Dyspnea

Dyspnea, or shortness of breath, is frequently a difficult symptom for the physician to evaluate because it is such a subjective feeling experienced by the patient. It is perhaps best defined as an uncomfortable sensation (or awareness) of one’s own breathing, to which little attention normally is paid. However, the term dyspnea probably subsumes several sensations that are qualitatively distinct. As a result, when patients are asked to describe in more detail their sensation of breathlessness, their descriptions tend to fall into three primary categories: (1) air hunger or suffocation, (2) increased effort or work of breathing, and (3) chest tightness.

Not only is the symptom of dyspnea highly subjective and describable in different ways, but the patient’s appreciation of it and its importance to the physician depend heavily on the stimulus or amount of activity required to precipitate it. The physician must take into account how the stimulus, when quantified, compares with the patient’s usual level of activity. For example, a patient who is limited in exertion by a nonpulmonary problem may not experience any shortness of breath even in the presence of additional and significant lung disease. If the person were more active, however, dyspnea would become readily apparent. A marathon runner who experiences a new symptom of shortness of breath after running 5 miles may warrant more concern than would an elderly man who for many years has had a stable symptom of shortness of breath after walking 3 blocks.

Dyspnea should be distinguished from several other signs or symptoms that may have an entirely different significance. Tachypnea is a rapid respiratory rate (greater than the usual value of 12–20/min). Tachypnea may be present with or without dyspnea, just as dyspnea does not necessarily entail the finding of tachypnea on physical examination. Hyperventilation is ventilation that is greater than the amount required to maintain normal CO₂ elimination. Hence, the criterion that defines hyperventilation is a decrease in the PCO₂ of arterial blood. Finally, the symptom of exertional fatigue must be distinguished from dyspnea. Fatigue may be due to cardiovascular, neuromuscular, or other nonpulmonary diseases, and the implication of this symptom may be quite different from that of shortness of breath.

There are some variations on the theme of dyspnea. Orthopnea, or shortness of breath on assuming the recumbent position, often is quantitated by the number of pillows or angle of elevation necessary to relieve or prevent the sensation. One of the main causes of orthopnea is an increase in venous return and central intravascular volume on assuming the recumbent position. In patients with cardiac decompensation and either overt or subclinical congestive heart failure, the increment in left atrial and left ventricular filling may result in pulmonary vascular congestion and pulmonary interstitial or alveolar edema. Thus, orthopnea frequently suggests cardiac disease and some element of congestive heart failure. However, orthopnea may be seen in other disorders. For example, some patients with primary pulmonary disease experience orthopnea, such as individuals with a significant amount of secretions who have more difficulty handling their secretions when they are recumbent. Bilateral diaphragmatic weakness may also cause orthopnea due to greater pressure on the diaphragm by abdominal contents and more difficulty inspiring when the patient is supine rather than upright.

Paroxysmal nocturnal dyspnea is waking from sleep with dyspnea. As with orthopnea, the recumbent position is important, but this symptom differs from orthopnea in that it does not occur soon after lying down. Although the implication with regard to underlying cardiac decompensation still applies, the increase in central intravascular volume is due more to a slow mobilization of tissue fluid, such as peripheral edema, than to a rapid redistribution of intravascular volume from peripheral to central vessels.

Variants that are much more uncommon are only mentioned here. Platypnea is shortness of breath when the patient is in the upright position; it is the opposite of orthopnea. Trepopnea is shortness of breath when the patient lies on his or her side. Patients with this symptom report dyspnea on either the right or left side. The symptom can be relieved by moving to the opposite lateral position.

Returning to the more general symptom of dyspnea, a number of sources or mechanisms are proposed rather than a single common thread linking the diverse responsible conditions. In particular, neural output reflecting central nervous system respiratory drive appears to be integrated with input from a variety of mechanical receptors in the chest wall, respiratory muscles, airways, and pulmonary vasculature. If central neural output to the respiratory system is not associated with the expected responses in ventilation and gas exchange, the patient experiences a sensation of dyspnea. Presumably, the relative contributions of each source differ from disease to disease and from patient to patient, and they are responsible for the qualitatively different sensations all subsumed under the term dyspnea. Detailed discussions of the mechanisms of dyspnea can be found in the references at the end of this chapter.

