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


Recently, carbocysteine, a mucolytic agent with antioxidant properties, has been shown in a randomized placebo-controlled trial to reduce mean exacerbation frequency by 24.5% in a Chinese population of COPD patients not treated with inhaled corticosteroids with frequent exacerbations.51


Inhaled corticosteroids have been shown to reduce the exacerbation rate by approximately 25% in several placebo-controlled trials52,53 have an even greater effect when combined with a LABA.45,54,55


and However,


increases in pneumonias, although poorly defined, have also been shown in association with inhaled corticosteroid treatment.45


It is worth


mentioning that the COPE study, which evaluated the effect of fluticasone withdrawal, found an increment in exacerbation frequency on withdrawal of treatment.56


Infections should be prevented by the use


of effective vaccines. Routine prophylaxis with pneumococcal and influenza vaccines is recommended.57,58 reduce serious illness59


and death by around 50%.60,61


Influenza vaccination can Pneumococcal


vaccine is recommended for COPD patients 65 years of age and over62 and has been shown to prevent community-acquired pneumonia in those under 65 years of age with FEV1 lower than 40% predicted.63


Pulmonary rehabilitation (PR) is another strategy with proven impact on exacerbation frequency. PR has been shown to reduce the number of days of hospitalization during a one-year follow-up period64–69 reduce the frequency of mild exacerbations.70


and to


Treatment of Stable Chronic Obstructive Pulmonary Disease Patients


Treatment of COPD includes pharmacological and non-pharmacological strategies. The most common pharmacological treatments for COPD and their impact on clinical outcomes are summarized in Table 2. Non-pharmacological treatments for patients are summarized in Table 3. Improving the survival of patients is an obvious objective of therapy. However, defining other outcomes that could be modified by treatment is more difficult. For example, the degree of airflow


limitation measured as FEV1 correlates poorly to the severity of symptoms, HRQoL, and survival.10,71,72


COPD is a multicomponent


disease characterized by a range of pathological changes both in the lungs (i.e. emphysema, chronic bronchitis, bronchioloitis, pulmonary hypertension) and systemically (i.e. decreased fat-free mass, muscle dysfunction, anemia, osteoporosis, depression, and cardiovascular disease). Thus, patients with COPD are heterogeneous in terms of their clinical presentation and disease progression and different phenotypes of the disease can be defined. The latter explains why a multidimensional grading system such as the body mass index, obstruction, dyspnea, and exercise capacity (BODE) index is a better predictor of mortality than FEV1 alone.10


The GOLD initiative defines


important goals for therapy, as summarized in Table 4. Improving Survival


Reducing mortality is without doubt a critical target in the treatment of COPD. A limited number of strategies have been shown to have a positive impact on survival in COPD patients. LTOT in hypoxemic patients73,74


is the first therapy to have a proven effect on long-term survival. LTOT is indicated in all patients with COPD and a partial pressure of oxygen in the arterial blood (PaO2) at rest below 55mmHg (7.3kPa) or


US RESPIRATORY DISEASE


Table 3: Non-pharmacological Treatments for Chronic Obstructive Pulmonary Disease


Pulmonary rehabilitation Oxygen therapy


Non-invasive ventilation Surgery


Bullectomy


Lung volume reduction surgery Lung transplant


Table 4: Defined Goals for Therapy for Chronic Obstructive Pulmonary Disease Patients


Prevent disease progression (improve lung function or rate of decline) Relieve symptoms (dyspnea, exercise tolerance) Improve health status


Prevent and treat complications Prevent and treat exacerbations Reduce mortality


in patients with a PaO2 between 55 and 60mmHg (7.3–8.0kPa) and evidence of pulmonary hypertension, peripheral edema, or polycythemia


(hematocrit >55%). LTOT has been shown to improve survival and reduce pulmonary hypertension in patients who received at least 15 hours of treatment daily.73,74


show benefits in terms of mortality.75


When given to less hypoxemic patients, LTOT failed to Similarly, it did not show benefits in


patients with isolated nocturnal hypoxemia.76


More recently, other interventions have been shown to modify mortality rates in COPD: influenza vaccination,60,61 acute exacerbations,78–80 exercise tolerance.81


smoking cessation,77 NIV in


and LVRS in upper-lobe emphysema with low LVRS is a possible treatment in highly selected


symptomatic COPD patients with hyperinflation of the lungs from emphysema. However, the effect on survival is seen only in patients


with unhomogeneous upper-lobe disease with an FEV1 between 20 and 35% predicted and limited exercise performance after rehabilitation.81,82


Patients with an FEV1 or a diffusion capacity for carbon monoxide <20% predicted are not recommended for LVRS since they have a high risk (~35%) of post-operative death.82


Other surgical treatments for severe COPD patients include lung transplantation (LT); however, the effect of LT on survival in COPD patients is controversial.83–86


Outcomes after LT show current one-year survival between 65 and 70%, with a reduction to 40–45% after five years.


Finally, recent evidence has emerged showing that, when provided after an acute exacerbation, pulmonary rehabilitation reduces the risk for hospital admission and mortality.87


Improving Lung Function


Although bronchodilators can produce small but statistically significant improvements in FEV1,88,89


normalization of FEV1 in COPD is, by definition


of the disease, not a target to pursue. Bronchodilators have not been shown to affect FEV1 decline in patients with COPD.47,90


the Towards a Revolution in COPD Health (TORCH)27


However, recently trial explored the


effect of fluticasone, salmeterol, both in combination or placebo and 17


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