Health-related quality of life (HRQoL) is an important outcome variable in many chronic diseases that have an impact on different aspects of a person’s life. Chronic Obstructive Pulmonary Disease (COPD) is one of those diseases in which HRQoL is affected and becoming a major environmental and public health issue . Globally, COPD is considered a significant cause of mortality and morbidity across the modern world  . COPD is likely to increase in the coming years due to higher smoking prevalence, aging populations in many countries, and the spreading of environmental pollutants . This made COPD the fourth leading cause of death and expected to become the third major cause of death by 2030 worldwide .
Chronic Obstructive Pulmonary Disease continues to be an important health burden . COPD is a complex, multifaceted disease. It affects patients in many ways and results in significant impairment in their quality of life (QoL) . It has a major impact on personal health status at large and HRQoL in specific. HRQoL was defined as a very broad concept referring to the quality of life that is directly related to health or illness . HRQoL and QoL are used interchangeably . HRQoL is composed of various aspects that involve physical, mental, emotional, and social wellbeing, which is completely different for each patient . Impaired quality of life among COPD patients is closely related to the symptoms of shortness of breath, dyspnea, and impaired physical activities, like fatigue, and mental problems, like anxiety   . Therefore, the evaluation of HRQoL is an important outcome measure in assessing patients with COPD which informs about the causes of the burden of this disease and leads to improve patient management and develops policy decisions .
Furthermore, COPD is a distressing, difficult, and progressive condition that makes life miserable for many patients . Thereby, COPD leads to a progressive worsening in HRQoL aspects among those patients who are having this disease . Many studies reported an impairment of HRQoL among COPD patients which measured through using generic or specific HRQoL tools    . COPD is a complicated and comorbid disease that has many associated risk factors that can contribute to a significant impairment in functional, psychosocial, emotional and economic costs on the individual, community, and health services . The associated factors lead to a gradual deterioration in the HRQoL, such as: severity of disease symptoms, the impact of symptoms on the subsequent reduction in daily activities, non-adherence management, and therapeutic noncompliance and psychosocial effect . The interest in the associated factors contributing to HRQoL among patients with COPD is increasing  . The associated factors were classified in to sociodemographic and clinical variables, functional, psychological, and emotional among patients with COPD. Also, these factors are significant in discovering the main factors that predict the worsening in HRQoL level and explaining the correlation of HRQoL with other variables, specifically the level of anxiety, fatigue, uncertainty among those patients.
The integrative review aimed to identify and summarize relevant kinds of literature which are described HRQoL predictors and correlation of HRQoL with other variables specifically limited to perceived anxiety, level of fatigue and perceived uncertainty in patients with COPD. The findings of this review will contribute in adopting these predictors for updating clinical practice guidelines, institutional policy regarding the routine assessment and clinical intervention options with COPD patients, and improve knowledge among healthcare providers about the potential impact of psychosocial and physiological wellness on the health status of COPD patients. In addition to providing healthcare researchers with needed information that will help them in appraising and discussing the study results according to their study purpose.
2.1. Data Sources and Search Strategies
The integrative review was conducted to identify studies describe the predictors of HRQoL and correlate HRQoL with other specific variables among COPD patients. The online databases used in the literature review were PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ProQuest, Medline, Google Scholar, SAGE Journals, Wiley online Library, Science Direct and EBSCOhost, Ovid journals, and Cochrane for systematic review articles. Literature searches were conducted for articles published up to October 1, 2019. The keywords used for searching in the online databases were COPD, pulmonary disease, anxiety, fatigue, uncertainty, HRQoL, QoL, and systematic review, and a combination thereof. The possible combinations of words were used using Boolean operators like AND or OR. Search in PubMed was conducted by utilizing a highly sensitive search filter technique. All the founded articles were screened for inclusion criteria. Each article retrieved in the search was independently assessed by the researcher in double methods. Researchers reviewed the titles and abstracts of each article. If the article indicated potential inclusion, the full-text of the article was assessed using the inclusion criteria. Any disagreement over the eligibility of particular articles was resolved through reviewing the article again in full or consulting another researcher.
