Seong Yong Lim

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.

Development and Application of Multiprobe Real-Time PCR Method Targeting the hsp65 Gene for Differentiation of Mycobacterium Species from Isolates and Sputum Specimens

ABSTRACT We developed a multiprobe real-time PCR assay targeting hsp65 (HMPRT-PCR) to detect and identify mycobacterial isolates and isolates directly from sputum specimens. Primers and probes for HMPRT-PCR were designed on the basis of the hsp65 gene sequence, enabling the recognition of seven pathogenic mycobacteria, including Mycobacterium tuberculosis, M. avium, M. intracellulare, M. kansasii, M. abscessus, M. massiliense, and M. fortuitum. This technique was applied to 24 reference and 133 clinical isolates and differentiated between all strains with 100% sensitivity and specificity. Furthermore, this method was applied to sputum specimens from 117 consecutive smear-positive patients with smear results of from a trace to 3+. These results were then compared to those obtained using the rpoB PCR-restriction analysis method with samples from cultures of the same sputum specimens. The HMPRT-PCR method correctly identified the mycobacteria in 89 samples (76.0%, 89/117), and moreover, the sensitivity level was increased to 94.3% (50/53) for sputa with an acid-fast bacillus score equal to or greater than 2+. Our data suggest that this novel HMPRT-PCR method could be a promising approach for detecting pathogenic mycobacterial species from sputum samples and culture isolates routinely in a clinical setting.

Lung function, coronary artery calcification, and metabolic syndrome in 4905 Korean males

BACKGROUND Impaired lung function is an independent predictor of cardiovascular mortality. We assessed the relationships of lung function with insulin resistance (IR), metabolic syndrome (MetS), systemic inflammation and coronary artery calcification score (CACS) measured by computed tomography (CT) scan an indicator of coronary atherosclerosis. METHODS We identified 4905 adult male patients of the Health Promotion Center in Samsung Medical Center between March 2005 and February 2008 and retrospectively reviewed the following data for these patients: pulmonary function, CT-measured CACS, anthropometric measurement, fasting glucose, insulin, lipid profiles, serum C-reactive protein (CRP) and homeostatic model assessment (HOMA-IR). MetS was defined according to the AHA/NHLBI criteria. RESULTS When the subjects were divided into four groups according to quartiles of FVC or FEV(1) (% pred), serum CRP level, HOMA-IR, prevalence of MetS and CACS significantly increased as the FVC or FEV(1) (% pred) decreased. The odds ratios (ORs) for MetS in the lowest quartiles of FVC and FEV(1) (% pred) were 1.85 (95% CI, 1.49-2.30; p<0.001) and 1.47 (95% CI, 1.20-1.81; p<0.001) respectively. The ORs for the presence of coronary artery calcification in the lowest quartiles of FVC and FEV(1) (% pred) were 1.31 (95% CI, 1.09-1.58; p=0.004) and 1.22 (95% CI, 1.02-1.46; p=0.029) respectively. Obesity, CRP, HOMA-IR, and the presence of coronary artery calcium were independent risk predictors for impaired lung function. CONCLUSION Metabolic syndrome, insulin resistance, coronary atherosclerosis, and systemic inflammation are closely related to the impaired lung function.

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.

Usefulness of open lung biopsy in mechanically ventilated patients with undiagnosed diffuse pulmonary infiltrates: influence of comorbidities and organ dysfunction

