated into one of three groups (maintaining low-dose ICS/LABA [G1], discontinuing LABA [G2], and reducing ICS/LABA to once daily [G3]), and were observed for 6 months. The primary end point was a change in Asthma Control Test (ACT) scores between randomization and the final 6-month follow-up. Results: The change in ACT was analyzed in the per-protocol population; noninferiority was not demonstrated in either step-down group compared with the maintenance group (95% confidence interval of the difference, G2 vs G1 = -1.40-0.55; G3 vs G1 = -1.19-0.77). Although over 90% of patients were fine, higher rates of treatment failure were observed in step-down groups (G1: 0%; G2: 9.46%; and G3: 9.09%; P = .027). There were no significant differences between step-down approaches in terms of ACT change or treatment failure. Conclusions: Both step-down methods were not noninferior to maintenance of treatment. Step-down therapy can be attempted when patients are stable, but appropriate monitoring and supervision are necessary with precautions regarding loss of disease control.

Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort Lee JH, An J, Won HK, Seo B, Kim JH, Park SY, Kim MH, Shin YS, Jung JW, Song WJ, Lee T, Kwon HS, Lee JH, Kim JH, Kim SH, Chang YS, Cho YS, Nahm DH, Jang AS, Park JW, Yoon HJ, Cho SH, Cho YJ, Choi BW, Moon HB, Kim TB; COREA Investigators Respiration

link : https://karger.com/res/article-abstract/101/5/465/829165/Clusters-of-Severe-Eosinophilic-Asthma-in-a-Korean?redirectedFrom=fulltext Abstract Background: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. Objectives: We aimed to describe the characteristics of SEA and identify its patient subgroups. Methods: Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. Results: Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status. Conclusions: Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.

Different Impacts of Blood and Sputum Eosinophil Counts on Lung Function and Clinical Outcomes in Asthma: Findings from the COREA Cohort Pham DD, Lee JH, Kim JY, An J, Song WJ, Kwon HS, Cho YS, Kim TB lung

link : https://link.springer.com/article/10.1007/s00408-022-00583-6 Abstract 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.