Sang-Do Lee

Penang Medical College, Penang, Penang, Malaysia

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Publications (93)210.48 Total impact

  • Byung Ju Kang · Yeon-Mok Oh · Sang-Do Lee · Jae Seung Lee ·

    The Korean Journal of Internal Medicine 10/2015; 30(6):837-845. DOI:10.3904/kjim.2015.30.6.837 · 1.43 Impact Factor
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    ABSTRACT: Background and objectiveTriple combination therapy with tiotropium plus budesonide/formoterol has improved lung function and reduced exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) in Western countries, but no such data exist for East Asian patients. This study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium compared with tiotropium alone in East Asian patients with severe/very severe COPD.Methods This 12-week, randomized, parallel-group, multicentre, open-label study was conducted in East Asia. After a 14-day run-in period during which patients received tiotropium 18 μg once daily, patients were randomized to tiotropium (18 μg once daily) + budesonide/formoterol (160/4.5 μg 2 inhalations twice daily) or tiotropium alone (18 μg once daily). The primary endpoint was change from baseline in pre-dose forced expiratory volume in 1 s (FEV1) to the mean of values measured at Weeks 1, 6 and 12.ResultsPre-dose FEV1 significantly increased from baseline with tiotropium plus budesonide/formoterol (n = 287) versus tiotropium alone (n = 291) (5.0% vs 0.6%; treatment difference: 4.4% (95% CI: 1.9–6.9), P = 0.0004). Triple therapy also reduced the COPD exacerbation rate by 40.7% (P = 0.0032) and prolonged time to first exacerbation (38.6% risk reduction, P = 0.0167) versus tiotropium alone and markedly improved health-related quality of life (HRQoL), measured using the St George's Respiratory Questionnaire. Incidence of adverse events was 26% for both groups.Conclusions In East Asian patients with severe/very severe COPD, adding budesonide/formoterol to tiotropium was associated with significant improvements in FEV1 and HRQoL and lower COPD exacerbation rates. Treatment was generally well tolerated.Clinical trial registration: NCT01397890 at
    Respirology 09/2015; DOI:10.1111/resp.12646 · 3.35 Impact Factor
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    ABSTRACT: 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.
    International Journal of COPD 09/2015; 10(1):1819-27. DOI:10.2147/COPD.S87766 · 3.14 Impact Factor
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    ABSTRACT: 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. Graphical Abstract
    Journal of Korean Medical Science 09/2015; 30(10):1459-1465. DOI:10.3346/jkms.2015.30.10.1459 · 1.27 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA5060. DOI:10.1183/13993003.congress-2015.PA5060 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA2485. DOI:10.1183/13993003.congress-2015.PA2485 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA2308. DOI:10.1183/13993003.congress-2015.PA2308 · 7.64 Impact Factor
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    ABSTRACT: Endobronchial valve (EBV) therapy is increasingly being seen as a therapeutic option for advanced emphysema, but its clinical utility in Asian populations, who may have different phenotypes to other ethnic populations, has not been assessed. This prospective open-label single-arm clinical trial examined the clinical efficacy and the safety of EBV in 43 consecutive patients (mean age 68.4±7.5, forced expiratory volume in 1 second [FEV1] 24.5%±10.7% predicted, residual volume 208.7%±47.9% predicted) with severe emphysema with complete fissure and no collateral ventilation in a tertiary referral hospital in Korea. Compared to baseline, the patients exhibited significant improvements 6 months after EBV therapy in terms of FEV1 (from 0.68±0.26 L to 0.92±0.40 L; P<0.001), 6-minute walk distance (from 233.5±114.8 m to 299.6±87.5 m; P=0.012), modified Medical Research Council dyspnea scale (from 3.7±0.6 to 2.4±1.2; P<0.001), and St George's Respiratory Questionnaire (from 65.59±13.07 to 53.76±11.40; P=0.028). Nine patients (20.9%) had a tuberculosis scar, but these scars did not affect target lobe volume reduction or pneumothorax frequency. Thirteen patients had adverse events, ten (23.3%) developed pneumothorax, which included one death due to tension pneumothorax. EBV therapy was as effective and safe in Korean patients as it has been shown to be in Western countries. ( NCT01869205).
    International Journal of COPD 08/2015; 10:1501-11. DOI:10.2147/COPD.S85744 · 3.14 Impact Factor

