The strength and newsworthy of the current study is the up-to date report on the impact of COPD on mortality. The identification of the study population and the observation time took place during the twenty first century when treatment for COPD as well as cardiovascular disease was recommended according to modern and current guidelines. Further, the distribution of disease severity among subjects with COPD in the cohort was representative for what has been reported for the general population, comprising of more than 90% of patients in GOLD stages I and II [4
]. COPD was a significant risk factor of increased mortality in this topical epidemiological context.
There are only a few previously published population based studies on mortality in subjects with COPD defined according to currently accepted spirometric criteria [7
]. As referred to in the introduction, these study populations were recruited during the nineteen-seventies and eighties. The mortality data in these studies were based on long term follow-ups from about ten years to more than twenty years, thus a healthy survivor effect must be taken into account when evaluating these data. Further, updated guidelines during the last decade for treatment of not only COPD, but also cardiovascular disease, have improved the prognosis compared to thirty years ago. Consequently, the starting point, the time and the length of the observation time are of importance when evaluating and comparing mortality data not only in COPD but also other diseases. There are mortality data collected in two large clinical trials started during the nineties with an observation time over three and four years respectively, the TORCH and the UPLIFT studies. The all-cause mortality reported from the TORCH-study was 14.3% [20
] in a population with moderate- to severe COPD (FEV1
< 60 percent of predicted). In the UPLIFT-study [21
] subjects with a post-bronchodilator FEV1
< 70 percent of predicted were included, and the crude mortality in the total population was 15.4% at the end of the treatment period. After the approximately four year's observation time, similar to the UPLIFT, the mortality was 10.9% among subjects with in COPD in our study. However, the UPLIFT-cohort had a lower baseline mean FEV1
compared with our study, further, as most clinical studies the UPLIFT-study included a selected population with regard not only to lung function but also to other factors such as age and co-morbidity. Further, in a 13-year follow-up of the ISOLDE study [22
], the mortality was 56% in the study population including subjects with moderate- to severe COPD.
The reported mortality in this study can be considered up-to-date as both the identification of the study population and the observation time took place after the turn of the century, where modern and current guidelines for treatment have been well established in Sweden. Subjects with COPD in the cohort are considered representative for the general population with regard to distribution by disease severity [4
]. There are, to the best of our knowledge, no other published similar studies. Further strengths of the study are the large size of the COPD-population, comparable to that of the NHANES I [7
], the accuracy of mortality data and that there was no loss of follow-up. However, possible limitations are the comparatively short time of follow up and that information on heart disease was self-reported and not collected from medical records. Another limitation is that the classification of COPD was strictly made by spirometric criteria without regard to respiratory symptoms. This has to be considered when interpreting the data, as respiratory symptoms are known to affect the prognosis in mild/moderate COPD [23
]. Further, the non-COPD population did also include subjects with restrictive lung function impairment, even though the ability for a dynamic spirometry to identify restrictive lung function can be questioned. The reasons for a restrictive pattern on dynamic spirometry are highly heterogeneous and reflect different underlying disorders as idiopathic pulmonary fibrosis, thoracic deformities, obesity, pleural effusion, cardiac insufficiency and neuromuscular diseases.
As expected, increasing age was the most prominent risk factor for death. Among all subjects born < 1940, the proportion of deceased was significantly larger among subjects with COPD. The use of a fixed ratio to define airway obstruction, FEV1
/FVC < 0.70, has been discussed with regard to identifying clinically relevant COPD among elderly [24
], but the results from our study indicate that the fixed ratio identifies a population with significantly increased mortality also among subjects older than 80 years. There is a recent report on 5-year mortality among subjects aged > 65 years, where COPD according to GOLD was not associated with increased mortality among those older then 75 years [25
]. However, the study population was recruited was from an out patient clinic, and can thus not be considered to reflect COPD in the general population.
was included in the multivariate analyse model, COPD was no longer a significant risk factor for death, but the level of FEV1
, reflecting disease severity at recruitment, was related to mortality. Our data exemplify that a decrease in FEV1
in the range of 100 to 50 percent of predicted will continuously increase the risk for death, and further, illustrated by Figure , a dramatic increased risk for death occurs when FEV1
continues to decrease below 50 percent of predicted. It is well-known that tobacco exposure contributes to the development of both COPD and cardiovascular diseases, and cardiovascular death is the most common cause of death in the world. In a multivariate model heart disease was a significant risk factor for death just as COPD, age and male gender, however, when smoking habits were added to the model there was a slight change. Smoking roughly doubled the risk for death while male gender and reported heart disease each increased the risk on a similar level, approximately 40%, even though heart disease did not reach statistical significance as a risk factor. Impaired lung function is a known risk factor for death [10
] and according to our results the risk for death in subjects with COPD, when adjusted for confounders including presence of heart disease, was increased by about 75% compared to in subjects without COPD. Maybe the impact of current treatment guidelines of cardiovascular disease has reduced mortality contributing to the borderline significance of heart disease as a risk factor while we found COPD and impaired lung function still being strong and significant risk factors for death.
Besides smoking, BMI is a known prognostic factor in COPD, and increased loss of weight is associated with a higher mortality in COPD [26
]. In this study BMI could not predict mortality; however, longitudinal data on weight loss were not included. An important message is also the benefit of smoking cessation, i.e. being an ex-smoker did not differ significantly from non-smokers with regard to risk for death, while current smoking roughly doubled the risk for death. According to a 9-year follow-up from the ECRHS non-smoking non-symptomatic young adults with mild/moderate COPD do not have worse outcome than subjects without COPD [23
]. Further follow-up of our cohort will give us corresponding data from middle aged and elderly subjects with mild/moderate COPD. There was surprisingly no significant difference in prevalence of heart disease in subjects with and without COPD, however, the dominance of GOLD stage I and II in the COPD-cohort might contribute to this finding.