Studies have attempted to link dyspnea with underlying pathophysiologic mechanisms. While the correlations are not perfect, a patient’s description can help guide the clinician to the correct diagnosis. Patients who describe their breathlessness as a sense of air hunger or suffocation often have increased respiratory drive, which can be related in part to either a high PCO₂ or a low PO₂ but also can occur even in the absence of respiratory system or gas-exchange abnormalities. The sensation of increased effort or work of breathing is commonly experienced by patients who have increased resistance to airflow or abnormally stiff lungs. The sensation of chest tightness, frequently noted by patients with asthma, probably arises from intrathoracic receptors that are stimulated by bronchoconstriction. Because most disorders may produce breathlessness by more than one mechanism (e.g., asthma may have components of all three mechanisms), overlap or a mixture of these different sensations often occurs.

The differential diagnosis includes a broad range of disorders that result in dyspnea (Table 2-1). The disorders can be separated into the major categories of respiratory disease and cardiovascular disease. Dyspnea may be present in the absence of underlying respiratory or cardiovascular disease in conditions associated with increased respiratory drive, such as hyperthyroidism, or in metabolic disorders, such as mitochondrial myopathies. In addition, dyspnea may have an anxiety-related or psychosomatic origin.

The first major category consists of disorders at many levels of the respiratory system (airways, pulmonary parenchyma, pulmonary vasculature, pleura, and bellows) that can cause dyspnea. Airway diseases that cause dyspnea result primarily from obstruction to airflow, occurring anywhere from the upper airway to the large, medium, and small intrathoracic bronchi and bronchioles. Upper airway obstruction, which is defined here as obstruction above or including the vocal cords, is caused primarily by foreign bodies, tumors, edema (e.g., with anaphylaxis), and stenosis. A clue to upper airway obstruction is the presence of disproportionate difficulty during inspiration and an audible prolonged gasping sound called inspiratory stridor. The pathophysiology of upper airway obstruction is discussed in Chapter 7.

Airways below the level of the vocal cords, from the trachea down to the small bronchioles, are more commonly involved with disorders that produce dyspnea. An isolated problem, such as an airway tumor, usually does not by itself cause dyspnea unless it occurs in the trachea or a major bronchus. In contrast, diseases such as asthma and chronic obstructive pulmonary disease have widespread effects throughout the tracheobronchial tree, with airway narrowing resulting from spasm, edema, secretions, or loss of radial support (see Chapter 4). With this type of obstruction, difficulty with expiration generally predominates over that with inspiration, and the physical findings associated with obstruction (wheezing, prolongation of airflow) are more prominent on expiration.

The category of pulmonary parenchymal disease includes disorders causing inflammation, infiltration, fluid accumulation, or scarring of the alveolar structures. Such disorders may be diffuse in nature, as with the many causes of interstitial or diffuse parenchymal lung disease, or they may be more localized, as occurs with a bacterial pneumonia.

Pulmonary vascular disease results in obstruction or loss of vessels in the lung. The most common acute type of pulmonary vascular disease is pulmonary embolism, in which one or many pulmonary vessels are occluded by thrombi originating in systemic veins. Chronically, vessels may be blocked by recurrent pulmonary emboli or by inflammatory or scarring processes that result in thickening of vessel walls or obliteration of the vascular lumen, ultimately causing pulmonary arterial hypertension.

Two major disorders affecting the pleura may result in dyspnea: pneumothorax (air in the pleural space) and pleural effusion (liquid in the pleural space). With pleural effusions, a substantial amount of fluid must be present in the pleural space to result in dyspnea, unless the patient also has significant underlying cardiopulmonary disease or additional complicating features.

The term bellows is used here for the final category of respiratory-related disorders causing dyspnea. It refers to the pump system that works under the control of a central nervous system generator to expand the lungs and allow airflow. This pump system includes a variety of muscles (primarily but not exclusively diaphragm and intercostal) and the chest wall. Primary disease affecting the muscles, their nerve supply, or neuromuscular interaction, including polymyositis, myasthenia gravis, and Guillain-Barré syndrome, may result in dyspnea. Deformity of the chest wall, particularly kyphoscoliosis, produces dyspnea by several pathophysiologic mechanisms, primarily through increased work of breathing. Disorders of the respiratory bellows are discussed in Chapter 19.

