Background: Exercise capacity is associated with lung function decline in chronicobstructive pulmonary disease (COPD) patients, but a discrepancy between exercisecapacity and airflow limitation exists. This study aimed to explore factors contributingto this discrepancy in COPD patients. Methods: Data for this prospective study were obtained from the Korean COPD SubgroupStudy. The exercise capacity and airflow limitation were assessed using the6-minute walk distance (6-MWD; m) and forced expiratory volume in 1 second (FEV1).Participants were divided into four groups: FEV1 >50%+6-MWD >350, FEV1 >50%+6-MWD ≤350, FEV1 ≤50%+6-MWD >350, and FEV1 ≤50%+6-MWD ≤350 and their clinicalcharacteristics were compared. Results: A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) wereenrolled. Among 591 patients with FEV1 >50%, 242 were in the 6-MWD ≤350 group, andamong 292 patients with FEV1 ≤50%, 185 were in the 6-MWD >350 group. The multipleregression analyses revealed that male sex (odds ratio [OR], 8.779; 95% confidence interval[CI], 1.539 to 50.087; p=0.014), current smoking status (OR, 0.355; 95% CI, 0.178to 0.709; p=0.003), and hemoglobin levels (OR, 1.332; 95% CI, 1.077 to 1.648; p=0.008)were significantly associated with discrepancies in exercise capacity and airflow limitationin patients with FEV1 >50%. Meanwhile, in patients with FEV1 ≤50%, diffusioncapacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantlyassociated with discrepancies between exercise capacity and airflow limitation. Conclusion The exercise capacity of COPD patients may be influenced by factors otherthan airflow limitation, so these aspects should be considered when assessing andtreating patients.

Background: Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. Methods: We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. Results: Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). Conclusion Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.

Background: Global Lung Function Initiative (GLI)-2012 reference equation is currently suggested for interpretation of spirometry results and a new local reference equation has been developed in South Korea. However, lung function profiles according to the different reference equations and their clinical relevance have not been identified in chronic obstructive pulmonary disease (COPD) patients. Methods: Our cross-sectional study evaluated Choi’s, Korean National Health and National Examination Survey (KNHANES)-VI, and GLI-2012 reference equations. We estimated the percentages of predictive forced expiratory volume in one second (FEV 1) and airflow limitation severity according to reference equations and analyzed their associations with patient reported outcomes (PROs): COPD assessment test (CAT) score, St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) score, and six minute walk distance (6MWD). Results: In the eligible 2,180 COPD patients, lower predicted values of FEV 1 and forced vital capacity (FVC) were found in GLI-2012 compared to Choi's and KNHANES-VI equations.GLI-2012 equation resulted in a lower proportion of patients being classified as FEV 1 < 80% or FVC < 80% compared to the other equations. However, the Z-scores of FEV 1 and FVC were similar between the KNHANES-VI and GLI-2012 equations. Three reference equations exhibited significant associations between FEV 1 (%) and patient-reported outcomes (CAT score, SGRQ-C score, and 6MWD). Conclusion GLI-2012 reference equation may not accurately reflect FEV 1 (%) in the Korean population, but the Z-score using GLI-2012 equation can be a viable option for assessing FEV 1 and airflow limitation in COPD patients. Similar to the other two equations, the GLI-2012 equation demonstrated significant associations with PROs.

Long-acting  2 -agonist (LABA)/long-acting muscarinic-antagonist (LAMA) dual therapy has been found to be more effective than LAMA monotherapy in the treatment of chronic obstructive pulmonary disease (COPD). However, among patients with group B or D COPD, the characteristics of patients for whom LABA/LAMA dual therapy is superior to LAMA monotherapy in minimizing acute exacerbations remain unknown.With data from a prospective COPD cohort, subgroup analyses were conducted to determine whether LABA/LAMA dual therapy was superior to LAMA monotherapy in reducing the rate of acute exacerbations in group B and D COPD patients. Group B and D COPD patients taking LAMA or LABA/LAMA were enrolled according to the 2022 Global initiative for Chronic Obstructive Pulmonary Disease guidelines. A total of 737 patients were included in this study: 600 with group B COPD and 137 with group D COPD. Compared with patients taking LAMA monotherapy, those taking LABA/ LAMA had a significantly lower incidence of acute exacerbations over 1 year. In the subgroup of patients ≥70 years old, there was a significantly lower risk of severe COPD exacerbations among group B patients taking LABA/LAMA than among those taking LAMA monotherapy (odds ratio [OR], 0.258; 95% confidence interval [CI], 0.095– 0.703). In contrast, in the subgroup of group D patients with COPD Assessment Test scores ≥25, compared with LAMA monotherapy, LABA/LAMA treatment was associated with lower risk of severe COPD exacerbations (OR, 0.115; 95% CI, 0.018-0.749).The combination of LABA and LAMA was found to be superior to LAMA monotherapy, especially for treating older adults with group B COPD, as well as for group D patients with severe symptoms.

