Correlations between Biological and Behavioral Factors and Fatigue in Sickle Cell Disease in Adolescents and Young AdultsSuzanne Ameringer, PhD, RNR. K. Elswick, Jr. PhDWally Smith, MDVirginia Commonwealth University

Council for the Advancement of Nursing Science2012 State of the Science Congress on Nursing Science

Washington, DC

Sickle Cell Disease

Genetic hemolytic disorders characterized by: Chronic profound hemolytic anemia

Vaso-occlusion

Inflammatory reactions

Worldwide: 300,000 infants born with SCD annually (WHO, 2010)

US: 1 in 500 AA, 1 in 36,000 HA (NHLBI)

Life expectancy- early middle age

Fatigue in SCDFatigue affects quality of life (cognitive function,

well-being, daily activities) (Falk, 2007; Kralik, 2005, Ream, 1997; Smith, 2010)

Illness characteristics that may lead to or increase SCD fatigue: Anemia, inflammation, pain, anxiety, depressive symptoms, stress

Research on SCD fatigue sparse Tired, lack energy (While, 2004) Vitality lower compared to healthy individuals (McClish, 2005)

Adolescents and young adults (AYA) with SCD particularly vulnerable as begin to pursue life goals

Potential Correlates of SCD fatigue

Anemia (Cella, 2002; Yeh, 2008)

Pain (Ballas, 2006; McClish, 2005)

Anxiety and depressive symptoms (Cathebras, 1992; Whitsett, 2008)

Stress (Aaronson, 2003; Kerr, 2008)

Sleep quality (Lavidor, 2003; Owen, 1999)

Inflammation Sickled RBCs disrupt and stimulate the vascular endothelium

causing inflammation.

Potential inflammatory cytokines involved with fatigue Interleukin (IL) – 1

Affects hippocampal activity (integral to sleep regulation) (Luk, 1999)

Tumor necrosis factor(TNF) – α Alters slow-wave activity associated with non-rapid eye movement

sleep (Yoshida, 2004)

IL - 1 and Tumor necrosis factor(TNF) – α associated with: Decreased muscle strength (Visser, 2002) Decreased exercise capacity (Carmichael, 2006)

IL - 6 Interferes with stage of REM sleep (Spath-Schwalbe, 1998)

Purpose

Examine the relationships between biological and behavioral factors and fatigue in adolescents and young adults with SCD

Conceptual Model of SCD Fatigue

Strategies to Manage Fatigue

Fatigue

Quality of Life

Neuroendocrine & Immunological

Mediators

Biological andBehavioralVariables

Inflammation, oxygenation, pain, anxiety, depressive symptoms, sleep

quality, stress Personal and

Disease-relatedCofactors

Age, gender, disease severity, crisis status

Sickle Cell

Disease

MethodsDesign: Cross-sectional, descriptiveSample:

Inclusion criteria: Ages 15-30 years with SCD

Exclusion criteria: Participant’s (and/or minor’s parent’s) inability to read and write

in English Women who were pregnant

Procedure: Recruited from VCUHS pediatric and adult hematology clinics

and units

• Brief Fatigue Inventory (BFI)• PROMIS Fatigue Short Form• Multidimensional Fatigue Symptom Inventory-SF (MFSI-SF)

Fatigue

• Inflammation: IL-1b, IL-6, IL-10, TNF-α• HemoglobinBiological

• Age• Sex• Disease Severity

Demo/Disease

• Pain: Brief Pain Inventory (BPI)• Stress: Perceived Stress Scale (PSS)• Anxiety and depression: State Trait Anxiety Inventory (STAI)• Sleep quality (Pittsburgh Sleep Quality Index (PSQI)

Behavioral

Sample Characteristics (N = 60)Variable

Mean (SD)Age (range 15-30 yrs) 22.53 (4.12)Hemoglobin (g/dL) (range 6 – 14.9) 9.6 (2.21)

n (%)Sex Male 24 (40.0) Female 36 (60.0)Genotype

SS 39 (65.0) SC 11 (18.4) Sβ+ Thalassemia 6 (10.0) Sβo Thalassemia 2 (3.3) Unknown 2 (3.3)

