The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Current Situation of Home Oxygen Therapy for Chronic Obstructive Pulmonary Disease Patients in Korea.

BACKGROUND: Long-term oxygen therapy provides various benefits, including prolonged survival for severely hypoxic chronic obstructive pulmonary disease (COPD) patients. However, adequate management strategies for home oxygen therapy are not well established in Korea. This study aimed to explore the current situation of home oxygen therapy to provide basic data for developing a strategy for COPD patients on home oxygen therapy. METHODS: In this cross-sectional study, we enrolled COPD patients using home oxygen therapy for at least 1 month. Face-to-face interviews were conducted, guided by a structured questionnaire about home oxygen therapy. RESULTS: A total of 195 patients were enrolled. The mean age was 72.6 ± 9.7 years, and 76.4% of patients were men. The mean modified Medical Research Council, COPD Assessment Test, and EuroQol-5D index scores were 3.4 ± 0.8, 29.7 ± 6.8, and 0.35 ± 0.44, respectively. At rest, patients were prescribed oxygen for 12.5 ± 7.3 hr/day and used 12.9 ± 8.5 hr/day on average. During exercise, the mean duration of prescribed oxygen was 6.6 ± 4.3 hr/day, and the actual use was 1.1 ± 2.9 hr/day. A total of 25.6% of patients used ambulatory oxygen; with financial burden the main reason for nonuse. The mean number of hospitalizations and emergency room visits were 2.5 and 2.6, respectively. CONCLUSION: This study revealed low adherence to home oxygen therapy, poor health-related quality of life, frequent hospitalizations, and a high financial burden among COPD patients using home oxygen therapy. The study highlights the need for adequate strategies to improve the quality of home oxygen therapy.

Hyperuricemia Is Not Predictive of Long-Term Outcome in Patients with Stable Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although the association of hyperuricemia with an increased risk of mortality has been demonstrated in the context of acute exacerbation of chronic obstructive pulmonary disease (COPD), the long-term outcomes of hyperuricemia have not been studied in the case of stable COPD. METHODS: We retrospectively analyzed baseline data of 240 men with stable COPD enrolled in the Korea Obstructive Lung Disease cohort. We evaluated associations between serum uric acid levels and clinical parameters, risk factors for all-cause mortality, and acute exacerbation of COPD. RESULTS: The mean age of subjects was 66.4 ± 7.7 years, and the median follow-up time was 5.9 years. We identified no significant difference in terms of lung function or laboratory findings between patients with hyperuricemia and those without. Serum uric acid level was negatively associated with systemic inflammation indicated by neutrophil-lymphocyte ratio (r = -0.211, P = 0.001). Univariate Cox regression analysis revealed hyperuricemia to not be associated with an increased risk of all-cause mortality in men with stable COPD (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.250-1.370; P = 0.213). In the multivariate Cox regression model, hyperuricemia was not an independent predictor of acute exacerbation (HR, 1.383; 95% CI, 0.977-1.959; P = 0.068). CONCLUSION: Among men with stable COPD, hyperuricemia is not an independent predictor of all-cause mortality or future acute exacerbation of COPD. These results differ from those of previous studies on patients with acute exacerbation of COPD.

The Economic Effect of Early Management in Patients with Early Chronic Obstructive Pulmonary Disease: Results from a Population-Based Nationwide Survey.

PURPOSE: The economic effect of regular follow-up and early management in patients with early chronic obstructive pulmonary disease (COPD) has not yet been clarified. Therefore, this study aimed to estimate the economic effect of regular follow-up and early management in these patients. METHODS: Patients with early COPD were identified from the Korea National Health and Nutrition Examination Survey. We analyzed medical utilization and cost for 2 years without any missing data by using the Korean National Health Insurance data. Patients with routine healthcare maintenance were defined as, after diagnosis, those with regular visits to the hospital and receiving early management of COPD. RESULTS: Among 1204 patients with early COPD, the patients who were classified as the group with routine healthcare maintenance (69/146; 47.3%) and the group with intermittent healthcare user (79/1058; 7.5%) visited to hospital for the next 2 years. The patients with routine healthcare maintenance had lower cost of inpatient service and frequencies of emergency room (ER) visit and intensive care unit (ICU) admission than intermittent healthcare users (cost of inpatient service, $4595 vs. $4953 per person; ER visit, 7.2 vs. 11.5; ICU admission, 4.3 vs. 7.7). Even in patients with COPD and FEV1 ≥ 80, early intervention through follow-up reduced the cost of inpatient service because these patients could have had less severe acute exacerbations than intermittent healthcare users. CONCLUSION: Patients with early COPD, even those with FEV1 ≥ 80, need regular follow-up for early management and disease control as well as for reducing the socioeconomic burden of the disease.

