COPD and its comorbidities: Impact,measurement and mechanisms

Chronic obstructive pulmonary disease (COPD) frequently coexists with other conditions often known as comorbidities. The prevalence of most of the common comorbid conditions that accompany COPD has been widely reported. It is also recognized that comorbidities have significant health and economic consequences. Nevertheless, there is scant research examining how comorbidities should be assessed and managed in the context of COPD. Also, the underlying mechanisms linking COPD with its comorbidities are still not fully understood. Owing to these knowledge gaps, current disease‐specific approaches provide clinicians with little guidance in terms of managing comorbid conditions in the clinical care of multi‐diseased COPD patients. This review discusses the concepts of comorbidity and multi‐morbidity in COPD in relation to the overall clinical outcome of COPD management. It also summarizes some of the currently available clinical scores used to measure comorbid conditions and their prognostic abilities. Furthermore, recent developments in the proposed mechanisms linking COPD with its comorbidities are discussed.     

Systemic manifestations of COPD

COPD is characterized by a poorly reversible airflow limitation resulting from chronic inflammation, mainly due to tobacco exposure. Over the past few years, the understanding of COPD has evolved from it being a disease affecting the lungs to it being a complex, heterogeneous, and generalized disorder in an aging population. Extrapulmonary comorbidities significantly complicate the management and influence the prognosis of patients with COPD. Although certain comorbidities like cardiovascular diseases share some risk factors with COPD, such as cigarette smoking, other frequently observed comorbidities, including musculoskeletal wasting, metabolic syndrome, and depression, cannot be easily attributed to smoking. There is increasing evidence that chronic inflammation is a key factor in COPD and that inflammation might be the common pathway linking these comorbidities and explaining why they typically develop together. Physicians treating patients with COPD need to become aware of these extrapulmonary aspects. Any patient with COPD should be carefully evaluated for comorbidities and the systemic consequences of COPD since they not only influence the prognosis but also have an impact on disease management. The treatment of COPD is no longer focused exclusively on inhaled therapy but is taking on a multidimensional approach, especially because the treatment of the comorbidities might positively affect the course of COPD itself.     

Comorbidities in COPD: a new challenge in clinical practice

Today it is a recognised fact that chronic obstructive pulmonary disease (COPD) is a real systemic disease that is respiratory-based. Recently, the focus has been on the importance of the comorbidities that are associated with COPD, such as all the cardiovascular diseases, lung cancer, diabetes, metabolic syndrome, peripheral muscular dysfunction, depression, anxiety, osteoporosis and anaemia, etc. These comorbidities constitute a new medical and therapeutic challenge with regard to COPD; their high frequency and considerable impact on the quality of life and the prognosis for survival of the patients make them a key element. The aims of this focus are to present the spectrum and prevalence of comorbidities in COPD, to obtain an objective view as to why and how these comorbidities should be systematically assessed and treated in patients, and subsequently to discuss the impact of this new data in clinical practice and in research. This recent data is another positive step in understanding the disease, optimising the diagnosis, and assessing and caring for COPD patients.     

Chronic obstructive pulmonary disease and comorbidities through the eyes of the patient

Patient's attitudes and illness beliefs have shown to be of great importance in chronic obstructive pulmonary disease (COPD). As former qualitative research has mainly focused on patients with end-stage COPD, who are recruited within hospital or pulmonary rehabilitation settings, and excluding patients with disabling comorbidities, this study specifically aims to explore the perspectives of patients with COPD and comorbidities in primary care. This study was designed as a qualitative, explorative study using open patient interviews. The study was conducted at three primary care practices, East Flanders, Belgium. A total number of seven patients, diagnosed with COPD and given a minimum score of 2 on the Charlson Comorbidity Index were included. In-depth interviews were recorded and transcribed verbatim. Thematic analysis was deductive using NVivo software. Researchers' triangulation was performed. Participants show high adaptation capabilities and report quite positively about their functional status, with an emphasis on social participation and partnership. Knowledge of the causes and consequences of COPD appears rather limited, and participants predominantly show an external locus of control in relation to the reported factors influencing the disease and strategies for self-management. Patients with COPD with comorbidity integrate their illness and symptoms into their lives. However, a lack of knowledge and education may leave them more anxious and more dependent on health care than necessary. Our results indicate that health care workers should adopt a positive approach toward patient's functioning and empower and inform their patients. We believe that chronic care for patients with COPD should provide personalized rehabilitation taking into account individual patient characteristics and self-management and coping attitudes. We believe that there is a generic core to be identified, which can tackle both COPD and comorbidities. Further research is mandatory to develop these generic programs focusing on patients with complicated needs. Primary care can provide the setting for exploration.     

