This study provides further evidence that depressive symptoms, independent of age, lung function, and exercise capacity, are prognostic factors for mortality in COPD. We found that type D personality is associated with depressive symptoms, but despite this moderate association, type D itself is not a prognostic factor for mortality in COPD.
Two previous studies in samples of patients with COPD who were hospitalized because of a recent exacerbation demonstrated that symptoms of depression were associated with mortality independent of disease severity and other risk factors [26
]. It has been argued that the possibility should be considered that these results may be a consequence of the difficulties of distinguishing affective dispositions from patients’ medical conditions [47
]. However, one past study found a similar effect in patients with clinically stable COPD [30
]. Moreover, in another recent study, we were able to obtain this result in a group of patients with clinically stable COPD in pulmonary rehabilitation. A similar association was found between depressive symptoms, assessed with the BDI and mortality, independent of sex, age, and exercise capacity [31
]. It is noteworthy that our finding was in a population of patients with stabilized COPD. Unlike some recent studies in which the assessment of depressive symptoms was following a recent exacerbation of COPD, our results are less obviously the product of a spurious relationship between depressive symptoms and mortality due to a confounding with physical distress that anticipates death. Our median follow-up period was also longer than would be affected by acute illness.
Some sources have argued that, in the assessment of depressive symptoms in patients with cardiovascular disease, scores obtained with instruments like the widely used BDI are inflated among patients with medical disease because of the confounding of vegetative symptoms [48
]. The HADS is constructed to avoid assessment of somatic symptoms. Still, in the present study, despite the use of a different instrument to assess depressive symptoms, the HADS, we found a similar effect of depressive symptoms on mortality. The fact that the depression–mortality association is consistent in two different groups of patients with stable COPD and with two different assessment tools for symptoms of depression, i.e., BDI and HADS, strengthens the evidence for this relation and adds to the established predictor variables.
With regard to the association of depressive symptoms and mortality, two hypothetical pathways are suggested. One may be through behavioral mechanisms such as that depression leads to low self-care and apathy resulting in avoidance of regular exercise, inadequate nutritional intake, low treatment adherence, and continued smoking, all of which are related to worse prognosis. Another pathway may be that depression affects the hypothalamic pituitary adrenal axis functioning which could deteriorate health status and influence prognosis [51
]. Evidence is consistent that inflammation occurs among a subset of depressed patients and thus may worsen prognosis in COPD [54
]. Still, the depression–mortality relation may still be confounded by other unmeasured factors related to both depressive symptoms and mortality, namely, overall chronic disease burden [55
Regardless, depressive symptoms represent a burden for patients because of its influence on their quality of life. Elderly persons reporting depressive symptoms are particularly at risk of chronic decline of health [56
]. Several studies have reported that major depression is reduced by psychological or antidepressant interventions [57
]. Also, pulmonary rehabilitation has been known to reduce depression and improve quality of life [58
]. Moreover, pulmonary rehabilitation is even potentially beneficial in reducing the risk of mortality [61
]. However, there are no studies yet that have established if decrease of depression symptoms in patients with COPD actually reduces the risk for mortality.
In cardiovascular research, Denollet and his coworkers offered type D personality as an explanation of the observed association between depressive symptoms and a variety of cardiovascular outcomes [33
]. Although there is evidence for substantial comorbidity between COPD and cardiovascular disease, with smoking and airflow limitation as independent risk factors for mortality [39
], we did not find that the presence of type D personality was related to mortality at a bivariate level nor in a multivariate model. While type D is correlated with symptoms of depression, it is apparently not a factor which could explain the depression–mortality relation in COPD. Perhaps, although unlikely, type D is specifically associated with cardiovascular morbidity and death.
On the other hand, we have already noted the moderate correlation between depressive symptoms and type D, but that depressive symptoms have a high correlation with one of the components, namely, NA. Use of median splits then to construct typology resulted in some high depressive patients being excluded and some relatively low in depressive symptoms, but still above the median split, being included. Also, Suls and Bunde have presented their concerns on the degree of overlap among different affective dispositions [47
]. The degree of overlap may provide a partial explanation for inconsistencies in our study. Despite the high correlation between NA and depressive symptoms, our null effect in the type D mortality association may be a consequence of minimal overlap with the cardiotoxic affect. However, we agree with Suls and Bunde that it is unlikely that this is the sole explanation for the inconsistency [47
In another context, Maxwell and Delaney have cautioned about the likelihood of spurious results when a typological construct, like type D, is created from two dichotomized variables:
When two (or more) continuous predictor variables are dichotomized, the resulting 2
2 analyses are not necessarily conservative. Instead, there is a potential for an effect that is truly zero for a continuous measure to be estimated as a small to medium effect in the 2
2 factorial design [63
, p. 188].
The present results thus offer no support for pursuing type D as an explanation for COPD mortality. However, it could be important to examine the potential statistical problems with type D construct in cardiovascular disease.
Some limitations of this study should be noted. First, data on the nature and numbers of comorbid conditions were not consistently recorded and, therefore, not included in the study. These data, especially on cardiovascular comorbidities, could have provided us with additional clues on a possible explanatory mechanism of the association between depressive symptoms and mortality and/or the null finding with regard to the type D–mortality association. Second, the cause of death was not determined. Variables in our study are prognostics for all-cause mortality and not just for respiratory causes. However, in studies of all-cause mortality, the actual cause of death is not independently validated and known to be less trustworthy [46
]. Third, our study includes several potential modifiable variables, such as smoking behavior, BMI, FEV1
, and exercise capacity, which may alter in time. In COPD, patient reported outcomes on health status, dyspnea, and psychological status, as well as physiological outcomes deteriorate over time, but intercorrelations between both types of outcomes are weak [64
]. In our study, assessment of depressive symptoms was limited to a single point in time. This assessment leaves unexplored questions about the stability and course over time. However, we believe our assessment allows demonstration of the predictive value of depressive symptoms in COPD. Finally, we observed our findings among patients with clinically stable COPD, which perhaps limits generalization to all patients with COPD. However, taken together with findings of the other studies demonstrating the predictive value of depressive symptoms in COPD, our results give support to further studies on the course of depressive symptoms in relation to mortality.
In conclusion, the present paper provides further evidence for the association of depressive symptoms and mortality. This association may very well reflect confounding by other unmeasured factors [55
]. In this study, we did not find that the presence of type D personality is related mortality or that it is a confounder in the depression–mortality relationship in patients with COPD. In contrast to cardiovascular disease, it seems that we can rule out type D as an explanation for the relationship between depressive symptoms and mortality observed in this sample. Further efforts are encouraged to disentangle the relationships found, and more attention should be paid to behavioral and physiological mechanisms.