CHAPTER 5: DYSPNEA

The American Thoracic Society defines dyspnea as a “subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social, and environmental factors and may induce secondary physiological and behavioral responses.” Dyspnea, a symptom, can be perceived only by the person experiencing it and must be distinguished from the signs of increased work of breathing.

MECHANISMS OF DYSPNEA

Respiratory sensations are the consequence of interactions between the efferent, or outgoing, motor output from the brain to the ventilatory muscles (feed-­forward) and the afferent, or incoming, sensory input from receptors throughout the body (feedback) as well as the integrative processing of this information that we infer must be occurring in the brain (Fig. 5-1). In contrast to painful sensations, which can often be attributed to the stimulation of a single nerve ending, dyspnea sensations are more commonly viewed as holistic, more akin to hunger or thirst. A given disease state may lead to dyspnea by one or more mechanisms, some of which may be operative under some circumstances (e.g., exercise) but not others (e.g., a change in position).

Motor efferents

Disorders of the ventilatory pump—most commonly, increased airway resistance or stiffness (decreased compliance) of the respiratory system—are associated with increased work of breathing or the sense of an increased effort to breathe. When the muscles are weak or fatigued, greater effort is required, even though the mechanics of the system are normal. The increased neural output from the motor cortex is sensed via a corollary discharge, a neural signal that is sent to the sensory cortex at the same time that motor output is directed to the ventilatory muscles.

Sensory afferents

Chemoreceptors in the carotid bodies and medulla are activated by hypoxemia, acute hypercapnia, and acidemia. Stimulation of these receptors and of others that lead to an increase in ventilation produce a sensation of “air hunger.” Mechanoreceptors in the lungs, when stimulated by bronchospasm, lead to a sensation of chest tightness. J-receptors, which are sensitive to interstitial edema, and pulmonary vascular receptors, which are activated by acute changes in pulmonary artery pressure, appear to contribute to air hunger. Hyperinflation is associated with the sensation of increased work of breathing, an inability to get a deep breath, or an unsatisfying breath. Metaboreceptors, which are located in skeletal muscle, are believed to be activated by changes in the local biochemical milieu of the tissue active during exercise and, when stimulated, contribute to breathing discomfort.

Integration: efferent-reafferent mismatch

A discrepancy or mismatch between the feed-forward message to the ventilatory muscles and the feedback from receptors that monitor the response of the ventilatory pump increases the intensity of dyspnea. This mismatch is particularly important when there is a mechanical derangement of the ventilatory pump, as in asthma or chronic obstructive pulmonary disease (COPD).

Contribution of emotional or affective factors to dyspnea

Acute anxiety or fear may increase the severity of dyspnea either by altering the interpretation of sensory data or by leading to patterns of breathing that heighten physiologic abnormalities in the respiratory system. In patients with expiratory flow limitation, for example, the increased respiratory rate that accompanies acute anxiety leads to hyperinflation, increased work and effort of breathing, and the sense of an unsatisfying breath.

ASSESSING DYSPNEA

Quality of sensation

Like pain assessment, dyspnea assessment begins with a determination of the quality of the patient’s discomfort (Table 5-1). Dyspnea questionnaires or lists of phrases commonly used by patients assist those who have difficulty describing their breathing sensations.

Sensory intensity

A modified Borg scale or visual analogue scale can be utilized to measure dyspnea at rest, immediately following exercise, or on recall of a reproducible physical task, such as climbing the stairs at home. An alternative approach is to gain a sense of the patient’s disability by inquiring about what activities are possible. These methods indirectly assess dyspnea and may be affected by nonrespiratory factors, such as leg arthritis or weakness. The Baseline Dyspnea Index and the Chronic Respiratory Disease Questionnaire are commonly used tools for this purpose.

Affective dimension

For a sensation to be reported as a symptom, it must be perceived as unpleasant and interpreted as abnormal. Laboratory studies have demonstrated that air hunger evokes a stronger affective response than does increased effort or work of breathing. Some therapies for dyspnea, such as pulmonary rehabilitation, may reduce breathing discomfort, in part, by altering this dimension.

DIFFERENTIAL DIAGNOSIS

Dyspnea most often results from deviations from normal function in the cardiovascular and respiratory systems. These deviations produce breathlessness as a consequence of increased drive to breathe; increased effort or work of breathing; and/or stimulation of receptors in the heart, lungs, or vascular system. Most diseases of the respiratory system are associated with alterations in the mechanical properties of the lungs and/or chest wall, and some stimulate pulmonary receptors. In contrast, disorders of the cardiovascular system more commonly lead to dyspnea by causing gas-exchange abnormalities or stimulating pulmonary and/or vascular receptors (Table 5-2).