Anxiety and depression—Important psychological comorbidities of COPD

Anxiety and depression are common and important comorbidities in patients with chronic obstructive pulmonary disease (COPD). The pathophysiology of these psychological comorbidities in COPD is complex and possibly explained by common risk factors, response to symptomatology and biochemical alterations. The presence of anxiety and/or depression in COPD patients is associated with increased mortality, exacerbation rates, length of hospital stay, and decreased quality of life and functional status. There is currently no consensus on the most appropriate approach to screening for anxiety and depression in COPD. Treatment options include psychological [relaxation, cognitive behavioural therapy (CBT), self-management] and pharmacological interventions. Although there is some evidence to support these treatments in COPD, the data are limited and mainly comprised by small studies. Pulmonary rehabilitation improves anxiety and depression, and conversely these conditions impact rehabilitation completion rates. Additional high quality studies are urgently required to optimise screening and effective treatment of anxiety and depression in patients with COPD, to enhance complex chronic disease management for these patients.     

COPD und psychische Komorbiditäten

Background

Patients with chronic obstructive pulmonary disease (COPD) suffer not only from pulmonary symptoms but also from additional extrapulmonary symptoms. These include psychological comorbidities, such as anxiety and depression, which can significantly influence the course of the disease.

Objectives

What is known about the prevalence and consequences of anxiety and depression in patients with COPD, the potential causes as well as diagnostics and treatment?

Material and methods

This article describes the identification, compilation and discussion of relevant research literature and gives a review of the current state of research.

Results

Comorbid anxiety and depression are widespread in COPD patients and their relatives and are associated with a considerably worse course of the disease. The exact causes for these findings are largely unclear but presumably include complex interactions between psychological, behavioral, peripheral physiological and neural processes. Psychological comorbidities often remain undetected and untreated in COPD patients. Several anxiolytic and antidepressive interventions seem to be effective in patients with COPD but these require further systematic study.

Conclusion

Comorbid anxiety and depression in patients with COPD are significant health problems, which require intensified future research activities. Besides an improved understanding of the underlying mechanisms and interactions, improvement of detection and treatment of these psychological comorbidities in the daily clinical routine in particular need to receive greater attention.

     

Admission for COPD Exacerbation Is Associated with the Clinical Diagnosis of Pulmonary Hypertension: Results from a Retrospective Longitudinal Study of a Veteran Population

Patients with chronic obstructive pulmonary disease and pulmonary hypertension (PH–COPD) have an increased risk of hospitalizations and death compared to COPD alone. Identifying PH in COPD is challenging because performing right heart catheterization, the gold standard for PH diagnosis, is invasive and not routinely performed. Clinical characterization of COPD patients at risk who are progressing toward PH will aid therapeutic development at earlier stages of progressively fatal PH–COPD. We studied the records of 5,45,086 patients in a large Veterans Affairs healthcare network (2000–2012) with a primary discharge diagnosis of COPD based on encounters' ICD-9 codes and further stratified into those who received an additional ICD-9 code for a PH diagnosis. Patients with PH–COPD were assigned to one of the four subgroups: those with (a) no history of exacerbation or hospital admissions, (b) history of exacerbations but no hospital admissions, (c) hospital admissions unrelated to COPD and (d) history of COPD exacerbation-related hospital admissions. We also examined the COPD and COPD-PH cohorts for associated comorbidities such as cardiac disease and the presence of obstructive sleep apnea (OSA). A regression analysis revealed that patients with COPD exacerbation-related hospital admissions had 7 × higher risk of having a concomitant clinical diagnosis of PH compared to non-hospitalized patients. COPD-PH patients had higher rates of cardiac comorbidities (89% vs. 66%) and OSA (34% vs. 16%) compared to COPD alone. We conclude that COPD patients hospitalized for COPD exacerbations are at a higher risk for developing PH, and hospitalized COPD patients with cardiac comorbidities and/or OSA should be screened as at-risk population for developing PH.     