BackgroundThe purpose of this study was to evaluate the clinical usefulness of open lung biopsy (OLB) in patients undergoing mechanical ventilation for diffuse pulmonary infiltrates of unknown etiology.MethodsThis was a 10-year retrospective study in a 10-bed medical intensive care unit. The medical records of 36 ventilator-dependent patients who underwent OLB for the diagnosis of unknown pulmonary infiltrates from 1994 to 2004 were reviewed retrospectively. Data analyzed included demographic data, Charlson age–comorbidity score, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, ventilation variables, and radiological patterns. Diagnostic yield, effect on subsequent treatment changes, and complications of OLB were also assessed.ResultsA specific clinico-pathologic diagnosis was obtained for 31 patients (86%). The most common diagnoses were interstitial pneumonia (n = 17, including 8 acute interstitial pneumonia) and viral pneumonia (n = 4). Therapeutic modifications were made in 64% of patients. Patients who received OLB less than 1 week after initiation of mechanical ventilation were more likely to survive (63% versus 11%; P = 0.018). There were no major complications associated with the procedure. Factors independently associated with survival were the Charlson age-comorbidity score, number of organ dysfunction and the PaO2/FiO2 ratio on the day of the OLB.ConclusionOLB can provide a specific diagnosis in many ventilator-dependent patients with undiagnosed pulmonary infiltrate. Early OLB seems to be useful in critically ill patients with isolated respiratory failure.

Metabolic Syndrome, Insulin Resistance and Systemic Inflammation as Risk Factors for Reduced Lung Function in Korean Nonsmoking Males

The aim of this study was done to assess the association of lung function with insulin resistance (IR), systemic inflammation, and metabolic syndrome (MetS). In 9,581 apparently healthy non-smoking male adults, pulmonary function, fasting glucose, insulin, lipid profiles and serum high-sensitivity C-reactive protein (hs-CRP) levels were measured, and homeostatic model assessment (HOMA) was used to assess IR. The presence of MetS was defined according to the AHA/NHLBI criteria. The prevalence of MetS was 19.3%. The odds ratio of MetS for restrictive ventilatory pattern was 1.55 (95% confidence interval, 1.12-2.14), and that for obstructive ventilatory pattern was 1.39 (0.66-2.94) after adjustment for confounders. When subjects were divided in 4 groups according to quartiles of FVC or FEV1 (% predicted [pred]), HOMA-IR significantly increased as the FVC or FEV1 (% predicted [pred]) decreased. Individuals in the lowest FVC or FEV1 quartile had the highest hs-CRP level. Prevalence of MetS increased as FVC or FEV1 (% predicted [pred]) quartiles decreased. The abdominal obesity, hs-CRP and HOMA-IR were the independent predictors for the lowest FVC and FEV1 (% predicted [pred]) even after adjustment for confounders. These results indicate that MetS, IR, and systemic inflammation are important risk factors for reduced lung function in nonsmoking Korean males.

Slope of Emphysema Index: An Objective Descriptor of Regional Heterogeneity of Emphysema and an Independent Determinant of Pulmonary Function

OBJECTIVE The purpose of this study was to compare quantitative and visual assessments of regional heterogeneity of emphysema and to investigate the influence of regional heterogeneity on pulmonary function in smoking-related emphysema. MATERIALS AND METHODS We developed an automatic computerized algorithm to quantitatively assess heterogeneity in the upper-lower, anterior-posterior, and central-peripheral directions. The emphysema index was plotted with a linear function (emphysema index slopes: slope of emphysema index in upper-lower direction, slope of emphysema index in anterior-posterior direction, and slope of emphysema index in central-peripheral direction) for consecutive 1-pixel-thick slices using volumetric CT data of 59 patients (58 men and one woman; mean age, 65.7 years). Emphysema index was defined as the percentage area of lung with attenuation values below -950 HU. Visual assessment was performed using a 5-point scoring system. Quantitative and visual assessments were compared. Multiple linear regression was performed to evaluate the influence of emphysema index and emphysema index slopes on the pulmonary function test. RESULTS Quantitative and visual assessments were significantly correlated in both upper-lower (r(2) = 0.40 and r(2) = 0.67 for observers 1 and 2, respectively) and central-peripheral (r(2) = 0.51 and r(2) = 0.47, respectively) directions. Multiple linear regression revealed that emphysema index, slope of emphysema index in upper-lower direction, and slope of emphysema index in anterior-posterior direction were independent determinants of forced expiratory volume in 1 second (FEV(1)) (r(2) = 0.30; p < 0.001). Emphysema index and slope of emphysema index in upper-lower direction were independent determinants of the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC) (r(2) = 0.32; p < 0.001). In addition to higher emphysema index, lower and posterior lung dominance was associated with a decrease in FEV(1) and FEV(1)/FVC. CONCLUSION Computerized, quantitative assessment using the emphysema index slope is comparable to visual assessment in the evaluation of regional heterogeneity of emphysema. In addition to the emphysema index, regional heterogeneity of smoking-related emphysema contributes to impairment of pulmonary function.