Respiratory system dyspnea

Diseases of the airways

Asthma and COPD, the most common obstructive lung diseases, are characterized by expiratory airflow obstruction, which typically leads to dynamic hyperinflation of the lungs and chest wall. Patients with moderate to severe disease have both increased resistive and elastic loads (a term that relates to the stiffness of the system) on the ventilatory muscles and experience increased work of breathing. Patients with acute bronchoconstriction also report a sense of tightness, which can exist even when lung function is still within the normal range. These patients are commonly tachypneic; this condition leads to hyperinflation and reduced respiratory system compliance and also limits tidal volume. Both the chest tightness and the tachypnea are probably due to stimulation of pulmonary receptors. Both asthma and COPD may lead to hypoxemia and hypercapnia from ventilation-perfusion (V̇/Q) mismatch (and diffusion limitation during exercise with emphysema); hypoxemia is much more common than hypercapnia as a consequence of the different ways in which oxygen and carbon dioxide bind to hemoglobin.

Diseases of the chest wall

Conditions that stiffen the chest wall, such as kyphoscoliosis, or that weaken ventilatory muscles, such as myasthenia gravis or the Guillain-Barré syndrome, are also associated with an increased effort to breathe. Large pleural effusions may contribute to dyspnea, both by increasing the work of breathing and by stimulating pulmonary receptors if there is associated atelectasis.

Diseases of the lung parenchyma

Interstitial lung diseases, which may arise from infections, occupational exposures, or autoimmune disorders, are associated with increased stiffness (decreased compliance) of the lungs and increased work of breathing. In addition, V̇/Q mismatch and the destruction and/or thickening of the alveolar-capillary interface may lead to hypoxemia and an increased drive to breathe. Stimulation of pulmonary receptors may further enhance the hyperventilation characteristic of mild to moderate interstitial disease.

Cardiovascular system dyspnea

Diseases of the left heart

Diseases of the myocardium resulting from coronary artery disease and nonischemic cardiomyopathies cause a greater left-ventricular end-diastolic volume and an elevation of the left-ventricular end-diastolic as well as pulmonary capillary pressures. These elevated pressures lead to interstitial edema and stimulation of pulmonary receptors, thereby causing dyspnea; hypoxemia due to V̇/Q mismatch may also contribute to breathlessness. Diastolic dysfunction, characterized by a very stiff left ventricle, may lead to severe dyspnea with relatively mild degrees of physical activity, particularly if it is associated with mitral regurgitation.

Diseases of the pulmonary vasculature

Pulmonary thromboembolic disease and primary diseases of the pulmonary circulation (primary pulmonary hypertension, pulmonary vasculitis) cause dyspnea via increased pulmonary-artery pressure and stimulation of pulmonary receptors. Hyperventilation is common, and hypoxemia may be present. However, in most cases, use of supplemental oxygen has only a minimal impact on the severity of dyspnea and hyperventilation.

Diseases of the pericardium

Constrictive pericarditis and cardiac tamponade are both associated with increased intracardiac and pulmonary vascular pressures, which are the likely cause of dyspnea in these conditions. To the extent that cardiac output is limited (at rest or with exercise) metaboreceptors may be stimulated if cardiac output is compromised to the degree that lactic acidosis develops; chemoreceptors will also be activated.

Dyspnea with normal respiratory and cardiovascular systems

Mild to moderate anemia is associated with breathing discomfort during exercise. This symptom is thought to be related to stimulation of metaboreceptors; oxygen saturation is normal in patients with anemia. The breathlessness associated with obesity is probably due to multiple mechanisms, including high cardiac output and impaired ventilatory pump function (decreased compliance of the chest wall). Cardiovascular deconditioning (poor fitness) is characterized by the early development of anaerobic metabolism and the stimulation of chemoreceptors and metaboreceptors. Dyspnea that is medically unexplained has been associated with increased sensitivity to the unpleasantness of acute hypercapnia.

