Archives of Palliative Care and Medicine

Article / research article

"What is the Personal Immune Price for Hospice Caregivers? A Case-Control Study "

Abdullah Ladha1, Wendy Kay Nevala2, Sarah Lee3, Robert A Vierkant4, Judith Salmon Kaur5

1Department of Hematology-Oncology, State University of New York, USA

2Oncology Research, Mayo Clinic MN, USA

3Division of Internal Medicine, Palliative Medicine, Kaiser Permanente, USA

4Division of Biomedical Statistics and Informatics, Mayo Clinic MN, USA

5Division of Hematology-Oncology, Mayo Clinic FL, USA

*Corresponding author(s): Abdullah Ladha, Department of Hematology-Oncology, State University of New York, USA. Tel: +1-3154648286; Fax: +1-3154648279; Email: ladhaa@upstate.edu;

Judith Salmon Kaur, Department of Hematology-Oncology, Mayo Clinic, USA. Tel: +1-9049532795; Fax: +1-9049532315; Email: kaur.judith@mayo.edu

Received Date: 21 July, 2018; Accepted Date: 16 November, 2018; Published Date: 23 November, 2018




Variables

N=37, Frequency (%)

Sex

Female

33 (89.2)

Male

4 (10.8)

Age, y, mean (range)

69.7 (45-88)

Marital status

Married

34 (91.9)

Single

2 (5.4)

Widowed

1 (2.7)

Annual household income

<$25K

2 (5.4)

$25-50K

17 (45.9)

$50-75K

8 (21.6)

$75-100K

4 (10.8)

>$100K

3 (8.1)

Unknown

3 (8.1)

Employment

Full-time

5 (13.5)

Part-time

6 (16.2)

Not working

4 (10.8)

Retired

21 (56.8)

Unknown

1 (2.7)

 

Table 1: Caregivers Demographics.

 

Variables

N=37, Frequency (%)

Hours per day spent as caregiver

0-10

16 (43.2)

>10

21 (56.8)

Total duration of caregiving in months

<1

12 (32.4)

1-12

9 (24.3)

12-24

3 (8.1)

>24

13 (35.1)

Relationship to patient

Spouse

33 (89.2)

Child

2 (5.4)

Parent

2 (5.4)

Medical Problems

Hypertension

16 (56.7)

Cardiac

3 (8.1)

Diabetes Mellitus

5 (13.8)

Pulmonary disease

2 (5.56)

Sleep disorder

3 (8.1)

History of cancer

9 (18.4)

Gastrointestinal disorder

7(19.4)

Mood disorder

7(19.4)

 

Table 2: Caregiver characteristics.

Biomarkers

Pairs

Caregiver, Median

Control, Median

Paired Difference, Median (IQR)

P Value

IL-2

38

3.2

1.9

0.3 (−1.1, 5.8)

0.01

IL-4

38

2.1

8.4

−1.3 (−23.3, 0.3)

<.001

IL-6

38

2.3

2.1

0.1 (−1.6, 1.5)

0.24

IL-8

38

4.2

1.6

1.4 (−0.4, 4.8)

0.005

IL-13

38

2.5

2.5

0.1 (−3.5, 2.1)

0.05

IL-12

38

12.2

7.7

5.5 (−0.6, 17.4)

0.003

IL-1α

38

6.2

3.9

−1.1 (−2.2, 15.2)

0.65

IL-1β

38

2.8

1.6

1.1 (−0.7, 6.1)

0.001

IFNγ

38

10.3

14.1

−1.8 (−10.0, 7.0)

0.33

TGFα

38

2.8

2.7

−0.2 (−0.9, 1.9)

0.54

TNFα

38

9.6

10

1.1 (−5.0, 4.2)

0.88

TNFβ

38

4.1

3.2

−0.9 (−2.7, 7.4)

0.21

CRP

38

2.3

0.9

1.2 (−0.1, 4.3)

<.001

CD3+CD8+

35

18.5

10.6

8.0 (−0.2, 15.6)

0.003

CD3+CD4+

35

35

25.9

9.1 (−1.1, 18.5)

0.001

CD16+56+

38

11.3

7.2

5.5 (−1.6, 10.6)

0.003

CD3+69+

39

5.4

2

3.4 (1.0, 6.5)

