Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort

Abstract

Background: Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD.

Methods and findings: We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network's density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking.

Conclusion: Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age.

Fig 1. Number of comorbidities per individual by age brackets and total mortality.

Each band represent the number of comorbidities/patient, and the width the proportion of individuals with that number of comorbidities at different age brackets (x-axis). Panel A represent those patients carrying the diagnosis of COPD and Panel B those without COPD. The stacked “Grim Reaper” represents the number of death at 3 years of follow-up (5,247 for COPD and 2,911 in the non-COPD) and their position is located at the mean age of death; one full “Grim Reaper” represents 1,000 deaths.

Fig 2. Comparison of network’s characteristics by 5-year age groups in both COPD and non-COPD groups.

We categorized both groups into five age groups and built their respective networks to compare the network’s density: total number of nodes (3^rd row), total number of connections (4^th row), and average degree per node. Between groups comparisons were calculated for the average degree (last row) and those without statistical difference have similar color and relate to brackets.

Fig 3. Prevalence of co-morbidities commonly seen in the elderly between COPD and non-COPD patients at five different age categories.

Solid dots ● represent COPD patients and hollow dots ○ represent non-COPD patients. The size of the dots is proportional to the number of links (degrees) in their respective networks. Note, the prevalence (vertical axis) is higher in the COPD group and reach those values seen in non-COPD at an earlier age (horizontal axis). Comorbidities where the prevalence in COPD is similar to controls 10–20 years earlier are highlighted with a solid arrow ↓ and hollow arrow ⇓ in non-COPD. We show in this Fig 2 representative examples of comorbidities of the elder (osteoporosis and atherosclerosis). For the complete list of comorbidities seen in the elders please refer to S9 Fig.