The second major category of disorders that produce dyspnea is cardiovascular disease. In the majority of cases, the feature that patients have in common is an elevated hydrostatic pressure in the pulmonary veins and capillaries that leads to a transudation or leakage of fluid into the pulmonary interstitium and alveoli. Left ventricular failure, from either ischemic or valvular heart disease, is the most common example. In addition, mitral stenosis, with increased left atrial pressure, produces elevated pulmonary venous and capillary pressures even though left ventricular function and pressure are normal. A frequent accompaniment of the dyspnea associated with these forms of cardiac disease is orthopnea, paroxysmal nocturnal dyspnea, or both. Although worsening of dyspnea in the supine position is not specific to pulmonary venous hypertension and can also be found in some patients with pulmonary disease, improvement of dyspnea in the supine position is a point against left ventricular failure as the causative factor.

A third category of conditions associated with dyspnea includes those characterized by increased respiratory drive but no underlying cardiopulmonary disease. Both thyroid hormone and progesterone augment respiratory drive, and patients with hyperthyroidism and pregnant women commonly complain of dyspnea. Dyspnea during pregnancy often starts before the abdomen is noticeably distended, indicating that diaphragmatic elevation from the enlarging uterus is not the primary explanation for the dyspnea.

Finally, dyspnea may be due to anxiety or other psychosomatic problems. Because the sensation of dyspnea is so subjective, any awareness of one’s breathing may start a self-perpetuating problem. The patient breathes faster, becomes more aware of breathing, and finally has a sensation of frank dyspnea. At the extreme, a person can hyperventilate and lower arterial PCO₂ sufficiently to cause additional symptoms of lightheadedness and tingling, particularly of the fingers and around the mouth. Of course, patients who seem anxious or have a history of psychological problems can also have lung disease. Similarly, patients with lung or heart disease can have dyspnea with a functional cause unrelated to their underlying disease process.

Cough

Cough is a symptom everyone has experienced at some point. It is a physiologic mechanism for clearing and protecting the airway and does not necessarily imply disease. Normally, cough is protective against food or other foreign material entering the airway. It also is responsible for helping clear secretions produced within the tracheobronchial tree. Generally, mucociliary clearance is adequate to propel secretions upward through the trachea and into the larynx so that the secretions can be removed from the airway and swallowed. However, if the mucociliary clearance mechanism is temporarily damaged or not functioning well, or if the mechanism is overwhelmed by excessive production of secretions, coughing becomes an important additional mechanism for clearing the tracheobronchial tree.

Cough usually is initiated by stimulation of receptors (called irritant receptors) at a number of locations. Irritant receptor nerve endings are found primarily in the larynx, trachea, and major bronchi, particularly at points of bifurcation. However, sensory receptors are also located in other parts of the upper airway as well as on the pleura, the diaphragm, and even the pericardium. Irritation of these nerve endings initiates an impulse that travels via afferent nerves (primarily the vagus but also trigeminal, glossopharyngeal, and phrenic) to a poorly defined cough center in the medulla. The efferent signal is carried in the recurrent laryngeal nerve (a branch of the vagus), which controls closure of the glottis, and in phrenic and spinal nerves, which effect contraction of the diaphragm and the expiratory muscles of the chest and abdominal walls. The initial part of the cough sequence is a deep inspiration to a high lung volume, followed by closure of the glottis, contraction of the expiratory muscles, and opening of the glottis. When the glottis suddenly opens, contraction of the expiratory muscles and relaxation of the diaphragm produce an explosive rush of air at high velocity, which transports airway secretions or foreign material out of the tracheobronchial tree.

The major causes of cough are listed in Table 2-2. Cough commonly results from an airway irritant, regardless of whether the person has respiratory system disease. The most common inhaled irritant is cigarette smoke. Noxious fumes, dusts, and chemicals also stimulate irritant receptors and result in cough. Secretions resulting from postnasal drip are a particularly common cause of cough, presumably triggering the symptom via stimulation of laryngeal cough receptors. Aspiration of gastric contents or upper airway secretions, which amounts to “inhalation” of liquid or solid material, can result in cough, the cause of which may be unrecognized if the aspiration has not been clinically apparent. In the case of gastroesophageal reflux, in which gastric acid flows retrograde into the esophagus, cough is due not only to aspiration of gastric contents from the esophagus or pharynx into the tracheobronchial tree, but also to reflex mechanisms triggered by acid entry into the lower esophagus and mediated by the vagal nerve.

