Associations of Fatigue and Patient-Reported Outcomes in Pulmonary

Arterial Hypertension

Lea Ann Matura, PhD, RNAssistant Professor

University of PennsylvaniaSchool of Nursing

Thank You

• Funding- Bouve College of Health Sciences, Northeastern University intramural grant and Sigma Theta Tau International Gamma Epsilon grant

• Co-Investigators– Diane L. Carroll, PhD, RN– Annette McDonough, PhD, RN

• Collaborators– Greg Ball, PhD

• Students• Participants

No conflicts of interest for the investigators

World Health Organization (WHO) Pulmonary Hypertension Groups

WHO Group I – Pulmonary Arterial Hypertension (PAH)

WHO Group II - Pulmonary hypertension due to left heart disease o Atrial or ventricular disease o Valvular disease

WHO Group III - Pulmonary hypertension due to lung diseases or hypoxemia o Chronic Obstructive Pulmonary Disease (COPD),

Interstitial Lung Disease o Sleep-disordered breathing, alveolar hypoventilationo Chronic exposure to high altitude

WHO Group IV - Pulmonary hypertension due to chronic thrombotic and/or embolic disease o Pulmonary embolism in the proximal or

distal pulmonary arteries o Embolization of other matter

WHO Group V – Miscellaneous Sarcoidosis(Galiè et al., 2009)

Pulmonary Arterial Hypertension (PAH)

• Elevated mean pulmonary artery pressure (PAP) > 25 mmHg (normal mean PAP ~ 9-12 mmHg) and pulmonary capillary wedge pressure < 15 mmHg

• Etiology– Idiopathic – Familial

– Connective tissue disease, congenital shunts between systemic and pulmonary circulation, sickle cell, portal hypertension, HIV infection, drugs/toxins

Pathobiology

• Vasoconstriction• Remodeling of the pulmonary vessel

and• Thrombosis (Galiè, 2009)

Pulmonary Arterial Hypertension (PAH)

• Primary symptoms-dyspnea on exertion and fatigue

• Affects women (~78%), mean age diagnosis ~50 years

• Approximately 20,000-30,000 cases in US

• Mean 2 years from symptom onset to diagnosis

• Mortality- 61% at 5 years

(Galiè, et al., 2009; Badesch, et al., 2010)

Fatigue

• Definition- a multidimensional concept defined as an overwhelming, debilitating, and sustained sense of exhaustion that decreases one’s ability to carry out daily activities, to work effectively, and to function (Cella et al., 2007)

Purpose

• To determine those socio-demographic/clinical variables and patient-reported outcomes (symptoms, health-related quality of life) associated with fatigue in people with PAH.

Methods

• Design-Cross sectional, descriptive• Sample- A convenience sample of adults with

World Health Organization Group I etiology (PAH) were recruited from an outpatient clinic, support groups

• Univariate- descriptive statistics• Bivariate analysis determined variables

associated with fatigue to include in multivariate analysis (multiple regression) (p<.20)

• Data analysis-SPSS 19

Measures• Socio-demographic/clinical data form

• PAH Symptom Scale- rating symptom intensity on 17 PAH symptoms

• Fatigue measured on this scale for current study

• Score range: 0-10; higher score indicates worse symptom intensity (cronbach alpha= .90)

• Medical Outcomes Study Short Form-36 v. 2-generic measure of health status/HRQOL

• Score range 0-100; higher scores indicate better health status/HRQOL (cronbach alpha=.84) (Brazier et

al., 1992).

• US Cambridge Pulmonary Hypertension Outcome Review (US CAMPHOR) to measure HRQOL (higher scores indicate worse symptoms, functioning and quality of life)

• Score range: Energy 0-10; Breathlessness 0-8; Mood 0-7; Symptom total 0-25; Activity total 0-30) (cronbach alpha= .89) (McKenna et al., 2008)

• Profile of Mood States-Short Form (POMS) to measure psychological states

• Score range- Higher scores indicate increased distress, except for vigor; Sub scores range from 0-20; Total scores range from -20-100 (cronbach alpha=.65) (McNair et al., 2009)

PAH Symptom Scale

Symptoms 

Rate Symptom Intensity

  None Worst Possible

Fatigue 0 1 2 3 4 5 6 7 8 9 10

Chest pain/discomfort 

0 1 2 3 4 5 6 7 8 9 10

Dizzy/Lightheaded 

0 1 2 3 4 5 6 7 8 9 10

Passing Out 

0 1 2 3 4 5 6 7 8 9 10

Fast Heart Beat/Palpitations 

0 1 2 3 4 5 6 7 8 9 10

Shortness of Breath at rest 

0 1 2 3 4 5 6 7 8 9 10

Shortness of Breath with exertion  

0 1 2 3 4 5 6 7 8 9 10

Shortness of Breath when lying down 

0 1 2 3 4 5 6 7 8 9 10

Awaken at night short of breath 

0 1 2 3 4 5 6 7 8 9 10

Swelling of ankles /feet 

0 1 2 3 4 5 6 7 8 9 10

Cough 

0 1 2 3 4 5 6 7 8 9 10

Hoarseness 

0 1 2 3 4 5 6 7 8 9 10

Abdominal Swelling 

0 1 2 3 4 5 6 7 8 9 10

Nausea 

0 1 2 3 4 5 6 7 8 9 10

Loss of appetite 

0 1 2 3 4 5 6 7 8 9 10

Difficulty Sleeping 0 1 2 3 4 5 6 7 8 9 10 

Numb, painful hands or feet with cold and stress (Raynaud’s phenomenon)

