Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction, which leads to the slow, progressive symptoms of persistent cough, exertional dyspnea, wheezing, and eventually functional impairment [1]. World Health Organization (WHO) has reported in the Global Burden of Disease Project that approximately 5 of 100 deaths worldwide are associated with COPD [2]. At this rate, COPD may rank as the third leading cause of death in the world by 2020 [3]. Given the complex symptoms and long duration of COPD, the medical expenses for curing the disease cannot be ignored. A study by Menzin et al. [4] found that the average medical expenses per COPD patient per year was estimated at US$27,656, which is nearly 4 times higher than the average cost for patients without COPD (US$7,126). In a review of the financial burden of COPD in USA, the authors estimated that the annual direct medical costs for COPD amounted to $21.8 billion, and the indirect costs for restricted days, lost workdays, and productivity were at $17 billion [5].

COPD does not only cause enormous economic burden, it also triggers subsequent illnesses. The risk of lung cancer for COPD patients is more than two folds higher than for those without the disease [6]. Curkendall et al. also confirmed that COPD patients have a 60%–80% higher risk of developing cardiovascular diseases compared with the general population [7]. Given the irreversible nature and unsatisfactory prognostic outcomes, COPD patients are frequently diagnosed with psychiatric disorders, particularly depression [8]. A systematic review of 64 studies on patients with chronic disease concluded that the prevalence of depression ranged from 37% to 71% in COPD patients, figures comparable to or higher than prevalence rate in patients with other chronic diseases, such as cancer, AIDS, heart disease, and renal disease [9]. Depression not only increases hospitalization and emergency visits by 48% and 77%, respectively, in COPD patients [10], but also doubles the likelihood of dying from the comorbidities of COPD-related depression [11]. Therefore, depression has become a matter of great healthcare concern for COPD patients and their families.

Studies on COPD-related depression have been conducted mainly on Western populations but rarely for people of Asian descent [12]. Chinese, in particular, often consider depression to be a taboo issue and they may suffer more in terms of emotional distress [13, 14]. Previous studies on Chinese COPD patients have focused on the effect of medical treatments [15], mortality [16], and the subsequent risk of skin disease following COPD [17]. In contrast, data related to the psychological issues, especially depression, among Asian patients with COPD are limited. Few studies investigating the influencing factor of depression among Chinese COPD patients have been conducted, but these studies were limited to a cross-sectional design and small sample sizes [18, 19]. We conducted a follow-up study to determine the association between depression risk and COPD using claims data from the National Health Insurance (NHI) of Taiwan to evaluate the risk of depression in Oriental patients with COPD. Apart from being a preliminary study of depression in COPD patients, its findings should be able to help healthcare providers identify potential cases of having depression and this will allow more efficient interventions to improve the quality of life for them.

Previous studies have shown that emotional impairments, depression in particular, are common among COPD patients, but mainly in Western populations. To the best of our knowledge, the present study is the first population-based cohort study addressing the association between COPD and the risk of subsequent depression in an Asian population. The results are consistent with findings in previous studies on Western populations [8, 23, 24]. The likely explanation for this finding was as follows. COPD patients may require more daily care due to gradually worsening physical conditions, which may lower self-esteem and self-efficacy, inducing a higher risk of depression [9]. Schane et al. found that COPD patients of lower education, living alone and female gender were more likely to have depression [8]. A cross-sectional study in China also found low income COPD patients are more likely depressive [25]. Our study revealed similar socioeconomic association, indicating the elderly and low income COPD patients are at higher risk of depression.

Additionally, the same debilitating and continuous physical symptoms may also trigger cognitions of “learned helplessness”, such that one’s inability to successfully cope with physical deterioration and life threatening situations result in increased levels of uncertainty, unpredictability and ultimately emotional distress and depression [26]. On the other hand, several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6), have been considered pathogenic factors associated with the mechanism of developing depression [27]. A meta-analysis containing 24 studies indicated that the inflammatory cytokines may regulate adult neurogenesis to induce hippocampal neurogenesis atrophy, which has been implicated as a key contributing mechanism in the pathophysiology and treatment of depression [28].

