Sang-Do Lee

University of Ulsan, Ulsan, Ulsan, South Korea

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Publications (86)166.75 Total impact

  • The International Journal of Tuberculosis and Lung Disease 06/2015; 19(6). DOI:10.5588/ijtld.14.0787 · 2.76 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 · 2.46 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; DOI:10.1513/AnnalsATS.201501-005OC
  • 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 · 3.50 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 · 3.50 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 · 4.45 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 01/2015; 2015:206937. DOI:10.1155/2015/206937
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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 · 1.25 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. ( ClinicalTrials.gov: NCT01869205).
    International Journal of COPD 01/2015; 10:1501-11. DOI:10.2147/COPD.S85744
  • 01/2015; 89(1):91. DOI:10.3904/kjm.2015.89.1.91
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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: 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 · 1.25 Impact Factor
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    ABSTRACT: Although many patients with severe emphysema have benefited from bronchoscopic lung volume reduction (BLVR) worldwide, experience of BLVR in Asian emphysema patients is scarce. Between July 2012 and March 2013, seven patients with advanced heterogeneous emphysema underwent BLVR in the Asan Medical Center. They had severe dyspnea and poor lung function (Modified Medical Research Council dyspnea scale 3-4; median forced expiratory volume in 1 sec [FEV1], 0.59 L [19.0 % predicted]; median 6-min walk distance [6MWD], 195 m). Endobronchial valves were inserted into the target lobe which was most hyperinflated and least perfused, and had no collateral ventilation with other lobes. Six patients showed clinical improvement after 1 month. Of them, 2 patients improved to dyspnea scale 1 and 4 patients did to scale 2 (P = 0.026). The median FEV1 increased from 0.59 to 0.89 L (51%; P = 0.028) and the median 6MWD increased from 195 to 252 m (29.2%; P = 0.028). Two patients developed a pneumothorax (one requiring drainage) and one patient experienced slight hemoptysis; however, there were no other serious adverse events. BLVR is effective in Asian advanced emphysema patients, with noted clinical improvements in lung function and exercise capacity. Graphical Abstract
    Journal of Korean Medical Science 10/2014; 29(10):1404-10. DOI:10.3346/jkms.2014.29.10.1404 · 1.25 Impact Factor
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    ABSTRACT: Objectives One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas. Methods One hundred and thirty-eight COPD patients and 29 nonsmokers were included in our study. The ATI, the emphysema index (EI), the gas trapping index (Exp -856) and expiration/inspiration ratio of mean lung density (E/Iratio of MLD) were measured on CT. The values of the whole lung, of emphysema, and of hyperinflated and normal lung areas were compared and then correlated with various PFT parameters. Results Compared with nonsmokers, COPD patients showed a higher ATI in the whole lung and in each lung lesion (all P
    European Radiology 09/2014; 25(2). DOI:10.1007/s00330-014-3418-0 · 4.34 Impact Factor
  • Byung Ju Kang · Sang-Do Lee · Yeon-Mok Oh · Jae Seung Lee
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    ABSTRACT: Objectives: We compared the survival of patients with idiopathic pulmonary arterial hypertension (IPAH), receiving conventional and targeted therapies. Background: IPAH is an incurable disease with high mortality. To manage IPAH, several targeted therapies have been used in Korea. Methods: We performed a retrospective study of 71 patients diagnosed with IPAH in a tertiary hospital between January 1994 and February 2013. Patients were classified into "conventional therapy group" (treated with conventional therapies and/or beraprost) and "targeted therapy group" (treated with targeted therapies other than beraprost). Results: The median age of the patients was 33 years and 50 patients were female. The survival rate at 1, 3, 5, and 10 years was 80.1% 62.0%, 51.5%, and 26.8%, respectively. The survival rate in the targeted therapy group was greater than in the conventional therapy group (p-value = 0.026). Conclusions: We believe targeted therapies would improve survival benefits in IPAH patients.
    Heart and Lung The Journal of Acute and Critical Care 08/2014; 43(6). DOI:10.1016/j.hrtlng.2014.07.003 · 1.32 Impact Factor
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    ABSTRACT: We aimed to investigate the treatment outcomes of patients with refractory Mycobacterium avium complex (MAC) lung disease treated with regimens containing drugs with unclear efficacy. Of all patients diagnosed with MAC lung disease between April 2004 and September 2012 at a tertiary referral center in South Korea, the outcomes of 51 patients treated with regimens containing drugs with unclear efficacy (clofazimine, moxifloxacin, rifabutin, and linezolid) because of treatment failure after receiving standard treatment were retrospectively analyzed. The mean age (standard deviation) of the 51 patients was 59.0 (10.3) years and 29 (56.9%) were male. The etiologic agent was M. avium in 17 patients (33.3%) and Mycobacterium intracellulare in 34 patients (66.7%); 42 patients (82.4%) had the fibrocavitary form of the disease. Of the 51 patients, 26, 28, 35, and 7 received clofazimine-, moxifloxacin-, rifabutin-, and linezolid-containing regimens (numbers are not mutually exclusive), with median drug administration durations of 147, 128, 209, and 88 days, respectively. Overall, 8 patients (15.7%) had a favorable response. Treatment outcomes did not differ by drug regimen or even by the combination of more than 2 drugs. The treatment outcomes of patients with refractory MAC lung disease were unsatisfactory with regimens containing possibly effective drugs such as clofazimine, moxifloxacin, rifabutin and linezolid.