Cough caused by respiratory system disease derives mainly but not exclusively from disorders affecting the airway. Upper airway infections, most commonly caused by viruses or certain bacteria (especially Mycoplasma, Chlamydophila, and Bordetella pertussis), also affect parts of the tracheobronchial tree, and the airway inflammation results in a bothersome cough that sometimes lasts from weeks to months. Bacterial infections of the lung, either acute (pneumonia, acute bronchitis) or chronic (bronchiectasis, chronic bronchitis, lung abscess), generally have an airway component and an impressive amount of associated coughing. Space-occupying lesions in the tracheobronchial tree (tumors, foreign bodies, granulomas) and external lesions compressing the airway (mediastinal masses, lymph nodes, other tumors) commonly manifest as cough secondary to airway irritation. Hyperirritable airways with airway constriction, as in asthma, are frequently associated with cough, even when a specific inhaled irritant is not identified. The more readily recognized manifestations of asthma (wheezing and dyspnea) may not be apparent, and cough may be the sole presenting symptom. An entity of unknown etiology called eosinophilic bronchitis, characterized by eosinophilic inflammation of the airway in the absence of asthma, has also been identified as a cause of chronic cough.

Patients with diffuse parenchymal (interstitial) lung disease may have cough, probably owing more to secondary airway or pleural involvement, inasmuch as few irritant receptors are in the lung itself. In congestive heart failure, cough may be related to the same unclear mechanism operative in patients with diffuse parenchymal lung disease, or it may be secondary to bronchial edema.

A variety of miscellaneous causes of cough, such as irritation of the tympanic membrane by wax or a hair or stimulation of one of the afferent nerves by osteophytes or neural tumors, have been identified but are not discussed in further detail here. With the widespread use of angiotensin-converting enzyme inhibitors (e.g., enalapril, lisinopril) for treatment of hypertension and congestive heart failure, cough has been recognized as a relatively common side effect of these agents. Because angiotensin-converting enzyme breaks down bradykinin and other inflammatory peptides, accumulation of bradykinin or other peptides in patients taking these inhibitors may be responsible by stimulating receptors capable of initiating cough. Of note, cough is a far less common side effect of angiotensin II receptor antagonists such as losartan. Finally, coughing may be a nervous habit that can be especially prominent when the patient is anxious, although the physician must not neglect the possibility of an organic cause.

The symptom of cough is generally characterized by whether it is productive or nonproductive of sputum. Virtually any cause of cough may be productive at times of small amounts of clear or mucoid sputum. However, thick yellow or green sputum indicates the presence of numerous leukocytes in the sputum, either neutrophils or eosinophils. Neutrophils may be present with just an inflammatory process of the airways or parenchyma, but they also frequently reflect the presence of a bacterial infection. Specific examples include bacterial bronchitis, bronchiectasis, lung abscess, and pneumonia. Eosinophils, which can be seen after special preparation of the sputum, often occur with bronchial asthma, whether or not an allergic component plays a role, and in the much less common entity of eosinophilic bronchitis.

In clinical practice, cough is often divided into three major temporal categories: acute, subacute, or chronic, depending on the duration of the symptom. Acute cough, defined by a duration of less than 3 weeks, is most commonly due to an acute viral infection of the respiratory tract, such as the common cold. Subacute cough is defined by a duration of 3 to 8 weeks, and chronic cough lasts 8 or more weeks. Whereas chronic bronchitis is a particularly frequent cause of cough in smokers, common causes of either subacute or chronic cough in nonsmokers are postnasal drip (also called upper airway cough syndrome), gastroesophageal reflux, and asthma. An important subacute cough is postinfectious cough that lasts for more than 3 weeks following an upper respiratory tract infection. It often is due to persistent airway inflammation, postnasal drip, or bronchial hyperresponsiveness (as seen with asthma). In all cases, however, the clinician must keep in mind the broader differential diagnosis of cough outlined in Table 2-2, recognizing that cough may be a marker and the initial presenting symptom of a more serious disease, such as carcinoma of the lung.

Hemoptysis

Hemoptysis is coughing or spitting up blood derived from airways or the lung itself. When the patient complains of coughing or spitting up blood, whether the blood actually originated from the respiratory system is not always apparent. Other sources of blood include the nasopharynx (particularly from the common nosebleed), mouth (even lip or tongue biting can be mistaken for hemoptysis), and upper gastrointestinal tract (esophagus, stomach, and duodenum). The patient often can distinguish some of these causes of pseudohemoptysis, but the physician also should search by examination for a mouth or nasopharyngeal source.

