Key points

Introduction

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.

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 ).

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
	COPD	COPD	COPD	Control	COPD	Control	COPD	Control	COPD	Control	COPD	COPD	COPD	COPD	COPD
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
GERD	18
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 ∗
AAA	7
Pulmonary fibrosis	6 ∗
DVT	5
Anemia		5							9	6			10.1 ∗	10
Cardiac arrhythmia			12	10	14	7									6 ∗

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