Chronic obstructive pulmonary disease (COPD) is a progressive disease, the prevalence of which has increased over the past three decades [1,2]. The prevalence of COPD in Korea (as revealed by the Korea National Health and Nutrition Examination Survey [KNHANES]) ranged from 13.1% to 14.6% from 2010 to 2015 [3]. COPD is associated with comorbidities including muscle weakness, osteoporosis, diabetes, cardiovascular disease, hypertension, depression, and lung cancer [4]. The economic burden imposed by COPD is enormous [1,5] and will continue to rise [6]; the significance of COPD cannot be overestimated. The significant worldwide burden of COPD, and the associated economic implications triggered the creation of the global initiative for chronic obstructive lung disease (GOLD) evidence-based guidelines, which are frequently updated [7].

As is true of all chronic diseases, the economic burden of COPD is both direct and indirect. Direct costs include the healthcare resources required (drugs and medical instruments); the indirect costs include travel expenses, loss of productivity, premature retirement of patients and caregivers, and time spent in visiting healthcare institutions [8], among others. The annual COPD costs in the USA are approximately US $50 billion (40% indirect costs and 60% direct healthcare expenditures) [9]. COPD patients are associated with a reduction in workforce participation and general activity limitation than individuals without COPD reflecting increased indirect costs [10]. Many reports have explored the direct and indirect economic burdens of COPD, including productivity losses [10]. However, few studies have considered the time expenditure and lost productivity of caregivers, which are indirect costs.

Patient-reported outcomes, including the health-related quality of life (HRQL), are useful for assessing COPD severity and treatment outcomes; COPD management is largely symptomatic. The HRQL is a valuable measure of clinical trial outcomes. The EuroQol five-dimensions (EQ-5D) assesses generic HRQL via both descriptive system and visual analog scale (VAS), and is widely used to evaluate COPD outcomes [11-13]. Original EQ-5D descriptive system was redesigned with five-level response (5L) [13], which was validated in Korean people recently [14]. We hypothesized that the required time to see a doctor, severity of airflow limitation or symptom affect the HRQL.

Our objectives here were to (1) assess the HRQL using the new EQ-5D-5L; (2) measure the informal, family, and caregiver-related indirect burdens (accompanying patients to outpatient clinics and quitting jobs to deliver home care); (3) measure the time required to visit outpatient clinics/pharmacies; and (4) assess the home care rate. Also, we evaluated the relationship between the HRQL and airflow limitation, dyspnea grade, and the time required to visit clinic.

We found that the HRQL of COPD patients, as measured by the EQ-5D, deteriorated as the COPD stage and dyspnea severity worsened. The disease-related indirect burden (home caregiving) increased as airflow limitation increased. Previous reports on the EQ-5D status of Korean COPD patients evaluated KNHANES data [15] or COPD patients treated in a single center [16]; both reports used the EQ-5D-3L [15,16]. COPD patients from KNHANES IV to V (2007 to 2010) data were diagnosed via pulmonary function test of on-site national survey [15]. However, uniquely, we gathered data from symptomatic COPD patients formally diagnosed and had ongoing treatment for COPD in several centers. For the first time, we used the EQ-5D-5L to measure quality of life of COPD patients in Korean setting. The EQ-5D utility index of COPD patients from KNHANES data [15] was higher than our utility index (0.89 vs. 0.74). We could not compare of both, because data from KNHANES did not showed severity of airflow limitations and used three leveled EQ-5D. The three leveled EQ-5D utility index of COPD patients from single center [16] was higher than our utility index (0.84 vs. 0.74). The EQ-5D indexes were decreased according to the severity of airflow limitation [16], which was similar with our study.

The EQ-5D was developed in 1987 by the EuroQol Group, involving five European countries. This instrument is self-completed, and is thus ideal for use in postal surveys and clinics, or during face-to-face interviews. The EQ-5D is simple and can be completed rapidly. Each dimension features three levels of response (no problem, some problems, and extreme problems; EQ- 5D-3L) [11,12]. To improve sensitivity and reduce ceiling effects, the EQ-5D-5L was introduced by the EuroQol Group in 2009 [13]. The EQ-5D-5L has been widely tested and used (in both general and patient populations) to describe and evaluate general health status. The instrument has been translated into over 130 languages and has been employed in clinical trials, observational studies, and health surveys [12]. The Korean version was validated by Kim et al. [14].