2.2. Inclusion and Exclusion Criteria
The articles met the following inclusion criteria were considered for full review: 1) discussed and reported at least two predictors of HRQoL or at least the correlations with one of following variables (i.e. anxiety, fatigue, uncertainty); 2) include HRQoL as outcome variable 3) the measurement of HRQoL was reported with valid and reliable tool; and 4) articles were provided in full text and published in English. Although excluding the publications written in another language than English will introduce a language bias, the English language is still generally perceived to be the universal language of science. The papers include overlapping pulmonary diseases like asthma, obstructive sleep apnea (OSA) or didn’t meet the inclusion criteria were excluded.
2.3. Process of Identifying the Relevant Studies and Data Extraction
The potential articles were first screened for their titles and abstracts. Then, the relevant articles were reviewed in full for consideration of inclusion in the current review. The selection was according to fixed inclusion and exclusion criteria. The primary search in PubMed databases retrieved (80059) articles including research articles and systematic reviews and (44) articles through other resources. After combing three specific variables (anxiety, fatigue, and uncertainty) in the same search engine, (569) articles were identified. After removing duplicates (219) articles were identified. (350) records were excluded because they did not meet the inclusion criteria. From the reviewed titles and abstracts, (140) articles met our search criteria and were reviewed in full. Afterward, the selected articles were assessed for eligibility based on their full text. Of these, (52) final articles were selected. The relatively low number of articles was reflected in the scarcity of evidence around the study variables. After an in-depth review of the included articles, results were summarized according to the following two headings: predictors of HRQoL among COPD patients and the correlation between HRQoL and other specific variables. Figure 1 demonstrates a flow chart for the selection of studies included in the literature review.
Figure 1. Prisma flow chart for the selection of studies included in the literature review.
Health-related quality of life (HRQoL) was recognized as an important outcome when evaluating patients with COPD . The fact that HRQoL is the result of the interaction of physical, psychological, and social factors can justify several predictors of HRQoL among COPD patients which were reported in the literature. These predictive factors were reported into five groups: demographic factors, comorbidity, factors related to the disease, psychological factors, and other related factors. HRQoL was comprised of several domains that involve physical, mental, and social wellbeing which significantly differs for each patient . Impaired quality of life is closely related to shortness of breath, impaired physical activities, and mental problems such as; anxiety . COPD was found clearly correlated with fatigue, anxiety and reduced HRQoL. Therefore, HRQoL should be measured in tools that assess physical, social, and psychological domains. Currently, many HRQoL tools are available. Although there are generic HRQoL tools, which can be used to evaluate HRQoL in general for any population, there are disease-specific tools that can be used in patients with a certain disease experience . So, the recommendation of using a disease-specific tool is needed to cover specific HRQoL aspects and patient-related experiences .
In this review, the predictive factors were described into two Tables; Table 1 presents the characteristics of the (30) studies analyzing factors predicting the HRQoL among patients with COPD and Table 2 presents characteristics of (22) studies describing the correlations and predictive factors between HRQoL and other variables limited to (anxiety, fatigue, and uncertainty). So, to address the purpose of this integrative review, the findings were categorized under the following headings; predictors related to sociodemographic and clinical variables and correlate and predictors between HRQoL and other variables.
Table 1. Characteristics of the studies analyzing factors predicting the HRQoL of patients with COPD (N = 30).
Abbreviations: HRQoL, Health-Related Quality of Life; QoL, Quality of Life; SGRQ, St George’s Respiratory Questionnaire; FEV1%, Forced Expiratory Volume in One Second; m MRC, Modified Medical Council Research Dyspnea scale; 6MWD, 6-minute walk distance; CAT, COPD Assessment Test; EQ5D, Euro Qol; CCQ, Clinical COPD Questionnaire; MOS SF-36, Medical Outcome Study of Short Form 36; QWB-SA, Self-Administered Quality of Well-Being Scale; MILQ, Multidimensional Index of Life Quality;
Table 2. Study characteristics of correlates and predictors between HRQoL and other variables (N = 22).