    Journal of Infection and Chemotherapy 06/2014; 20(9-10). DOI:10.1016/j.jiac.2014.05.010 · 1.38 Impact Factor
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    ABSTRACT: Abstract Despite extensive effort, only a few chronic obstructive pulmonary disease (COPD)-associated genes have been suggested, indicating that there must be additional risk-associated loci. Here we aimed to identify additional COPD-associated SNPs and to explore the potential relationship between COPD subgroups and the SNPs in the Korean population. We performed a genome-wide association study (GWAS) with 990 Korean individuals; 102 COPD cases and 544 controls for GWAS using Affymetrix SNP array 5.0, and 173 COPD cases and 171 controls for replication. After validating the candidate single nucleotide polymorphisms (SNP), we performed subgroup analysis by disease phenotype. Through GWAS, we identified a novel SNP in the phosphodiesterase-4D (PDE4D) gene [rs16878037 (C>T), p = 1.66 × 10(-6)] that was significantly associated with COPD. This signal in PDE4D was successfully replicated in the independent set (p = 0.041). When we combined the discovery and replication data, the association signal became more significant (p = 5.69 × 10(-7)). In the COPD subgroup analysis, the T allele of rs16878037 was significantly more frequent in COPD patients without severe diffusion capacity impairment (mild mixed and obstruction-dominant group) than in patients with severe impairment (severe mixed and emphysema-dominant groups). This result supports that PDE4D polymorphisms might be involved in the susceptibility to COPD especially in non-emphysematous individuals and that they could also affect the responsiveness of the PDE4 inhibitor treatment.
    COPD Journal of Chronic Obstructive Pulmonary Disease 06/2014; 11(6). DOI:10.3109/15412555.2014.898045 · 2.62 Impact Factor
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    ABSTRACT: Background The Korean Obstructive Lung Disease (KOLD) Cohort Study is a prospective longitudinal study of patients with chronic obstructive pulmonary disease (COPD), asthma, or other unclassified obstructive lung diseases. It was designed to develop new classification models and biomarkers that predict clinically relevant outcomes for patients with obstructive lung diseases. Methods Patients over 18 years old who have chronic respiratory symptoms and airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers in South Korea. After a baseline visit, the subjects were followed up every 3 months for various assessments. Results From June 2005 to October 2013, a total of 477 subjects (433 [91%] males; 381 [80%] diagnosed with COPD) were enrolled. Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with COPD, and predictors of therapeutic responses and exacerbations as well as the factors related to pulmonary hypertension in COPD. In addition, several genotypes were associated with radiological phenotypes and therapeutic responses among Korean COPD patients. Conclusion The KOLD Cohort Study is one of the leading long-term prospective longitudinal studies investigating heterogeneity of the COPD and is expected to provide new insights for pathogenesis and the long-term progression of COPD.
    Tuberculosis and Respiratory Diseases 04/2014; 76(4):169. DOI:10.4046/trd.2014.76.4.169
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    ABSTRACT: Background We aimed to identify the 1-year relapse rate and risk factors for patients with pulmonary tuberculosis (TB) treated with a 6-month daily regimen. Methods A total of 317 patients with pan-susceptible pulmonary TB who completed a 6-month daily course of treatment [2HRZ(E)/4HR(E)] were retrospectively analyzed. Results The mean age was 50.0±16.8 years and men were predominant (61.2%). All of 137 adults tested for HIV were negative. Six (1.9%) cases relapsed within one year. Relapse rate was higher in patients with a positive culture after 2 months of treatment (10.0%, p = 0.049) and in patients with both a positive culture after 2 months of treatment and cavitation on initial chest radiograph (18.2%, p = 0.015), whereas relapse rate in patients with cavitation alone was comparable to that of the total population (2.7%). Among various risk factors known to increase risk of relapse, the combined variable of cavitation and positive culture at 2 months (OR=15.56, 95% CI 2.56-98.71, p = 0.003) was only associated with increased relapse rate in a multivariate analysis. Conclusions Even with a 6-month daily treatment regimen throughout the intensive and continuation phases, the relapse rate was unacceptably high in patients with both a positive culture at 2 months of treatment and cavitation on baseline chest radiography. Intensification of treatment, such as an extension of treatment duration, should be considered in this category of patients.
    Respiratory medicine 04/2014; 108(4). DOI:10.1016/j.rmed.2014.01.010 · 2.92 Impact Factor

Publication Stats

688 Citations
166.75 Total Impact Points

Institutions

  • 2005–2015
    • University of Ulsan
      • • 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