We found that the mean EQ-5D-5L index and the EQ-VAS score fell significantly as COPD became more severe, particularly in patients with advanced airflow limitations, as previously reported [17]. Approximately 60% of COPD patients experienced limitations in usual activities; 64% reported limited mobility. Lin et al. [17] found that about 64% of COPD patients reported mobility problems and about 55% had problems in the performance of daily activities. Thus, many COPD patients cannot work. Patel et al. [10] reported COPD patients were less likely to be working than non-COPD subjects. The most common problem revealed by the EQ-5D was in the mobility domain; 25% of patients were accompanied by family caregivers when visiting outpatient clinics/pharmacies. One-third of all patients received in-home care from family caregivers. COPD (with or without comorbidities) imposes a high economic burden not only on healthcare systems, but also on society in general, being associated with disability, loss of productivity, and premature mortality. The true burden of a disease is not reflected in the direct medical costs alone; indirect costs constitute a substantial proportion of the burden. No prior Korean report on the burden imposed on family caregivers has appeared. We measured the time contributed by family caregivers to assist COPD patients in accessing medical treatment.

About 25% of COPD patients visited outpatient clinics accompanied by family caregivers, and > 50% were accompanied when visiting emergency rooms or during admission. However, no linear relationship between the accompaniment rate and COPD severity was apparent. Gautun et al. [18] reported that about 70% of COPD patients had informal caregivers and 67% of caregivers accompanied patients to healthcare facilities. COPD patients often require continuous care; the EQ-5D showed that this may be attributable to limitations in mobility or usual activities. A previous report found that up to 66% of COPD patients received informal home care [19]. We found that 33% of patients were supported by family caregivers at home, as were 50% of those with advanced airflow limitation. The indirect costs increase as airflow limitation deteriorates [5]; we found that the in-home care rate increased as airflow limitation progressed. Of all caregivers, 13.6% quit their jobs to stay home. The proportion of home care increased with COPD severity, but caregiver work loss was not associated with the severity of airflow limitation. A previous study found that 7% of caregivers quit their jobs [20]. Family-related caregivers are at high risk of such loss; they perform housework, arrange transportation, and accompany patients to healthcare services. In one study, 43% of informal caregivers were employed, but 44% took time off from work and 4% quit working to care for COPD patients [18]. Indeed, the work loss is greater than reported. Caregivers take days off, leave the office earlier, or are late to work. This compromises financial security, in turn reducing the availability of care resources.

Most family caregivers had mood- and health-related problems [19], emphasizing the need to improve support. Effective strategies assisting caregivers to deliver usual care, providing emotional and psychosocial support, and enhancing adherence to treatment, are required. Almost all caregivers in the present study were females > 60 years of age, as in a previous report [19]. The principal caregivers were relatives or friends in 88.6% of cases [19]. The most common caregiver was the patient’s spouse (70%) or an adult child (21%) [18]. Caregivers greatly influence the well-being of COPD patients. The availability of an informal caregiver (compared to no caregiver) was associated with better adherence to treatment [21], a reduced rate of smoking [21], and less frequent emergency room visits [22]. Interventions for patients with and without caregivers are required to optimize COPD management. Both clinicians and researchers are increasingly studying informal COPD caregiving; the prevalence of severe disease continues to rise, associated with substantial health, social, and economic impacts [23]. Healthcare systems must economically optimize the quality of life of COPD patients. Thus, a shift from hospital to home care may be inevitable; patients will increasingly rely on informal caregivers [24]. Informal family caregiver status is not evaluated by the GOLD guideline [7]; no validated questionnaire explores this topic. COPD management must focus not only on optimal therapy, but also on home management, including the role of the informal caregiver. Such caregiving is complex [24]. Caregivers may lack knowledge on COPD and be unaware that palliative care is available. Informal caregivers play critical roles; most COPD home care is provided by family and friends, not healthcare professionals [25].

Most COPD-associated expenditures are incurred when complications require hospitalization; many complications are preventable. As is true of other chronic diseases, improved healthcare management improves COPD outcomes and lowers costs. Better care and treatment adherence lowers avoidable costs and improves health; productivity increases and absenteeism falls [26]. We found that COPD was associated with substantial indirect costs (the time required to visit outpatient clinics, the extent of home care, time required by caregivers to accompany patients to outpatient clinics, and caregiver work loss). Thus, apart from COPD prevention, patient activity levels must be improved to reduce indirect COPD costs. The time required to visit outpatient clinics/ pharmacies was > 2 hours, associated with both patient and caregiver work loss. This lost time constitutes part of the COPD economic burden. Rapid and more appropriate medical treatments are required to reduce costs, increase productivity, and decrease absenteeism.

Our study had several limitations. First, our sample size was small. However, we recruited patients from primary clinics through to tertiary hospitals. Second, almost all subjects (91%) were male, although this reflects the COPD demographic in Korea [27]. Third, although we explored job quitting or changing, we did not explore absenteeism; thus, the work loss of caregivers may have been underestimated. Fourth, we did not investigate caregiver/patient relationships, but all caregivers were family members. Our results cannot be generalized to countries with different healthcare systems and/ or workplace illness policies.

In conclusion, the EQ-5D revealed that higher COPD severity was associated with a lower quality of life, and major indirect burdens in terms of family caregiver work loss and home caring, and the time required for medical treatment. Our findings will inform COPD management strategies.