Abbreviation: CAT, COPD assessment test; HADS, Hospital Anxiety and Depression Scale; SGRQ, St George’s Respiratory Questionnaire; PHQ, Patient Health Questionnaire; RCT, Randomized Clinical Trial; MUIS-A, Mishel’s Uncertainty in Illness Scale-Adult version; STAI, State-Trait Anxiety Inventory; QLI, Quality of Life Index; FACIT-Fatigue, Functional Assessment of Chronic Illness-Fatigue; GAD-7, Generalized Anxiety Disorder 7-item scale; RQLQ, Respiratory Quality of Life Questionnaire; BFI, Brief Fatigue Inventory; DI, Dyspnea Inventory; CCQ, Clinical COPD questionnaire; CRQ, Chronic Respiratory Questionnaire.
3.1. Predictors Related to Sociodemographic and Clinical Variables
The correlation between HRQoL and age was discussed in several studies, and the results were controversial. Almost seven studies were reported a positive correlation between age and HRQoL   - . The SGRQ-c tool was used to measure the HRQoL primarily and the EQ-5D tool was the second. In addition, a few tools were developed by the study researchers. On the other hand, in SGRQ-c the impact of the score was high indicating more worsening of social function and psychosocial disturbances with aging, this could be clarified by the fact that aging is usually linked with impaired activity, depressive symptoms, and anxiety    . On the contrary, nearly twelve studies were found a nonsignificant correlation between age and HRQoL indicating age didn’t cause impaired HRQoL among those patients   - .
The gender was correlated with HRQoL. A huge variation was between studies in predicting the gender correlation with HRQoL. Although many studies were found a correlation between two variables as shown in Table 1. The female patients had lower scores of HRQoL compared with male patients in the following studies     . The following five studies showed no significant correlation or difference between the two variables     .
The educational level was correlated with impaired HRQoL indicating lower educational levels causing worse HRQoL in four studies    . In contrast, five studies were showed no correlation between educational level and better HRQoL according to the type of HRQoL measures that have been utilized in these studies     .
The comorbidities’ status and type of disease as clinical variables were correlated with HRQoL. Moreover, the majority of studies should report more than two diseases to confirm the existence of comorbidities associated with HRQoL. The six studies have reported a correlation indicating the presence of two or more of the following diseases, ischemic heart disease or diabetes, or hypertension      . While only two studies confirm the correlation between HRQoL with comorbidities status and types  . However, many studies have reported the existence of comorbidities without explaining the type of comorbidities as it is shown in Table 1.
The severity of disease was considered the main factor to evaluate the disease progression and effectiveness of treatment. Sometimes it was linked with medication status and type of medication given to the patients through the course of treatment. The severity indicator factors are FEV1% predicted, GOLD staging, ABCD Criteria, CAT score, mMRC score, and FEV1/FVC%. Six studies were reported more than two factors as a predictor regarding the severity of disease       while only three studies were reported not more than two factors that non predicting the HRQoL    . However, most factors were reported, FEV1% predicted, FEV1/FVC%, CAT score, and GOLD stages.
Furthermore, the duration of disease, a number of hospitalizations, smoking behaviors and packs/year, and effect of weight measured by BMI were other clinical variables which discussed the correlation with HRQoL. Although many studies had confirmed these factors as a predictor, other studies reporting inconsistency with the same variables as not predicting factors as shown in Table 1. Moreover, there were widespread debates about the amount of smoke and behavior and it is a correlation with HRQoL. Six studies were reported no correlation between smoking behavior and the smoking indexes with HRQoL      , while in the following eight studies         were reported an existence of correlation between smoking behaviors, smoking index, and HRQoL.
On the other hand, an old study carried out by Wijnhoven and his colleagues  reported a controversial result indicating better HRQoL in current smokers. The reasons that patients who are still smoking might be those with a less advanced stage of the disease. While another new study showed current smokers have a poorer quality of life (high total HRQoL score) compared with previous smokers .
