Three-Month Variability of Commonly Evaluated Biomarkers in Clinically Stable COPD

Seon Cheol Park; Narongkorn Saiphoklang; Jonathan Phillips; May-Lin Wilgus; Russell G Buhr; Donald P Tashkin; Christopher B Cooper; Igor Barjaktarevic

doi:10.2147/COPD.S396549

Three-Month Variability of Commonly Evaluated Biomarkers in Clinically Stable COPD

Int J Chron Obstruct Pulmon Dis. 2023 Jul 18:18:1475-1486. doi: 10.2147/COPD.S396549. eCollection 2023.

Authors

Seon Cheol Park^{1

2}, Narongkorn Saiphoklang^{1

3}, Jonathan Phillips⁴, May-Lin Wilgus¹, Russell G Buhr¹, Donald P Tashkin¹, Christopher B Cooper^{1

5}, Igor Barjaktarevic¹

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
² Division of Pulmonology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.
³ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Thammasat University, Pathum Thani, Thailand.
⁴ Inflammation Discovery Research, Amgen, Thousand Oaks, CA, USA.
⁵ Exercise Physiology Research Laboratory, Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Abstract

Introduction: Clinical decisions in chronic obstructive pulmonary disease (COPD) treatment often utilize serially assessed physiologic parameters and biomarkers. To better understand the reliability of these tests, we evaluated changes in commonly assessed biomarkers over 3 months in patients with clinically stable COPD.

Methods: We performed an observational prospective cohort study of 89 individuals with clinically stable COPD, defined as no exacerbation history within 3 months of enrollment. Biomarkers included lung function and functional performance status, patient-reported outcomes of symptoms and health status, and blood markers of inflammation. The correlation between testing at baseline and at 3-month follow-up was reported as the intraclass correlation coefficient (ICC). "Outliers" had significant variability between tests, defined as >1.645 standard deviations between the two measurements. Differences in clinical features between outliers and others were compared.

Results: Participants with COPD (n = 89) were 70.5 ± 6.7 years old, 54 (61%) male, had a 40 pack-year smoking history with 24.7% being current smokers, and postbronchodilator forced expiratory volume in one second (FEV₁) 62.3 ± 22.7% predicted. The biomarkers with excellent agreement between the initial and the follow-up measurements were FEV₁ (ICC = 0.96), Saint George's Respiratory Questionnaire (SGRQ) (ICC = 0.98), COPD Assessment Test (CAT) (ICC = 0.93) and C-reactive protein (CRP) (ICC = 0.90). By contrast, parameters showing less robust agreement were 6-minute walking distance (ICC = 0.75), eosinophil count (ICC = 0.77), erythrocyte sedimentation rate (ICC = 0.75) and white blood cell count (ICC = 0.48). Individuals with greater variability in biomarkers reported chronic bronchitis more often and had higher baseline SGRQ and CAT scores.

Conclusion: Our study evaluated the stability of commonly assessed biomarkers in clinically stable COPD and showed excellent agreement between baseline and three-month follow-up values for FEV₁, SGRQ, CAT and CRP. Individuals with chronic bronchitis and more symptomatic disease at baseline demonstrated greater variability in 3-month interval biomarkers.

Keywords: COPD; biomarkers; repeatability; stability; variability.

Publication types

Observational Study

MeSH terms

Aged
Biomarkers
Bronchitis, Chronic*
C-Reactive Protein
Female
Forced Expiratory Volume
Humans
Male
Prospective Studies
Pulmonary Disease, Chronic Obstructive* / diagnosis
Quality of Life
Reproducibility of Results

Substances

Biomarkers
C-Reactive Protein

Grants and funding

This study was supported by an investigator-initiated grant to Dr Christopher B Cooper from Amgen, Inc. (CTR#20147154).