Dynamic hyperinflation in patients with COPD

INTRODUCTION — Exercise or hyperpnea-induced air trapping is referred to as dynamic hyperinflation. Patients with chronic obstructive pulmonary disease (COPD) are particularly susceptible to dynamic hyperinflation. Common questions include:

●What causes dynamic hyperinflation?

●What are its clinical manifestations?

●How is it diagnosed?

●What is the treatment?

The pathophysiology, clinical presentation, diagnosis, and treatment of dynamic hyperinflation in patients with COPD are reviewed here. The diagnosis and treatment of COPD are discussed separately. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging" and "Stable COPD: Initial pharmacologic management".)

DEFINITIONS — Two types of lung hyperinflation can be distinguished, dynamic and static:

●Static hyperinflation – Static hyperinflation refers to an increase in end-expiratory lung volume (EELV) at rest. It develops over time in patients with COPD due to a combination of small airway obstruction and decreased elastic recoil pressure compared with healthy adults.

●Dynamic hyperinflation – Dynamic hyperinflation refers to an increase in EELV during hyperpnea induced by exertion, anxiety, pain, or mechanical ventilation in patients with airflow limitation (eg, asthma, COPD).

PATHOPHYSIOLOGY — In healthy adults, end-expiratory lung volume (EELV) remains stable or decreases during exercise, despite the increase in tidal volume (figure 1), because the tidal volume is completely exhaled prior to the initiation of the next breath. In patients with COPD, EELV increases (hyperinflation) when compensatory mechanisms are insufficient to overcome airflow limitation and/or loss of elastic recoil.

Static hyperinflation — Static hyperinflation develops at rest, most commonly in patients with COPD and occasionally in patients with chronic obstructive asthma. Normally, elastic recoil pressure declines during expiration, reaching zero at EELV. Patients with COPD have decreased elastic recoil pressure at a given lung volume (due to emphysematous loss of lung tissue) compared with healthy patients; therefore, the elastic recoil pressure falls to zero at a larger EELV (figure 2). This is referred to as static hyperinflation, which exists at rest.

Dynamic hyperinflation — Dynamic hyperinflation occurs when airflow limitation prevents complete exhalation and results in an increase in EELV, usually in the setting of the increased minute ventilation associated with exercise or other causes of hyperpnea. Hyperinflation generally acts as a compensatory mechanism; at higher lung volumes, airway resistance decreases and elastic recoil increases, resulting in improved expiratory flow.

However, in the setting of airflow limitation, hyperinflation can have a negative impact. During exertion, individuals with COPD recruit expiratory muscles to increase pleural and alveolar pressures in an effort to increase expiratory flow and completely exhale the increased tidal volume prior to the next breath. However, the airways of patients with COPD typically compress or collapse when the pleural pressure is positive, thereby preventing increased expiratory flow [1,2]. As a result, exhalation may not be completed prior to the onset of the next breath, causing progressive hyperinflation (figure 2) [3,4]. This is referred to as dynamic hyperinflation; it occurs during exercise and can exist in the presence or absence of static hyperinflation [5-7].

Dynamic hyperinflation limits ventilation during exercise and can negatively impact cardiac function [8-12]. The increase in EELV can lead to increased end-expiratory pressure, which in turn can decrease venous return, compromising cardiac output. Studies that demonstrate improvement in cardiac function after interventions to reduce dynamic hyperinflation, such as lung volume reduction surgery, support this concept [13-17]. Similarly, reducing minute ventilation can help restore cardiac output in patients with asthma or COPD who develop hypotension due to dynamic hyperinflation during mechanical ventilation. (See "Invasive mechanical ventilation in adults with acute exacerbations of asthma", section on 'Dynamic hyperinflation'.)

CLINICAL PRESENTATION

●During exertion – The cardinal symptom of dynamic hyperinflation is dyspnea on exertion. Although hyperinflation is a compensatory mechanism that increases expiratory flow, it increases the work of breathing, places the inspiratory muscles at a mechanical disadvantage due to length-tension effects, and produces a positive alveolar pressure that must be overcome to initiate a breath [18,19]. The net effect is a marked disparity between the level of inspiratory effort (approaches maximum) and the actual mechanical response of the respiratory system (greatly diminished tidal volume), which manifests as dyspnea, initially with exertion and later at rest.

