Author Affiliations

1. Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States
2. Division of Pulmonary, Allergy, Critical Care, and Sleep, University of Minnesota, Minneapolis, Minnesota, United States
3. Division of Biostatistics and Health Data Science, University of Minnesota, Minneapolis, Minnesota, United States
4. Pulmonary and Critical Care, VA Puget Sound Health Care System, Seattle, Washington, United States
5. Tsinghua University, Beijing, China
6. Division of Health Services Research and Implementation, Kaiser Permanente Southern California, Pasadena, California, United States

Address correspondence to:

David MacDonald, MD, MS
Minneapolis VA Health Care System
Pulmonary, Critical Care, and Sleep (111N)
One Veterans Drive
Minneapolis, MN, 55417
Email: macdo147@umn.edu

Abstract

Rationale: Physical activity, lung function, and grip strength are associated with exacerbations, hospitalizations, and mortality in people with chronic obstructive pulmonary disease (COPD). We tested whether baseline inflammatory biomarkers were associated with longitudinal outcomes of these physiologic measurements.

Methods: The COPD Activity: Serotonin Transporter, Cytokines, and Depression (CASCADE) study was a prospective observational study of individuals with COPD. A total of 14 inflammatory biomarkers were measured at baseline. Participants were followed for 2 years. We analyzed associations between baseline biomarkers and forced expiratory volume in 1 second (FEV₁), physical activity, and grip strength.

We used a hierarchical hypothesis testing procedure to reduce type I error. We used Pearson correlations to test associations between baseline biomarkers and longitudinal changes in the outcomes of interest. We used Fisher’s linear discriminant analysis to test if linear combinations of baseline biomarkers predict rapid FEV₁ decline. Finally, we used linear mixed modeling to test associations between baseline biomarkers and outcomes of interest at baseline, year 1, and year 2; models were adjusted for age, smoking status, baseline biomarkers, and FEV₁.

Results: A total of 302 participants (age 67.5 ± 8.5 years, 19.5% female, 28.5% currently smoking) were included. Baseline biomarkers were not associated with longitudinal changes in grip strength, physical activity, or rapid FEV₁ decline. Higher interleukin-6 and C-reactive protein were associated with lower physical activity at baseline and these relationships persisted at year 1 and year 2.

Conclusion: Baseline inflammatory biomarkers did not predict changes in lung function or physical activity, but higher inflammatory biomarkers were associated with persistently low levels of physical activity.

Citation

Citation: MacDonald DM, Samorodnitsky S, Lock EF, et al. Biomarkers of inflammation and longitudinal evaluation of lung function, physical activity, and grip strength: a secondary analysis in the CASCADE study. J COPD F. 2024; 11(4): 396-405. doi: http://doi.org/10.15326/jcopdf.11.4.2024.0500

Keywords

chronic obstructive pulmonary disease, biomarkers, exercise, inflammation, hand strength

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Click to read Biomarkers of Inflammation and Longitudinal Evaluation of Lung Function, Physical Activity, and Grip Strength: A Secondary Analysis in the CASCADE Study

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Author Affiliations

1. Makerere University Lung Institute, Kampala, Uganda
2. Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
3. Soroti District Local Government, Soroti, Uganda
4. Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, United States
5. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
6. Faculty of Health, University of Plymouth, Plymouth, United Kingdom
7. Respiratory, University College London, London, United Kingdom
8. Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami, Miami, Florida, United States

*Joint senior authorship

Address correspondence to:

Patricia Alupo, MBChB, MMed
Makerere University Lung Institute
Phone: +256701124540
Email: alupopat@gmail.com

Abstract

Background: The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive biomarker that potentially predicts acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). We evaluated the association of baseline NLR and respiratory hospitalization risk within one year among chronic obstructive pulmonary disease (COPD) patients in Uganda, a low- and middle-income country.