Validity of the COPD Assessment Test Translated Into Local Languages for Asian Patients

OBJECTIVE Our objective was to evaluate the validity of the COPD Assessment Test (CAT), translated locally, for measuring the health status of patients in Asian countries. METHODS A pooled analysis of cross-sectional studies from Indonesia, Korea, Vietnam, and Hong Kong was performed. Smokers or ex-smokers, aged ≥ 40 years, with a smoking history of ≥ 10 pack-years and a COPD diagnosis in the past 6 months or more were recruited. Demographic, smoking, and COPD history and spirometry data were collected from patients who completed the CAT or St. Georges Respiratory Questionnaire (SGRQ) and had their dyspnea assessed. RESULTS The study included 333 patients with mean age of 69 ± 9 years and smoking history of 38 ± 25 pack-years; 82% had ceased smoking. One-third suffered from cardiovascular comorbidities, 72% reported at least one exacerbation in the past year, and 82% recorded at least moderate health impairment (CAT scores ≥ 10 units). The CAT score was positively correlated with the SGRQ score (r = 0.72, P < .001) and Medical Research Council (MRC) dyspnea score (r = 0.50, P < .001) and poorly correlated with the FEV1 (r = -0.23, P < .001) and number of exacerbations in the past year (r = 0.11, P = .04). The relationships between the CAT score and SGRQ score, MRC dyspnea score, or FEV1 did not differ between countries (P value for interaction term = 0.76, 0.75, and 0.06, respectively). CONCLUSIONS The CAT correlated well with the SGRQ and MRC dyspnea score in all countries, and the relationship did not differ between countries despite varying patient characteristics. This suggests that a CAT score in one of these countries has the same clinical significance as the same score in another.

Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease.

Background Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A–D were introduced, the lung function changes according to group have been evaluated rarely. Objective We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines. Methods Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression. Results A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline. Conclusion There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification.

Association of blood eosinophils and plasma periostin with FEV1 response after 3-month inhaled corticosteroid and long-acting beta2-agonist treatment in stable COPD patients

Background COPD patients with increased airway eosinophilic inflammation show a favorable response to inhaled corticosteroids (ICS) in combination with a long-acting bronchodilator. Recent studies have demonstrated a significant correlation of sputum eosinophilia with blood eosinophils and periostin. We investigated whether high blood eosinophils and plasma periostin were associated with an improvement in forced expiratory volume in 1 second (FEV1) after 3-month treatment with ICS/long-acting beta2-agonist (LABA) in stable COPD patients. Patients and methods Blood eosinophils and plasma periostin levels were measured in 130 stable COPD subjects selected from the Korean Obstructive Lung Disease cohort. Subjects began a 3-month ICS/LABA treatment after washout period. Results High blood eosinophils (>260/µL, adjusted odds ratio =3.52, P=0.009) and high plasma periostin (>23 ng/mL, adjusted odds ratio =3.52, P=0.013) were significantly associated with FEV1 responders (>12% and 200 mL increase in FEV1 from baseline after treatment). Moreover, the addition of high blood eosinophils to age, baseline positive bronchodilator response, and FEV1 <50% of the predicted value significantly increased the area under the curve for prediction of FEV1 responders (from 0.700 to 0.771; P=0.045). Conclusion High blood eosinophils and high plasma periostin were associated with improved lung function after 3-month ICS/LABA treatment. In particular, high blood eosinophils, in combination with age and baseline lung function parameters, might be a possible biomarker for identification of COPD patients with favorable FEV1 improvement in response to ICS/LABA treatment.