Health-related Quality of Life in Pulmonary Arterial Hypertension
Citation: Advances in Pulmonary Hypertension 8, 4; 10.21693/1933-088X-8.4.215
Living with a life-limiting serious disease such as pulmonary arterial hypertension (PAH) can present many challenges. The uncertainty of illness and disability can have a profound impact on relationships, cognitive ability, emotions, and spirituality. Promoting health and support in health-related domains may improve the patient's perception of disability and ability to cope.
Quality of life reflects how one views one's own satisfaction with life. Health-related quality of life (HRQoL) is defined as a person's perceived quality of life representing satisfaction in those areas of life likely to be affected by health status. Health-related quality of life is subjective, multidimensional, and temporal.1 It has developed from the concept of quality of life but is more specific to health-related domains that are affected by health or lack of health and wellness. The most commonly identified domains include physiological, psychosocial, sociological, and spiritual.
Measuring HRQoL can illuminate how illness may affect different dimensions within the patient's life and aid understanding of patient perceptions of illness. A key indicator of quality care should be the patient's perceived improvement of HRQoL, and therefore, it is an important tool in measuring health care outcomes. The purpose of this literature review is to assess the state of HRQoL research in PAH.
Burden of Disease
Pulmonary arterial hypertension is characterized by increasing pulmonary vascular resistance with progressive right ventricular dysfunction. Most people suffering from PAH present with shortness of breath or exertional dyspnea. Other symptoms include fatigue, dizziness, peripheral edema, chest pain, syncope, and palpitations. As the disease progresses, signs of cor pulmonale present with leg swelling, increased abdominal girth, anorexia, and profound fatigue.
The cost of treatment and the physically and psychologically disabling nature of PAH can severely impact the patient's relationships with family, friends, and employers, as well as the patient's financial security.2 Society is impacted by extended disability and early mortality. Persons with PAH may reach maximum insurance caps, may be unable to maintain employment, but have difficulty qualifying for medical disability benefits.3 Several investigators have found that the psychological impact of PAH can be severe and cause isolation.24 This is illustrated by depression and anxiety noted in PAH patients. Other affected aspects of life may include altered personal appearance and body image disturbances. Figure 1 illustrates the complexity of living with PAH.
Citation: Advances in Pulmonary Hypertension 8, 4; 10.21693/1933-088X-8.4.215
Measurements of Health-related Quality of Life in Pulmonary Arterial Hypertension
Measuring HRQoL to determine the effectiveness of interventions for PAH is important. A variety of tools have been used as researchers have attempted to measure HRQoL in the PAH patient. Generic measurements can apply to a wide variety of populations and are not specific to a disease. Disease-specific tools have been used recently to provide more sensitivity to the unique qualities of individual diseases. Physical function is a common dimension that is identified as an important measure in disease states; other measures address psychosocial dimensions. Some measurements may focus only on a single factor such as a symptom. Symptom measurement typically focuses on the physical characteristics of HRQoL. The 3 types of measures typically used to assess HRQoL in PAH are described in Table 1.
Until 2006, there was no disease-specific tool for measuring quality of life in PAH. Investigators used tools designed for similar diseases such as heart failure or pulmonary conditions. Some of the features of PAH may appear similar to other disease states; however, the condition cannot be adequately described by a tool designed for another disease. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a disease-specific tool for PAH that was developed in 2006.13
The CAMPHOR was developed to provide a valid and reliable outcome measure of the impact of PAH and its treatment on quality of life and HRQoL. It was derived from qualitative interviews conducted with 35 adult patients in England. These interviews provided insight into affected domains for PAH patients in relationship to HRQoL and quality of life. The CAMPHOR was intended to consist of both a HRQoL measure to assess symptoms and functional status and a separate quality of life measure. It contains 3 separate scales that measure symptoms, functioning, and quality of life.
Methods
The review of the literature covered a period from 1996 to October 2009. The search included use of electronic bibliographic databases. Key words included: pulmonary hypertension, pulmonary arterial hypertension, quality of life, and health-related quality of life. Only empirical studies and reviews of literature with reference to quality of life and PAH were accepted. Thirty-one papers were examined, 23 of which met the criteria for review of HRQoL in PAH. All articles reviewed were written in English, with the exception of one qualitative nursing study in French which included an abstract translated into English by the authors.18
Each study was abstracted using critical appraisal and organized into topics of author, purpose, and study design including sample and instruments, and results. Studies were categorized by nursing research, pharmaceutical research, nonpharmaceutical research, and HRQoL studies. Table 2 identifies key studies focused on HRQoL in PAH.
Results
Study of HRQoL in PAH began as a secondary end point to pharmaceutical clinical drug trials. Researchers are now beginning to focus on the HRQoL measurements, effects of a specific intervention, and the use of patient-reported outcomes. All researchers concluded that quality of life is negatively impacted in the PAH patient population. All acknowledged challenges, complexities, and issues in assessing HRQoL. Despite increased interest, significant gaps to understanding HRQoL in PAH remain.
