Asthma is a common airway inflammatory disorder characterized by variable airway obstruction and hyperresponsiveness. It affects over 300 million people worldwide [1]. Uncontrolled asthma is a major cause of hospital admission and increased psychological morbidity in all ages. Boulet and Boulay [17] in a recent review identified that the most common comorbidities in patients with Asthma include rhinitis, sinusitis, gastroesophageal reflux disease, obesity, obstructive sleep apnoea, hormonal disorders and psychopathologies. These respiratory disorders share similar pathophysiological mechanism with asthma may influence asthma control, its phenotype and treatment.

Chronic asthma may coexist or develop to COPD especially in smoking asthmatic patients. Studies have shown that asthmatic patients who smoke may have early COPD, as indicated by more severe airway obstruction and lower carbon monoxide diffusion capacity [17, 18]. A recent systematic review [18] reported about 15–20% of COPD patients may have the asthma-COPD overlap syndrome (ACOS). ACOS is defined as with symptoms increased variability of airflow in association with an incompletely reversible airflow obstruction. Furthermore, patients with ACOS have more frequent exacerbations, more wheezing and dyspnoea, but similar cough and sputum production compared with COPD [18].

Recent clinical guidelines advocate [19] the identification and treatment of comorbidities should be an integral part of the chronic asthma management. Therefore, a comprehensive disease-management approach that is individually tailored which include education, weight loss management (diet and exercise), cognitive behavioural therapy and smoking cessation program are worthy of consideration for asthmatic patients with comorbid disorders.

In 2007, in the USA, the overall cost of COPD, pneumonia and asthma was approximately $85 billion. Out of these, $66 billion was for in direct healthcare expenditures (hospital and professional services, medication, medical equipment), and $19 billion was for in indirect mortality costs [20]. Of these expenditures, the large proportion of the healthcare budget was spent on patients with COPD. In 2002, Mannino et al. [9] reported that COPD was responsible for 8 million physician office and hospital outpatient visits, 1.5 million emergency department visits, 726,000 hospitalizations and 119,000 deaths. In five-year surveillance population-based study in Denmark, Blide et al. [21] examined the healthcare utilization in patients with COPD compared with the general population. The findings showed that COPD patients were (12 times per year) more likely to consult general practitioners for their health problems than patients without COPD. The total cost of managing COPD was over 256 million euro (approximately US$332 million). Further detailed analysis revealed that only one third of the cost was accounted for the primary diagnosis of COPD. Two-thirds of the COPD-related costs were mainly due to admissions for other diseases such as comorbid cardiovascular diseases, other respiratory diseases (e.g. pneumonia) and cancer. Thus, signify COPD patients with comorbid diseases are most likely to be high healthcare users compared without comorbidities. In a separate study [22] in the USA, COPD patients were more likely to utilize healthcare services and had excess total healthcare costs about $20,500 higher (p < 0.0001) than the comparison cohort of non-COPD patients. Comorbidities in COPD patients were high, accounting for 46% of the observed excess cost. Of these, ‘the impact on total healthcare costs was greatest for anaemia ($10,762 more, on average, than a patient with COPD without anaemia)’ [16].

Undiagnosed and/or in-adequately treated comorbidities in COPD patients will have detrimental effect on patients’ health status and substantial care burden to caregivers. COPD patients with several comorbidities are most likely to consult their general practitioners more frequently compared with one or two comorbidities [14, 19, 21]. COPD patients with multiple comorbidities are most likely to experience frequent episodes of acute exacerbations, with longer days of hospitalization and use more intensive care or high-dependency units compared without comorbidities [19, 20].

Cardiovascular diseases (CVD) and COPD are projected to be the second and fifths leading causes of mortality worldwide by 2030 [23]. In addition, COPD patients with comorbid CVD are most likely to live with increased burden of physical disability and impaired quality of life. The direct and indirect economic costs to the healthcare providers and the society are most likely to be enormous. In 2008, a retrospective cohort study in the USA by Dalal et al. [24] examined the total healthcare costs of COPD patients with CVD aged ≥40 years from the administrative data (n = 6000). They showed that the annual average direct medical costs per patient for COPD patients with comorbid CVD was $22,775 compared without CVD was $8036 (p < 0.001) and total costs were $27,032 versus $11,506 (p < 0.001), respectively. Furthermore, COPD patients with comorbid CVD twice most likely to be hospitalized and 47% more likely to have emergency room visits in a previous year compared with COPD patients alone. This provides some evidence that the healthcare professionals should treat CVD aggressively in order to reduce the burden in COPD patients, improve their quality of life and reduce healthcare cost.

