Eun Kyung Kim

Rosiglitazone attenuates hypoxia-induced pulmonary arterial hypertension in rats.

Background and objective:  Expression of peroxisome proliferator‐activated receptor gamma (PPARγ) is decreased in the lungs of patients with pulmonary hypertension, and PPARγ ligands have been associated with the release of vasoactive substances from vascular endothelial cells and prevention of vascular remodelling. We hypothesized that PPARγ may play a critical role in the development of pulmonary hypertension induced by chronic hypoxia.

Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype☆

RATIONALE Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disorder in which a number of different pathological processes lead to recognition of patient subgroups that may have individual characteristics and distinct responses to treatment. OBJECTIVES We tested the hypothesis that responses of lung function to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid might differ among patients with various COPD subtypes. METHODS We classified 165 COPD patients into four subtypes according to the severity of emphysema and airflow obstruction: emphysema-dominant, obstruction-dominant, mild-mixed, and severe-mixed. The emphysema-dominant subtype was defined by an emphysema index on computed tomography of more than 20% and FEV(1) more than 45% of the predicted value. The obstruction-dominant subtype had an emphysema index < or = 20% and FEV(1) < or = 45%, the mild-mixed subtype had an emphysema index < or = 20% and FEV(1) > 45%, and the severe-mixed subtype had an emphysema index > 20% and FEV(1) < or = 45%. Patients were recruited prospectively and treated with 3 months of combined inhalation of long-acting beta-agonist and corticosteroid. RESULTS After 3 months of combined inhalation of long-acting beta-agonist and corticosteroid, obstruction-dominant subtype patients showed a greater FEV(1) increase and more marked dyspnea improvement than did the emphysema-dominant subgroup. The mixed-subtype patients (both subgroups) also showed significant improvement in FEV(1) compared with the emphysema-dominant subgroup. Emphysema-dominant subtype patients showed no improvement in FEV(1) or dyspnea after the 3-month treatment period. CONCLUSION The responses to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid differed according to COPD subtype.

Smoking status-dependent association of the 27-bp repeat polymorphism in intron 4 of endothelial nitric oxide synthase gene with plasma nitric oxide concentrations.

BACKGROUND Both positive and negative associations between a rare allele of 27-bp repeat polymorphism (eNOS4b/a polymorphism) in intron 4 of endothelial nitric oxide synthase and plasma nitric oxide (NO) concentrations were previously reported. Although these conflicting results were suggested to be partly accounted for smoking status of subjects, no further studies have been accomplished. METHODS We analyzed eNOS4b/a polymorphism in a group of 393 healthy Korean subjects and measured their plasma nitrite and nitrate (NO(x)) concentrations. NO(x) concentrations were measured by the Griess method and the genotypes of eNOS4b/a polymorphism determined by the banding pattern on gel electrophoresis. RESULTS The frequency of eNOS4a allele in this study was 11.6%. The plasma NO(x) concentrations (in micromol/l) in subjects with eNOS4a allele was found to be significantly higher relative to those in eNOS4b allele (49.68 +/- 18.62 and 55.25 +/- 20.87, respectively, P < 0.05), which was valid only in smokers. Multiple regression analysis revealed that the most predictive contributing factor for plasma NO(x) concentrations was eNOS4a allele (P < 0.01), followed by smoking (P < 0.05), total cholesterol (P < 0.05), and triglycerides (P < 0.05). CONCLUSION Our data indicate that there is substantial effect of eNOS4b/a polymorphism on the variance of plasma NO(x) concentrations in Korean population and that this effect is dependent on smoking status.

Association between CRHR1 polymorphism and improved lung function in response to inhaled corticosteroid in patients with COPD

Background and objective:  Inhaled corticosteroids are used to treat COPD and asthma. An association between sequence variants in the corticotrophin‐releasing hormone receptor 1 (CRHR1) gene and improved lung function in asthmatics treated with inhaled corticosteroids was reported recently. This study investigated the association between the change in lung function in response to inhaled corticosteroids and single‐nucleotide CRHR1 polymorphisms in patients with COPD.

CT scanning-based phenotypes vary with ADRB2 polymorphisms in chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by varying degrees of involvement of airway and lung parenchyma. Although cigarette smoke is the major risk factor for COPD, the principal determining factors of involvement of the airway or lung parenchyma have not been clearly defined. Genetic variability in COPD patients might influence the varying degrees of involvement of airway and parenchyma. We therefore studied whether airway and parenchyma involvement might be associated with the ADRB2 genotype, which has been reported to be associated with COPD susceptibility and the bronchodilator response. METHODS One hundred and eleven COPD subjects, whose post-bronchodilator FEV(1)/FVC values were less than 0.7, and who had histories of smoking exceeding 10 pack-years, were prospectively recruited from pulmonology clinics of 11 hospitals in Seoul, Korea. The degrees of involvement of airway and parenchyma were evaluated by volumetric computed tomography (CT) scans. In-house software automatically calculated luminal areas, airway wall areas, percentages of wall areas in segmental bronchi, emphysema indices, and mean lung densities in the whole lung parenchyma. The ADRB2 genotypes at codon 16 were determined for all patients. RESULTS Gly16 was associated with lumen diameter, luminal area, and percentage of wall area in patients with COPD (p=0.02), whereas neither wall area nor wall thickness differed with ADRB2 genotype. Neither emphysema index nor mean lung density was associated with ADRB2 genotype. CONCLUSION Gly16 variant in ADRB2 gene was associated with airway wall phenotypes measured using CT scanning in COPD patients.

