Chronic Obstructive Pulmonary Disease


showed a significantly lower rate of decrease in FEV1 with the combination salmeterol/fluticasone or with either of the two agents


alone compared with placebo. On the other hand, the recently published Understanding Potential Long-Term Impacts on Function with Tiotropium


(UPLIFT) failed to show differences in the decline in FEV1 after four years of treatment with tiotropium compared with usual care.47 LVRS has been shown to improve FEV1 by approximately 10%.81,91,92


New


techniques capable of achieving volume reduction without the associated operative risk for LVRS are currently evolving. One-way valves93


biological substances94 thereby facilitating lung deflation,95


or closure of airways leading to emphysematous areas using or the introduction of stents to bypass airways, constitute a new exciting research


area with a promising future for the treatment of patients with COPD.


In patients with severe diffuse emphysema, LT may result in normalization of pulmonary function.83–86


LT is a therapeutic modality


reserved for selected patients with chronic respiratory failure due to end-stage lung disease. Clinically relevant modes of LT include the implant of one lung (single LT) or both lungs (bilateral LT). Transplantation of the cardiopulmonary block is reserved for special situations. Criteria for referral for lung transplantation include


age <65 years, predicted survival ≤2 years, FEV1 <35% predicted, PaO2 <55–60mmHg (7.3–7.8kPa), PaCO2 >50mmHg (6.7kPa) and secondary pulmonary hypertension.96,97


As the degree of airflow limitation measured as the FEV1 is poorly correlated to the severity of symptoms, HRQoL, or survival, more effort


should be invested in modifying outcomes that better relate to the


patient’s health status. Indeed, patients with the same FEV1 may present with different functional capacities, exacerbation rates, and mortality. Moreover, dyspnea during exercise is more closely related to the development of dynamic hyperinflation than to changes discovered in FEV1.98–102 FEV1.103


on peripheral muscle bioenergetics,110,111 improving the efficiency of exercise with reduced production of lactate for similar work rates. The


latter reduces the work of breathing by lowering the amount of CO2 production by more efficient muscles, with a subsequent impact on respiratory pattern and dynamic hyperinflation.112,113


The addition of


long-acting inhaled bronchodilators to pulmonary rehabilitation further increases exercise tolerance,114


improvements in dyspnea and health status compared with pulmonary rehabilitation alone.114


There are abundant data to show that administering O2 during exercise improves exercise performance and reduces the severity of


breathlessness at the end of exercise.115,116 dynamic hyperinflation.115,116


This reflects a reduction in However, there is no convincing evidence to


support the routine use of ambulatory O2 in patients without hypoxemia at rest but who develop hypoxemia during exercise.117,118


One randomized


cross-over trial has shown that ambulatory O2 improves HRQoL in the three-month treatment period,119


improvement in HRQoL.120


suggested that compliance with the use of ambulatory O2 is poor.117 seems reasonable to evaluate the occurrence of desaturation during


while another did not show an


Furthermore, a small randomized trial has It


exercise and the effect of O2 administration on exercise tolerance before prescribing ambulatory O2, although evidence of effectiveness is poor.


Finally, surgical strategies have shown benefits in improving the symptoms of COPD patients: both LVRS81,91,92


and LT83–86


improve dyspnea and exercise tolerance. Improving Health Status


Hyperinflation predicts survival better than


Taking this into account, assessment of lung volume seems to be a more rational outcome to assess the effects of treatment


strategies than FEV1. Short- and long-acting β2-agonists, short- and long-acting anticholinergics, and theophylline all have a significant effect on lung volumes.98–101,104


Improving Symptoms (Dyspnea, Exercise Tolerance) Exercise tolerance and dyspnea associated with exercise are independent predictors of mortality and hospitalization.10,105


Dyspnea


during exercise is more closely related to the development of dynamic hyperinflation than to changes in FEV1.98–102


Both major classes of


long-acting inhaled bronchodilators increase exercise endurance and improve exercise-related dyspnea by improving dynamic hyperinflation.100,101


combination of an inhaled corticosteroid and a LABA.106


Pulmonary rehabilitation has been one of the success stories in respiratory medicine over the past decade. Pulmonary rehabilitation programs increase exercise performance and reduce dyspnea associated with exercise. Constant work-rate protocols appear to be the most sensitive way to detect changes in exercise capacity after training programs.107–109


Pulmonary rehabilitation has beneficial effects 18 Similar improvements have been seen with the


Limitation of exercise performance, the recurrence of exacerbations and the systemic effects of the disease contribute to the impairment of health status in COPD patients. HRQoL can be measured with validated multidimensional questionnaires that assess symptoms and physical, psychological, and social domains.


Limitation of exercise tolerance in COPD patients is mainly due to dyspnea associated with exercise and muscle dysfunction;121,122 some patients, a cardiac component is also present.123 hyperinflation124


in Dynamic


and abnormalities in relation to ventilation/perfusion125 leading to alterations in gas exchange are major components determining dyspnea during exercise. Exertional dyspnea often causes patients to unconsciously reduce their activities of daily living (ADLs) in order to reduce the intensity of their distress. The reduction in ADLs leads to deconditioning, which, in turn, further increases dyspnea.126 Both dyspnea and fatigue are important factors affecting HRQoL.


ECOPD are also associated with poor HRQoL.30 The recovery period after


an ECOPD is long, even in patients who have no further exacerbations. A second episode within six months limits recovery markedly.127 Treatments that improve exercise tolerance and reduce exacerbation frequency could have a significant impact on health status. Drugs with a positive outcome on HRQoL include LABAs, tiotropium, inhaled corticosteroids, combinations of a LABA and inhaled corticosteroids, and theophylline. Pulmonary rehabilitation has also been shown to improve health status in patients with stable COPD.64,128,129 LT83–86


LVRS81,91,92 also significantly improve HRQoL. US RESPIRATORY DISEASE and significantly incurring clinically meaningful


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