The major causes of hemoptysis can be divided into three categories based on location: airways, pulmonary parenchyma, and vasculature (Table 2-3). Airway disease is the most common cause, with bronchitis, bronchiectasis, and bronchogenic carcinoma leading the list. Bronchial carcinoid tumor (formerly called bronchial adenoma), a less common neoplasm with variable malignant potential, also originates in the airway and may cause hemoptysis. In patients with acquired immunodeficiency syndrome, hemoptysis may be due to endobronchial (and/or pulmonary parenchymal) involvement with Kaposi sarcoma.

Parenchymal causes of hemoptysis frequently are infectious in nature: tuberculosis, lung abscess, pneumonia, and localized fungal infection (generally attributable to Aspergillus organisms), termed mycetoma (“fungus ball”) or aspergilloma. Rarer causes of parenchymal hemorrhage are Goodpasture syndrome, idiopathic pulmonary hemosiderosis, and Wegener granulomatosis, some of which are discussed in Chapter 11.

Vascular lesions resulting in hemoptysis are generally related to problems with the pulmonary circulation. Pulmonary embolism, with either frank infarction or transient bleeding without infarction, is often a cause of hemoptysis. Elevated pressure in the pulmonary venous and capillary bed may also be associated with hemoptysis. Acutely elevated pressure, as in pulmonary edema, may have associated hemoptysis, commonly seen as pink- or red-tinged frothy sputum. Chronically elevated pulmonary venous pressure results from mitral stenosis, but this valvular lesion is a relatively infrequent cause of significant hemoptysis. Vascular malformations, such as arteriovenous malformations, may also be associated with coughing of blood.

Other miscellaneous etiologic factors in hemoptysis should be considered. Some of these belong in more than one of the aforementioned categories; others are included here because of their rarity. Cystic fibrosis affects both airways and pulmonary parenchyma. Although either component theoretically can cause hemoptysis, bronchiectasis (a common complication of cystic fibrosis) is most frequently responsible. Patients with impaired coagulation may rarely have pulmonary hemorrhage in the absence of other obvious causes of hemoptysis. An interesting but rare disorder is pulmonary endometriosis, in which implants of endometrial tissue in the lung can bleed coincident with the time of the menstrual cycle. Other causes are even more rare, and discussion of them is beyond the scope of this chapter.

Chest Pain

Chest pain as a reflection of respiratory system disease does not originate in the lung itself, which is free of sensory pain fibers. When chest pain does occur in this setting, its origin usually is the parietal pleura (lining the inside of the chest wall), diaphragm, or mediastinum, each of which has extensive innervation by nerve fibers capable of pain sensation.

For the parietal pleura or the diaphragm, an inflammatory or infiltrating malignant process generally produces the pain. When the diaphragm is involved, the pain commonly is referred to the shoulder. In contrast, pain from the parietal pleura usually is relatively well localized over the area of involvement. Pain involving the pleura or diaphragm is often worsened on inspiration; in fact, chest pain that is particularly pronounced on inspiration is described as pleuritic.

Inflammation of the parietal pleura producing pain is often secondary to pulmonary embolism or to pneumonia extending to the pleural surface. A pneumothorax may result in acute onset of pleuritic pain, although the mechanism is not clear, inasmuch as an acute inflammatory process is unlikely to be involved. Some diseases, particularly connective tissue disorders such as lupus, may result in episodes of pleuritic chest pain from a primary inflammatory process involving the pleura. Inflammation of the parietal pleura as a result of a viral infection (e.g., viral pleurisy) is a common cause of pleuritic chest pain in otherwise healthy individuals.

Infiltrating tumor can produce chest pain by affecting the parietal pleura or adjacent soft tissue, bones, or nerves. In the case of malignant mesothelioma, the tumor arises from the pleura itself. In other circumstances, such as lung cancer, the tumor may extend directly to the pleural surface or involve the pleura after bloodborne (hematogenous) metastasis from a distant site.

A variety of disorders originating in the mediastinum may result in pain; they may or may not be associated with additional problems in the lung itself. These disorders of the mediastinum are discussed in Chapter 16.

References