Methods: A total of 312 COPD patients were followed for one year. Clinical characteristics and exacerbation rates were collected. Poisson regression with robust variance estimators was used to measure the association between NLR and hospital admissions due to COPD exacerbations. Receiver-operator characteristic (ROC) curves and the area under the curve were used to assess the ability of NLR to predict AECOPDs.

Results: The median (Q 1, Q 3) age was 64 years (53, 71). Females comprised 50.96% (n=159) of the cohort, and 71.2% (n=222) of participants had moderate or severe COPD. A total of 9.9% (n=31) of participants experienced a COPD exacerbation during the period of follow-up. At baseline, the median (Q 1, Q 3) NLR ratio among participants who experienced an exacerbation was 1.46 (0.92, 2.33) compared to 1.03 (0.72,1.42) among those who did not experience one during the follow-up period (p=0.002). Using Youden and Liu’s methods, the optimal NLR cutoff for predicting COPD exacerbation was 1.17. This cutoff resulted in a ROC curve area of 0.64 (95% confidence interval: 0.56, 0.73).

Conclusions: The NLR could be used as a risk predictor, in low- and middle-income countries, for hospital admissions due to COPD exacerbations. A cutoff of 1.17 was an independent predictor of hospitalization due to acute exacerbations of COPD within one year.

Citation

Citation: Alupo P, Katagira W, Mukunya D, et al. The neutrophil-to-lymphocyte ratio as a predictor of acute exacerbations among patients with COPD in Uganda. J COPD F. 2024; 11(2): 187-195. doi: http://doi.org/10.15326/jcopdf.11.2.2023.0443

Keywords

COPD, biomarkers, exacerbations, acute exacerbations of COPD, neutrophil-to-lymphocyte ratio

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Click to read The Neutrophil-to-Lymphocyte Ratio as a Predictor of Acute Exacerbations Among Patients With COPD in Uganda

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Author Affiliations

1. Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, United States
2. Department of Radiology, Johns Hopkins University, Baltimore, Maryland, United States
3. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States
4. Division of Cardiology, Johns Hopkins University, Baltimore, Maryland, United States

Address correspondence to:

Ashraf Fawzy, MD, MPH
5501 Hopkins Bayview Circle
Baltimore MD, 21224
Phone: (410) 550-6305
Email: afawzy1@jhmi.edu

Abstract

Introduction: Antiplatelet therapy has been associated with fewer exacerbations and reduced respiratory symptoms in chronic obstructive pulmonary disease (COPD). Whether platelet activation is associated with respiratory symptoms in COPD is unknown.

Methods: Former smokers with spirometry-confirmed COPD had urine 11-dehydro-thromboxane B2 (11dTxB2), plasma soluble CD40L (sCD40L), and soluble P-selectin (sP-selectin) repeatedly measured during a 6- to 9-month study period. Multivariate mixed-effects models adjusted for demographics, clinical characteristics, and medication use evaluated the association of each biomarker with respiratory symptoms, health status, and quality of life.

Results: Among 169 participants (average age 66.5±8.2 years, 51.5% female, 47.5±31 pack years, forced expiratory volume in 1 second percent predicted 53.8±17.1), a 100% increase in 11dTxB2 was associated with worse respiratory symptoms reflected by higher scores on the COPD Assessment Test (β 0.77, 95% confidence interval [CI]: 0.11–1.4) and Ease of Cough and Sputum Clearance Questionnaire β 0.77, 95%CI: 0.38–1.2, worse health status (Clinical COPD Questionnaire β 0.13, 95%CI: 0.03-0.23) and worse quality of life (St George’s Respiratory Questionnaire β 1.9, 95%CI: 0.39-3.4). No statistically significant associations were observed for sCD40L or sP-selectin. There was no consistent statistically significant effect modification of the relationship between urine 11dTxB2 and respiratory outcomes by history of cardiovascular disease, subclinical coronary artery disease, antiplatelet therapy, or COPD severity.