Disease Severity Mild 15 (25.0) Severe 45 (75.0)

Mean (SE) Fatigue Measures: Total Scores

Measure# of

Items M (SE)Potential

Range

BFI Total 9 4.3 (0.28) 0–10

MFSI-SF Total 30 14.9 (2.62) -24–96

PROMIS Fatigue SF 7 19.8 (0.68) 7–35

Correlations between Fatigue Measures and Cytokines

IL-1b IL-6 IL-10 TNF-α

BFI

BFI Usual -0.06 0.19 -0.20 0.03

BFI Worst -0.15 0.17 -0.22 -0.16

BFI Interference -0.10 0.13 -0.12 -0.09

PROMIS -0.13 0.17 0.09 0.03

MFSI-SF -0.18 0.06 -0.01 -0.18

Hemoglobin (g/dL)

6 8 10 12 14 16

BFI

Tot

al

0

2

4

6

8

10

p-value = 0.19

Hemoglobin (g/dL)

6 8 10 12 14 16

MFS

I-SF

Tota

l

-40

-20

0

20

40

60

80

p-value = 0.82

Hemoglobin (g/dL)

6 8 10 12 14 16

PR

OM

IS F

atig

ue S

F

5

10

15

20

25

30

35

p-value = 0.03

Fatigue and HemoglobinScatterplot with Linear Regression Line

BFI MFSI-SF

PROMIS

Variable BFI PROMIS MFSI-SFBPI average pain 0.51*** 0.31* 0.48***

BPI worst pain 0.65*** 0.41*** 0.40**

BPI interference 0.55*** 0.42*** 0.45***STAI – State anxiety 0.44*** 0.45*** 0.70***STAI – Trait anxiety 0.38** 0.35** 0.55***PSS – stress 0.41*** 0.37** 0.69***CESD – depressive mood 0.42*** 0.45*** 0.45***PSQI – sleep quality 0.53*** 0.47*** 0.51***Age 0.24 0.07 0.14

* p < 0.05, **p < 0.01, ***p≤0.001

Correlations between Fatigue and Behavioral Variables

Mean (SE) Fatigue Scores by Sex

Measure Female (n = 36) Male (n = 24) t P-value

BFI Total 4.63 (0.39) 3.82 (0.37) -1.51 0.07

PROMIS 21.31 (0.85) 17.58 (0.97) -2.89 0.0029*

MFSI total 15.42 (3.70) 14.09 (3.59) -0.26 0.4

Mean (SE) Fatigue Scores by Disease Severity

Measure Mild (n = 15) Severe (n = 45) t P-value

BFI Total 4.24 (0.55) 4.33 (0.33) 0.14 0.56

PROMIS 19.20 (1.63) 20.02 (0.73) 0.46 0.67

MFSI total 15.41 (5.85) 14.72 (2.95) -0.11 0.46

Summary

All fatigue measures were significantly associated with stress, anxiety, sleep, depressive symptoms, pain

Fatigue scores were not significantly associated with cytokines (inflammation), hemoglobin (except PROMIS), or age

Fatigue scores did not differ by sex(except PROMIS) or disease severity

Limitations

Cross-sectional

Sample – convenience, one institution

No age-matched controls

Small sample size

Conclusions Various correlates of fatigue suggest common

etiologies may be at play

Distinguishing etiologies may be difficult

Fatigue may be a measure of health -May be important to screen for other conditions

Longitudinal studies needed to examine the trajectory of fatigue

Need interventions to better manage or reduce fatigue

AcknowledgementsNINR (P30 NR011403,

Center of Excellence for Biobehavioral Approaches to Symptom Management (Grap, PI).

Mary Jo GrapNancy McCainDebra LyonRita PicklerShari CordonYui Matsuda

Julie StillmanErica GregoryVirginia Smith India SislerJennifer NewlinPatients and families at the

VCU pediatric and adult clinics