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.

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.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

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: 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.

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.

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.

Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once-daily in COPD patients in Korea. Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once-daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted postbronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV1 at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment. Results: Of the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV1 versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, –0.81), and rescue medication use (Δ, –0.09 puffs/day). Both treatments were well tolerated by patients. Conclusion A direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is regarded as a potential biomarker for identifying eosinophilic inflammation. We aimed to evaluate the clinical implication of FeNO and its influence on inhaled corticosteroids (ICS) prescription rate in Korean chronic obstructive pulmonary disease (COPD) patients. METHODS: FeNO level and its association with clinical features were analyzed. Changes in the prescription rate of ICS before and after FeNO measurement were identified. RESULTS: A total of 160 COPD patients were divided into increased (≥25 parts per billion [ppb], n=74) and normal (<25 ppb, n=86) FeNO groups according to the recommendations from the American Thoracic Society. Compared with the normal FeNO group, the adjusted odds ratio for having history of asthma without wheezing and with wheezing in the increased FeNO group were 2.96 (95% confidence interval [CI], 1.40–6.29) and 4.24 (95% CI, 1.37–13.08), respectively. Only 21 out of 74 patients (28.4%) with increased FeNO prescribed ICS-containing inhaler and 18 of 86 patients (20.9%) with normal FeNO were given ICS-containing inhaler. Previous exacerbation, asthma, and wheezing were the major factors to maintain ICS at normal FeNO level and not to initiate ICS at increased FeNO level. CONCLUSION Increased FeNO was associated with the history of asthma irrespective of wheezing. However, FeNO seemed to play a subsidiary role in the use of ICS-containing inhalers in real-world clinics, which was determined with prior exacerbation and clinical features suggesting Th2 inflammation.