0 1 2 3 4 5 6 7 8 9 10

Results

Socio-Demographics

&

Clinical Characteristics

Variable (N=191) Totaln=191

Mean + SD age (years) 53.2 + 15.1

Gender: female 162 (85%)

Ethnicity: Caucasian

 168 (88%)

Marital Status Married

 97 (51%)

Living Arrangements With family/friends

 141 (74%)

Education:College graduate

 113 (59%)

Working Status Full-time Part-time Retired Disabled

 36 (19%)21 (11%)43 (23%)77 (43%)

PAH Etiology Idiopathic Connective Tissue Disease Congenital Heart Disease Drugs (fenfluramine/phentermine)

 104 (55%)34 (18%)8 (4%)8 (4%)

Functional Class I II III IV

 22 (12%)36 (19%)54 (28%)79 (41%)

Oxygen Use 115 (60%)Medications Calcium Channel Blockers Endothelin Receptor Antagonists Phosphodiesterase Type-5 inhibitors (PDE-5) Prostanoid analogs Diuretics Digoxin

 46 (24%)95 (50%)110 (58%)75 (39%)117 (61%)29 (15%)

0102030405060708090

100

Symptom Prevalence

0102030405060708090

100 * *Symptom Prevalence

Symptom Intensity (0-10) Mean+SDSOB with exertion 6.2 + 2.7Fatigue 5.0 + 2.5Difficulty sleeping 3.2 + 3.4Swelling of ankles/feet 2.9 + 3.1Fast heart beat/palpitations 2.9 + 2.6Raynaud’s phenomenon 2.7 + 3.4Dizzy/Lightheaded 2.6 + 2.5Abdominal swelling 2.3 + 3.2Cough 2.3 + 2.6Chest pain/discomfort 2.2 + 2.4Loss of appetite 1.9 + 2.5SOB at rest 1.8 + 2.3SOB while lying down 1.7 + 2.2Nausea 1.5 + 2.4Hoarseness 1.5 + 2.3Awaken at night short of breath 0.9 + 1.8

Passing out 0.4 + 1.5

Symptom Intensity Scores

SF-36

Subscale PAH (N=191) Mean + SD

General Health 37.1 + 25.9

Physical function 41.5 + 25.9

Role physical 36.4 + 40.3

Pain 66.4 + 27.6

Vitality 41.3 + 22.7

Social function 65.5 + 26.4

Mental health 71.9 + 19.3

Role emotional 67.0 + 41.5

Composite Summary scores  

Mental health 61.5 + 21.0

Physical health 45.4 + 22.7

US CAMPHOR

 N=191 Mean + SD 

Energy 4.8 + 3.3

Breathlessness 3.5 + 2.3

Mood 1.8 + 2.0

Symptom total 10.2 + 6.4

Activity total 9.8 + 6.2

Quality of life total 8.7 + 6.2

Higher scores indicate worse symptoms, functioning and quality of life. Score ranges: Energy 0-10; Breathlessness 0-8; Mood 0-7; Symptom total 0-25; Activity total 0-30

POMS

N=191 Mean + SD

Anxiety 4.2 + 4.3

Anger 3.0 + 3.4

Depression 3.6 + 4.2

Fatigue 8.7 + 5.3

Vigor 6.4 + 4.5

Confusion 4.7 + 3.2

Total 17.5 + 18.8Higher scores indicate increased distress, except for vigor; Sub scores range from 0-20; Total scores range from -20-100

Regression Results

Fatigue

Variable St. Coefficients

Std. Err

P value

Shortness of breath on exertion

.304 .055 <.001

Swelling ankles/feet

.179 .043 .001

Loss of appetite .162 .051 .002

Physical composite -.156 .008 .038

Mental composite -.270 .008 <.001

Endothelin receptor antagonist

-.106 .234 .022

R2=66%

Limitations

• Convenience sample– Self-identified PAH

• Recruitment sites• Self-report measures• Low cronbach alpha for POMS

Implications

• Assessment of symptoms are imperative• Fatigue is a moderate-severe symptom in PAH

• Fatigue is associated with HRQOL• Improving symptoms such as fatigue

may improve HRQOL• Although medications may improve

mortality, but may worsen symptoms or induce side effects that affect HRQOL/function

Conclusions

• Fatigue associated with:– Shortness of breath with exertion– Swelling of ankles/feet– Loss of appetite– Physical composite–Mental composite– ERA use

Future

• Design, test, implement interventions – Exercise?– Target symptom clusters?

Thank You!

Questions?