●During mechanical ventilation – Dynamic hyperventilation can also develop during mechanical ventilation in patients with asthma or COPD when the expiratory time is insufficient to completely exhale the tidal volume, leading to breath stacking. In this setting, dynamic hyperinflation can present as ventilator dyssynchrony, elevated plateau pressure at end-inspiration, hypotension, and sometimes pneumothorax. When this occurs, ventilator graphics will typically reveal commencement of inspiratory flow before expiratory flow reaches zero and a progressive rise in peak airway pressures during mandatory volume-targeted ventilation. (See "Invasive mechanical ventilation in acute respiratory failure complicating chronic obstructive pulmonary disease", section on 'Dynamic hyperinflation'.)

DIAGNOSIS — Dynamic hyperinflation may be suspected in patients with COPD who experience dyspnea on exertion, particularly when dyspnea seems more severe than would be suggested by spirometry. The occurrence of dynamic hyperinflation is not clearly predicted by the severity of COPD (based on the reduction in forced expiratory volume in one second), as patients with the most severe COPD tend to have less dynamic hyperinflation [20]. It is possible that the degree of baseline hyperinflation in severe COPD inhibits further dynamic hyperinflation. We evaluate for dynamic hyperinflation when the cause of dyspnea is unclear and identifying the cause of dyspnea will enable specific treatment and avoid unnecessary treatments.

Definitive diagnosis of dynamic hyperinflation requires measurement of end-expiratory lung volume (EELV) during exercise. This is time consuming, labor intensive, and technically difficult. Therefore, these indirect measures obtained before and after exercise are more common: measurement of inspiratory capacity (decreases with dynamic hyperinflation) and comparison of flow-volume loops.

Decreased inspiratory capacity with exertion — Hyperinflation is defined as an elevated EELV. Decreased inspiratory capacity (IC) is used as a surrogate measure of increased EELV. This is based upon the assumption that total lung capacity (TLC) is constant; therefore, an increase of the EELV must be accompanied by a decrease of the IC since the sum of the two measures is the total lung capacity (ie, EELV + IC = TLC) [21,22].

During exercise, healthy individuals increase their tidal volume. To ensure that the entire tidal volume is exhaled prior to their next breath, they recruit expiratory muscles and increase their expiratory flow, which results in an increased IC and decreased EELV. In contrast, patients with COPD are unable to sufficiently increase their expiratory flow and completely exhale the increased tidal volume prior to the next breath; as a result, the IC decreases and the EELV increases during exercise (figure 2 and figure 3). Progressive decrease of IC during exercise is highly suggestive of dynamic hyperinflation.

In an observational study of 22 subjects with moderately severe COPD, inspiratory capacity was monitored every two minutes during a six-minute walk test [23]. During the first two minutes of the test, tidal volume increased, suggesting that dyspnea during that time frame was due to increased respiratory effort. Subsequently, the increase in dyspnea correlated with a progressive decrease in inspiratory capacity without further increase in tidal volume, suggesting that dynamic hyperinflation contributed to dyspnea.

Exercise flow-volume loop encroaching on maximal flow-volume loop — Another method compares the maximal flow-volume loop (MFVL) versus the tidal flow-volume loop during exercise (extFVL), such as during a six-minute walk test or cardiopulmonary exercise test [4]. In healthy individuals, the extFVL and the MFVL are distinct, whereas the flow-volume loops become increasingly similar (ie, there is encroachment of the extFVL on the MFVL) with an increasing EELV as dynamic hyperinflation progresses (figure 2).

The MFVL is obtained by spirometry with the patient resting prior to exercise, while the extFVL is obtained at several different work intensities during exercise. Either a single representative extFVL or the mean of two or more extFLVs is plotted within the largest MFVL (figure 2) [24-27]. Since bronchodilation or bronchoconstriction may occur during exercise, additional MFVLs are often obtained during or immediately after exercise. IC is also determined during rest and exercise, and then used to correctly align the extFVL within the MFVL.

DIFFERENTIAL DIAGNOSIS — Dyspnea on exertion cannot be assumed to be due to dynamic hyperinflation, as patients with COPD may have dyspnea due to other processes related to COPD, including the following [28,29]:

●Dynamic airway compression due to increased pleural pressure during exhalation.

●Respiratory and skeletal muscle weakness/fatigue due to chronic disease and possibly systemic glucocorticoid use.

●Mechanical disadvantage of diaphragm caused by hyperinflation.

●Increased ventilatory demand due to airflow limitation, increased physiologic dead space, hypoxemia (eg, due to secondary pulmonary hypertension or severe emphysema), hypercapnia, early-onset lactic acidosis, or deconditioning.

