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, 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

Abstract

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: Clinicaltrials.gov, NCT01074515 .

Keywords: Anxiety; COPD; Depression; Dyspnea; Fatigue; Inflammation; Pain; Symptoms.

Figures

Fig. 1
Fig. 1
Pattern of COPD symptom classes based on normalized symptom scores. *Z-scores on Y-axis; higher z-scores indicate worse symptoms. Class 1 (diamond): Low physical and low psychological symptom burden (Low-Phys/Low-Psych); 26%. Class 2 (square): Low physical and moderate psychological symptom burden (Low-Phys/Mod-Psych); 18%. Class 3 (triangle): High physical and moderate psychological symptom burden (High-Phys/Mod-Psych); 25%. Class 4 (circle): High physical and high psychological symptom burden (High-Phys/High-Psych); 30%

References

    1. Garcia-Aymerich J, Gomez FP, Benet M, et al. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes. Thorax. 2011;66(5):430–437. doi: 10.1136/thx.2010.154484.
    1. Rennard SI, Locantore N, Delafont B, et al. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis. Ann. Am. Thorac. Soc. 2015;12(3):303–312. doi: 10.1513/AnnalsATS.201403-125OC.
    1. Park SK, Larson JL. Symptom cluster, healthcare use and mortality in patients with severe chronic obstructive pulmonary disease. J Clin Nurs. 2014;23(17–18):2658–2671. doi: 10.1111/jocn.12526.
    1. Park SK, Meldrum CA, Larson JL. Subgroup analysis of symptoms and their effect on functioning, exercise capacity, and physical activity in patients with severe chronic obstructive pulmonary disease. Heart Lung. 2013;42(6):465–472. doi: 10.1016/j.hrtlng.2013.08.008.
    1. Clark N, Fan VS, Slatore CG, et al. Dyspnea and pain frequently co-occur among Medicare managed care recipients. Ann. Am. Thorac. Soc. 2014;11(6):890–897. doi: 10.1513/AnnalsATS.201310-369OC.
    1. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46–56. doi: 10.1038/nrn2297.
    1. Musselman DL, Lawson DH, Gumnick JF, et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med. 2001;344(13):961–966. doi: 10.1056/NEJM200103293441303.
    1. Eagan TM, Ueland T, Wagner PD, et al. Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study. Eur Respir J. 2010;35(3):540–548. doi: 10.1183/09031936.00088209.
    1. Al-shair K, Kolsum U, Dockry R, Morris J, Singh D, Vestbo J. Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD. Respir Res. 2011;12:3. doi: 10.1186/1465-9921-12-3.
    1. Marinho PE, Castro CM, Raposo MC, Guerra RO, de Andrade AD. Depressive symptoms, inflammatory markers and body composition in elderly with and without chronic obstructive pulmonary disease (COPD) Arch Gerontol Geriatr. 2012;54(3):453–458. doi: 10.1016/j.archger.2011.05.006.
    1. Hanania NA, Mullerova H, Locantore NW, et al. Determinants of Depression in the ECLIPSE Chronic Obstructive Pulmonary Disease Cohort. Am J Respir Crit Care Med. 2011;183(5):604–611. doi: 10.1164/rccm.201003-0472OC.
    1. Janssen DJ, Mullerova H, Agusti A, et al. Persistent systemic inflammation and symptoms of depression among patients with COPD in the ECLIPSE cohort. Respir Med. 2014;108(11):1647–1654. doi: 10.1016/j.rmed.2014.07.013.
    1. Quint JK, Baghai-Ravary R, Donaldson GC, Wedzicha JA. Relationship between depression and exacerbations in chronic obstructive pulmonary disease. Eur Respir J. 2008;32(1):53–60.
    1. Spitzer RL, Williams JB, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry. 1992;49(8):624–629. doi: 10.1001/archpsyc.1992.01820080032005.
    1. Eakin EG, Resnikoff PM, Prewitt LM, Ries AL, Kaplan RM. Validation of a new dyspnea measure: the UCSD Shortness of Breath Questionnaire. University of California, San Diego. Chest. 1998;113(3):619–624. doi: 10.1378/chest.113.3.619.