The depression incidence among COPD patients in this study is somewhat lower than that in a previous report [24]. The difference may stem from the different composition of the two groups of participants. In addition, the stigma of mental illness is particularly entrenched in Asian patients and they may be unwilling to acknowledge or admit feelings of depression [13]. Depression, in many Asian countries, is an embarrassing issue for the general population to openly seek regular psychotherapy. Most importantly, less than 20% of patients with COPD have ever received appropriate psychiatric treatment since they were diagnosed with COPD [19]. Therefore, the implementation of a standardized care process, including some screening tools applicable to COPD patients, may be of utmost importance.

Our study indicated that women are at a 1.19-fold greater risk of depression than men in the COPD cohort, which supports the findings of previous studies [8, 24]. Two reasons may account for this phenomenon. First, women are more health consciousness than men and more likely to seek medical care during irregularities in their well-being [29]. Moreover, women are traditionally more obedient, passive, and emotional, which may insidiously elevate the risk of depression [30]. In contrast, our finding contradicts those reported by van Manen et al. [31]. A small sample size of 162 subjects used in their study may lead to a null association between the depression risk and gender.

We found a lower risk of depression in patients with higher monthly incomes than in those with lower monthly incomes, which is in line with previous studies [30, 32]. Patients with higher incomes may have better financial resources in dealing with the challenges engendered by COPD. This result, however, is inconsistent with that reported by Lin et al. [33], which may stem from the use of a different study design. Given that establishing a clear causality with the cross-sectional design is difficult, erroneously determining the effect of risk factors is possible [34].

Consistent with previous studies [8, 18, 31], we found that younger COPD patients were at a higher hazard for depression than the elderly. Most of the young COPD patients were employed; therefore their workload may have contributed to additional emotional distress. More importantly, our results demonstrated that the incidence of depression is higher in COPD inpatients than in outpatients. This finding indicates that severe COPD, which requires hospitalization, may trigger an increased risk of depression. Similar to previous report [35], we also noted that the risk of depression in COPD patients was higher within one year after diagnosis. The newly diagnosed patients may be highly fragile and overwhelmed by COPD symptoms. These findings suggest that healthcare providers need to pay closer attention to newly diagnosed patients with COPD, particularly inpatients. Interventions geared toward providing emotional support to enhance the psychological adjustment of patients may be of utmost importance.

COPD patients with other comorbidities, such as hypertension, arthritis, heart disease, or cancer had a significantly higher risk of depression, whereas those with diabetes mellitus and chronic kidney disease were at borderline significance. Our findings are partially paralleled with those of a previous study [8], indicating that comorbidities are associated with the predisposition for depression among COPD patients. The occurrence of comorbidities could play a role in weakening the perceptions of health status among COPD patients, thus leading to increased risk of depression. Additionally, a review article demonstrated that a depressive mood might be related to medication, such as antihypertensive agents, corticosteroids, or other biological agents [36]. So it was suggested that clinicians should actively assess existing medications prior to initiating depression-related treatments for COPD patients, which may reduce the risk of depression after COPD diagnosis.

Several limitations in this study should be mentioned. First, information on tobacco use, social network relationships, religious belief, and education level was unavailable from the claims data, which may be related to depression. Further study linking administrative data and the above mentioned information is warranted to examine the impact of these potential confounding variables on depression. Second, inaccurate diagnoses may occur. Therefore, we selected only those subjects with COPD or depression with at least two consistent outpatient visits or one inpatient admission to minimize this error. Furthermore, NHI has randomly sampled claims from hospitals and randomly interviewed patients, as well as reviewed medical charts to verify the accuracy of medical records. Finally, data regarding the severity of COPD, such as lung function data, were not available in the database. We were unable to estimate the dose–response relations between COPD severity and depression. Despite these methodological concerns, this population-based cohort study has been successful in examining the relationship between COPD and the subsequent risk of depression among Chinese patients. The retrospective cohort study design per se provided stronger evidence on the relationship between COPD and depression risk compared with previous studies.

Findings from this study reveal that the depression risk is nearly two folds higher for COPD patients than for general population. The risk of depression is related to being female and young, as well as with lower monthly income and comorbidity, such as hypertension, arthritis, cancer, and heart disease. Healthcare providers could be able to better understand the demographic and diseases characteristics that may contribute to the depression risk from this population-based study. The need to routinely screen COPD patients for depression and institute culturally appropriate interventions should be emphasized, especially within the first year since COPD diagnosis. Healthcare providers must be cognizant of the existence of depression among COPD patients and inform them by standard care process to avoid potential embarrassment when discussing psychiatric-related issues; this will help to achieve better therapeutic outcomes for them.