In addition, comorbidities related to COPD may be contributory, such as coronary heart disease, heart failure (with or without preserved ejection fraction), deconditioning, and fatigue. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Reassess COPD' and "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions", section on 'Comorbid diseases' and "Management of refractory chronic obstructive pulmonary disease", section on 'Assess for complicating diseases' and "Approach to the patient with dyspnea".)

TREATMENT — The mainstay of treatment for dynamic hyperinflation during exertion is bronchodilation; additional steps may include decreasing ventilatory load. Small decreases in end-expiratory lung volume (EELV) are often associated with substantial clinical improvement, suggesting that hyperinflation is an important cause of dyspnea. Reduction of hyperinflation can be achieved by multiple approaches, and combination treatments have been shown to have additive benefits, as described below [30].

Studies of interventions to improve dynamic hyperinflation suggest that clinical improvement results from not only respiratory mechanics but also improvements in cardiac function [13-15]. (See "Stable COPD: Initial pharmacologic management".)

Decrease airflow obstruction — Long-acting bronchodilators reduce dynamic hyperinflation at rest and during exercise, resulting in improved exercise capacity and reduced dyspnea on exertion. A systematic review of long-acting bronchodilators in COPD included a meta-analysis of the effects of monotherapy with long-acting muscarinic antagonists or long-acting beta agonists on exercise capacity. With treatment, exercise time increased by 67 seconds (95% CI 55-79 seconds), inspiratory capacity during exercise increased by 196 mL (95% CI 162-229 mL), and dyspnea improved with a change of -0.41 units (-0.56 to -0.27) on the Borg scale [31].

Long-acting muscarinic antagonists — Long-acting muscarinic antagonists (LAMAs) produce sustained reductions in hyperinflation during rest and exercise, resulting in improved exercise capacity and reduced dyspnea with exertion [31,32]. This was illustrated by the following studies:

●In a crossover study, 29 patients with stable COPD performed spirometry and exercise before and one hour after receiving nebulized ipratropium bromide (500 mcg) or placebo [33]. The inspiratory capacity at rest increased 14 percent following ipratropium, consistent with decreased static hyperinflation. This was accompanied by improved exercise endurance and dyspnea during exercise. There were no significant changes in spirometry, exercise endurance, or exertional dyspnea after receiving placebo.

●A parallel-group trial randomly assigned 187 patients with COPD to receive tiotropium (18 mcg) or placebo once daily for 42 days [32]. Spirometry, plethysmographic lung volumes, exercise endurance, and exertional dyspnea of the tiotropium group were compared with the placebo group. Tiotropium increased the inspiratory capacity and decreased the end-expiratory lung volume at rest, consistent with decreased static hyperinflation. In addition, tiotropium increased exercise capacity and improved exertional dyspnea. These findings were supported by a subsequent randomized trial in 261 COPD patients that demonstrated that tiotropium reduces hyperinflation at rest and with exercise and improves symptom-limited exercise tolerance after six weeks of treatment. In this study, improvement with tiotropium versus placebo was demonstrated at two hours and eight hours after dosing [34].

●In a randomized trial, 181 participants with moderate-to-severe COPD were assigned to once-daily aclidinium 200 mcg or placebo for six weeks [35]. Aclidinium treatment improved exercise tolerance and reduced hyperinflation.

Long-acting beta-agonists — Long-acting beta-agonists (LABAs) similarly decrease static hyperinflation, allowing greater dynamic hyperinflation during exercise before intolerable dyspnea develops [31,36,37]. This was illustrated by a crossover study that randomly assigned 23 patients with COPD to receive salmeterol (50 mcg) or placebo twice daily for two weeks and then compared spirometry and exercise capacity in the salmeterol group versus the placebo group [36]. Salmeterol increased the inspiratory capacity during rest and exercise, consistent with decreased static and dynamic hyperinflation. It also increased exercise endurance and decreased dyspnea during exercise. In a study of 21 individuals with advanced GOLD III-IV COPD, formoterol was associated with improvement in exercise tolerance and dynamic hyperinflation compared with placebo [38].

Combination LAMA and LABA — Combination LAMA-LABA therapy has been shown to reduce hyperinflation before and during exercise in two randomized, replicate crossover trials of tiotropium/olodaterol combination therapy versus monotherapy with either component or placebo [39]. Combination therapy also yielded improvements in dyspnea and exercise tolerance versus placebo. Two randomized crossover studies of umeclidinium/vilanterol demonstrated that combination therapy was associated with improvement in forced expiratory volume in one second (FEV₁) and exercise capacity [40].