Conclusions: In stable moderate-severe COPD, elevated urinary11dTxB2, a metabolite of the platelet activation product thromboxane A2, was associated with worse respiratory symptoms, health status, and quality of life.

Citation

Citation: Fawzy A, Putcha N, Raju S, et al. Urine and plasma markers of platelet activation and respiratory symptoms in COPD. J COPD F. 2023; 10(1): 22-32. doi: http://doi.org/10.15326/jcopdf.10.1.2022.0326

Keywords

chronic obstructive pulmonary disease, biomarkers, aspirin, platelet activation

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Author Affiliations

1. Center for Tobacco Control Research and Education, University of California, San Francisco, California, United States
2. Cardiovascular Research Institute, University of California, San Francisco, California, United States
3. Medical Service, San Francisco Veterans Affairs Medical Center; San Francisco; California, United States
4. Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington, United States
5. Flight Attendant Medical Research Institute, Bland Lane Center of Excellence on Secondhand Smoke, University of California, San Francisco, California, United States
6. Department of Epidemiology and Biostatistics, University of California, San Francisco, California, United States
7. Department of Medicine, Mount Sinai-St. Luke's-Roosevelt Hospital, New York, New York, United States
8. Division of Cardiology, University of California, San Francisco, California, United States
9. Division of Pulmonary, Critical Care, Allergy and Immunology, and Sleep Medicine, University of California, San Francisco, California, United States
10. Division of Occupational and Environmental Medicine; University of California, San Francisco, California, United States

*These authors contributed equally to this work.
**Co-senior authors

Address correspondence to:

Mehrdad Arjomandi, MD
Department of Medicine
University of California, San Francisco
San Francisco Veterans Affairs Medical Center
Building 203, Room 3A-128, Mailstop 111-D
4150 Clement Street, San Francisco, CA 94121
Phone: (415) 221-4810 x24393
Email: mehrdad.arjomandi@ucsf.edu

Abstract

Background: Prolonged past exposure to secondhand tobacco smoke (SHS) in never-smokers is associated with abnormal lung function and reduced diffusing capacity suggestive of an associated lung tissue injury and damage. The mechanisms by which past SHS exposure may contribute to lung tissue damage are unknown. Elastin is a major constituent of extracellular matrix in lung parenchyma.

Objective: To determine whether past exposure to SHS is associated with ongoing lung tissue damage as indicated by elevated elastin degradation products that are linked to lung function.

Methods: We measured the plasma levels of elastin degradation markers (EDM) from 193 never-smoking flight attendants with a history of remote SHS exposure in aircraft cabins and 103 nonsmoking flight attendants or sea-level control participants without such history of cabin SHS exposure and examined those levels versus their lung function with adjustment for covariates. The cabin SHS exposure was estimated based on airline employment history and years of the smoking ban enactment.

Results: The median [interquartile range] plasma EDM level for all participants was 0.30 [0.24–0.36] ng/mL with a total range of 0.16–0.65 ng/mL. Plasma EDM levels were elevated in those with a history of exposure to cabin SHS compared to those not exposed (0.33±0.08 versus 0.26±0.06 ng/mL; age- and sex-adjusted P<0.001). In those with a history of cabin SHS exposure, higher EDM levels were associated with a lower diffusing capacity (parameter estimate [PE] 95% [confidence interval(CI)]=4.2 [0.4–8.0] %predicted decrease per 0.1 ng/mL increase in EDM; P=0.030). Furthermore, EDM levels were inversely associated with forced expiratory volume in 1 second (FEV₁), FEV₁ to forced vital capacity (FVC) ratio , and forced expiratory flow rate between 25% and 75% ( FEF_25%-75%) (PE [95%CI]=5.8 [2.1–9.4], 4.0 [2.2–5.7], and 12.5 [5.8–19.2] %predicted decrease per 0.1 ng/mL increase in EDM, respectively; P<0.001). Plasma EDM mediated a substantial fraction of the association of SHS with FEV₁, FVC, and FEF_25%-75% (P<0.05).