    1. Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax. 1987;42(10):773–778. doi: 10.1136/thx.42.10.773.
    1. Ware JE, Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–483. doi: 10.1097/00005650-199206000-00002.
    1. Ng TP, Niti M, Tan WC, Cao Z, Ong KC, Eng P. Depressive symptoms and chronic obstructive pulmonary disease: effect on mortality, hospital readmission, symptom burden, functional status, and quality of life. Arch Intern Med. 2007;167(1):60–67. doi: 10.1001/archinte.167.1.60.
    1. Choudhury G, Rabinovich R, MacNee W. Comorbidities and systemic effects of chronic obstructive pulmonary disease. Clin Chest Med. 2014;35(1):101–130. doi: 10.1016/j.ccm.2013.10.007.
    1. Muthen B. Latent variable analysis: Growth mixture modeling and related techniques for longitudinal data. In: Kaplan D, editor. Handbook of quantitative methodology for the social sciences. Newbury Park: Sage; 2004. pp. 345–368.
    1. Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):435–452. doi: 10.1164/rccm.201111-2042ST.
    1. Singh D, Fox SM, Tal-Singer R, Bates S, Riley JH, Celli B. Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort. PLoS One. 2014;9(9):e107381. doi: 10.1371/journal.pone.0107381.
    1. Fan VS, Gharib SA, Martin TR, Wurfel MM. COPD disease severity and innate immune response to pathogen-associated molecular patterns. Int J COPD. 2016;11:467–477. doi: 10.2147/COPD.S94410.
    1. Tak LM, Bakker SJ, Slaets JP, Rosmalen JG. Is high-sensitive C-reactive protein a biomarker for functional somatic symptoms? A population-based study. Brain Behav Immun. 2009;23(7):1014–1019. doi: 10.1016/j.bbi.2009.05.059.
    1. Agusti A, Edwards LD, Rennard SI, et al. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One. 2012;7(5):e37483. doi: 10.1371/journal.pone.0037483.
    1. Duivis HE, de Jonge P, Penninx BW, Na BY, Cohen BE, Whooley MA. Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the heart and soul study. Am J Psychiatry. 2012;168(9):913–920. doi: 10.1176/appi.ajp.2011.10081163.
    1. Illi J, Miaskowski C, Cooper B, et al. Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression. Cytokine. 2012;58(3):437–447. doi: 10.1016/j.cyto.2012.02.015.
    1. Bremmer MA, Beekman AT, Deeg DJ, et al. Inflammatory markers in late-life depression: results from a population-based study. J Affect Disord. 2008;106(3):249–255. doi: 10.1016/j.jad.2007.07.002.
    1. John U, Meyer C, Rumpf HJ, Hapke U. Smoking, nicotine dependence and psychiatric comorbidity--a population-based study including smoking cessation after three years. Drug Alcohol Depend. 2004;76(3):287–295. doi: 10.1016/j.drugalcdep.2004.06.004.
    1. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101–2107. doi: 10.1001/archinte.160.14.2101.
    1. Naberan K, Azpeitia A, Cantoni J, Miravitlles M. Impairment of quality of life in women with chronic obstructive pulmonary disease. Respir Med. 2012;106(3):367–373. doi: 10.1016/j.rmed.2011.09.014.
    1. Laurin C, Lavoie KL, Bacon SL, et al. Sex differences in the prevalence of psychiatric disorders and psychological distress in patients with COPD. Chest. 2007;132(1):148–155. doi: 10.1378/chest.07-0134.
    1. Blinderman CD, Homel P, Billings JA, Tennstedt S, Portenoy RK. Symptom distress and quality of life in patients with advanced chronic obstructive pulmonary disease. J Pain Symptom Manage. 2009;38(1):115–123. doi: 10.1016/j.jpainsymman.2008.07.006.
    1. Tinetti ME, McAvay GJ, Chang SS, et al. Contribution of multiple chronic conditions to universal health outcomes. J Am Geriatr Soc. 2012;59(9):1686–1691. doi: 10.1111/j.1532-5415.2011.03573.x.

Source: PubMed

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