APPROACH TO PATIENT

TREATMENT

MECHANISMS OF FLUID ACCUMULATION

The extent to which fluid accumulates in the interstitium of the lung depends on the balance of hydrostatic and oncotic forces within the pulmonary capillaries and in the surrounding tissue. Hydrostatic pressure favors movement of fluid from the capillary into the interstitium. The oncotic pressure, which is determined by the protein concentration in the blood, favors movement of fluid into the vessel. Levels of albumin, the primary protein in the plasma, may be low in conditions such as cirrhosis and nephrotic syndrome. While hypoalbuminemia favors movement of fluid into the tissue for any given hydrostatic pressure in the capillary, it is usually not sufficient by itself to cause interstitial edema. In a healthy individual, the tight junctions of the capillary endothelium are impermeable to proteins, and the lymphatics in the tissue carry away the small amounts of protein that may leak out; together, these factors result in an oncotic force that maintains fluid in the capillary. Disruption of the endothelial barrier, however, allows protein to escape the capillary bed and enhances the movement of fluid into the tissue of the lung.

CARDIOGENIC PULMONARY EDEMA

(See also Chap. 34) Cardiac abnormalities that lead to an increase in pulmonary venous pressure shift the balance of forces between the capillary and the interstitium. Hydrostatic pressure is increased and fluid exits the capillary at an increased rate, resulting in interstitial and, in more severe cases, alveolar edema. The development of pleural effusions may further compromise respiratory system function and contribute to breathing discomfort.

Early signs of pulmonary edema include exertional dyspnea and orthopnea. Chest radiographs show peribronchial thickening, prominent vascular markings in the upper lung zones, and Kerley B lines. As the pulmonary edema worsens, alveoli fill with fluid; the chest radiograph shows patchy alveolar filling, typically in a perihilar distribution, which then progresses to diffuse alveolar infiltrates. Increasing airway edema is associated with rhonchi and wheezes.

NONCARDIOGENIC PULMONARY EDEMA

In noncardiogenic pulmonary edema, lung water increases due to damage of the pulmonary capillary lining with consequent leakage of proteins and other macromolecules into the tissue; fluid follows the protein as oncotic forces are shifted from the vessel to the surrounding lung tissue. This process is associated with dysfunction of the surfactant lining the alveoli, increased surface forces, and a propensity for the alveoli to collapse at low lung volumes. Physiologically, noncardiogenic pulmonary edema is characterized by intrapulmonary shunt with hypoxemia and decreased pulmonary compliance leading to lower functional residual capacity. On pathologic examination, hyaline membranes are evident in the alveoli, and inflammation leading to pulmonary fibrosis may be seen. Clinically, the picture ranges from mild dyspnea to respiratory failure. Auscultation of the lungs may be relatively normal despite chest radiographs that show diffuse alveolar infiltrates. CT scans demonstrate that the distribution of alveolar edema is more heterogeneous than was once thought. Although normal intracardiac pressures are considered by many to be part of the definition of noncardiogenic pulmonary edema, the pathology of the process, as described above, is distinctly different, and a combination of cardiogenic and noncardiogenic pulmonary edema is observed in some patients.

It is useful to categorize the causes of noncardiogenic pulmonary edema in terms of whether the injury to the lung is likely to result from direct, indirect, or pulmonary vascular causes (Table 5-3). Direct injuries are mediated via the airways (e.g., aspiration) or as the consequence of blunt chest trauma. Indirect injury is the consequence of mediators that reach the lung via the bloodstream. The third category includes conditions that may result from acute changes in pulmonary vascular pressures, possibly due to sudden autonomic discharge (in the case of neurogenic and high-altitude pulmonary edema) or sudden swings of pleural pressure as well as transient damage to the pulmonary capillaries (in the case of reexpansion pulmonary edema).

DISTINGUISHING CARDIOGENIC FROM NONCARDIOGENIC PULMONARY EDEMA

The history is essential for assessing the likelihood of underlying cardiac disease as well as for identification of one of the conditions associated with noncardiogenic pulmonary edema. The physical examination in cardiogenic pulmonary edema is notable for evidence of increased intracardiac pressures (S3 gallop, elevated jugular venous pulse, peripheral edema) and rales and/or wheezes on auscultation of the chest. In contrast, the physical examination in noncardiogenic pulmonary edema is dominated by the findings of the precipitating condition; pulmonary findings may be relatively normal in the early stages. The chest radiograph in cardiogenic pulmonary edema typically shows an enlarged cardiac silhouette, vascular redistribution, interstitial thickening, and perihilar alveolar infiltrates; pleural effusions are common. In noncardiogenic pulmonary edema, heart size is normal, alveolar infiltrates are distributed more uniformly throughout the lungs, and pleural effusions are uncommon. Finally, the hypoxemia of cardiogenic pulmonary edema is due largely to V̇/Q to mismatch and responds to the administration of supplemental oxygen. In contrast, hypoxemia in noncardiogenic pulmonary edema is due primarily to intrapulmonary shunting and typically persists despite high concentrations of inhaled oxygen.