The Connection Between Chronic Obstructive Pulmonary Disease Symptoms and Hyperinflation and Its Impact on Exercise and Function

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Abstract

Forced expiratory volume in 1 second (FEV1) has served as an important diagnostic measurement of chronic obstructive pulmonary disease (COPD) but has not been found to correlate with patient-centered outcomes such as exercise tolerance, dyspnea, or health-related quality of life. It has not helped us understand why some patients with severe FEV1 impairment have better exercise tolerance compared with others with similar FEV1 values. Hyperinflation, or air trapping caused by expiratory flow limitation, causes operational lung volumes to increase and even approach the total lung capacity (TLC) during exercise. Some study findings suggest that a dyspnea limit is reached when the end-inspiratory lung volume encroaches within approximately 500 mL of TLC. The resulting limitation in daily physical activity establishes a cycle of decline that includes physical deconditioning (elevated blood lactic acid levels at lower levels of exercise) and worsening dyspnea. Hyperinflation is reduced by long-acting bronchodilators that reduce airways resistance. The deflation of the lungs, in turn, results in an increased inspiratory capacity. For example, the once-daily anticholinergic bronchodilator tiotropium increases inspiratory capacity, 6-minute walk distance, and cycle exercise endurance time, and it decreases isotime fatigue or dyspnea. Pulmonary rehabilitation and oxygen therapy both reduce ventilatory requirements and improve breathing efficiency, thereby reducing hyperinflation and improving exertional dyspnea. Thus, hyperinflation is directly associated with patient-centered outcomes such as dyspnea and exercise limitation. Furthermore, therapeutic interventions—including pharmacotherapy and lung volume–reduction surgery—that reduce hyperinflation improve these outcomes.

Section snippets

Limitation of forced expiratory volume in 1 second as a predictor of patient-centered outcomes

Forced expiratory volume in 1 second (FEV1) serves a useful purpose in the diagnosis and physiologic staging of COPD. The progressive decline in FEV1 over time illustrates its utility in disease staging and also correlates with mortality.3 However, FEV1 has limited application in assessing response to bronchodilators or predicting patient-centered outcomes in terms of exercise ability or dyspnea. For example, in the large cohort from the National Emphysema Treatment Trial (NETT), FEV1

Central role of hyperinflation in the pathophysiology of chronic obstructive pulmonary disease

As described above, one of the enigmas of COPD is that baseline FEV1 correlates weakly with patient-centered outcomes. Furthermore, patients with COPD typically present when there has already been a significant decrease in FEV1 accompanied by some degree of hyperinflation and exertional dyspnea. This reinforces the importance of recognizing COPD early, when it might be possible to implement disease-modifying strategies. However, detecting dyspnea early is difficult, because patients tend to

Progression of static hyperinflation in chronic obstructive pulmonary disease

The extent of hyperinflation—or air trapping—depends on the ability to empty the lungs in a satisfactory fashion during an exhalation. Expiratory flow limitation is one of the factors that influences lung emptying and contributes to hyperinflation.11 During the progression of COPD, hyperinflation develops over a long period, just as does the worsening of the airflow obstruction.12, 13 However, the progression of hyperinflation in mild-to-moderate COPD has yet to be studied in detail. It is

Development of dynamic hyperinflation during exercise in chronic obstructive pulmonary disease

Superimposed on static hyperinflation is the phenomenon of exercise-induced hyperinflation, or dynamic hyperinflation, which is particularly dependent on airway caliber. During exercise in healthy individuals, the EELV decreases slightly, and breathing uses part of the expiratory reserve volume. The EILV increases, using part of the inspiratory reserve volume (IRV), and tidal volume (Vt) increases substantially. In patients with COPD, lung emptying is retarded by increased airway resistance and

Clinical evidence of hyperinflation in chronic obstructive pulmonary disease

O’Donnell and colleagues7 studied dynamic hyperinflation in 105 patients with severe COPD (FEV1 of 37% of predicted). They found that EELV increased during exercise, and IC declined by a mean of 0.37 L. EILV approached TLC and, consequently, elastic work of breathing was increased.

Babb and associates15 compared a group of patients with moderate COPD (mean FEV1/FVC of 58% and FEV1 of 72% of predicted) with healthy individuals. While FRC at rest was comparable in the 2 groups at maximal exercise

Evidence for a dyspnea limit related to hyperinflation

Several studies offer evidence of the existence of a dyspnea limit, which seems to occur when EILV approaches within 500 mL of TLC. Interventions that delay the moment when operational lung volumes reach the dyspnea limit by reducing dynamic hyperinflation have been shown to prolong exercise endurance. In a randomized, double-blind, crossover study,17 23 patients with COPD (mean FEV1 of 42% of predicted) received salmeterol or placebo for 2 weeks. Exertional dyspnea tended to improve and its

Exercise testing in chronic obstructive pulmonary disease

The pathophysiology of exercise in COPD is complex because of multiple interlinked abnormalities, including reduced ventilatory capacity, increased work of breathing, skeletal muscle dysfunction due to deconditioning and possibly skeletal muscle apoptosis due to systemic inflammation in advanced disease, and destruction of the pulmonary capillary bed by emphysema. Exercise is traditionally measured by aerobic performance but is more difficult to measure in patients with disability, particularly

Effect of bronchodilators on hyperinflation, exercise performance, and dyspnea

Hyperinflation results from elevated airway resistance, reduced lung recoil, and shortened available expiratory time; these are worsened by exacerbations (which increase airway resistance), exercise (which increases ventilatory requirements), and hypoxemia and anxiety (both of which increase respiratory rate and thereby reduce expiration time). Bronchodilator therapy reduces hyperinflation by decreasing airway resistance and increasing deflation of the hyperinflated lungs. Although dynamic

Effect of other interventions on hyperinflation, exercise performance, and dyspnea

Table 2 summarizes the effects of other interventions such as supplemental oxygen, rehabilitative exercise, helium-oxygen breathing, and lung volume–reduction surgery on hyperinflation, exercise performance, and dyspnea.18, 27, 28, 29, 30, 31, 32, 33 Pulmonary rehabilitation and supplemental oxygen are other interventions that may reduce dynamic hyperinflation by lowering the ventilatory requirements and may improve breathing efficiency during exercise.27, 28 After completing 6 to 8 weeks of

Summary

Limitations of expiratory flow cause air trapping and hyperinflation, which precipitate a cycle of decline that has an adverse impact on patient-centered outcomes, such as dyspnea and activity level. Bronchodilator therapy reduces airway resistance, and pulmonary rehabilitation decreases ventilatory requirements during exercise. In both cases, these changes lead to an improvement in IC, which is indicative of reduced hyperinflation. Importantly, the improvement in IC is associated with a

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