Both CVD and COPD share similar risk factors for developing the disease such as cigarette smoking and environmental air pollutions. However, the mechanism by which COPD patients develop CVD is unclear. Atherosclerosis is the main cause of CVD. Therefore, the early detection of atherosclerosis is crucial to identify patients with high risk in developing CVD and in planning appropriate intervention. Vascular function can be assessed non-invasively by measuring endothelial function and arterial stiffness, using pulse wave analysis derived measures (pulse wave velocity and augmentation index).

A recent study by MacLay et al. [25] with a relative small sample size (n = 18 COPD patients, n = 17 healthy controls) examined the vascular dysfunction of the participants with a lifetime exposure of smoking, controlling for the cardiovascular risk factors. They found that COPD patients have greater stiffness mean (SD) [pulse wave velocity, 11 (2) vs. 9 (2) m/s; p = 0.003; augmentation index, 27 (10) vs. 21 (6)%; p = 0.02] compared with health controls, independent of cigarette smoking exposure. In a larger prospective study (n = 102 COPD and n = 103 healthy controls), Mills and et al. [26] examined whether the occurrence of arterial stiffness and blood pressure in patients with COPD was higher than with age in a smoking matched healthy controls. Increased arterial stiffness and high blood pressure were exhibited in COPD patients compared with the healthy controls. In addition, serum C-reactive protein concentrations were threefold higher in COPD patients compared with healthy controls mean (SD), (6.1 (0.9) vs. 2.3 (0.4) mg/l; p = 0.001). Systemic inflammation and vascular dysfunction are the potential risk factors through which for COPD patients to develop cardiovascular disease. However, the exact mechanistic link is unclear, because of the study designs and relative small sample size to determine the causal association between COPD and vascular dysfunction. Larger randomised control trials are required.

Curkendall et al. [27] in a three-year follow-up study (n = 11,493) examined the incidence of cardiovascular events in patients with COPD. Their findings indicate that COPD patients with CVD experienced threefold to fourfold of increase in the rate of fatal cardiovascular events compared without COPD. In addition, COPD patients with comorbid CVD had twice the risk of premature mortality 2.07 (CI: 1.82–2.36) and all cause of mortality 2.82 (CI: 2.61–3.05) in comparison without CVD. In a separate study by Sidney et al., in a longitudinal study, [28] examined the relationship between COPD, incidence of CVD, hospitalization and mortality of patients with COPD (n = 45,966), with a similar number of the control group in four-year follow-up. They found that COPD was a risk factor for elevated cardiovascular-related mortality and hospitalization. Younger COPD patients (aged < 65 years) and female patients were at high risk of developing CVD. Therefore, CVD risk should be monitored and treated with particular care in younger adults with COPD. Hackett et al. [29] examined between the gene environment interactions, smoking and inflammatory markers (IL-6, interferon-y, interleukin-1b,) and COPD. Findings from this study showed that a polymorphism in the gene encoding IL-6 interacts with smoking history to influence the rate of lung function decline in patients with COPD as well as their risk of cardiovascular disease. A recent systematic review by Clarenbach et al. [30] postulated that systematic inflammation, oxidative stress, hypoxia, sympathetic activation and physical inactivity might be potential mechanisms in COPD leading to vascular dysfunction and cardiovascular disease as Shown in Fig. 9.1.

Periodical evaluation of these clinical markers may play an important role to improve prognosis and reduce premature mortality in this patient group.