<.001

CD3+62L+

39

19

5.9

11.9 (6.4, 21.5)

<.001

CD4+TIM3+

39

4.1

1

3.1 (0.6, 4.5)

<.001

Treg

39

64.9

57

6.3 (−1.7, 15.3)

0.005

G-CSF

38

75.8

134.6

−59.3 (−107.3, 1.3)

<.001

GM-CSF

38

21.7

7.5

8.4 (−5.1, 29.9)

<.001

EGF

38

61

13.8

49.9 (5.5, 93.4)

<.001

Abbreviations:

CRP         : C-Reactive Protein

EGF         : Epidermal Growth Factor

G-CSF     : Granulocyte–Colony-Stimulating Factor

GM-CSF : Granulocyte Macrophage–Colony-Stimulating Factor

IFN         :  Interferon

IL            :  Interleukin

IQR         : Interquartile Ranges

TGF        :  Transforming Growth Factor

TNF        : Tumor Necrosis Factor

Treg        : Regulatory T Cell


Table 3: Cytokines.

Biomarkers

Pairs

Caregiver, Median

Control, Median

Paired Difference Median (IQR)

P Value

Eotaxin (CCL11, CCL24, CCL26)

38

95.3

241.7

−148.3 (−246.3, −94.5)

<.001

Fractalkine (CX3CL1)

38

93.4

127.4

−32.6 (−85.3, 13.0)

0.009

GRO (CXCL1, CXCL2, CXCL3)

37

356.7

239

127.7 (−73.0, 339.1)

0.007

IP10 (CXCL10)

38

335.8

1506.5

−1,092 (−2,211, −538.8)

<.001

MCP-3 (CCL7)

38

17

159.6

−144.2 (−151.7, −132.5)

<.001

MDC (CCL22)

38

784.8

1434

−698.4 (−1051, −355.0)

<.001

MIP1b (CCL4)

38

20.8

37.6

−14.5 (−32.9, 2.6)

<.001

MCP-1 (CCL2)

38

241

199.8

−0.8 (−75.6, 190.4)

0.351

Abbreviations:

GRO  :  Growth-regulated oncogene;

IP       :  Induced protein;

IQR    :  Interquartile range;

MCP  :  Monocyte chemotactic protein;

MDC : Macrophage-derived chemokine;

MIP   :   Macrophage inflammatory protein;


Table 4: Chemokines.