  • The International Journal of Tuberculosis and Lung Disease 06/2015; 19(6). DOI:10.5588/ijtld.14.0787 · 2.32 Impact Factor
  • Li-Cher Loh · Yeon-Mok Oh · Sang-do Lee ·

    QJM: monthly journal of the Association of Physicians 05/2015; DOI:10.1093/qjmed/hcv109 · 2.50 Impact Factor
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    ABSTRACT: 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. The objective of this study is to evaluate the relationship of leptin, adiponectin, and leptin/adiponectin ratio with the COPD severity and progression according to COPD phenotypes. Plasma leptin and adiponectin levels were measured in 196 COPD subjects 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 leptin/adiponectin ratio with COPD severity and progression over 3 years. The concentration of adiponectin in plasma positively correlated with percent (%) emphysema on initial computed tomography (CT) (adjusted P = 0.022), while plasma leptin concentrations and leptin/adiponectin ratio exhibited an independent inverse correlation with initial forced expiratory volume in 1 second (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 % emphysema over 3 years (adjusted P = 0.037 for leptin and adjusted P = 0.029 for leptin/adiponectin ratio), while none of the adipokines demonstrated an association with FEV1 decline over the 3 year period. Plasma adiponectin and leptin vary according to COPD phenotypes. Plasma leptin and 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 COPD patients.
    Annals of the American Thoracic Society 05/2015; 12(7). DOI:10.1513/AnnalsATS.201501-005OC
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    ABSTRACT: Background: Although smoking is the most important and modifiable cause of chronic obstructive pulmonary disease (COPD), other risk factors including asthma and tuberculosis (TB) are also associated. It is common for COPD patients to have more than one of these risk factors. The aims of this study were to determine the prevalence of airflow limitation (FEV1/FVC<0.7) according to the risk factors and to investigate their impact and interaction in airflow limitation. Methods: From the Korean National Health and Nutrition Examination Survey between 2008 and 2012, we analyzed participants over 40 years of age by spirometry, chest radiograph and questionnaire about asthma and smoking history. Results: Of 12,631 participants, 1,548 (12.3%) had airflow limitation. The prevalence of airflow limitation in smokers (≥10 pack-year), asthmatics, and those with inactive TB was 23.9%, 32.1%, and 33.6%. The prevalence increased with the number of risk factors: 86.1% had airflow limitation if they had all three risk factors. Impacts of inactive TB and asthma on airflow limitation were equivalent to 47 and 69 pack-years of smoking, respectively. Airflow limitation resulted from lower levels of smoking in those with inactive TB and asthma. A potential interaction between smoking and inactive tuberculosis in the development of airflow limitation was identified (p = 0.054). Conclusions: Asthma and inactive TB lesions increase susceptibility to smoking in the development of airflow limitation. People with these risk factors should be seen as a major target population for anti-smoking campaigns to prevent COPD.
    PLoS ONE 04/2015; 10(4):e0125020. DOI:10.1371/journal.pone.0125020 · 3.23 Impact Factor
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    ABSTRACT: The relationship between blood vitamin D level and clinical parameters in patients with chronic obstructive pulmonary disease (COPD) has been reported with conflicting results. We explored the effects of vitamin D on clinical characteristics of patients with COPD in Korea. The study population comprised 193 patients with COPD from Korean Obstructive Lung Disease Cohort. The plasma level of 25-OH vitamin D3 (25-OH-VitD3) was measured every year along with various clinical parameters such as lung function, 6-min walking (6MW) distance, quality of life, exacerbations and emphysema index. Generalized estimating equations and linear mixed model were used for statistical analysis. Of the 193 patients, 12 (6.2%), 28 (14.5%) and 153 (79.3%) were categorized into normal, insufficiency and deficiency groups. Clustered analysis showed that the plasma 25-OH-VitD3 level was associated with the post-bronchodilator ratio of force expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) (estimated = 0.001; P = 0.022). The vitamin D deficiency group showed lower FEV1 (estimated = -0.129, P = 0.043), FEV1 % predicted (estimated = -4.994, P = 0.029) and FEV1 /FVC ratio (estimated = -0.048, P = 0.001) than did the non-deficiency group. The 6MW distance tended to be shorter in deficiency group (estimated = -17.26, P = 0.069) than in non-deficiency group. Quality of life, exacerbation and emphysema index were not associated with plasma 25-OH-VitD3 level. We demonstrated a high prevalence of vitamin D deficiency in Korean patients with COPD and a significant relationship between vitamin D deficiency and airflow limitation. The exercise capacity tended to be decreased in the vitamin D deficiency group. © 2015 Asian Pacific Society of Respirology.
    Respirology 04/2015; 20(5). DOI:10.1111/resp.12538 · 3.35 Impact Factor