A recent UK primary care-based survey [31] by Schneider and colleagues investigated the prevalence of comorbidities in COPD patients (n = 35,700) identified that patients with COPD have a higher risk of developing myocardial infarction (40%), cardiac arrhythmia (19%), stroke (13%) and deep vein thrombosis (35%) compared with COPD-free counterparts. In a similar setting, Feary et al. [32] examined factors that are associated with COPD from computerized database primary care records of 1,204,100 million people in the UK. Physician-diagnosed COPD was associated with increased risks of CVD (odds ration 4.98, 95% CI 4.85–5.81; p < 0.001), stroke (odds ratio 3.34, 95% CI 3.21–3.48; p < 0.001) and diabetes mellitus (odds ration 2.04, 95% CI 1.97–2.12; p < 0.001). Further analysis was performed adjusting for the confounding factors sex and smoking status and stratifying for age. Their findings indicate that the greatest increase in the rate of ‘acute arteriovascular events was found in the youngest age groups, the hazard ratio for acute MI was 10.34 (95% CI 3.28–32.60; p < 0.001) and for stroke the hazard ratio was 3.44 (95% CI 0.85–13.84; p < 0.001) compared with the oldest age group’. They have highlighted the importance of an integrated collaborative treatment approach to deal with the excess comorbidities. McAllister et al. [33] in a prospective study (n = 242) COPD patients aged 40 years and above admitted with acute exacerbations with a smoking history of 10 pack-years were examined at discharge to determine the potential risk factors to develop MI. Their findings showed that 1 in 12 of patients met the diagnosis criteria for MI. None of the patients was receiving appropriate care for comorbid MI. This indicates undiagnosed MI was relatively common in patients with COPD. Future research has to focus on early detection and treatment strategies to reduce the risk of MI in COPD patients.

Pulmonary arterial hypertension (PAH) is common in patients with severe advanced COPD, but the prevalence in mild-to-moderate COPD is unknown. Thabut et al. [34] explored the prevalence of PAH in severe COPD patients (n = 251) who had a lung volume reduction surgery or lung transplantation surgery. Over fifty per cent of the COPD patients were identified with hypertension with mean pulmonary artery pressure (PAPm) > 25 mm Hg, but in patients with moderate (PAPm, 35–45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of COPD patients, respectively. The severity of pulmonary hypertension was associated with the severity of lung function impairment and with hypoxia. The exact mechanism in how pulmonary hypertension manifest in COPD patients is unclear. It is most likely to be multifactorial. Variables that increase pulmonary vascular resistance may also increase the ‘pulmonary wedge pressure of left ventricular dysfunction or severe airway obstruction with wide intrathroacic pressure swings, and destruction of lung parenchyma leading to loss of part of the pulmonary vascular bed may play a role’ [35]. Given this proposition in patients with mild-to-moderate COPD, the pulmonary arteries may exhibit an enlarged intima, because of the proliferation of poorly differentiated smooth muscle cells and deposition of elastic and collagen fibres, with reduction in the lumen and arteriolar muscularization [36]. However, the contribution of hypoxic vasoconstriction to the ventilation-perfusion ratio balances to be greater in mild COPD but is less active in moderate-to-severe COPD. All these changes may contribute to the dysfunction of the vascular structure and function in COPD patients, for detailed review see [35]. The exact role of systemic inflammation in PAH patients is unknown. Peinado et al. [36] have shown that (current cigarette smoking was associated with elevated CD8+ T-lymphocytes and neutrophils) inflammatory process in the pathogenesis of pulmonary vascular abnormalities in the early stage of COPD. Furthermore, vascular abnormalities impair gas exchange and may result in pulmonary hypertension, which is one of the principal factors associated with reduced survival in COPD patients [35, 36].

The management of COPD patients with PAH requires a systematic and coherent treatment approach. Minai et al. provide [35] the most helpful strategy in the management of PAH in COPD patients: (1) confirm the diagnosis using Doppler echocardiography; (2) optimize COPD management; (3) rule out other comorbidities; (4) assess and treat hypoxemia; and (5) enrol the patient to pulmonary rehabilitation programme.

Table 9.2 provides variable related to develop cardiovascular diseases the majority are modifiable risk factors, which fall under the umbrella lifestyle issues. Thus, coordinated, integrated and innovative public healthcare programme is most likely to be beneficial for patients with COPD. Therefore, the focus should be to change attitudes and maximize lifestyle-related interventions for self-management. Those COPD patients with high-risk CVD profiles should be referred to experts in the field for proper assessment and treatment and periodically monitored by their general practitioners. It is advisable for patients to be encouraged in a self-management programme to stop cigarette smoking, to be involved in a regular physical exercise programme, e.g. regular walking exercise 2–3 times per week for the duration of 30 min. It is beyond the scope of this chapter to discuss the whole medical management for patients with cardiovascular diseases. Therefore, readers are encouraged to read the detail guidance provided by the WHO and the National Institute for Clinical Excellence guidelines for cardiovascular diseases [37, 38].

