Dyspnea (Greek dys, meaning “painful,” “difficult,” and pneuma, meaning “breath”) is a clinical term for the sensation of breathlessness or shortness of breath experienced by both normal subjects and patients with diseases affecting the respiratory system. Its importance has been recognized by the release of an updated American Thoracic Society Statement. Dyspnea assumes clinical significance when it is felt at a level of exertion that is unacceptably low for the individual or modifies a patient’s lifestyle dramatically in an effort to avoid breathing discomfort. It is increasingly regarded as an important outcome for both prognostic and therapeutic purposes across a wide range of clinical conditions, principally chronic obstructive pulmonary disease (COPD), heart failure, advanced cancer, and interstitial lung diseases.
There are no precise data on the prevalence of dyspnea. A meta-analysis suggests a worldwide prevalence of 10% for COPD in adults older than 40 years, making its cardinal symptom, dyspnea, a substantial cause of morbidity, especially in older people. A high prevalence of dyspnea due to all causes is indicated by a survey of 4900 middle-aged and older adults in which 27.2% reported having dyspnea, whereas only 12.5% reported having COPD. In a survey of 1556 seriously ill patients admitted to hospital, 49% reported having dyspnea compared with 51% who reported pain. Morbidity associated with dyspnea is variable, ranging from minor annoyance to functional incapacity. Moreover, dyspnea is a strong independent predicator of mortality in COPD, heart failure and aging. Compared with pain, dyspnea is relatively refractory to effective symptom management, likely affecting not only patients but also their care providers (including health professionals) during terminal or severe chronic conditions.
Dyspnea encompasses a variety of sensations experienced when breathing feels uncomfortable, labored, and unsatisfying, sensations likely to be linked to discrete physiologic mechanisms. As a symptom, dyspnea can be reported only by the patient and is distinct from objective findings or signs associated with physical examination, such as tachypnea, hyperinflation, and cyanosis. Dyspnea is multifactorial and, although it results from pathophysiologic events, is likely to be influenced by such factors as psychological state, bodily preoccupation, level of awareness, usual level of physical activity, body weight, state of nutrition, and medications. These many modifying factors may explain the variable correlation between dyspnea ratings and airflow limitation or exercise performance. Because most diseases for which dyspnea is a common symptom are essentially irreversible (e.g., chronic lung disease, heart failure, cancer), effective management of the dyspnea symptom to improve quality of life is a desirable goal.
Definition of Dyspnea
Over the years there have been many attempts to define dyspnea, and these have shared a common theme of an uncomfortable perception associated with the act of breathing. However, the more formalized definition given in the consensus statement of the American Thoracic Society is now widely accepted and has provided a sound basis for researchers and clinicians concerned with understanding and managing this symptom. This states: “Dyspnea is a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social, and environmental factors, and it may induce secondary physiological and behavioral responses.” The American Thoracic Society dyspnea statement also emphasizes that “distinct sensations most often do not occur in isolation,” and that the sensations “vary in their unpleasantness and their emotional and behavioral significance.”
Language of Dyspnea
The breathing discomfort associated with various cardiopulmonary derangements is characterized by a range of words and phrases used to describe the sensation and can trigger strong affective responses. Studies of the language of dyspnea provide insights into the patient’s perception of the problem, and these descriptors often offer clues to the underlying physiologic derangements. A multidimensional model for dyspnea, which includes sensory intensity, qualitative descriptors, and affective elements has been proposed.
Qualitative Phrases—the Descriptive Dimension of Dyspnea
When patients complain of being short of breath, they are usually reporting familiar sensations that have become noticeable at lower levels of exertion. When questioned further, patients may volunteer comments such as “hard to breathe,” “can’t get enough air,” or “feeling tight” but often have difficulty being more specific. Overlaying this, cultural or language differences may result in patients using different words to describe the same sensory experience. Modeled on the proven clinical utility of evaluating the language of pain (e.g., assessing ischemic heart disease), researchers have asked if the language of dyspnea might be similarly useful.