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    ABSTRACT: Background and Objectives. Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airflow limitation. Although airway inflammation and oxidative stress are known to be important in the pathogenesis of COPD, the mechanism underlying airflow obstruction is not fully understood. Gene expression profiling of lung tissue was performed to define the molecular pathways that are dysregulated in COPD. Methods. RNA was isolated from lung tissues obtained from 98 subjects with COPD and 91 control subjects with normal spirometry. The RNA samples were processed with RNA-seq using the HiSeq 2000 system. Genes expressed differentially between the two groups were identified using Student's t-test. Results. After filtering for genes with zero counts and noncoding genes, 16,676 genes were evaluated. A total of 2312 genes were differentially expressed between the lung tissues of COPD and control subjects (false discovery rate corrected q < 0.01). The expression of genes related to oxidative phosphorylation and protein catabolism was reduced and genes related to chromatin modification were dysregulated in lung tissues of COPD subjects. Conclusions. Oxidative phosphorylation, protein degradation, and chromatin modification were the most dysregulated pathways in the lung tissues of COPD subjects. These findings may have clinical and mechanistic implications in COPD.
    International Journal of Genomics 04/2015; 2015:206937. DOI:10.1155/2015/206937 · 0.95 Impact Factor
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    ABSTRACT: It remains difficult to differentiate between chronic obstructive pulmonary disease (COPD) and asthma in clinical practice, especially in a primary care setting. The purpose of this study was to develop a new scoring system for differentiating between COPD and asthma, and to evaluate its effectiveness. First, to identify important variables differentiating COPD from asthma, the data of 197 patients with COPD and 138 patients with asthma were assessed retrospectively. Secondly, a scoring system that was based on these variables was then developed, and its performance was internally validated using a bootstrapping-based method. Thirdly, the scoring system was externally validated using prospectively collected data from patients with COPD (n = 104) or asthma (n = 96). The final scoring system was composed of the four variables: age of onset of breathlessness (<40 years, 0 points; 40-60 years, 2 points; >60 years, 4 points), continuous breathlessness (no, 0 points; yes, 1 point), diurnal variation of breathlessness (yes, 0 points; no, 1 point) and emphysematous change in chest X-ray (no, 0 points; yes, 1 point). The patients were classified by their total score into three categories: 0-2 points, probable asthma; 3-4 points, difficult-to-differentiate; 5-7 points, probable COPD. The new scoring system performed well in the external validation dataset (area under the curve, 0.86; 95% confidence interval: 0.813-0.911; P < 0.001). The new scoring system that was developed in this study may be a useful tool for differentiating between COPD and asthma in primary care. © 2015 Asian Pacific Society of Respirology.
    Respirology 03/2015; 20(4). DOI:10.1111/resp.12511 · 3.35 Impact Factor
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    ABSTRACT: This study analyzed the recurrence rate and risk factors for recurrence of Mycobacterium avium complex (MAC) lung disease in patients successfully treated for this disease. The medical records of 158 patients successfully treated for MAC lung disease at a tertiary referral center in South Korea between March 2000 and December 2009 were retrospectively analyzed. Recurrence was recorded, and factors associated with recurrence were analyzed. The mean age of the 158 patients was 60.7 ± 11.1 years. The etiologic agent was Mycobacterium avium in 77 patients (48.7%) and Mycobacterium intracellulare in 81 (51.3%). Radiographic features included nodular bronchiectatic disease in 95 (60.1%), fibrocavitary disease in 49 (31.0%), and unclassifiable form in 14 patients (8.9%). Almost all (98.7%, 156/158) patients had been previously treated with a macrolide-containing regimen and 68 (43.0%) had received treatment with an aminoglycoside. During a median follow-up of 43.8 months after completion of therapy, 50 patients (31.6%) experienced recurrence, at a median 11.9 months after treatment completion. Multivariate analysis showed that only the nodular bronchiectatic form of the disease (Hazard ratio 2.39, 95% confidence interval 1.19-4.81) was independently associated with an increased risk of recurrence. Recurrence after successful treatment is frequent in patients with MAC lung disease. The recurrence rate was significantly higher in patients with the nodular bronchiectatic form than in those with the fibrocavitary form or an unclassifiable form of the disease. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 03/2015; 59(6). DOI:10.1128/AAC.04577-14 · 4.48 Impact Factor
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    ABSTRACT: AMP-activated protein kinase (AMPK) not only functions as an intracellular energy sensor and regulator, but is also a general sensor of oxidative stress. Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence. Thus, it may oppose the development of chronic obstructive pulmonary disease. To investigate the role of AMPK in cigarette smoke-induced lung inflammation and emphysema we first compared cigarette smoking and polyinosinic-polycytidylic acid [poly(I:C)]-induced lung inflammation and emphysema in AMPKα1-deficient (AMPKα1-HT) mice and wild-type mice of the same genetic background. We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells. Cigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in AMPKα1-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an AMPK activator, decreased CSE-induced IL-8 production while Compound C, an AMPK inhibitor, increased it, as did pretreatment with an AMPKα1-specific small interfering RNA. AMPKα1-deficient mice have increased susceptibility to lung inflammation and emphysema when exposed to cigarette smoke, and AMPK appears to reduce lung inflammation and emphysema by lowering IL-8 production.
    Tuberculosis and Respiratory Diseases 01/2015; 78(1):8-17. DOI:10.4046/trd.2015.78.1.8
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    ABSTRACT: 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. Graphical Abstract
    Journal of Korean Medical Science 01/2015; 30(1):54-59. DOI:10.3346/jkms.2015.30.1.54 · 1.27 Impact Factor