Combination beta-agonist and inhaled glucocorticoid — Combined long-acting beta-agonist plus inhaled glucocorticoid decreases hyperinflation and improves exercise endurance. This was illustrated in a trial of 185 patients with COPD who were randomly assigned to receive placebo, salmeterol alone (50 mcg), or fluticasone (250 mcg) plus salmeterol (50 mcg) twice daily for eight weeks [41]. Compared with placebo, combination therapy increased the inspiratory capacity during rest and exercise, consistent with decreased static and dynamic hyperinflation. It also increased exercise endurance. Static hyperinflation was the only outcome for which combination therapy and salmeterol were compared, with combination therapy demonstrating a greater impact.

Inhaled glucocorticoids alone enhance bronchodilator-mediated improvement of dyspnea [42]. However, it is unknown whether this observation is due to improvement in dynamic hyperinflation. Monotherapy with inhaled glucocorticoids is not recommended for COPD.

Reduce ventilatory load — One way to reduce dynamic hyperinflation is to decrease the ventilatory drive, which reduces the respiratory rate and prolongs expiratory time. Supplemental oxygen may decrease both the metabolic demand at a given workload and also influence the neural drive to breathe. Pulmonary rehabilitation and exercise training at submaximal intensities can improve endurance and reduce the ventilatory demand for a given level of exercise.

Oxygen — Supplemental oxygen therapy is well known to be beneficial in patients with COPD and hypoxemia. It also appears to decrease dynamic hyperinflation by decreasing ventilatory demand, even in patients who are not hypoxemic with exercise [30]. This was best illustrated by an observational study of 10 patients with COPD who underwent spirometry and exercise testing while receiving different concentrations of oxygen [43]. Compared with room air, hyperinflation was progressively reduced when breathing 30 and 50 percent oxygen. There was no additional reduction of hyperinflation when the patients breathed 75 or 100 percent oxygen. Similarly, a randomized trial demonstrated faster resolution of dynamic hyperinflation following exercise among patients who received oxygen [44]. While of interest in a research setting, supplemental oxygen at these levels carries the risk of hypercapnia and is not advised for this indication.

Pulmonary rehabilitation — Rehabilitative exercise training generally yields the greatest improvement in exercise tolerance [30]. At least part of this improved exercise capacity is due to reduced dynamic hyperinflation. An observational study evaluated dynamic hyperinflation in 24 patients with COPD following a seven-week training program [45]. Inspiratory capacity dropped less precipitously and exercise capacity increased following the training program, suggesting that dynamic hyperinflation was less, although still present. (See "Pulmonary rehabilitation".)

A preliminary study found that nasal-positive expiratory pressure (PEP) during exercise reduced dynamic hyperinflation and increased six-minute walk distance [46]. Further study is needed to determine whether PEP could enhance endurance training in COPD.

Lung volume reduction — Lung volume reduction can be performed surgically (LVRS) or bronchoscopically (BLVR). (See "Lung volume reduction surgery in COPD".)

Surgical — Dyspnea relief following LVRS has also been shown to correlate well with reduced dynamic hyperinflation [47,48].

Bronchoscopic — BLVR using endobronchial valves prolongs exercise time by reducing dynamic hyperinflation. Endobronchial valves have gained US Food and Drug Administration (FDA) approval, and there have been an increasing number of clinical trials demonstrating a reduction in hyperinflation at rest and increase in exercise tolerance [50]. Fewer studies have directly assessed dynamic hyperinflation as an outcome measure. In an observational study, 19 patients with advanced COPD, who received unilateral valve insertion, were evaluated with spirometry, lung volumes, and exercise before and four weeks after BLVR [49]. BLVR increased exercise capacity and decreased end-expiratory lung volume, during rest and exercise, compared with baseline. (See "Bronchoscopic treatment of emphysema".)

Therapies of unclear benefit — Some therapies can reduce dynamic hyperinflation but are not used clinically for this purpose. As examples, theophylline use has declined due to improved bronchodilation and fewer adverse effects with LAMAs and LABAs; heliox has limited availability; oral N-acetylcysteine (NAC) confers minimal benefit; and inhaled NAC has potential adverse effects.