Validation of Previous Spirometric Reference Equations and New Equations.

BACKGROUND: Pulmonary functions are interpreted using predicted values from reference equations that vary with ethnicity, gender, age, height, and weight. The universally used Choi's reference equations are not validated for Korean populations, and the purpose of this study was to validate them and develop new reference equations. METHODS: Subjects with normal spirometry and chest radiographs, no co-morbidities, and non-smokers, from the Korean National Health and National Examination Survey (KNHANES)-VI were enrolled (n = 117). Intraclass correlation coefficient (ICC) was assessed for reliability of reference equations. New reference equations were developed using linear regression analysis. Differences between observed and predicted values were assessed to compare the reference equations from Choi's, Global Lung Function Initiative 2012, KNHANES-IV, and newly developed equations. RESULTS: The ICC of Choi's reference equations was 0.854 (P < 0.001). The new reference equations for men were: forced vital capacity (FVC) (L) = - 4.38775 - 0.01184 × age + 0.05547 × height, forced expiratory volume - 1 second (FEV1) (L) = - 2.40147 - 0.02134 × age + 0.04103 × height; and for women: FVC (L) = - 3.09063 + 0.003904 × age + 0.038694 × height; FEV1 (L) = - 1.32933 - 0.00872 × age + 0.02762 × height. The differences between the predicted and observed means were largest in Choi's equations, but lowest in the new equations with highest goodness of fit. CONCLUSION: Because Choi's reference equations presented larger differences from the observed values, despite reliability, and the new reference equations showed better goodness of fit, we suggest the latter for Korean populations.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort.

BACKGROUND: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD. METHODS: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/µL. Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope. RESULTS: Among 239 patients, 47 were diagnosed with ACO (19.7%). During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting ß2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO. Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (- 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline. CONCLUSION: Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.

Urinary desmosine is associated with emphysema severity and frequent exacerbation in patients with COPD.

BACKGROUND AND OBJECTIVE: Matrix degradation is a key feature of chronic obstructive pulmonary disease (COPD). Desmosine and isodesmosine (desmosines) are excreted in urine following matrix degradation. The main purpose of this study was to investigate the association between computed tomography (CT) emphysema indices and urinary desmosines in patients with COPD. METHODS: A total of 152 subjects were selected from the Korean Obstructive Lung Disease cohort. Their urine samples were assayed for desmosines using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The cohort was divided into emphysema-dominant (n = 80) and non-emphysema dominant- (n = 72) groups according to the CT emphysema index. RESULTS: The level of urinary desmosines was significantly higher in the emphysema-dominant group. Significant differences were also observed between the two groups for body mass index and lung function. Multivariate analysis indicated that a high level of urinary desmosines was a significant independent predictor of emphysema (relative risk: 2.6; 95% CI: 1.11-6.09; P = 0.028). The percentage of frequent exacerbators was significantly higher in the high urinary desmosine group in the first year of follow-up (P = 0.041). The mean number of exacerbations was higher in the high urinary desmosine group, although this difference was not statistically significant (P = 0.067). The changes in emphysema index did not differ between the two urinary desmosine groups over 3 years of follow-up. CONCLUSION: This study indicates that the level of urinary desmosines measured by LC-MS/MS methods is associated with the CT emphysema index. Urinary desmosine can be a useful predictor in identifying frequent exacerbators.

Which bronchodilator reversibility criteria can predict severe acute exacerbation in chronic obstructive pulmonary disease patients?

BACKGROUND: It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients. METHODS: Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models. RESULTS: Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants. CONCLUSIONS: Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship.