Depression is common in patients with COPD. A recent systematic review in our department [39] identified the prevalence clinically significant depression was between 8 and 80%. This is comparable to patients with chronic heart failure with clinically importance of depression range between 10 and 60%. The recent update of the National Institute Clinical Excellence for the management of COPD highlighted the importance of early screening and treating depression effectively to remission [40]. Untreated and under-recognized depressive symptoms in patients with COPD were associated with poor adherence with medical treatment [41], early dropout from pulmonary rehabilitation [42], frequent consultations with the general practitioners and frequent episodes of emergency care and hospital admission, and all these factors may contribute to premature mortality [39–41].

There are a number of risk factors that are associated with elevated depression in patients with COPD including increase in physical disability, low socio-economic status, social isolation, reduced lung function and low body mass index [39, 40]. In addition, an increase in physical disability was a predictive factor for the subsequent onset of depression in the preceding year. Depression in COPD patients often interferes with self-care management, adherence to medical treatment, persistence in active smoking and loss of interest in pleasurable activities, in turn all these factors may lead to a gradual decline in health status and social interaction [39–42]. However, there is limited understanding in terms of the pathways to trigger depression in patients with COPD. The interaction between COPD and developing depressive symptoms in older patients is dynamic in nature, but the exact mechanism it manifests is not fully understood. It is likely to be a multifactorial.

The pathway in which COPD patients develop depression is not clear. It is most likely as the result of complex interaction between physiological, physical and psychosocial factors. There is a possibility of a bidirectional two-way relationship. Smoking cigarette is the main cause of developing COPD. It is possible that COPD patients with depression are most likely to continue smoking because of loss of interest or motivation to quit due to the low mood. Therefore, there is a link between smoking cigarettes and depression but the particular mechanism is not clear. It does not follow a single pathway. Future studies may explore the bidirectional relationship in a longitudinal study, and the aetiology of depression in elderly patients with COPD, e.g. the relationship with cardiovascular diseases and degenerative changes in the brain.

Minor depressive symptoms that do not meet the criteria for major depression are common in patients with COPD [43] and point of prevalence estimated at 25%. They are associated with increased physical disability and impaired quality of life in patients with COPD and part of continuum with major depression [44, 45]. Depression has been associated with increased healthcare utilization [45], episodes for frequent hospital readmission and longer days of hospital stay [46] and premature mortality [47]. Katz et al. [48] in a longitudinal study identified increased physical disability was a strong predictive factor for the new onset of depression.

A recent review [49] showed that pulmonary rehabilitation in a short term may be useful in reducing anxiety and depressive symptoms in patients with COPD. However, the long-term efficacy is unknown. A few studies [50, 51] have shown that cognitive behavioural therapy (CBT) helps to reduce depressive symptoms in patients with COPD. It is quiet promising and novel treatment approach to incorporate CBT as part of routine clinical practice. Currently, CBT is quiet scarce for the wider healthcare provision. Innovative approach such as web-based CBT is worthy of consideration.

The use of antidepressant drug therapy for COPD patients with depression is inconclusive [52]. It is partly to do patients refusals to receive antidepressant drug therapy. It is possible that patients do not see the relevance of treatment seeing the gloomy picture of their condition or the impact of depression in their life. Some of the perceived barriers reported by the COPD patients include: Stigma attached to depression, afraid of side effects, Fed up, angry, denial and not bothered, fear of being addicted to antidepressant medication, belief that having depression is a weakness and frustrated with taking too many drugs [43, 52].

Therefore, it is important to teach and educate patients about the perceived barriers of treatment of depression in COPD patients. The collaborative care model using a case manager has been shown to be beneficial to improve treatment adherence and improve depression treatment [53]. Therefore, further work is required to determine the cost efficacy of this kind of treatment approach.

The prevalence of potentially clinical anxiety symptoms ranges between 6 and 74% in patients with COPD [39]. This figure is similar to patients with chronic heart failure with anxiety symptoms, which was between 11 and 45%. Anxiety has been shown to be associated with poor health outcomes including decreased in exercise tolerance, with greater risk of self-related functional limitations, frequent episodes of hospital readmission and impaired quality of life [54, 55].