Symptom profiles and inflammatory markers in moderate to severe COPD

Huong Q. Nguyen, Jerald R. Herting, Kenneth C. Pike, Sina A. Gharib, Gustavo Matute-Bello, Soo Borson, Ruth Kohen, Sandra G. Adams, Vincent S. Fan

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15 Scopus citations


Background: Physical and psychological symptoms are the hallmark of patients' subjective perception of their illness. The purpose of this analysis was to determine if patients with COPD have distinctive symptom profiles and to examine the association of symptom profiles with systemic biomarkers of inflammation. Methods: We conducted latent class analyses of three physical (dyspnea, fatigue, and pain) and two psychological symptoms (depression and anxiety) in 302 patients with moderate to severe COPD using baseline data from a longitudinal observational study of depression in COPD. Systemic inflammatory markers included IL1, IL8, IL10, IL12, IL13, INF, GM-CSF, TNF-α (levels >75thcentile was considered high); and CRP (levels >3 mg/L was considered high). Multinominal logistic regression models were used to examine the association between symptom classes and inflammation while adjusting for key socio-demographic and disease characteristics. Results: We found that a 4-class model best fit the data: 1) low physical and psychological symptoms (26%, Low-Phys/Low-Psych), 2) low physical but moderate psychological symptoms (18%, Low-Phys/Mod Psych), 3) high physical but moderate psychological symptoms (25%, High-Phys/Mod Psych), and 4) high physical and psychological symptoms (30%, High-Phys/High Psych). Unadjusted analyses showed associations between symptom class with high levels of IL7, IL-8 (p ≤ .10) and CRP (p < .01). In the adjusted model, those with a high CRP level were less likely to be in the High-Phys/Mod-Psych class compared to the Low-Phys/Low-Psych (OR: 0.41, 95%CI 0.19, 0.90) and Low-Phys/Mod-Psych classes (OR: 0.35, 95%CI 0.16, 0.78); elevated CRP was associated with in increased odds of being in the High-Phys/High-Psych compared to the High-Phys/Mod-Psych class (OR: 2.22, 95%CI 1.08, 4.58). Younger age, having at least a college education, oxygen use and depression history were more prominent predictors of membership in the higher symptom classes. Conclusions: Patients with COPD can be classified into four distinct symptom classes based on five commonly co-occurring physical and psychological symptoms. Systemic biomarkers of inflammation were not associated with symptom class. Additional work to test the reliability of these symptom classes, their biological drivers and their validity for prognostication and tailoring therapy in larger and more diverse samples is needed. Trial registration:, NCT01074515.

Original languageEnglish (US)
Article number173
JournalBMC Pulmonary Medicine
Issue number1
StatePublished - Dec 3 2016

Bibliographical note

Funding Information:
Drs. Nguyen, Herting, Pike, Gharib, Matute-Bello, Borson, Kohen, and Fan have no conflicts of interest to disclose. Sandra G. Adams, MD, MS, FCCP, discloses the following: Investigator/Grant Research: National Institute of Health, Veterans Affairs Cooperative Studies Program, Bayer Pharmaceuticals Corp; Boehringer Ingelheim Pharmaceuticals, Inc; Centocor Inc, GlaxoSmithKline; Novartis Pharmaceuticals AG; Pfizer Inc; Schering-Plough Corp; Honoraria for Speaking at Continuing Education Programs (Unrestricted Grants for Continuing Education): AstraZeneca Pharmaceuticals LP; Bayer Pharmaceuticals Corp; Boehringer Ingelheim Pharmaceuticals, Inc; GlaxoSmithKline; Novartis Pharmaceuticals AG; Pfizer Inc; Schering-Plough Corp.

Funding Information:
This work was supported in part by: 5R01HL093146 and UL1RR025014. Dr. Fan has funding through the Department of Veterans Affairs. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the Department of Veterans Affairs. The funding agencies did not participate in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Publisher Copyright:
© 2016 The Author(s).


  • Anxiety
  • COPD
  • Depression
  • Dyspnea
  • Fatigue
  • Inflammation
  • Pain
  • Symptoms


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