Elsevier

Respiratory Investigation

Volume 53, Issue 6, November 2015, Pages 249-258
Respiratory Investigation

Review
Comorbidity in chronic obstructive pulmonary disease

https://doi.org/10.1016/j.resinv.2015.02.004Get rights and content

Abstract

Patients with chronic obstructive pulmonary diseases (COPD) often experience comorbid conditions. The most common comorbidities that have been associated with COPD include cardiovascular diseases, lung cancer, metabolic disorder, osteoporosis, anxiety and depression, skeletal muscle dysfunction, cachexia, gastrointestinal diseases, and other respiratory conditions. Not only are comorbidities common but they also considerably influence disease prognosis and patients׳ health status, and are associated with poor clinical outcomes. However, perusal of literature indicates that little has been done so far to effectively assess, manage, and treat comorbidities in patients with COPD. The aim of this review is to comprehensively narrate the comorbid conditions that often coexist with COPD, along with their reported prevalence and their significant impacts in the disease management of COPD. A perspective on integrated disease management approaches for COPD is also discussed.

Introduction

Chronic obstructive pulmonary disease (COPD) is a progressive disabling illness associated with an abnormal inflammatory response of the airways and the lung to noxious stimuli [1]. It is characterized by persistent airflow limitation that is not fully reversible and airway inflammation [1]. According to the estimates of the Burden of Lung Disease Initiative (BOLD) study [2], the overall global prevalence of COPD in adults over the age of 40 is 10.1%, with the prevalence being slightly higher in men (11.8%) than women (8.5%). In 2010, nearly 2.9 million people were reported to have died of COPD globally [3]. The illness burden associated with COPD is projected to rise with continued exposure to COPD risk factors [4].

Cigarette smoking is the single most important cause of COPD, with emerging data suggesting the presence of airflow limitation in nearly 50% of smokers [5]. Nevertheless, a significant proportion of patients with COPD are also non-smokers [6]. This is particularly true in developing countries where indoor air pollution such as biomass fuel exposure is most common [7], [8]. Nevertheless, even in developed countries between 10% and 30% of COPD patients are believed to be never-smokers [2], [9]. Other etiological factors for developing COPD include genetic susceptibility (α1-antitrypsin deficiency) [10], occupational exposure to dust and chemicals such as vapors, irritants, and fumes, severe respiratory infections during childhood [11], and childhood severe asthma [12].

The major pathological changes that cause the inexorable airflow limitation in COPD include remodeling and narrowing of the small airways and destruction of the lung parenchyma [13]. Many converging lines of argument suggest that these pathological changes are secondary to chronic inflammation in the periphery of the lung, which increases as the disease progresses [13], [14]. It is now recognized that this inflammation in patients with COPD is not just confined within the lungs and may contribute to the extra pulmonary effects of the disease [15], [16], [17]. So whilst COPD primarily affects the lungs, it is a complex, heterogeneous, and multicomponent disease characterized by chronic systemic inflammation and often coexists with other disorders known as comorbidities [15], [16], [17]. Comorbidities in COPD are known to pose a challenge in the clinical care of COPD patients, are likely to add to the complexity and cost of care, and are now recognized as key components of the disease [18], [19]. Comorbidities that have been associated with COPD include cardiovascular diseases, lung cancer, metabolic disorder, osteoporosis, anxiety and depression, skeletal muscle dysfunction, cachexia, gastrointestinal diseases, and other respiratory conditions [19], [20], [21], [22], [23]. In this review, we have tried to comprehensively describe the comorbid conditions that are often coexistent with COPD, along with their reported prevalence and their significant impact in the management of patients with COPD. A perspective on integrated disease management approaches is also provided.

Section snippets

Comorbidities in COPD

The majority of COPD patients suffer from at least one comorbid condition [19], [24]. Schnell and co-workers found that over 96% of 995 physician-diagnosed patients with COPD aged 45 and over had at least one comorbidity [19]. Moreover, nearly 52% of the patients with COPD were reported to take more than four medications compared to those without COPD (32%). A subsequent study by Vanfleteren et al. [24] showed similar results with nearly 98% of a cohort of 213 well-characterized COPD patients

Implications of comorbidities for clinical practice

As may be evident from the foregoing discussion, comorbidities in COPD have a considerable impact on the overall clinical care of patients with COPD. The coexistence of multiple chronic conditions in COPD patients has also been associated with multiple parallel treatments or polypharmacy [102], which may result in increased incidences of inappropriate prescriptions and drug interactions culminating in adverse events [32], [103], [104]. Clinical decision making is further complicated by the lack

Summary

In this review, we have described the most common comorbid conditions that co-occur with COPD with particular emphasis on their reported prevalence and detrimental impacts on clinical outcome such as severity of symptoms, quality of life, hospitalization, health care utilization, and mortality. Although the impacts of comorbid conditions in the management of COPD has now been acknowledged, little has been done so far on how to provide improved care for comorbid COPD patients. What is now

Conflict of interest

Netsanet A. Negewo has no competing interests to declare. A/Prof. Vanessa M. McDonald is supported by Lung Foundation of Australia and Boehringer Ingelhiem COPD Research fellowship. Professor Peter G. Gibson has no competing interest to declare.

