Multimorbidity in Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a complex disease manifested primarily as airflow limitation that is partially reversible as confirmed by spirometry. COPD patients frequently develop systemic manifestations, such as skeletal muscle wasting and cachexia. COPD patients often develop other comorbid diseases, such as ischemic heart disease, heart failure, osteoporosis, anemia, lung cancer, and depression. Comorbidities complicate management of COPD and need to be evaluated because detection and treatment have important consequences. Novel approaches aimed at integrating the multiple morbidities seen in COPD and other chronic diseases will provide new avenues of research and allow developing more comprehensive and effective therapeutic approaches.

Key points

  • Patients with COPD also suffer from major concurrent diseases that are more frequent in them than in patients without COPD.

  • These comorbidities not only are more frequent but also appear a decade or 2 earlier in patients with the disease.

  • Coronary artery disease, cardiac arrhythmias, heart failure, lung cancer, osteoporosis, gastroesophageal reflux, interstitial lung disease, and depression, independently increase the risk of death in those patients.

  • The novel use of system network analysis highlights the potential interaction of multiple diseases occurring simultaneously.

  • Advances in high throughput and big data analysis provide new avenues to help understand the possible pathobiological mechanisms explaining multimorbidity co-occurrence.


Life expectancy has increased, partly due to significant improvements in the treatment of communicable diseases. This has resulted in an epidemiologic transition from early mortality caused by transmissible diseases toward a higher prevalence of noncommunicable diseases causing deaths at an older age. The challenge today is to achieve not only a longer life but also a healthier one. Given this paradigm change, we must be prepared to manage individuals with concomitant chronic diseases.

Noncommunicable chronic conditions are characterized by their slow, cumulative progression, making them clinically apparent at later stages in life, often when they can be controlled but not cured. As age advances, individuals are likely to have more than 1 co-occurring chronic condition, a phenomenon known as multimorbidity. Chronic obstructive pulmonary disease (COPD), a classic model of a complex disease, may start in early life, progress very slowly over time, and often is diagnosed when patients reach their sixth or seventh decade. The disease is defined by the presence of respiratory symptoms, in particular dyspnea, and is confirmed by the presence of airflow limitation that is not fully reversible using a spirometry. COPD is a syndrome rather than a single disease, with distinct phenotypes, each with its own natural course and prognosis and frequently associated with important systemic consequences, such as skeletal muscle dysfunction and impaired functional capacity. Once clinically expressed, it is a disabling disease, affecting a patient’s quality of life and increasing the risk of hospitalizations and death. From the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study, it has been learned that the degree of airway obstruction alone cannot identify by itself patients at risk of developing those outcomes. The development of multidimensional indices like the BODE index, which includes body mass index (BMI), degree of airflow obstruction, dyspnea compromise, and exercise capacity ( Table 1 ), has changed the understanding, by highlighting the importance of the extrapulmonary domains in COPD that in the end influence the clinical presentation and ultimate prognosis of these patients. It also has been learned that COPD rarely presents as the only disease of a particular patient, because more than 80% of those attending clinics have 1 or more comorbidities when carefully evaluated.

Table 1

The BODE index

Points on BODE Index
Variables 0 1 2 3
FEV 1 (% of predicted) ≥65 50–64 36–49 ≤35
Distance walked in 6 min (m) ≥350 250–349 150–249 ≤149
Modified Medical Research Council dyspnea scale 0–1 2 3 4
BMI >21 ≤21

Dying from or with chronic obstructive pulmonary disease

COPD is the third cause of death worldwide, yet up to two-thirds of individuals suffering from COPD die of nonpulmonary causes, mainly cardiovascular diseases (congestive heart failure, myocardial infarction, and stroke) and lung cancer. , This means that two-thirds of COPD patients, usually those with milder degrees of COPD severity, contribute to the cardiovascular and cancer death pool. Respiratory causes of death become more prevalent in patients with more advanced disease, as measured by degree of obstruction or better yet with the BODE index.

In addition, compared with the general population, comorbidities develop at an earlier age and with a higher point prevalence in patients with COPD , ( Fig. 1 ).

Fig. 1

Number of comorbidities per individual by age bracket and total mortality. Each band represent the number of comorbidities per patient and the width the proportion of individuals with that number of comorbidities at different age brackets (X axis). ( A ) Represent those patients carrying the diagnosis of COPD and ( B ) those without COPD.

( From Divo MJ, Celli BR, Poblador-Plou B, et al. Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort. PLoS ONE . 2018;13(2):e0193143; with permission.)

Epidemiology of chronic obstructive pulmonary disease–related comorbidities

Most studies have centered primarily on the identification of the most frequently observed comorbidities, their prevalence in COPD patients compared with the general population without this diagnosis, and their impact on patient-centered outcomes, such as mortality, quality of life, response to pulmonary rehabilitation, and hospitalizations. A summary of selected studies is presented in Table 2 , which compares the methods used to ascertain comorbidities in those studies, the setting where they were conducted, and the number of patients and controls included. In bold (first column), those settings with direct impact on patient-centered outcomes (listed in the fifth row) are highlighted. In this context, some general conclusions can be drawn.

Table 2

Summary of chronic obstructive pulmonary disease comorbidities studies describing the setting, methodology of disease ascertainment, number of subjects, prevalence, and impact on important outcomes

Data from Refs.

Divo et al, 2012 Vanfleteren et al, 2013 Mapel et al, 2000 Cazzola et al, 2010 van Manen et al, 2001 Schnell et al, 2012 Putcha et al, 2014 Crisafulli et al, 2008 Terzano et al, 2010 Almagro et al, 2012 Antonelli Incalzi et al, 1997
Disease ascertainment Self-reported Measured Administrative database Administrative database Administrative database Self-reported/measured Administrative database Self-reported Self-reported/measured
N 1659 213 200 200 15,000 325,000 290 421 995 14,828 843 2962 288 606 288
Outcome Mortality QOL QOL Response to Rehab Readmission Readmission/mortality Mortality

Setting Outpatient Acute Outpatient Outpatient Outpatient Outpatient Outpatient Acute Acute Acute Acute
Prevalence (%)
HTN 52 48 45 37 23 21 60 52 38 63
Hyperlipidemia 44 36 48 41 9 8
CAD 30 9 22 15 16 7 23.4 9 16 12 21
Obesity 29 23 40 34 40.9 2 29
DJD 29 22 20 55 37 58.6
Diabetes mellitus 22 54 8 7 19 11 7 5 16 13 13.9 14 25 28
PAD 17 53 6 2 18 17
Depression 17 16 17 13 7 5 9 4 21 13 42.5 15
CRF 17 22 2 1 16 11 26 16 6
CHF 16 14 3 8 2 12 15.1 15 33
Underweight 15 14
Substance abuse 14
Atrial fibrillation 13 2 21
Anxiety 12 21 9 4 18
Erectile dysfunction 12
Gastric/duodenal Ulcer 12 32 17 7 2 5 10
CVA 11 4 4 3 4 9 5 11
Pulmonary HTN + CP 10 4 60
OSA 10 2
Lung cancer 9 2 0 2 2
Osteoporosis 8 31 15 11 17 9 7 16
Hypothyroidism 7
Breast cancer 7
Pulmonary fibrosis 6
Anemia 5 9 6 10.1 10
Cardiac arrhythmia 12 10 14 7 6

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Aug 16, 2020 | Posted by in GENERAL | Comments Off on Multimorbidity in Patients with Chronic Obstructive Pulmonary Disease
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