Recently, new studied variables were discussed as a factors which correlates and predicting HRQoL, such as; type of work which was reported in one study , socioeconomic status in two studies  , nutrition type in one study , and the presence of family help and support in one study . In contrast, the following studies were found type of works      , socioeconomic status   , and living status     not predicting the HRQoL in their population sample. Moreover, one study has reported the factors of areas of residency and seasonal variation effect. These factors were found not predicting the HRQoL . Only one study has reported the correlation with pain, this factor was found not predicting the HRQoL .
A few studies have discussed the effectiveness of an interventional program. The 6MWD test is widely used among COPD patients. This test was correlated with lower scores of HRQoL in recent tow studies (best HRQoL)  . Regarding the medication use was verified as a predictor of HRQoL. Shah and colleagues , Sharma and Joshi , Raherison and colleagues  demonstrated that deterioration in HRQoL was seen correlating with the number of prescribed medications, whereas other studies    were showed that the patients with the greatest impairment of HRQoL are those who are taking more than one medication, and those contained especially inhaled corticosteroids.
Together, numerous studies identified that lower education levels, more breathlessness, fatigue, lower BMI, anxiety, and depressive symptoms adversely affect the HRQoL.      . In conclusion, the most common predictors of HRQoL among COPD patients were age, GOLD severity stage of the disease, dyspnea grade, and the number of exacerbations/hospitalizations. Other predicting factors include comorbidity, sex, body mass index, socioeconomic status, and educational level.
The Health-related quality of life was measured by using different generic and specific tools including general short-form (SF-12) health survey questionnaire which was utilized in three studies   , MOS SF 36 was utilized in one study , and the specific one such as SGRQ-c was utilized in nine studies         , EQ-5D was utilized in two studies  , Clinical COPD Questionnaire (CCQ) was utilized in four studies.    , and a newly developed one by study researchers was utilized in three studies   . The frequently utilized tool was the SGRQ-c through all reported studies. The SGRQ-c is a specific tool to measure the severity and HRQoL among patients with COPD. Out of all reported studies, most of the studies were solely used one tool to measure HRQoL, only two studies were used two types of tools in order to compare the level of HRQoL from two types of measurement and to report if there is a significant difference between each tool  . Before it was common to see more than two types of tools were utilized to test HRQoL because of the need to cover all aspects of HRQoL, but now utilizing one specific tool is enough which covered the main aspects of HRQoL.
On the other hand, the majority of the study was utilized observational design in cross-sectional and longitudinal time series. The sample size was adequate the minimum in some studies was not less than 40 participants and the maximum, not more than 2734 participants. However, a few studies such as web-based surveys or prospective studies were failed to report the data collection period as shown in Table 1.
3.2. Correlates and Predictors between HRQoL and Other Variables
3.2.1. Perceived Anxiety and Fatigue
The patients with COPD experience a wide range of burdens which were represented with several symptoms, such as breathlessness, anxiety, and fatigue. These symptoms affect disease assessment and management. Fatigue was reported to be one of the most common symptoms among patients with COPD . The patients with a chronic disease rated fatigue often as one of the key factors leading to reduced QoL . However, the prevalence rate of fatigue was shown that almost half of all patients experienced abnormal fatigue: 23% mild and 24% severe fatigue in a study concerning the severity of fatigue in patients with stable, moderate to severe COPD . While the prevalence rates for anxiety range from 17% to 51% . Further, two studies supported that COPD patients have a higher incidence of anxiety 21% to 96% compared to 20% in the general population  . Other studies were found that 90% of patients diagnosed with severe COPD suffered from severe breathing difficulty which was complicated by psychological distress related to anxiety and/or depression. The combination of factors resulted in an increased number of severe symptoms, hospitalization, and hospital mortality  .