Link between chronic obstructive pulmonary disease and coronary artery disease: implication for clinical practice

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are global epidemics that incur significant morbidity and mortality. These diseases are frequently found in combination, and they can also be found independent of the common causal factors, primarily smoking. Both conditions are systemic disorders with overlapping mechanisms and pathophysiologic processes. CAD has a strong effect on the severity and prognosis of COPD and vice versa, including acute exacerbations. Even the most recent practical clinical recommendations driven by Clinical Practice Guidelines still focus on one disease at a time, and do not provide advice for the management of patients with associated chronic conditions. COPD should be approached in a more comprehensive manner, including the treatment of cardiac comorbidities, particularly CAD. To focus treatment on these comorbidities might modify the natural course of the disease in patients with COPD who may not find relief from treatment of COPD alone.     

COPD and erythropoiesis: interactions and consequences

Erythropoiesis is modified in chronic obstructive pulmonary disease (COPD). Tobacco smoke, hypoxaemia, systemic inflammation, and infectious exacerbations are the main factors involved. Polymorphisms in genes involved in the regulation of erythropoiesis probably explain the individual susceptibility and variability in the response. The roles of comorbidities related to COPD and the impact of treatment on erythropoiesis are important confounding factors. While polycythaemia is often related to tobacco smoke and hypoxaemia, it has become less common due to the improvement of COPD follow-up and especially the initiation of long-term oxygen therapy. The control of the main causes is often sufficient, but in cases of severe polycythaemia an erythrapheresis is indicated. Anaemia has recently been reported as a more common and serious complication. It increases dyspnoea and reduces physical activity and quality of life. Its impact on survival and the requirements for healthcare has recently been confirmed. The main approach to the management of anaemia remains exclusion of any curable causes, reducing exacerbations and systemic inflammation, and controlling the comorbidities. Though erythropoietin has some benefits in the so-called "anaemia of chronic disease", this still remains to be confirmed in patients with COPD.     

Cognitive impairment in COPD: a systematic review

The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.     

Treating the systemic effects of chronic obstructive pulmonary disease

Many patients with chronic obstructive pulmonary disease (COPD) also suffer from other disorders that are considered to be comorbidities and that may have a major impact on morbidity and mortality. So far, it is not clear if these diseases in the context of COPD need specific drugs or if patients diagnosed with COPD should receive certain medications to prevent the development of systemic effects of COPD. Cachexia may be caused by many contributing factors and thus may prove to be very difficult to reverse. For the treatment of osteoporosis in patients with COPD, treatment recommendations have been published. COPD is associated with reduced systemic levels of vitamin D, which has not only calcemic, but also extracalcemic effects that may play a role in the development of COPD and its consequences. Available evidence suggests that statins have a high potential, although definitive studies have not been published yet. Physical inactivity may be a major cause for systemic inflammation. In turn, exercise training may be an effective form of therapy. Although smoking cessation is very effective, it is not successful in the majority of cases.     

The impact of chronic obstructive pulmonary disease in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the EVEREST Trial