Conclusions: Long after past exposure to SHS, there is ongoing elastin degradation beyond what is expected from the aging process, which likely contributes to lower lung function and a reduced pulmonary capillary bed as seen in chronic obstructive pulmonary disease (COPD).

Citation

Citation: MustraRakic J, Zeng S, Rohdin-Bibby L, et al. Elastin degradation and lung function deterioration with remote secondhand tobacco smoke exposure in never-smokers. J COPD F. 2022; 9(3): 377-393. doi: http://doi.org/10.15326/jcopdf.9.3.2022.0289

Keywords

biomarkers, desmosine/isodesmosine, flight attendants, lung damage, secondhand tobacco smoke exposure

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Author Affiliations

1. Department of Internal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
2. Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio, United States
3. Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
4. Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, Maryland, United States
5. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States

Address correspondence to:

M. Bradley Drummond, MD, MHS
Marsico Hall Room 7207, CB# 7248
125 Mason Farm Road
Chapel Hill, NC 27599
Phone: (919) 966-7054
brad_drummond@med.unc.edu

Abstract

Introduction: Cathelicidin is a vitamin D-regulated, antimicrobial peptide involved in the innate immune response of the airways. Reduced plasma cathelicidin concentrations are independently associated with worse pulmonary outcomes in current and former smokers. This study aimed to determine whether oral vitamin D supplementation in vitamin D-deficient current smokers increases plasma and bronchoalveolar lavage (BAL) cathelicidin levels.

Methods: Vitamin D-deficient (25-hydroxy vitamin D [25-OH vitamin D] <20 ng/ml) smokers (n=17) underwent collection of plasma and BAL for cathelicidin and 25-OH vitamin D measurements before and after 8 weeks of oral supplementation with 50,000 IU vitamin D3 weekly. Differences between baseline and 8-week levels of cathelicidin and 25-OH vitamin D in blood and BAL were assessed along with correlations between serum 25-OH vitamin D, plasma cathelicidin, and BAL cathelicidin.

Results: At baseline, there was no correlation between BAL and plasma cathelicidin. There was a significant increase in 25-OH vitamin D (median 17.0 to 43.3 ng/mL, p<0.001) after 8 weeks of vitamin D supplementation. There was no change in plasma cathelicidin (p=0.86), BAL cathelicidin (p=0.31), or BAL 25-OH vitamin D (p=0.89). There was no correlation between serum 25-OH vitamin D and either BAL or plasma cathelicidin post-supplementation.

Conclusion: Oral vitamin D supplementation, while increasing serum 25-OH vitamin D levels, does not increase plasma or BAL cathelicidin levels in vitamin D-deficient, active smokers. The lack of increased BAL cathelicidin may be explained by multiple factors related to dosing, smoking effects, or putative mechanisms of engagement. Future studies are needed to determine the effects of vitamin D supplementation on lung and blood functional activity.

Citation

Citation: Sanders EC, Burkes RM, Mock JR, et al. Bronchoalveolar lavage and plasma cathelicidin response to 25-hydroxy vitamin D supplementation: a pilot study. J COPD F. 2021; 8(3): 371-381. doi: http://doi.org/10.15326/jcopdf.8.3.2021.0220

Keywords

biomarkers, vitamin D, antimicrobial cationic peptides

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Click to read Bronchoalveolar Lavage and Plasma Cathelicidin Response to 25-Hydroxy Vitamin D Supplementation: A Pilot Study

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Author Affiliations

1. Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora
2. Department of Medicine, National Jewish Health, Denver, Colorado
3. Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor
4. Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora
5. Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
6. Division of Biostatistics and Bioinformatics, Office of Academic Affairs, National Jewish Health, Denver, Colorado
7. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore Maryland
8. VA Boston Healthcare System, Boston, Massachusetts
9. Department of Radiology, National Jewish Health, Denver, Colorado

Address correspondence to:

Kendra A. Young, MSPH, PhD
Department of Epidemiology
Colorado School of Public Health
University of Colorado Anschutz Medical Campus
13001 East 17th Avenue
Room W3142, Campus Box B-119
Aurora, CO 80045
Phone: 303-724-4441
Email: Kendra.Young@UCDenver.edu

Abstract

Background: Previous attempts to explore the heterogeneity of chronic obstructive pulmonary disease (COPD) clustered individual patients using clinical, demographic, and disease features. We developed continuous multidimensional disease axes based on radiographic and spirometric variables that split into an airway-predominant axis and an emphysema-predominant axis.

Methods: The COPD Genetic Epidemiology study (COPDGene^®) is a cohort of current and former smokers, > 45 years, with at least 10 pack years of smoking history. Spirometry measures, blood pressure and body mass were directly measured. Mortality was assessed through continuing longitudinal follow-up and cause of death was adjudicated. Among 8157 COPDGene^® participants with complete spirometry and computed tomography (CT) measures, the top 2 deciles of the airway-predominant and emphysema-predominant axes previously identified were used to categorize individuals into 3 groups having the highest risk for mortality using Cox proportional hazard ratios. These groups were also assessed for causal mortality. Biomarkers of COPD (fibrinogen, soluble receptor for advanced glycation end products [sRAGE], C-reactive protein [CRP], clara cell secretory protein [CC16], surfactant-D [SP-D]) were compared by group.

Findings: High-risk subtype classification was defined for 2638 COPDGene^® participants who were in the highest 2 deciles of either the airway-predominant and/or emphysema-predominant axis (32% of the cohort). These high-risk participants fell into 3 groups: airway-predominant disease only (APD-only), emphysema-predominant disease only (EPD-only) and combined APD-EPD. There was 26% mortality for the APD-only group, 21% mortality for the EPD-only group, and 54% mortality for the combined APD-EPD group. The APD-only group (n=1007) was younger, had a lower forced expiratory volume in 1 second (FEV₁) percent (%) predicted and a strong association with the preserved ratio-impaired spirometry (PRISm) quadrant. The EPD-only group (n=1006) showed a relatively higher FEV₁ % predicted and included largely GOLD stage 0, 1 and 2 partipants. Individuals in each of the 3 high-risk groups were at greater risk for respiratory mortality, while those in the APD-only group were additionally at greater risk for cardiovascular mortality. Biomarker analysis demonstrated a significant association of the APD-only group with CRP, and sRAGE demonstrated greatest significance with both the EPD-only and the combined APD-EPD groups.

Interpretation: Among current and former smokers, individuals in the highest 2 deciles for mortality risk on the airway-predominant axis and the emphysema-predominant axis have unique associations to spirometric patterns, different imaging characteristics, biomarkers and causal mortality.

Citation

Citation: Young KA, Regan EA, Han MK, et al and the COPDGene Investigators. Subtypes of COPD have unique distributions and differential risk of mortality. J COPD F. 2019; 6(5): 400-413. doi: http://doi.org/10.15326/jcopdf.6.5.2019.0150

Keywords

COPD, chronic obstructive pulmonary disease, biomarkers, mortality, COPD Genetic Epidemiology, COPDGene, PRISm, preserved ratio-impaired spirometry, subtypes, airway-predominant disease, emphysema-predominant disease

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Click to read Subtypes of COPD Have Unique Distributions and Differential Risk of Mortality

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Author Affiliations

1. Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston
2. Division of Nephrology, Medical University of South Carolina, Charleston
3. Biomedical Informatics Center, Departments of Public Health Sciences and Oral Health Sciences, Medical University of South Carolina, Charleston
4. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston
5. Centre for Heart Lung Innovation and Department of Radiology, University of British Columbia, Vancouver, Canada
6. Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston
7. Oregon Health and Science University, Portland
8. University of Florida Health Science Center, Gainesville
9. National Jewish Health, Denver, Colorado
10. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
11. Cleveland Clinic Foundation, Ohio
12. University of Cincinnati/Cincinnati Children's Hospital Medical Center, Ohio

* QUANTitative lung CT UnMasking emphysema progression in AATD. A list of the QUANTUM investigators is provided in the Acknowledgements section at the end of the article.