Vitamin D Deficiency Is Associated with Rapid Decline in Exercise Capacity in Male Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Vitamin D is suggested to play a role in airway and systemic inflammation in chronic obstructive pulmonary disease (COPD). Low serum 25-hydroxyvitamin D (25-OHD) levels have been suggested to be associated with lower lung function and poorer exercise capacity in COPD. OBJECTIVES: The main purpose of this study was to investigate the effects of vitamin D deficiency on the change in exercise capacity in male COPD patients. METHODS: A total of 156 male subjects were selected from the Korean Obstructive Lung Disease cohort. Vitamin D deficiency was subdivided into three subgroups: mild, moderate, and severe deficiency groups. Rapid decline was defined as an annual rate of change in exercise capacity ≥17 m. Exercise capacity was assessed by 6-minute walk distance (6MWD). RESULTS: Significant differences were observed in the serum levels of 25-OHD, the number of patients with vitamin D sufficiency, and moderate-to-severe deficiency between rapid decliners (n = 40) and non-rapid decliners (n = 116). No differences were found between the groups for age, smoking status, lung function, and 6MWD. Multivariate analysis showed that vitamin D deficiency was independently related to rapid decline in exercise capacity (p = 0.028). A statistically significant difference was observed among the subgroups of vitamin D deficiency in terms of the change in exercise capacity (p < 0.001). The annual decline in exercise capacity was prominent in the severe deficiency group (23.1 m/year). CONCLUSION: This study shows that vitamin D deficiency is associated with rapid decline in exercise capacity in male patients with COPD.

The relationship between serum fatty-acid binding protein 4 level and lung function in Korean subjects with normal ventilatory function.

BACKGROUND: The aim of this study was to assess the association of lung function with serum fatty-acid binding protein 4 (FABP4) in apparently healthy Korean adults. METHODS: In 495 participants in a health screening program, Force Exploratory Volume (FEV) 1 and Forced Vital Capacity (FVC) were assessed with standard spirometry. Subjects with obstructive (n = 19) and restrictive (n = 45) lung function were excluded from the analysis. Serum FABP4 level was measured by enzyme-linked immunosorbent assay and transformed into Ln(FABP4). 431 subjects with normal ventilator function (72.4% men, mean age 41 years) were included in the final analysis. RESULTS: Mean Ln(FABP4) significantly decreased in subjects from 1(st) quartile to 4(th) quartile of FVC (p = 0.008). Ln(FABP4) did not show significant differences across the quartile groups of FEV1. The odds ratio (OR) of being in the lowest quartile of FVC was 2.704 in subject with 3(rd) tertile of Ln(FABP4) after full adjustment for confounding variables {95% confidence interval (CI) 1.397 ~ 5.357}. OR of being in the lowest quartile of FEV1 was 1.822 (95% CI 1.021 ~ 3.298) in subjects with 3(rd) tertile of Ln(FABP4) after adjustment of age and sex, which was attenuated after full adjustment for confounding variables. CONCLUSION: Increased FABP4 level showed increased risk for reduced lung function in subjects with normal ventilatory function.

The Prognostic Value of Residual Volume/Total Lung Capacity in Patients with Chronic Obstructive Pulmonary Disease.

The prognostic role of resting pulmonary hyperinflation as measured by residual volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease (COPD) remains poorly understood. Therefore, this study aimed to identify the factors related to resting pulmonary hyperinflation in COPD and to determine whether resting pulmonary hyperinflation is a prognostic factor in COPD. In total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort recruited from 16 hospitals were enrolled. Resting pulmonary hyperinflation was defined as RV/TLC ≥ 40%. Multivariate logistic regression analysis demonstrated that older age (P = 0.001), lower forced expiratory volume in 1 second (FEV1) (P < 0.001), higher St. George Respiratory Questionnaire (SGRQ) score (P = 0.019), and higher emphysema index (P = 0.010) were associated independently with resting hyperinflation. Multivariate Cox regression model that included age, gender, dyspnea scale, SGRQ, RV/TLC, and 6-min walking distance revealed that an older age (HR = 1.07, P = 0.027), a higher RV/TLC (HR = 1.04, P = 0.025), and a shorter 6-min walking distance (HR = 0.99, P < 0.001) were independent predictors of all-cause mortality. Our data showed that older age, higher emphysema index, higher SGRQ score, and lower FEV1 were associated independently with resting pulmonary hyperinflation in COPD. RV/TLC is an independent risk factor for all-cause mortality in COPD.

Three-month treatment response and exacerbation in chronic obstructive pulmonary disease.

The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.

Roles of Inflammatory Biomarkers in Exhaled Breath Condensates in Respiratory Clinical Fields.

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.

Necking Reduction at Low Temperature in Aspect Ratio Etching of SiO2 at CF4/H2/Ar Plasma.