BackgroundChronic obstructive pulmonary disease (COPD) is prevalent in heart failure (HF) patients, yet these patients are poorly characterized. We aimed to describe the characteristics and outcomes of patients with systolic dysfunction and COPD in a contemporary HF randomized trial.Methods and ResultsEVEREST investigated 4,133 patients hospitalized with worsening HF and an ejection fraction (EF) ≤40%. We analyzed the characteristics and outcomes (all-cause mortality and cardiovascular mortality/HF hospitalization) of patients according to baseline COPD status. COPD was present in 10% (n = 416) of patients. Patients with COPD had a higher prevalence of comorbidities and were less likely to receive a β-blocker, angiotensin-converting enzyme inhibitor, or aldosterone antagonist. On univariate analysis, COPD was associated with increased all-cause mortality (HR 1.41, 95% CI 1.18–1.67) and cardiovascular mortality/HF hospitalization (HR 1.29, 95% CI 1.11–1.49). After adjusting for potential confounders, the risk associated with COPD remained increased, but was not statistically significant.ConclusionThe presence of COPD in HF patients is associated with an increased burden of comorbidities, lower use of HF therapies, and a trend toward worse outcomes. These findings provide a starting point for prospective investigations of the treatment of HF comorbidities to reduce the high postdischarge event rates.     

Patterns of comorbidities in newly diagnosed COPD and asthma in primary care

STUDY OBJECTIVES: There is increasing interest in the frequency and nature of comorbidities in patients with obstructive lung disease: COPD and asthma. We aimed to quantify baseline rates of comorbidities in COPD and asthma patients and to compare the risks to the general population. DESIGN, SETTING, AND PARTICIPANTS: Within the UK General Practice Research Database, we compared incident patients with COPD (n = 2,699) and asthma (n = 7,931) physician diagnosed in 1998 with age, gender, time, and practice-matched cohorts. Rates were calculated and relative risks (RRs) were estimated for comorbidities in major organ systems and selected medical events of a priori interest. MEASUREMENTS AND RESULTS: In both COPD and asthma, the total sum of diagnoses related to major organ systems was higher than in their matched population controls. Among incident COPD patients, a frequency > 1% within the first year after diagnosis was observed for angina, cataracts, bone fractures, osteoporosis, pneumonia, and respiratory infections, the highest being angina with 4.0%. Compared to the non-COPD cohort, COPD patients were at increased risk for pneumonia (relative risk [RR] = 16.0), osteoporosis (RR = 3.1), respiratory infection (RR = 2.2), myocardial infarction (RR = 1.7), angina (RR = 1.7), fractures (RR = 1.6), and glaucoma (RR = 1.3) [all p < 0.05]. Of note, 2.0% of COPD patients had cataracts recorded, but this rate was no different than that of the non-COPD cohort (RR = 0.9). Among incident asthma patients, the occurrence of events was generally lower, likely due to the younger age distribution, except for 4.0% with respiratory infection (RR = 1.84) and 1.7% with fractures (RR = 1.5). Angina prevalence was 0.7% in the asthma cohort and 1.4 times more common than in patients without asthma. CONCLUSION: COPD and asthma are conditions associated with many comorbidities, albeit asthma to a lesser extent than COPD, which had not been systematically reviewed before. Baseline rates of cardiovascular-, bone-, and other smoking-related conditions are high.     

Multimorbidity in COPD,does sleep matter?

A good night's sleep is a prerequisite for sustainable mental and physical health. Sleep disorders, including sleep disordered breathing, insomnia and sleep related motor dysfunction (e.g., restless legs syndrome), are common in patients with chronic obstructive pulmonary disease (COPD), especially in more severe disease. COPD is commonly associated with multimorbidity, and sleep disorders as a component of this multimorbidity spectrum have a further negative impact on COPD-related comorbidities. Indeed, concomitant diseases in COPD and in obstructive sleep apnea (OSA) are similar, suggesting that the combination of COPD and OSA, the so called OSA-COPD overlap syndrome (OVS), affects patient outcomes. Potential clinically important interactions of OVS exist in cardiovascular and metabolic disease, arthritis, anxiety, depression, neurocognitive disorder and the fatigue syndrome. Correct diagnosis for recognition and treatment of sleep-related disorders in COPD is recommended. However, surprisingly limited information is available and further research and improved diagnostic tools are needed. In the absence of clear evidence, we agree with the recommendation of the Global Initiative on Chronic Obstructive Lung Disease that sleep disorders should be actively searched for and treated in patients with COPD. We believe that both aspects are important components of the holistic approach required in patients with chronic multimorbid conditions.     