The small sample sizes in PAH research make drawing conclusions for the overall group difficult. Differences in the etiology of PAH affect HRQoL. The variables in PAH, especially when associated with other comorbid diseases, may produce confounding variables and further reduce the sample size. There may also be different responses to oral, inhaled, subcutaneous, or intravenous routes of therapies.
Nearly all knowledge about HRQoL in PAH has been gathered through the use of instruments designed for other cardiac or pulmonary diseases. Tools that are not designed to measure PAH may not accurately capture or reflect the PAH experience. These factors make it difficult to compare HRQoL findings across studies. The recently developed CAMPHOR tool specifically designed to study HRQoL and quality of life in PAH has not yet been widely used in published research.
Most studies were conducted over a short period, usually 12 to 16 weeks. This time interval may not be long enough to assess the impact of an intervention on HRQoL for an individual or a group.
Pharmaceutical Studies
Pharmaceutical randomized controlled trials (RCTs) of PAH medications have used HRQoL as secondary end points. Nearly half of all the literature available concerning HRQoL in PAH is from pharmaceutical studies that included assessment of the impact of drug therapy on quality of life. Improvements in at least some measures of HRQoL have been reported with epoprostenol,20 iloprost,21 and treprostinil.22 However, iloprost did not change SF-3621 and in another study, treprostinil did not change Borg or Dyspnea Fatigue Scale (DFS) and showed only a trend toward improvement in the physical dimension of the Minnesota Living With Heart Failure Questionnaire (MLHFQ).25 Sildenafil has shown improvement compared to bosentan measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ).27 Sildenafil improved all dimensions of the SF-36 and some dimensions of European quality of life (EuroQoL) with the greatest impact on physical dimensions.30 The endothelin receptor antagonists have also shown improvement in HRQoL by some measures. Bosentan improved all SF-36 and some Australian Assessment of Quality of Life (AQoL) dimensions, which were maintained over time.29 Ambrisentan showed improvement in quality of life as measured by a visual analog scale.26 Although one study showed no improvement with sitaxsentan in SF-36,24 another trial using the drug in connective tissue disease showed improvement in the Physical Functioning and Role-Physical scales of SF-36.28
Data relating to HRQoL in pharmaceutical clinical trials are often sparsely reported, with only broad statements about improved HRQoL, without specifics about dimensions used or details of the review. None of the tools used in pharmaceutical clinical trials were specific to PAH. The instruments used varied from trial to trial, though the majority used the SF-36 or the MLHFQ. Variations on data, study design, and reporting make it difficult to compare findings.
Nursing Studies
Nursing research in HRQoL in PAH is limited to 2 small qualitative studies exploring the patient's perceptions of HRQoL and its relationship to treatment.1819 Qualitative research reflects the richness of patient experience. Peloquin et al identified that prostacyclin therapy may not improve perceived HRQoL.18 In this study, women just beginning and adjusting to therapy were interviewed. Though extremely limited because of sample size, it was the first to study patient perceptions. Subsequent research refutes these results, demonstrating that treatment with intravenous epoprostenol improved HRQoL, possibly related to the patient's sense of mastery of the medication regimen.33
Flattery et al found that uncertainty is a common experience in this disease state. Coping with uncertainty was characterized by respondents as information seeking, making memories, humor, spirituality, and seeking support.19 The perceptions of coping and living with established therapy were characterized as doing what I have to do, adjusting to treatment, and resuming life's activities.19 These themes show how a patient eventually copes with treatment and adapts to a new reality. Limitations of these qualitative studies include extremely small sample size and scope, yet this important initial research helps us gain understanding of what it is like to live with PAH by eliciting the patient's perception.
Nonpharmaceutical Studies and Health-related Quality of Life
Other researchers have evaluated the benefits of exercise or examined the relationship between cognitive impairment and HRQoL. Mereles et al31 studied the safety and effectiveness of exercise training in PAH. Significant improvement in SF-36 was found in physical health (Physical Functioning and Role-Physical scales) and mental health (Social Functioning, Mental Health, and Vitality scales), indicating the value of exercise as safe adjunctive therapy in patients with PAH.31 White et al32 found that depression, anxiety, and quality of life were similar for PAH patients with and without cognitive dysfunction. However, impaired working memory was correlated with lower SF-36 Role-Physical scores.32 These studies introduce other influences on HRQoL beyond pharmaceutical therapy.