Acknowledgment

Netsanet A. Negewo is supported by the Priority Research Centre for Asthma and Respiratory Diseases Ph.D. Scholarship and Emlyn and Jennie Thomas Postgraduate Medical Research Scholarship through the Hunter Medical Research Institute (Grant number is G1401393).

Vanessa M. McDonald is supported by Boehringer Ingelheim Chronic Obstructive Pulmonary Disease Research Fellowship through the Lung Foundation Australia (Grant number G1300813).

Peter G. Gibson is supported by a NHMRC practitioner

References (106)

  • G Thabut et al.

    Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

    Chest

    (2005)
  • SM Curkendall et al.

    Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada: cardiovascular disease in COPD patients

    Ann Epidemiol

    (2006)
  • B Zvezdin et al.

    A postmortem analysis of major causes of early death in patients hospitalized with COPD exacerbation

    Chest

    (2009)
  • A Lehouck et al.

    COPD, bone metabolism, and osteoporosis

    Chest

    (2011)
  • L Graat-Verboom et al.

    Correlates of osteoporosis in chronic obstructive pulmonary disease: an underestimated systemic component

    Respir Med

    (2009)
  • JB Soriano et al.

    The proportional Venn diagram of obstructive lung disease: two approximations from the United States and the United Kingdom

    Chest

    (2003)
  • DM Mannino et al.

    Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study

    Respir Med

    (2006)
  • AM Menezes et al.

    Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma

    Chest

    (2014)
  • D Hiestand et al.

    The overlap syndrome: chronic obstructive pulmonary disease and obstructive sleep apnea

    Crit Care Clin

    (2008)
  • B Mokhlesi et al.

    Increased prevalence of gastroesophageal reflux symptoms in patients with COPD

    Chest

    (2001)
  • MW Zhang et al.

    Prevalence of depressive symptoms in patients with chronic obstructive pulmonary disease: a systematic review, meta-analysis and meta-regression

    Gen Hosp Psychiatry

    (2011)
  • TE Abrams et al.

    Acute exacerbations of chronic obstructive pulmonary disease and the effect of existing psychiatric comorbidity on subsequent mortality

    Psychosomatics

    (2011)
  • ME Kunik et al.

    Surprisingly high prevalence of anxiety and depression in chronic breathing disorders

    Chest

    (2005)
  • JW Dodd et al.

    Cognitive dysfunction in patients hospitalized with acute exacerbation of COPD

    Chest

    (2013)
  • RG Barr et al.

    Comorbidities, patient knowledge, and disease management in a national sample of patients with COPD

    Am J Med

    (2009)
  • Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and...
  • GJ Gibson et al.

    Respiratory health and disease in Europe: the new European Lung White Book

    Eur Respir J

    (2013)
  • OP Kurmi et al.

    COPD and chronic bronchitis risk of indoor air pollution from solid fuel: a systematic review and meta-analysis

    Thorax

    (2010)
  • JY Po et al.

    Respiratory disease associated with solid biomass fuel exposure in rural women and children: systematic review and meta-analysis

    Thorax

    (2011)
  • WHO. Causes of COPD. Available from: 〈http://www.who.int/respiratory/copd/causes/en〉 [last accessed...
  • A Tai et al.

    The association between childhood asthma and adult chronic obstructive pulmonary disease

    Thorax

    (2014)
  • JC Hogg et al.

    The nature of small-airway obstruction in chronic obstructive pulmonary disease

    N Engl J Med

    (2004)
  • S Baraldo et al.

    Pathophysiology of the small airways in chronic obstructive pulmonary disease

    Respiration

    (2012)
  • A Agusti et al.

    COPD as a systemic disease

    COPD

    (2008)
  • AG Agusti et al.

    Systemic effects of chronic obstructive pulmonary disease

    Eur Respir J

    (2003)
  • M Decramer et al.

    COPD as a lung disease with systemic consequences – clinical impact, mechanisms, and potential for early intervention

    COPD

    (2008)
  • K Schnell et al.

    The prevalence of clinically-relevant comorbid conditions in patients with physician-diagnosed COPD: a cross-sectional study using data from NHANES 1999–2008

    BMC Pulm Med

    (2012)
  • A Corsonello et al.

    Comorbidities of chronic obstructive pulmonary disease

    Curr Opin Pulm Med

    (2011)
  • LE Vanfleteren et al.

    Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2013)
  • DM Mannino et al.

    Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD

    Eur Respir J

    (2008)
  • P de Lucas-Ramos et al.

    Chronic obstructive pulmonary disease as a cardiovascular risk factor. Results of a case-control study (CONSISTE study)

    Int J Chronic Obstr Pulmon Dis

    (2012)
  • A Agusti et al.

    Characterisation of COPD heterogeneity in the ECLIPSE cohort

    Respir Res

    (2010)
  • FH Rutten et al.

    Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease

    Eur Heart J

    (2005)
  • M Divo et al.

    Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2012)
  • L Garcia-Olmos et al.

    Comorbidity in patients with chronic obstructive pulmonary disease in family practice: a cross sectional study

    BMC Fam Pract

    (2013)
  • IG Tsiligianni et al.

    Managing comorbidity in COPD: a difficult task

    Curr Drug Targets

    (2013)
  • SK Chhabra et al.

    Coexistent chronic obstructive pulmonary disease-heart failure: mechanisms, diagnostic and therapeutic dilemmas

    Indian J Chest Dis Allied Sci

    (2010)
  • Y Wang et al.

    Factors associated with a prolonged length of stay after acute exacerbation of chronic obstructive pulmonary disease (AECOPD)

    Int J Chronic Obstr Pulmon Dis

    (2014)
  • CE Berry et al.

    Mortality in COPD: causes, risk factors, and prevention

    COPD

    (2010)
  • ARC Patel et al.

    Extrapulmonary comorbidities in chronic obstructive pulmonary disease: state of the art

    Expert Rev Respir Med

    (2011)
  • Cited by (49)

    • Stability of distinct symptom experiences in patients with chronic obstructive pulmonary disease (COPD)

      2022, Respiratory Medicine
      Citation Excerpt :

      Common comorbidities in our study are back and neck pain (47%), depression (26%), headache (24%), osteoarthritis (19%), and heart disease (18%), which could potentially explain the high symptom burden in this class. Consistent with findings from the present study, COPD patients often suffer from several comorbidities [53,54]. In terms of understanding the COPD patient's symptoms, research highlights the influence of various comorbidities that need to be taken into consideration when caring for these patients [54].

    • Factors affecting length of hospital stay in chronic obstructive pulmonary disease patients in a tertiary hospital of Nepal: A retrospective cross-sectional study

      2022, Annals of Medicine and Surgery
      Citation Excerpt :

      Our study showed a significant association between length of stay with the number of comorbidities COPD patients were having at admission. Four out of five COPD inpatients in this study had at least one comorbidity, which was similar to previous studies [8,14,15]. A similar association has been established by various studies, thus reaffirming comorbidities as an important predictor of prolonged hospitalization [10,16–19].

    • Short-term exposures to atmospheric evergreen, deciduous, grass, and ragweed aeroallergens and the risk of suicide in Ohio, 2007–2015: Exploring disparities by age, gender, and education level

      2021, Environmental Research
      Citation Excerpt :

      Additionally, those with lower education levels have a higher burden of chronic physical conditions, such as respiratory conditions (Basagaña et al., 2004; Prescott et al., 1999) and autoimmune disorders (Pons-Estel et al., 2010), which may increase vulnerability to the effects of aeroallergens on suicide. These conditions have a high comorbidity with depressive disorders (Negewo et al., 2015; Ettinger et al., 2004; Palagini et al., 2013), and atmospheric environmental factors can exacerbate symptoms of these conditions (Sasha and MichelPineau Christian, 2011; Hansel et al., 2016; Guarnieri and Balmes, 2014). We also noted some of our ancillary findings from the bivariate associations for the environmental covariates in our model.

    • Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation

      2019, European Journal of Pharmacology
      Citation Excerpt :

      The patients of COPD associated with smoke are more susceptible to depression (Zhang et al., 2014). Other studies have reported that the amount of exposure to cigarette smoke was also closely correlated with declines in psycho-emotional state and in cognitive function (Iyer et al., 2016; Negewo et al., 2015) However, the interrelationship among smoking, COPD, and depression has not been fully characterized until now. The COPD model established by cigarette smoke was used in our study.

    • An analysis of the relationship between chronic obstructive pulmonary disease, smoking and depression in an integrated healthcare system

      2020, General Hospital Psychiatry
      Citation Excerpt :

      In fact, COPD may be an independent risk factor for depression, regardless of medical comorbidity [6–8]. Among patients with COPD, a comorbid diagnosis of depression is associated with worse health outcomes, more hospitalizations, higher health care costs, and increased mortality [9–12]. Importantly, COPD has been linked to an increased risk of suicidal behavior including death by suicide [13].

    View all citing articles on Scopus
    View full text