Almost three studies discussed the correlation of HRQoL with fatigue. The qualitative study conducted by Kouijzer and colleagues , the authors pointed out the purpose of the study was to examine the patient’s perspective on COPD-related fatigue, the impact on activity daily life, and possible treatment opportunities to tackle the burden of fatigue. The study results showed the COPD-related fatigue causes a severe, negative impact on the physical, emotional, cognitive and social functioning of all participants. The negative impacts on daily functioning were negatively influenced by the HRQoL of patients leading to a heavy mental burden, decreasing patients’ joy in life, and even in some cases their will to live. A qualitative study with face to face interviews was conducted to identify the domains of HRQoL from the perspectives of health care professionals. The study found fatigue and anxiety were the most important aspect correlated with impairment in HRQoL . The two cross-sectional descriptive studies found a high correlation between disease symptoms like dyspnea, breathlessness with anxiety and fatigue which have an impact on the HRQoL among COPD patients   .
Furthermore, a population-based study of (795) participants. The study was conducted to evaluate the correlation and compare between fatigue and HRQoL among COPD and Non-COPD patients. The study found clinically significant fatigue was correlated with worse HRQoL and independently correlated with anxiety . Moreover, an observational study from secondary collected data was embedded within a randomized trial to test the effectiveness of pulmonary rehabilitation program on the level of activity and fatigue. The study results found that high fatigue patients had a greater improvement in both fatigue score in a chronic respiratory questionnaire and the SGRQ scores which indicate a high level of fatigue cause deterioration in the level of HRQoL with COPD patients .
Further studies about the correlation of HRQoL with anxiety, about five cross-sectional studies with an adequate sample size were conducted to evaluate the correlation between HRQoL and anxiety as shown in Table 2. Numerous studies had confirmed the results of COPD patients with anxiety had a poorer HRQoL and anxiety was the predictor of low mental HRQoL score    - . Two qualitative studies with a focused group method were conducted. The studies aimed to explore patients’ views and perceptions regarding COPD and their impacts on daily living. The results emerged four themes indicating that most patients with COPD experiencing difficulties in their psychosocial like anxiety and physical functions that affect their HRQoL and ultimately lead to social isolation .
On the other hand, fatigue was measured by using different tools including HADS were utilized in seven studies       , STAI was utilized in one study , FACIT was utilized in one study , GAD-7 was used in two studies  , LFS was used in one study , BFI was used in one study . The most frequently used tool was the HADS among all reported studies. This tool is a generic tool used to test anxiety and depression. Regarding fatigue, the GAD-7 was utilized as the most specific tool that has been used among COPD patients.
3.2.2. Uncertainty among COPD
Uncertainty is defined as ‘‘inability to determine the meaning of illness-related events’’ . However, if the expectations of health care providers differ from the expectations of patients, further confusion and patient uncertainty may be added . Uncertainty about prognosis and symptoms is fundamental in living with a chronic health condition. COPD is characterized by breathlessness and airflow limitation that is not fully reversible. Thus, treatment focuses on managing symptoms and maintaining the HRQoL. The patients must recognize and appropriately understand their symptoms to take inhaler medications and seek evaluation for appropriate management . There was a scarcity in the studies test a correlation of HRQoL with uncertainty. The old two studies were examined uncertainty among COPD patients based on a sample of (26) hospitalized patients  . One more study has tested the effectiveness of a specific intervention to manage uncertainty . In this study, the authors found a reduction in uncertainty and improvement in anxiety, depression, and quality of life among the intervention group.
A relatively recent longitudinal study over two years was used to determine which aspect of illness uncertainty (i.e., ambiguity or complexity) has a significant correlation with psychological and selected clinical outcomes over a two year period among patients with COPD. The study results showed the greater uncertainty is correlated with more symptoms of depression and anxiety and reduced QoL. In addition, it was also correlated with worse physical symptoms (i.e., pain and fatigue) . Further studies are needed to investigate more about the uncertainty concept, and it is a correlation with HRQoL.