Response patterns to bronchodilator and quantitative computed tomography in chronic obstructive pulmonary disease

Background:  Patients with chronic obstructive pulmonary disease (COPD) show different spirometric response patterns to bronchodilator, such that some patients show improvement principally in expiratory flow (forced expiratory volume in 1 s; FEV1), whereas others respond by improvement of lung volume (forced vital capacity; FVC). The mechanisms of these different response patterns to bronchodilator remain unclear. We investigated the associations between bronchodilator responsiveness and quantitative computed tomography (CT) indices in patients with COPD.

The efficacy and safety of prone positioning in adults patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

BACKGROUND Prone positioning for acute respiratory distress syndrome (ARDS) has no impact on mortality despite significant improvements in oxygenation. However, a recent trial demonstrated reduced mortality rates in the prone position for severe ARDS. We evaluated effects of prone position duration and protective lung strategies on mortality rates in ARDS. METHODS We extensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) reporting on prone positioning during acute respiratory failure in adults for inclusion in our meta-analysis. RESULTS Eight trials met our inclusion criteria, Totals of 1,099 and 1,042 patients were randomized to the prone and supine ventilation positions. The mortality rates associated with the prone and supine positions were 41% and 47% [risk ratio (RR), 0.90; 95% confidence interval (CI), 0.82-0.98, P=0.02], but the heterogeneity was moderate (P=0.01, I(2)=61%). In a subgroup analysis, the mortality rates for lung protective ventilation (RR 0.73, 95% CI, 0.62-0.86, P=0.0002) and duration of prone positioning >12 h (RR 0.75, 95% CI, 0.65-0.87, P<0.0001) were reduced in the prone position. Prone positioning was not associated with an increased incidence of cardiac events (RR 1.01, 95% CI, 0.87-1.17) or ventilator associated pneumonia (RR 0.88, 95% CI, 0.71-1.09), but it was associated with an increased incidence of pressure sores (RR 1.23, 95% CI, 1.07-1.41) and endotracheal dislocation (RR 1.33, 95% CI, 1.02-1.74). CONCLUSIONS Prone positioning tends to reduce the mortality rates in ARDS patients, especially when used in conjunction with a lung protective strategy and longer prone position durations. Prone positioning for ARDS patients should be prioritized over other invasive procedures because related life-threatening complications are rare. However, further additional randomized controlled design to study are required for confirm benefit of prone position in ARDS.

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. Georges 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.

Predictors of Pulmonary Function Response to Treatment with Salmeterol/fluticasone in Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable. The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively. The prediction models for the FEV1, FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis. The prediction model for the FEV1 change after 3 months of treatment included wheezing history, pre-bronchodilator FEV1, post-bronchodilator FEV1 change and emphysema extent on CT (R = 0.578). The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV1 change (R = 0.401). Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD.

Association of Plasma Adipokines with Chronic Obstructive Pulmonary Disease Severity and Progression

RATIONALE Two adipokines, leptin and adiponectin, regulate metabolic and inflammatory systems reciprocally. The role of adiponectin in chronic obstructive pulmonary disease (COPD) has been studied. However, there are few data evaluating the relationship of plasma leptin with COPD severity or progression. OBJECTIVES The objective of this study was to evaluate the relationship of leptin, adiponectin, and the leptin/adiponectin ratio with COPD severity and progression according to COPD phenotypes. METHODS Plasma leptin and adiponectin levels were measured in 196 subjects with COPD selected from the Korean Obstructive Lung Disease cohort. Using a linear regression model and mixed linear regression, we determined the relationship of plasma leptin and adiponectin levels and the leptin/adiponectin ratio to COPD severity and progression over 3 years. MEASUREMENTS AND MAIN RESULTS The concentration of adiponectin in plasma positively correlated with percent emphysema on initial computed tomography (CT) (adjusted P = 0.022), whereas plasma leptin concentrations and the leptin/adiponectin ratio exhibited a significant inverse correlation with initial FEV1 (adjusted P = 0.013 for leptin and adjusted P = 0.041 for leptin/adiponectin ratio). Increased plasma leptin and leptin/adiponectin ratio were significantly associated with change in percent emphysema over 3 years (adjusted P = 0.037 for leptin and adjusted P = 0.029 for leptin/adiponectin ratio), whereas none of the adipokines demonstrated an association with FEV1 decline over the 3-year period. CONCLUSIONS Plasma adiponectin and leptin vary according to COPD phenotypes. Plasma leptin and the leptin/adiponectin ratio, but not adiponectin, were significantly associated with changes in CT-assessed emphysema, suggesting a potential role as a biomarker in emphysema progression in patients with COPD.