Background/Aims: Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD. Methods: This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities. Results: A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease. Conclusion Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.

Background/Aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD).We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals.Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the noninferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Conclusions Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Background: Asthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. AsthmaCOPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype. Methods: Patients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and postbronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL). Results: The prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) – 9.1%; group B (light smoker with low BEC) – 3.7%; group C (moderate to heavy smoker with high BEC) – 73.8%; and group D (moderate to heavy smoker with low BEC) – 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups. Conclusion The prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Background/Aims: Functional dyspepsia is a disease involving a range of upper gastrointestinal symptoms derived from various pathophysiologies. Tablets containing a combination of rabeprazole and controlled-release (CR) mosapride were recently developed.To investigate a more effective treatment, this trial evaluated the efficacy and safety of UIC201609/UIC201610 as a preliminary study. Methods: A multicenter, double-blind, randomized study was performed on 30 subjects. UIC201609/UIC201610 (combination of rabeprazole and CR mosapride) was the case group, and the two control groups were rabeprazole 10 mg once a day and mosapride 15 mg CR tablet once a day. As a primary efficacy endpoint of the study, the changes in the total score of eight items of the Nepean Dyspepsia Index-Korean version were analyzed at 2 weeks and 4 weeks. The outcomes regarding safety were collected. Results: The total symptom score of Nepean Dyspepsia Index-Korean decreased in the rabeprazole single group (29.4±17.1), mosapride CR single group (33.4±15.6), and UIC201609/UIC201610 group (33.4±11.8) at 4 weeks without significant differences. On the other hand, the UIC201609/UIC201610 combination group showed more score reduction of pain in the upper abdomen, burning in the upper abdomen compared to each control group, but it did not reach statistical significance. No difference was found in safety analysis. Conclusions UIC201609/UIC201610 once daily showed some improvement in epigastric pain and dyspepsia in patients with functional dyspepsia, but there was no significance. Further study based on the advanced clinical trial design will be needed to confirm the efficacy of UIC201609/UIC201610 combination therapy in the future.

Background/Aims: Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than 0.7 using spirometry is the golden standard to diagnose airf low limitation of chronic obstructive pulmonary disease (COPD). Recently, measuring FEV6 has been suggested as an alternative to measure FVC. Studies about the cut-off value for FEV1/FEV6 to diagnose airflow limitation have shown variable results, with values between 0.7 and 0.8. The purpose of this study was to determine the best cut-off value of FEV1/FEV6 to detect airflow limitation using handheld spirometry. Methods: We recruited subjects over 40 years of age with smoking history over 10 pack-years. Participants underwent measurements with both handheld spirometry and conventional spirometry. We calculated the sensitivity and specificity of the value of FEV1/FEV6 using receiver-operating characteristic (ROC) curve analysis to obtain the diagnostic accuracy of handheld spirometry to detect airflow limitation. Results: A total of 290 subjects were enrolled. Their mean age and smoking amount were 63.1 years and 31.6 pack-years, respectively. According to our ROC curve analysis, when FEV1/FEV6 ratio was 73%, sensitivity and specificity were the maximum and the area under the ROC curve was 0.93, showing an excellent diagnostic accuracy. Sensitivity, specificity, positive predictive value, and negative predictive value were 86.7%, 89.7%, 88.0%, and 88.5%, respectively. Participants with FEV1/FEV6 ≤ 73% had lower FEV1 predicted value compared to those with FEV1/FEV6 > 73% (65.4% vs. 86.5%, p < 0.001). Conclusions In summary, we demonstrate that the value of 73% in FEV1/FEV6 using handheld spirometry has the best sensitivity and specificity to detect airflow limitation in subjects with risk of COPD.