Management of Chronic Obstructive Pulmonary Disease—A Review of the Latest Therapies Improving Systemic Effects


A percentage of patients with COPD have significant loss of weight, mainly due to loss of muscle mass.130


Interestingly, a low body mass index (BMI) is associated with a faster rate of decline in FEV1.27


Muscle dysfunction is one of the most important systemic effects of COPD and is a prominent contributor to exercise limitation131 independent predictor of morbidity and mortality.9


and an Muscle dysfunction


is characterized by two related phenomena: malfunctioning of the muscle and net loss of muscle mass, which occurs in a subgroup of patients.9


Various strategies have been suggested to improve muscle dysfunction and muscle wasting in COPD patients. Without doubt, pulmonary rehabilitation has been the most successful in achieving improvements in muscle function that are translated into improvements in exercise capacity,107


with exercise intolerance independent of the degree of severity of airway obstruction.24


Anabolic hormones132–136 creatinine137


and nutritional supplementation with


potentiates the effects on muscle strength. However, it is not clear whether anabolic therapy will lead to improvements in exercise capacity or health status. Specific indications for this treatment are not yet defined.


Increasing calorie intake is difficult in COPD and has been found to have no benefit in outpatients.138


Studies show that a gain of 2kg of bodyweight140 Failure of nutritional intervention has been


results in significantly improved survival. Future studies need to target specific subgroups of patients to assess whether this therapy is worthwhile.


found to be associated with increased circulating inflammatory markers.139 of BMI141


or one unit


have a proven impact on weight, muscle mass, and strength. Moreover, the combination of anabolic hormones with exercise training133–136


Improving the Body Mass Index, Obstruction, Dyspnea, and Exercise Capacity Index


The BODE index, which integrates BMI, airflow limitation (FEV1), dyspnea, and six-minute walking distance, predicts mortality better


Change in BODE may be a good surrogate measure of survival in therapeutic trials in severe COPD. Pulmonary rehabilitation improves some components of BODE and has been shown to improve the BODE score, which, in turn, was related to better outcomes.153,154


than FEV1 alone.10 and is clearly indicated in COPD patients


patients with predominantly upper-lobe disease155 with reduced mortality.156,157


LVRS for emphysema improved the BODE index in and was associated


Treatment for Exacerbations of Chronic Obstructive Pulmonary Disease ECOPD are defined as events in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset and may warrant a change in regular medication in a patient with underlying COPD.24


systemic and pulmonary inflammation in these patients should be further studied, including the use of phosphodiesterase 4 inhibitors151,152 and angiotensin-converting enzyme inhibitors.148


Mild exacerbations can be managed as an


outpatient by increasing the dose of the β2-agonists, adding an anticholinergic agent, considering antibiotics if purulent sputum is


present and considering a short course of systemic corticosteroids. If hospital admission is required, oxygen therapy when needed to maintain tissue oxygenation without inducing hypercapnia, nebulized bronchodilators, adequate antibiotics, and systemic corticosteroids are the main drugs used.


In addition, increased systemic inflammation and oxidative stress are well-established features of COPD and may contribute to the important extra-thoracic effects seen in this condition, such as muscle wasting, cardiovascular disease, and osteoporosis.143


However, these effects could not


Other important systemic effects in COPD that need consideration for therapy are anemia, osteoporosis, pulmonary hypertension, and depression. Enhanced inflammatory responses and increased oxidative stress locally in the lungs are major features in the pathogenesis of COPD.142


Initial studies


suggested that treatment with inhaled corticosteroids could reduce circulating markers of inflammation.144


be confirmed in larger multicentre trials assessing the effect of fluticasone alone or in combination with salmeterol on circulating inflammatory markers.145


In a retrospective analysis, the risk for


myocardial infarction was reduced by 32% with inhaled corticosteroids.146 No evidence of benefit has been shown with the use of antitumour necrosis factor-alpha (TNF-α) antibodies when tested in moderate to severe COPD.147


Observational studies have suggested that statin treatment is associated with improved survival after COPD exacerbations.148,149


Statins


are therefore promising agents for addressing the local and systemic features of COPD.150


US RESPIRATORY DISEASE Other novel therapies with potential effects on


The exact dose and duration of treatment with corticosteroids in COPD is not known. High doses are associated with a significant risk for side effects. While 30–40mg of oral prednisolone daily for seven to 10 days is safe and effective, prolonged treatment does not result in greater efficacy and is associated with an increased risk for side effects.24


The aforementioned therapies for ECOPD have not changed substantially in the last 30 years. NIV is probably the main change introduced in the last few years in the management of ECOPD and should be considered if patients have persistent hypoxemia and/or hypercapnia with low pH (<7.35) despite maximal medical therapy.5


NIV


has been shown in several randomized trials to reduce the need for invasive mechanical ventilation and improve survival.36,73,74


Summary


The paradigm of COPD has changed in many ways in the last 10 years. COPD is now considered to be a preventable and treatable disease and is recognised as a disease that goes beyond the lungs and incurs significant systemic effects with an impact on several important outcomes. This new understanding of COPD makes it possible to focus on more realistic outcomes and offer a more tailored treatment to patients. Primary and secondary prevention are important in the management of COPD. Once diagnosed, both pharmacological and non-pharmacological treatments are available to offer the best chance of treatment to patients at all stages of disease severity. n


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