Health-related Quality of Life Studies
The next group of studies describe HRQoL in PAH,33 explore the determinates of HRQoL in PAH,34 and evaluate the relevance and validity of instruments used in PAH HRQoL research.13353638 Shafazand et al33 found significant impairment in HRQoL of PAH patients with moderate or severe anxiety (19%) and depression (26%). However, patients on epoprostenol reported better energy and emotional reactions on the Nottingham Health Profile (NHP) and less fatigue, emotional distress, and greater feelings of control on the Chronic Heart Disease Questionnaire (CHFQ). Patients who were not on epoprostenol had significantly more anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS).33 The authors theorized that mastery of complex medical therapy and time might help a person cope with the illness. Also, because of the complex nature of medication delivery, these patients have stronger support from physicians and nurses, which may lead to improved control and mastery, and, therefore, positively influence HRQoL perception. Mastery, time, and support are all part of coping with uncertainty.
Taichman et al34 found that PAH patients were severely impaired in both physical and mental dimensions of quality of life, with systemic sclerosis patients being more impaired than idiopathic PAH (IPAH) patients. Health-related quality of life was unrelated to the type of therapy prescribed and was not correlated with hemodynamics.
The MLHFQ has been tested in PAH patients. It has been shown to correlate with Borg scores,35 6 minute-walk test distance,36 and NYHA/WHO functional class,3536 but not hemodynamics.3536 Most scales of the SF-36 correlated well with 6-minute walk (except General Health) and NYHA/WHO functional class (except Mental Health).36
The interviews used to develop the CAMPHOR also identified needs expressed by patients with PAH. These interviews, like the nursing research described previously, revealed a sense of insecurity or uncertainty of support or the future.13 Responding to these needs may improve HRQoL perceptions. The recently developed CAMPHOR tool specifically designed to study HRQoL and quality of life in PAH has not yet been used widely in published research as an end point in interventional studies. It has been validated for use in the United States and Canada.3940
Discussion
Health-related quality of life understanding within the PAH community remains underdeveloped. Continued work is needed in HRQoL measurement and understanding the experience of living with PAH. Current PAH therapy allows people with PAH to live longer. Finding a cure has been evasive, and living with PAH presents uncertainty, but new treatments continue to offer hope. Alleviation of suffering may include more than just treating physical symptoms. Only a few researchers asked patients with PAH about their perspectives and gained new understanding of living with PAH.131819
The MLHFQ has been the most widely used tool in the study of HRQoL in PAH. It was also modified and validated as a measurement tool for PAH.3538 This tool may have value in some applications, but it has limitations as a disease-specific HRQoL measurement for PAH. It may not always capture the PAH patient's perspective, will only describe certain aspects similar to chronic heart failure, and may miss unique variables important to PAH patients.
Much of the HRQoL research in PAH focuses on physical and functional status. There are some patients who should have profoundly depressed HRQoL, yet when asked, seem to differentiate the physical aspects and report joy and satisfaction with their lives. Perhaps the focus of HRQoL in PAH should include those factors not just affected directly by health but also factors that contribute to one's overall sense of well-being and quality of life. The CAMPHOR considers these by including indicators for overall quality of life, yet it does have limitations for other dimensions of HRQoL measurement. Additional areas of exploration are dimensions of hope, self-image, role changes, sexuality, self-efficacy, and spirituality. One of the first steps would be to identify key influencers of quality of life domains in PAH and determine factors and interventions to improve HRQoL.
Everyday interventions can sometimes have the biggest impact. Some areas for further investigation include examples such as the impact of an indwelling catheter for infusion, oxygen, or the red flushed face on body image. Clinical experience shows patients and partners report concern with sexuality as a major health focus, although there is no research in this area.
In the socioeconomic domain, patients are severely impacted by the financial burdens of therapy and the need for many to seek disability. Researchers comment about these implications, but further exploration of the socioeconomic impact of the disease would be beneficial.
There has been further inquiry in the psychological domain of PAH.2 Because there is no cure for PAH, factors influencing psychological adjustment to chronic disease require attention along with functional health domains. Work is needed in this area, including further study of the influence of interventions to promote self-care on psychological adjustment.
Pulmonary arterial hypertension is a life-limiting progressive disease. It is important that patients and their families have a pragmatic understanding of the illness and understand that end-of-life preferences must be considered and communicated. Since the disease trajectory may be uncertain, these conversations can be infused with hope and allow the patient to focus on and maintain control over what is important in his or her life. Further research in the area of palliative care in PAH may provide additional support for end-of-life services for this patient population. This support would enhance care at a time when support is needed the most.
Health-related quality of life is a dynamic process, and adaptation may occur over a period of years. The effect of interventions and changes in HRQoL may take months to actualize or produce measurable results in a study. By continued exploration and collaboration with a multidisciplinary team using a longitudinal approach, the health care team can improve the quality of life for those with PAH.
Conclusions
This literature analysis highlights how little is known about the HRQoL in PAH. The literature reveals many confounding variables influencing our knowledge base. Future research is needed in areas of patient perceptions and influencers of HRQoL. Continued exploration to understand the illness experience of PAH will identify methods to improve outcomes and enhance the lives of those with PAH.
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LifeSource
St Paul, MN
Burden of pulmonary arterial hypertension.
Contributor Notes