Address correspondence to:

Tatsiana Beiko, MD, MSCR
Medical University of South Carolina
96 Jonathan Lucas Street
Charleston, SC 29425
Email: beiko@musc.edu

Abstract

Computed tomography (CT) lung density is an accepted biomarker for emphysema in alpha-1 antitrypsin deficiency (AATD), although concerns for radiation exposure limit its longitudinal use. Serum proteins associated with emphysema, particularly in early disease, may provide additional pathogenic insights. We investigated whether distinct proteomic signatures characterize the presence and progression of emphysema in individuals with severe AATD and normal forced expiratory volume in 1 second (FEV₁). QUANTitative lung CT UnMasking emphysema progression in AATD (QUANTUM-1) is a multicenter, prospective 3-year study of 49 adults with severe AATD and FEV₁ post-bronchodilator values (Post-BD) ≥ 80% predicted. All participants received chest CT, serial spirometry, and contributed to the serum biobank. Volumetric imaging display and analysis (VIDA) software defined the baseline 15^th percentile density (PD15) which was indexed to CT-derived total lung capacity (TLC). We measured 317 proteins using a multiplexed immunoassay (Myriad Discovery MAP^® panel) in 31 individuals with a complete dataset. We analyzed associations between initial PD15/TLC, PD15/TLC annual decline, body mass index (BMI), and protein levels using Pearson’s product moment correlation. C-reactive protein (CRP), adipocyte fatty acid-binding protein (AFBP), leptin, and tissue plasminogen activator (tPA) were found to be associated with baseline emphysema and all but leptin were associated with emphysema progression after adjustments were made for age and sex. All 4 proteins were associated with BMI after further adjustment for multiple comparisons was made. The relationship between these proteins and BMI, and further validation of these findings in replicative cohorts require additional studies.

Citation

Citation: Beiko T, Janech MG, Alekseyenko AV, et al; for QUANTUM-1 Investigators. Serum proteins associated with emphysema progression in severe alpha-1 antitrypsin deficiency. J COPD F. 2017; 4(3): 204-216. doi: http://doi.org/10.15326/jcopdf.4.3.2016.0180

Keywords

COPD, emphysema, chronic obstructive pulmonary disease, biomarkers, alpha-1 antitrypsin deficiency, proteins, lung densitometry, multiplexed assay

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Click to read Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency

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Author Affiliations

1. Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
2. San Juan Bautista School of Medicine, Caguas, Puerto Rico
3. University of California, San Diego
4. Genentech, San Francisco, California

Address correspondence to:

Craig P. Hersh, MD, MPH
Channing Division of Network Medicine
Brigham and Women’s Hospital
181 Longwood Ave
Boston, MA 02115
Phone: 617-525-0729
Email: craig.hersh@channing.harvard.edu

Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder. COPD patients may have different clinical features, imaging characteristics and natural history. Multiple studies have investigated heterogeneity using statistical methods such as unsupervised clustering to define different subgroups of COPD based largely on clinical phenotypes. Some studies have performed clustering using genetic data or limited numbers of blood biomarkers. Our primary goal was to use proteomic data to find subtypes of COPD within clinically similar individuals. In the Treatment of Emphysema with a gamma-Selective Retinoid Agonist (TESRA) study, multiplex biomarker panels were run in serum samples collected prior to randomization. After implementing an algorithm to minimize missing values, the dataset included 396 COPD individuals and 87 biomarkers. Using hierarchical clustering, we identified 3 COPD subgroups, containing 267 (67.4%), 104 (26.3%), and 25 (6.3%) individuals, respectively. The third cluster had less emphysema on quantitative analysis of chest computed tomography scans (p=0.03) and worse disease-related quality of life based on the St. George’s Respiratory Questionnaire (total score cluster 1: 45.6, cluster 2: 45.4, cluster 3: 56.6; p=0.01), despite similar levels of lung function impairment (forced expiratory volume in 1 second (49.2%, 49.2%, 48.2 % predicted, respectively). Enrichment analysis showed the biomarkers distinguishing cluster 3 mapped to platelet alpha granule and cell chemotaxis pathways. Thus, we identified a subgroup which has less emphysema but may have greater inflammation, which could be potentially targeted with anti-inflammatory therapies.