The aim of this integrative review was to update, identify, and summarize kinds of literature that described HRQoL predictors and correlation of HRQoL with other variables limited to anxiety, fatigue, and uncertainty in patients with COPD. After a comprehensive search, the authors believe this is the first review conducted to cover the HRQoL correlations with variables of fatigue, anxiety, and uncertainty in specific and identifying between predicting and non predicting factors with HRQoL from (52) studies were included in this review. However, the previous review has described only the factors predicting the HRQoL, it was limited in the scope of articles, keywords of search engines, and searching coverage periods . In the current study, Table 1 “characteristics of the studies analyzing factors predicting the HRQL of patients with COPD” was included to evaluate the predictors of HRQoL across different studies. Table 2 “study characteristics of correlates and predictors between HRQoL and other variables” was included to evaluate the correlation with HRQoL and other important variables. The tables were classified according to sample size, study design, data collection period, sampling methods, and type of tool used to measure HRQoL. The two tables have presented a disagreement in the literature about the factors that predicting and non predicting the HRQoL among COPD patients.
The predictor factors were categorized according to factors related to demographic and clinical variables. What is new in this review, some related factors were examined which not discussed before in the literature. The factors were found as predictors of HRQoL such as; patient living status, work status and type, and help and support provider. Although numerous studies have been devoted to studying predictors of HRQoL and correlated factors in recent years among COPD patients, some HRQoL aspects remain unclear and need more investigations. A group of physical, emotional, and psychosocial factors was identified that correlated and altered of HRQoL. In conclusion, there is a discrepancy in the factors predicting and correlated HRQoL among COPD patients within the literature when utilizing specific tools to measure HRQoL.
Furthermore, this review identifies the instruments that had been used for collecting data indicating the SGRQ-c was the most utilized tool in the mentioned studies to measure HRQoL, the HADS to measure the anxiety, and the GAD-7 to measure fatigue, and the MUIS to measure uncertainty. Further, about the correlation with HRQoL, there was a significant correlation between anxiety, fatigue, and HRQoL among COPD patients. The literature still lacks clarity about the correlation of HRQoL with uncertainty among COPD patients. Further researches are needed to verify the validity of the reported correlation between HRQoL and other variables. In addition to a correlation with other sociodemographic and clinical variables to confirm the significant predictors.
Moreover, most of the reported studies have been carried out in developed countries. A few types of research have been carried out in developing countries. Cultural variations, pollution-related exposure, and special behaviors must be considered when disseminating the findings obtained from these studies. Contradicting findings are apparent in certain predictors of HRQoL as shown earlier in the provided tables. Additionally, the correlation with HRQoL was categorized according to correlation with perceived anxiety and fatigue and correlation with uncertainty. On the other hand, the studies included in this review were different in reporting quantitative and qualitative research design, sample size, and data collection methods and time period.
Despite the important integrated findings in this review, the authors suggest that there are some limitations to be acknowledged. Excluding non-English language articles can minimize the chance of accessing some relevant literature. Additionally, most samples included participants from diverse cultural groups, complicating the generalizability of these studies, and making generalizations with respect to each study difficult. Finally, the heterogeneity among the studies in terms of the methodologies used and assessment tools makes it difficult to accurately compare various aspects of the outcomes reported.
Health-related quality of life was low among patients with COPD. The HRQoL was decreased with the presence of anxiety and fatigue with COPD. There are many predictors that affect HRQoL with COPD. These predictors need more investigation and evaluation. The evaluation of HRQoL predictors among COPD patients should need to consider the measurement tools of HRQoL. The assessment of physical and psychological factors is important for improving COPD symptoms, preventing the consequent deterioration of HRQoL, and choosing the appropriate treatments. The literature demonstrated that HRQoL among COPD patients is apparent as an issue that needs further investigation from cultural perspectives. Certain predictors still have contradictory findings in the non-empirical literature. This review will expect to help in resolving discrepancies in the existing literature about predictors and correlated factors among COPD patients. It would be valuable to rule out which of these factors remain valid to predict HRQoL in a specific population and cultures. In clinical practice, screening for anxiety, fatigue, and uncertainty would refer potentially affected patients to specific care facilities for further assessment that may be promising approaches to improve the HRQoL among those patients. The findings from this review should encourage health care providers to explore carefully the predictors during patient history taking and interviews as an aid to help them understand why some patients may not respond to provided care options and why some of them are at high risk to a certain limit. This review will guide health care professionals to understand their patients in a more holistic manner.
The authors thank the School of Nursing, University of Jordan for their support in conducting this review.