  • 01/2015; 89(1):91. DOI:10.3904/kjm.2015.89.1.91
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    ABSTRACT: We aimed to identify a vasoreactive subset of patients with idiopathic pulmonary arterial hypertension (IPAH) in Korea and to show their clinical characteristics and prognosis. Data on patients who were diagnosed with IPAH at Asan Medical Center between January 1994 and March 2013 were retrospectively collected. Acute vasodilator testing was performed with inhaled nitric oxide during diagnostic right heart catheterization. A positive acute response was defined as a reduction in mean pulmonary arterial pressure (PAP) ≥10 mmHg to an absolute level of mean PAP <40 mmHg without a decrease in cardiac output. Among a total of 60 IPAH patients included for analysis, 9 (15%) showed a positive acute response to acute vasodilator testing. Acute responders showed significantly lower peak velocity of a tricuspid regurgitation jet on echocardiography (4.1±0.3 m/s vs. 4.6±0.6 m/s; P=0.01) and significantly lower mean PAP hemodynamically (47±10 mmHg vs. 63±17 mmHg; P=0.003) than non-responders at baseline. The survival rate of acute responders was 88% at 1, 3, 5, and 10 yr, respectively, which was significantly higher than that of non-responders (85%, 71%, 55%, and 40%, respectively; P=0.029). In conclusion, Korean IPAH patients with vasoreactivity showed better baseline hemodynamic features and survival than those without vasoreactivity. Graphical Abstract
    Journal of Korean Medical Science 12/2014; 29(12):1665-71. DOI:10.3346/jkms.2014.29.12.1665 · 1.27 Impact Factor

Publication Stats

800 Citations
210.48 Total Impact Points


  • 2015
    • Penang Medical College
      Penang, Penang, Malaysia
  • 2005-2015
    • University of Ulsan
      • • Asan Medical Center
      • • College of Medicine
      • • Department of Internal Medicine
      Ulsan, Ulsan, South Korea
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
    • CHA University
      • College of Medicine
      Sŏul, Seoul, South Korea
  • 2002-2015
    • Asan Medical Center
      • • Department of Pulmonary and Critical Care Medicine
      • • Department of Rheumatology
      Sŏul, Seoul, South Korea
  • 2012
    • Ewha Womans University
      Sŏul, Seoul, South Korea
  • 2011
    • ASTHMA, Inc. Clinical Research Center
      Seattle, Washington, United States