This study investigated the effect of temperature on the aspect-ratio etching of SiO2 in CF4/H2/Ar plasma using patterned samples of a 200 nm trench in a low-temperature reactive-ion etching system. Lower temperatures resulted in higher etch rates and aspect ratios for SiO2. However, the plasma property was constant with the chuck temperature, indicated by the line intensity ratio from optical emission spectroscopy monitoring of the plasma. The variables obtained from the characterization of the etched profile for the 200 nm trench after etching were analyzed as a function of temperature. A reduction in the necking ratio affected the etch rate and aspect ratio of SiO2. The etching mechanism of the aspect ratio etching of SiO2 was discussed based on the results of the surface composition at necking via energy-dispersive X-ray spectroscopy with temperature. The results suggested that the neutral species reaching the etch front of SiO2 had a low sticking coefficient. The bowing ratio decreased with lowering temperature, indicating the presence of directional ions during etching. Therefore, a lower temperature for the aspect ratio etching of SiO2 could achieve a faster etch rate and a higher aspect ratio of SiO2 via the reduction of necking than higher temperatures.

Efficacy and safety of mixture of ivy leaf extract and coptidis rhizome in the treatment of acute bronchitis: multicenter, randomized, double-blinded, active-controlled, parallel, therapeutic confirmatory clinical trial.

BACKGROUND: Acute bronchitis is the most common respiratory disease. Mixture of Ivy Leaf Extract and Coptidis rhizome syrup has shown good treatment efficacy against chronic bronchitis and acute respiratory infections. This study aimed to evaluate the efficacy and safety of Mixture of Ivy Leaf Extract and Coptidis rhizome compared with those of Pelargonium sidoides extract, for the treatment of acute bronchitis. METHODS: We performed a multicenter, randomized, double-blind, active-controlled, parallel phase III study in 220 patients with acute bronchitis. The participants were offered either Mixture of Ivy Leaf Extract and Coptidis rhizome syrup (AGS) and placebo of P. sidoides tablet or placebo syrup and active tablet of P. sidoides (AGU) for 7 days. The primary endpoint was the change in the Bronchitis Severity Score (BSS) from the baseline visit (visit 2) to day 7 (visit 3). RESULTS: For the primary outcome, there was no significant difference in the change of total BSS between visits 2 and 3 (-4.10 ± 1.93 vs. -4.24 ± 1.85, p = 0.5125), and since the upper limit of the confidence interval (1.00) was smaller than the predetermined non-inferiority margin (1.17), it was confirmed that the AGS group was non-inferior to the AGU group. The changes in each symptom in the BSS between visits 2 and 3 also showed no significant differences. The overall improvement rate measured by the investigator (91.7 vs. 89.7%; p = 0.3506) and the satisfaction rate of the participants at visit 3 also showed no significant differences (97.2 vs. 94.4%; p = 0.4388). Regarding safety issues, adverse reactions were noted in both groups similarly, with no serious adverse events (4.55 vs. 3.64%, p > 0.999). CONCLUSION: Mixture of Ivy Leaf Extract and Coptidis rhizome syrup is as effective and safe as P. sidoides in controlling symptoms of acute bronchitis.

Pulmonary Rehabilitation Is Associated With Decreased Exacerbation and Mortality in Patients With COPD: A Nationwide Korean Study.

BACKGROUND: Poor uptake to pulmonary rehabilitation (PR) is still challenging around the world. There have been few nationwide studies investigating whether PR impacts patient outcomes in COPD. We investigated the change of annual PR implementation rate, medical costs, and COPD outcomes including exacerbation rates and mortality between 2015 and 2019. RESEARCH QUESTION: Does PR implementation improve outcomes in patients with COPD in terms of direct cost, exacerbation, and mortality? STUDY DESIGN AND METHODS: Data of patients with COPD extracted from a large Korean Health Insurance Review and Assessment service database (2015-2019) were analyzed to determine the trends of annual PR implementation rate and direct medical costs of PR. Comparison of COPD exacerbation rates between pre-PR and post-PR, and the time to first exacerbation and mortality rate according to PR implementation, were also assessed. RESULTS: Among all patients with COPD in South Korea, only 1.43% received PR. However, the annual PR implementation rate gradually increased from 0.03% to 1.4% during 4 years, especially after health insurance coverage commencement. The direct medical cost was significantly higher in the PR group than the non-PR group, but the costs in these groups showed decreasing and increasing trends, respectively. Both the incidence rate and frequency of moderate-to-severe and severe exacerbations were lower during the post-PR period compared with the pre-PR period. The time to the first moderate-to-severe and severe exacerbations was longer in the PR group than the non-PR group. Finally, PR implementation was associated with a significant decrease in mortality. INTERPRETATION: We concluded that health insurance coverage increases PR implementation rates. Moreover, PR contributes toward improving outcomes including reducing exacerbation and mortality in patients with COPD. However, despite the well-established benefits of PR, its implementation rate remains suboptimal.