Komorbiditäten bei COPD

Chronic obstructive pulmonary disease (COPD) is often associated with comorbidities. Cardiovascular diseases, weight loss, loss of fat free mass combined with muscle dysfunction, osteoporosis and depression are the main comorbidities in COPD. Cardiovascular comorbidities, weight loss and loss of fat free mass are predictors of mortality of patients with COPD. Thus, the extrapulmonary manifestations are meaningful parameters of clinical assessment. Systemic inflammation is probably the key to the extrapulmonary signs of COPD.     

Comorbidities of COPD

Chronic obstructive pulmonary disease (COPD) is often associated with comorbidities. Cardiovascular diseases, weight loss, loss of fat free mass combined with muscle dysfunction, osteoporosis and depression are the main comorbidities in COPD. Cardiovascular comorbidities, weight loss and loss of fat free mass are predictors of mortality of patients with COPD. Thus, the extrapulmonary manifestations are meaningful parameters of clinical assessment. Systemic inflammation is probably the key to the extrapulmonary signs of COPD.     

Rehabilitation and supportive therapy in elderly patients with Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) very often coexists with cardiovascular, musculoskeletal and metabolic comorbidities. This condition significantly impact on the general health, function, frailty and disability of such patients, and consequently on their prognosis. Indeed, complex and recurrent symptoms of general dysfunction are commonly present and burden on the health status.Symptomatic COPD patients, even with chronic and complex comorbidities or with different degree of severity, may benefit from rehabilitation including exercise and maintenance of physical activity, in order to reducing symptoms and restoring the highest possible level of independent function.This review will focus on the associated and relevant clinical problems of these patients at the onset of disability, methods of assessment and useful non-pharmacological treatments for caring and supporting them.     

Sleep, hypnotics and chronic obstructive pulmonary disease

The quality of sleep is significantly compromised in many patients with chronic obstructive pulmonary disease (COPD) and may be further diminished when certain comorbidities are present. A reduced sleep quality is associated with daytime consequences like fatigue, psychiatric problems and an impaired quality of life. Sleep induces physiologic alterations in respiratory function, which can become pathologic and may provoke or worsen hypoxemia and hypercapnia in COPD. Dyspnea, cough and excessive mucus production should be optimised to minimise causes for sleep disturbance. Pharmacological therapy may be helpful; sedatives like benzodiazepines and non-benzodiazepine benzodiazepine-receptor agonists (NBBRAs) are (equally) effective in improving sleep quality. Whether or not these hypnotics produce serious adverse respiratory effects during sleep, remains unclear due to opposing studies. Therefore, their use should be as short as possible.     

Gender and asthma-chronic obstructive pulmonary disease overlap syndrome

Objective: To assess relationships between obstructive lung diseases, respiratory symptoms, and comorbidities by gender. Methods: Data from 12?594 adult respondents to the 2012 South Carolina Behavioral Risk Factor Surveillance System telephone survey were used. Five categories of chronic obstructive airway disease (OAD) were defined: former asthma only, current asthma only, chronic obstructive pulmonary disease (COPD) only, asthma-COPD overlap syndrome (ACOS), and none. Associations of these categories with respiratory symptoms (frequent productive cough, shortness of breath, and impaired physical activities due to breathing problems), overall health, and comorbidities were assessed using multivariable logistic regression for men and women. Results: Overall, 16.2% of men and 18.7% of women reported a physician diagnosis of COPD and/or asthma. Former asthma only was higher among men than women (4.9% vs. 3.2%, t-test p = 0.008). Current asthma only was more prevalent among women than men (7.2% vs. 4.7%, p < 0.001), as was ACOS (4.0% vs. 2.2%, p < 0.001). Having COPD only did not differ between women (4.3%) and men (4.4%). Adults with ACOS were most likely to report the 3 respiratory symptoms. COPD only and ACOS were associated with higher likelihoods of poor health and most comorbidities for men and women. Current asthma only was also associated with these outcomes among women, but not among men. Conclusions: In this large population-based sample, women were more likely than men to report ACOS and current asthma, but not COPD alone. Gender differences were evident between the OAD groups in sociodemographic characteristics, respiratory symptoms, and comorbidities, as well as overall health.