Systematic Review
Depression is associated with poor prognosis in patients with chronic obstructive pulmonary disease – a systematic review
1. okt. 2015
16 min.
Faktaboks
Fakta
Chronic obstructive pulmonary disease (COPD) is defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as a condition characterised by airway obstruction that is not fully reversible. The airway obstruction is progressive and associated with an abnormal inflammatory response to obnoxious particles or gasses [1]. Co-morbidity in COPD patients is more a rule than an exception [2], and it poses a substantial risk for mortality, increased frequency of exacerbations and poorer quality of life. In Denmark, 85-90% of COPD cases are caused by smoking [3]. In a Danish cohort followed through 25 years, the absolute risk for developing COPD was 25%, while subclinical COPD was found in 30-40% [4].
A number of studies have investigated how various somatic co-morbidities affect COPD patients’ prognoses. In a meta-analysis by Smith et al in 2014, ten of the most common co-morbidities were analysed. The 3 co-morbidities leading to the highest total mortality were lung cancer, cirrhosis and diabetes, with respective hazard ratios of 2.02, 1.68 and 1.54-1.7 [2]. These co-morbidities also proved to have a considerable impact on the number of exacerbations and on quality of life.
Depression is highly prevalent in patients with COPD, even when compared with other chronic diseases such as stroke and cancer [5]. Patients with depression show a high mortality rate for somatic disease. This has been studied extensively in various medical fields, particularly in cardiology. One investigation found that severe depression increases is associated with a three-fold increased relative risk of mortality due to cardiac causes [6]. In a meta-analysis investigating mortality in patients with COPD, a relative risk for mortality of 1.8 was found in patients with depression as co-morbidity [7]. Similar results have been replicated in several studies [8, 9]. It is worth noticing that only 30-40% of the increased mortality is due to suicide.
The prevalence of depression among patients with COPD has been estimated to be between 8% and 80% [2, 10-15]. This significant variation reflects differences in study populations, diagnostic classification systems, and whether questionnaires or clinical interviews were used. Despite the significant prevalence, depression – especially in its milder forms – is possibly under-diagnosed. In an American cross-sectional study from 2005 of 1,334 patients with COPD, only 31% of the patients with depression as co-morbidity and/or anxiety received antidepressive treatment [16]. Studies investigating risk factors for depression in patients with COPD show diverging results. In an Argentinean cohort, Lopez Jove et al found female gender (odds ratio (OR) = 4.14) and dyspnoea (OR = 4.48) to be risk factors, while physical activity (OR = 0.29) was protective. No significant association was found between the severity of COPD and smoking status [17]. Funk et al found the prevalence of depressive symptoms to be increased with both increasing GOLD and The Burden of Obstructive Lung Disease (BOLD) stages [18].
COPD exacerbations are important causes of the significant morbidity and mortality associated with COPD, and exacerbations have been proven to accelerate the progression of COPD [19]. COPD exacerbations are defined by GOLD as an event in the natural course of the disease characterised by a change in the patient’s baseline dyspnoea, cough and/or sputum that is beyond normal day-to-day variations; it is acute in onset; and it may warrant a change in regular medication [1]. The frequency of exacerbations is one of the most important determinants for health-related quality of life in COPD patients [20].
COPD exacerbations are more common than previously presumed. In a prospective cohort study, Seemungal et al found that on average patients with COPD had 2.5-3 exacerbations annually. 50% of the cases were not reported to the researchers, but were discovered by looking through the patients’ symptoms diary [20]. The international epidemiologic studies of COPD are characterised by a large variation in prevalence and mortality.
The BOLD initiative conducted an international
multi-centre study in which the total prevalence of COPD was found to be 10.1% for stage two or higher COPD. If stage one had been included, the prevalence would have approached 20% [21]. Another large international meta-analysis reported the COPD prevalence to be between 0.2% and 37% [22]. The large variation clearly expresses differences in the diagnostic approach, classification methods and population characteristics. Mortality was found to be 3-111/100,000. This reflects differences in length of patient follow-up, which sequelae were registered for COPD, and differences between patients, for instance in terms of GOLD stage. A Scandinavian retrospective register study found that patients with COPD had a reduction of life expectancy of 8.3 ± 6.8 years [23].
METHODS
Search strategy
The article is based on a review of cohort studies and other review articles. The searches were conducted on the 16 December 2014. The search was first done at PubMed with the MeSH terms “pulmonary disease, chronic obstructive” AND “prognosis” AND “depression”. The same search was repeated in OVID Medline, Cochrane and Embase. Other search words used in various combinations were COPD, mortality, hospital admission, hospital readmission, exacerbation, health-care use, suicide, depressive disorder primary care and drug prescriptions. Linguistic and methodological limitations were not applied in the searches. For relevant articles, abstracts were reviewed and the articles obtained. Literature references in the chosen studies as well as general review or status articles for COPD were also used to find relevant studies, although this ended up primarily being duplicates, which were removed when the studies were reviewed together.
Study selection
The searches resulted in 136 abstracts, which were reduced to 39 articles after being reviewed (Figure 1). The following inclusion criteria were chosen: studies highlighting the prognostic significance of co-morbid depression in patients with COPD in terms of mortality, hospital admission/exacerbations, use of primary care, use of pharmaceuticals and suicide risk; retro- and prospective cohort studies; and studies which used a validated depression scale or structured diagnostic interviews.
Depression was defined as either a depressive episode, a recurrent depressive disorder, or elevated depressive symptoms. Studies deviating in outcomes, study design and studies with significant methodological faults were excluded. We only found studies with mortality and exacerbation/hospital admissions as outcomes.
Of the 39 articles, only 22 met the inclusion criteria: 20 of these studies were prospective cohort studies, one was a retrospective, and one was a combined retrospective and prospective cohort study.
Methodological quality assessment
The studies were reviewed using the Critical Appraisal Skills Programme (CASP) checklist for cohort studies [24]. The checklist consists of 12 points, but since several of these are general and were fulfilled by all the studies, and several of them overlap, we chose the six with largest methodological discriminatory potential, and the ones which could more easily be presented schematically. The included studies were thus assessed by the following six methodological quality criteria: 1) number of patients in the cohort (ideally 30 or more patients per group); 2) generalisability of the cohort (whether the population had specific inclusion or exclusion criteria reducing its external validity); 3) whether 20% or more of the patients were lost during the course of the study;
4) whether the studies controlled for three or more of the following confounders: age, sex, smoking status, co-morbidities and forced expiratory volume in the first second (FEV1); 5) whether clinical outcomes were scored adequately (by a central mortality registry, hospital registry or through an interview with a person who was blinded to the depression status); 6) whether depression was diagnosed through interview or was self-reported. The overview is presented in Table 1Table 1.
COPD was diagnosed clinically and spirometrically in all the studies except from that of Dalal et al [25] where patients were identified by earlier prescription of at least one medication against COPD, and afterwards verified by checking that the patient had at least one COPD-related International Classification of Diseases (ICD), version nine (ICD-9) diagnosis. Everyone stated that validated depression diagnostic instruments had been used, but there was a consistent lack of depression diagnostic instruments specifically validated to patients with COPD.
Data analysis
The studies presented great heterogeneity in relation to demographics, severity of COPD, whether the condition was stable or characterised by many exacerbations, follow-up and with regard to how depression or depressive traits were diagnosed. For this reason, we have chosen not to summarise the results statistically.
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