CHRNA3 variant for lung cancer is associated with chronic obstructive pulmonary disease in Korea.

BACKGROUND: Genome-wide association studies have identified CHRNA3 as a lung cancer and chronic obstructive pulmonary disease (COPD) candidate gene in non-Hispanic Caucasian cohorts. However, there are differences in minor allele frequencies among ethnic groups, and limited data exists for Asian populations. OBJECTIVES: The aim of this case-control study was to determine whether there is an association between COPD and genetic variation in CHRNA3 in the Korean population. In addition, we investigated the association of CHRNA3 with intermediate disease phenotypes including emphysema and lung function in COPD subjects. METHODS: Two single-nucleotide polymorphisms (SNPs) in CHRNA3 (rs660652 and rs12910984) were genotyped in 219 COPD subjects registered in the Korean Obstructive Lung Disease cohort study and in 305 control subjects. Volumetric computed tomography was performed in all COPD subjects. Emphysema severity was measured quantitatively by determining the volume fraction of the lung below -950 Hounsfield units. Logistic regression analysis for case-control analysis and linear regression modeling for quantitative analysis were performed using SAS. RESULTS: This case-control analysis of 219 COPD patients and 305 control participants identified a significant association between an SNP of CHRNA3 (rs12910984) and COPD (p = 0.049). Analysis in COPD subjects revealed that genetic variations were not associated with FEV1. There was no association between SNPs and emphysema severity. However, both SNPs were significantly associated with DLCO. CONCLUSION: Genetic variations in CHRNA3 are associated with COPD in the Korean population.

Exertional desaturation as a predictor of rapid lung function decline in COPD.

BACKGROUND: To date, no clinical parameter has been associated with the decline in lung function other than emphysema severity in COPD. OBJECTIVES: The main purpose of this study was to explore whether the rate of lung function decline differs between COPD patients with and without exertional desaturation. METHODS: A total of 224 subjects were selected from the Korean Obstructive Lung Disease cohort. Exertional desaturation was assessed using the 6-min walk test (6MWT), and defined as a post-exercise oxygen saturation (SpO2) of < 90% or a ≥ 4% decrease. The cohort was divided into desaturator (n = 47) and non-desaturator (n = 177) groups. RESULTS: There was a significant difference between the desaturator and non-desaturator groups in terms of the change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) over a 3-year period of follow-up (p = 0.006). The mean rate of decline in FEV1 was greater in the desaturator group (33.8 ml/year) than in the non-desaturator group (11.6 ml/year). A statistically significant difference was also observed between the two groups in terms of the change in the St. George's Respiratory Questionnaire (SGRQ) total score over 3 years (p = 0.001). CONCLUSIONS: This study suggests, for the first time, that exertional desaturation may be a predictor of rapid decline in lung function in patients with COPD. The 6MWT may be a useful test to predict a rapid lung function decline in COPD.

Longitudinal lung volume changes in patients with chronic obstructive pulmonary disease.

BACKGROUND: The progression of lung hyperinflation in patients with chronic obstructive pulmonary disease (COPD) has not been studied in a long-term prospective cohort. We explored the longitudinal changes in lung volume compartments with the aim of identifying predictors of a rapid decline of the inspiratory capacity to total lung capacity ratio (IC/TLC). METHODS: The study population comprised 324 patients with COPD who were recruited prospectively. Annual rates of changes in pulmonary function, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), vital capacity (VC), IC, and IC/TLC, were estimated using the random coefficient models. RESULTS: The mean annual rates of changes in pre- and post-bronchodilator FEV1 were -23.0 mL/year (p < 0.001) and -26.5 mL/year (p = 0.004). The mean annual rates of changes in VC, IC, TLC, and IC/TLC were -33.7 mL/year (p = 0.007), -53.9 mL/year (p < 0.001), -43.7 mL/year (p = 0.012), and -0.65%/year (p = 0.001), respectively. RV, FRC, and RV/TLC did not change significantly during the study period. Multivariate logistic regression analysis showed that a high modified Medical Research Council (MMRC) dyspnea scale score, a high Charlson comorbidity index value, and low post-bronchodilator FEV1 were associated with rapid decline in IC/TLC. CONCLUSION: MMRC dyspnea scale, post-bronchodilator FEV1, and the Charlson comorbidity index at baseline were independent predictors of a rapid decline in IC/TLC.