Citation

Citation: Zarei S, Mirtar A, Morrow JD, Castaldi PJ, Belloni P, Hersh CP. Subtyping chronic obstructive pulmonary disease using peripheral blood proteomics. J COPD F. 2017; 4(2): 97-108. doi: http://doi.org/10.15326/jcopdf.4.2.2016.0147

Keywords

emphysema, biomarkers, inflammation, cluster analysis

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Click to read Subtyping Chronic Obstructive Pulmonary Disease Using Peripheral Blood Proteomics

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Author Affiliations

1. Fundació Clínic per a la Recerca Biomèdica, IDIBAPS, Barcelona, Spain
2. CIBER Enfermedades Respiratorias (CIBERES), Spain
3. Thorax Institute, Hospital Clinic, University of Barcelona, Spain

Address correspondence to:

Álvar Agusti, MD, PhD
Thorax Institute Hospital Clinic
Villarroel 170 (Escalera 3, Planta 5)
Barcelona 08036, Spain
Tel.: +34 93 227 1701;
Fax: +34 93 227 1716
e-mail: alvar.agusti@clinic.ub.es

Abstract

This article does not contain an abstract.

Citation

Citation: Faner R, Agusti A. Fibrinogen and COPD: Now what?

J COPD F. 2015; 2(1): 1-3. doi: http://doi.org/10.15326/jcopdf.2.1.2014.0127

Keywords

COPD, biomarkers, fibrinogen

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Click to read Fibrinogen and COPD: Now what?

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Author Affiliations

1. Division of Lung Diseases
   National Heart, Lung, and Blood Institute
   National Institutes of Health
   Bethesda, MD 20892-7952

Address correspondence to:

James P. Kiley, PhD
Ph: 301-435-0203
kileyj@nhlbi.nih.gov

Abstract

The past decade of research in chronic obstructive pulmonary disease (COPD) has seen a new age of understanding both pathogenic mechanisms and clinical manifestations of the disease. The National Heart, Lung, and Blood Institute (NHLBI) has helped guide this progress with a series of initiatives to stimulate COPD research in various ways. These initiatives were designed to promote a precision medicine approach to treating COPD, one that takes advantage of targeting particular molecular pathways and the individual pathobiologies of the diversity of COPD patients. This review describes the strategic objectives of these initiatives, as well as some of their observed and anticipated outcomes. In addition, we address parallel steps NHLBI has taken to promote COPD awareness among the public. As we look toward the immediate future of COPD research and education, we see a time of great progress in terms of understanding and treatment. Furthermore, while this remains a debilitating and disturbingly prevalent disease, as NHLBI looks even farther ahead, we envision emerging efforts toward COPD prevention.

Citation

Citation: Postow L, Punturieri A, Croxton TL, Weinmann GG, Kiley JP. A decade of National Heart, Lung, and Blood Institute programs supporting COPD research and education. J COPD F. 2014; 1(1): 64-72. doi: http://doi.org/10.15326/jcopdf.1.1.2014.0123

Keywords

COPD, education, Lung, biomarkers, National Heart, Blood Institute, National Institutes of Health, request for applications, funding opportunity announcement, initiative, subpopulations, genomics, resource grant

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Click to read A Decade of National Heart, Lung, and Blood Institute Programs Supporting COPD Research and Education

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