Theophylline — While uncommonly used for this purpose, theophylline decreases hyperinflation and increases exercise capacity in a dose-dependent fashion [51]. As an example, in a randomized trial, 38 patients with COPD received placebo, low-dose, medium-dose, or high-dose theophylline consecutively for two months each [51]. Spirometry, lung volumes, and exercise were performed at the end of each two-month treatment period. There was a dose dependent decrease in lung volumes and increase in exercise capacity, accompanied by a modest improvement in dyspnea. An effect of theophylline to improve respiratory muscle function has also been hypothesized. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Theophylline'.)

Heliox — Another approach to reducing airflow limitation is to decrease the density of gas exhaled through obstructed airways, as occurs when breathing a mixture of helium and oxygen (heliox). While heliox is not available for routine use during exercise, study of its effects adds to our understanding of dynamic hyperinflation. The addition of helium decreases turbulence within medium and large airways and increases expiratory flow.

As an example, a crossover trial randomly assigned 10 patients to breathe room air (ie, 21 percent oxygen), hyperoxic air (40 percent oxygen), normoxic helium (21 percent oxygen plus 79 percent helium), or hyperoxic helium (40 percent oxygen plus 60 percent helium) [52]. All three gases improved exercise duration and dyspnea compared with room air, although only the helium-containing gases improved the inspiratory capacity during exercise (ie, decreased dynamic hyperinflation). (See "Physiology and clinical use of heliox".)

N-acetylcysteine — The antioxidant agent NAC has mucolytic properties when administered by nebulizer. However, nebulized NAC can cause bronchospasm, so oral preparations have been assessed for use in COPD. (See "Role of mucoactive agents and secretion clearance techniques in COPD", section on 'N-acetylcysteine (NAC)'.)

The effect of oral NAC on lung hyperinflation at rest and after exercise was examined in 24 patients with moderate to severe COPD (FEV₁ <70 percent of predicted, FEV₁/forced vital capacity [FVC] ratio <0.7, functional residual capacity >120 percent of predicted) [53]. Patients were randomly assigned to placebo or NAC 1200 mg/day for six weeks, followed by a two-week washout period, and then a cross over to alternate therapy for six weeks. Based on increases in IC, FVC, and endurance with NAC, NAC treatment appeared to reduce dynamic hyperinflation, probably due to a reduction in air trapping. However, routine long-term use of oral acetylcysteine is not recommended for COPD because of the minimal potential therapeutic benefit, the inconvenience of therapy, and potential adverse effects. (See "Role of mucoactive agents and secretion clearance techniques in COPD", section on 'N-acetylcysteine (NAC)'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic obstructive pulmonary disease".)

SUMMARY AND RECOMMENDATIONS

●Overview – Chronic obstructive pulmonary disease (COPD) is the most common disease in which hyperinflation occurs. Static hyperinflation exists at rest and is predominantly due to decreased elastic recoil. Dynamic hyperinflation is induced by exercise and is primarily due to impaired expiratory flow. Dynamic hyperinflation may occur in the absence of static hyperinflation. (See 'Pathophysiology' above.)

●Clinical presentation – Dyspnea with exertion is the most common manifestation of dynamic hyperinflation. Dynamic hyperinflation can also occur during hyperpnea from other causes, such as an exacerbation of COPD, anxiety, pain, or mechanical ventilation. (See 'Clinical presentation' above.)

●Evaluation – Dynamic hyperinflation may be suspected in patients with COPD who experience dyspnea on exertion, particularly when dyspnea seems more severe than would be suggested by spirometry. We evaluate for dynamic hyperinflation when the cause of dyspnea is unclear and identifying the cause of dyspnea will enable specific treatment and avoid unnecessary treatments. (See 'Diagnosis' above.)

●Diagnosis – Direct diagnosis of dynamic hyperinflation requires lung volume measurements during exercise. Due to the technical difficulties of measuring lung volumes during exercise, spirometric techniques are more commonly used. Progressive decrease of the inspiratory capacity during exercise, and/or similarity of the exercise and maximal flow-volume loops suggest dynamic hyperinflation. (See 'Diagnosis' above.)

●Treatment – Therapies commonly used in the management of COPD, such as long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs), and inhaled glucocorticoids, reduce airflow limitation and thereby improve static and/or dynamic hyperinflation.

Therapies to reduce ventilatory demand, such as supplemental oxygen and pulmonary rehabilitation, also decrease dynamic hyperinflation. For patients with advanced COPD, lung volume reduction may improve exercise tolerance by decreasing dynamic hyperinflation. (See "Stable COPD: Initial pharmacologic management" and 'Decrease airflow obstruction' above and 'Reduce ventilatory load' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Martin Kohlhäufl, MD, PhD who contributed to an earlier version of this topic review.