  1. (2017) National Hospice and Palliative Care Organization. Facts and Figures, 2017 (Ed).
  2. Gomes B, Higginson IJ (2006) Factors influencing death at home in terminally ill patients with cancer: systematic review. BMJ 332: 515-521.
  3. Schulz R, Beach SR (1999) Caregiving as a risk factor for mortality: the Caregiver Health Effects Study. JAMA 282: 2215-2219.
  4. Brown SL, Smith DM, Schultz R (2009) Caregiving behavior is associated with decreased mortality risk. Psychol Sci 20: 488-494.
  5. Roth DL, Haley WE, Hovater M (2013) Family caregiving and all cause mortality: findings from population based propensity based analysis. Am J Epidemiol 178: 1571-1578.
  6. O'Reilly D, Connolly S, Rosato M (2008) Is caring associated with an increased risk of mortality? A longitudinal study. Soc Sci Med 67: 1282-90.
  7. Waldrop DP, Meeker MA (2011) Crisis in caregiving: when home-based end-of-life care is no longer possible. J Palliat Care 27: 117-125.
  8. Schulz R, Mendelsohn AB, Haley WE (2003) End-of-life care and the effects of bereavement on family caregivers of persons with dementia. N Engl J Med 349: 1936-1942.
  9. Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5: 243-251.
  10. Mausbach BT, von Kanel R, Roepke SK, Moore R, Patterson TL, et al. (2011) Self-efficacy buffers the relationship between dementia caregiving stress and circulating concentrations of the proinflammatory cytokine interleukin-6. Am J Geriatr Psychiatry. 19: 64-71.
  11. Gouin JP, Glaser R, Malarkey WB, Beversdorf D, Kiecolt-Glaser J (2012) Chronic stress, daily stressors, and circulating inflammatory markers. Health Psychol 31: 264-268.
  12. Rohleder N, Marin TJ, Ma R, Miller GE (2009) Biologic cost of caring for a cancer patient: dysregulation of pro- and anti-inflammatory signaling pathways. J Clin Oncol 27: 2909-2915.
  13. von Kanel R, Dimsdale JE, Mills PJ (2006) Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and D-dimer. J Gerontol A Biol Sci Med Sci 61: 963-969.
  14. Kiecolt-Glaser JK, Glaser R, Gravenstein S, Malarkey WB, Sheridan J (1996) Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci 93: 3043-3047.
  15. Glaser R, Sheridan J, Malarkey WB, Mac Callum RC, Kiecolt-Glaser JK (2000) Chronic stress modulates the immune response to a pneumococcal pneumonia vaccine. Psychosom Med 62: 804-807.
  16. Glaser R, Kiecolt-Glaser JK, Malarkey WB, Sheridan JF. (1998) The influence of psychological stress on the immune response to vaccines. Ann N Y Acad Sci 840: 649-655.
  17. Esterling BA, Kiecolt-Glaser JK, Glaser R (1996) Psychosocial modulation of cytokine-induced natural killer cell activity in older adults. Psychosom Med 58: 264-272.
  18. Damjanovic AK, Yang Y, Glaser R, Janice K Kiecolt-Glaser, Huy Nguyen, et al. (2007) Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients. J Immunol 179: 4249-4254.
  19. Olson JE, Ryu E, Johnson KJ, Koenig BA, Maschke KJ, et al. (2013) The Mayo Clinic Biobank: a building block for individualized medicine. Mayo Clin Proc 88: 952-962.
  20. Nevala WK, Vachon CM, Leontovich AA, Scott CG, Thompson MA, et al. (2009) Evidence of systemic Th2-driven chronic inflammation in patients with metastatic melanoma. Clin Cancer Res 15: 1931-1939.
  21. Masopust D, Schenkel JM (2013) The integration of T cell migration, differentiation and function. Nat Rev Immunol 13: 309-320.
  22. Dinarello CA (2011) A clinical perspective of IL-1beta as the gatekeeper of inflammation. Eur J Immunol 41: 1203-1217.
  23. Xu J, Yin Z, Cao S, Liu L, Yin Y, et al. (2013) Systematic review and meta-analysis on the association between IL-1B polymorphisms and cancer risk. PLoS One 8: e63654.
  24. Liu M, Guo S, Stiles JK (2011) The emerging role of CXCL10 in cancer (Review). Oncol Lett 2: 583-589.
  25. Nagarsheth N, Wicha MS, Zou W (2017) Chemokines in the cancer miocroenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 17: 559-572.
  26. Zhang Y, Cai P, Liang T, Wang L, Hu L, et al. (2017) TIM-3 is a potential prognostic marker for patients with solid tumor: A systematic review and meta-analysis. Oncotarget 8: 31705-31713.
  27. Qamar A, Rader DJ (2012) Effect of interleukin 1beta inhibition in cardiovascular disease. Curr Opin Lipidol 23: 548-553.
  28. von Kanel R, Mausbach BT, Patterson TL, Dimsdale JE, Aschbacher K, et al. (2008) Increased Framingham Coronary Heart Disease Risk Score in dementia caregivers relative to non-caregiving controls. Gerontology 54: 131-137.
  29. von Kanel R, Ancoli-Israel S, Dimsdale JE, Mills PJ, Mausbach BT, et al. (2010) Sleep and biomarkers of atherosclerosis in elderly Alzheimer caregivers and controls. Gerontology 56: 41-50.
  30. Zieziulewicz TJ, Mondal TK, Gao D, Lawrence DA (2013) Stress-induced effects, which inhibit host defenses, alter leukocyte trafficking. Cell Stress Chaperones 18: 279-291.
  31. Mills PJ, Ziegler MG, Patterson T, Dimsdale JE, Hauger R, et al. (1997) Plasma catecholamine and lymphocyte beta 2-adrenergic receptor alterations in elderly Alzheimer caregivers under stress. Psychosom Med 59: 251-256.

Citation: Ladha A, Nevala WK, Lee S, Vierkant RA, Kaur JS (2018) What is the Personal Immune Price for Hospice Caregivers? A Case-Control Study. Arch Palliat Care Med: APCM-111. DOI:10.29011/APCM-111.00011

free instagram followers instagram takipçi hilesi