Since the early 1980s, studies in healthy subjects and dyspneic patients have identified distinctive clusters of descriptors from commonly used expressions of breathing discomfort. In general, four primary categories of breathing discomfort can be identified by the following descriptors: “tightness,” “need or urge to breathe,” (often labeled “air hunger”), “work or effort of breathing,” and “depth and frequency of breathing.” In patient populations, “tightness” appears to be clearly associated with bronchoconstriction, whereas “urge to breathe” is associated with enhanced central drive and/or limitations of tidal volume, and “effort of breathing” is seen in conditions characterized by alterations in the respiratory pump (e.g., ventilatory muscle weakness or increased airway resistance). The “depth and frequency of breathing” descriptor, typically associated with activity or exercise, probably relates more to awareness of chest wall movement than to awareness of breathing discomfort but may nonetheless be worrisome to the patient.
Although there are few cross-cultural studies of the language of dyspnea, the basic categories of phrases noted previously appear consistent across countries. In addition, children use qualitative descriptors to describe the respiratory discomfort associated with asthma in a manner quite similar to adults, and their use of language is reliable over time. Other factors, such as obesity, may be associated with different sensory qualities that relate to the intensity of the breathlessness. The primary studies that have defined and explored the utility of qualitative descriptors have been summarized.
Emotional Phrases—the Affective Dimension of Dyspnea
The pain model of symptom attributes has been further applied to explore the importance of the affective component (e.g., unpleasantness, fear, anxiety) of dyspnea in addition to its intensity and quality. One study reported that for a given intensity of dyspnea, a stimulus with a greater “air hunger” component is perceived as a substantially more unpleasant experience than one with a strong “work/effort” component. These authors have developed a multidimensional profile for dyspnea, based on an analogous instrument for pain, which should provide a better understanding of the affective component of dyspnea with a view to developing more-targeted therapeutic approaches; reliability and validity of the instrument have been demonstrated. Similar efforts have produced a single dyspnea tool that incorporates both the descriptive and affective dimension into one instrument.
In patients with COPD, those with more severe degrees of respiratory system dysfunction, as evidenced by the BODE ( body mass index, airflow obstruction, dyspnea, and exercise capacity ) index, volunteered more extreme affective phrases, such as “frightening” and “worried.” Furthermore, those patients expressing higher dyspnea-related fear may have greater improvements in dyspnea with a pulmonary rehabilitation program. Interestingly, there appears to be no difference in the affective response in patients with COPD when they have dyspnea at home compared to when dyspnea is stimulated in a laboratory setting, which suggests that the ability to control dyspnea by reducing activity may mitigate the emotional dimension in a manner similar to telling an investigator to stop the experiment.
A more careful consideration of the language and emotional impact of dyspnea by health practitioners might yield important diagnostic insights or improved management of breathless patients and is increasingly becoming a marker of quality of care for evaluating dyspnea.
Mechanisms of Dyspnea
The neurophysiologic mechanisms that give rise to the perception of dyspnea are incompletely understood ( Fig. 29-1 ). Current thinking suggests that the discomfort of dyspnea comprises two primary components: (1) an “urge to breathe” (referred to as “air hunger”) and (2) a “sense of excessive effort” associated with breathing. Although sensations of urge to breathe and effort increase together with exertion, they can be separated experimentally with the former being reported as more unpleasant in healthy subjects. A third quality of respiratory discomfort, “chest tightness,” is commonly reported by asthmatics. Dyspnea in an individual patient may well represent a combination of these component sensations and account for the different qualities of dyspnea mentioned previously.
As with all sensations, the experience of dyspnea must result from changes in neural activity within the cortical and subcortical structures of the brain involved in perception. Respiratory-related afferent information from the upper airway, lungs, thoracic cage, and chemoreceptors as well other signals from, for example, exercising limbs and the cardiovascular system provide numerous peripheral inputs relating to cardiorespiratory function. Such information may integrate with central neural respiratory networks, notably in the cerebral cortex, limbic system, and brain stem to generate a range of respiratory sensations. Moreover, these experiences are likely to be modulated by neural traffic related to cognitive, emotional, and nonrespiratory sensory input. The fact that clinical dyspnea can arise with or without deficiencies in gas exchange and in the presence or absence of impaired respiratory mechanics underscores the complexity of this symptom. As indicated earlier, the use of language to identify qualitative variations in dyspnea, perhaps related to different patterns of central neural activation, may lead to a more comprehensive understanding of the origin of dyspnea and better therapeutic strategies for its management in individual patients.
Because dyspnea is a perception, studies on its mechanisms must be confined to humans and are limited by the difficulty of measuring a subjective experience and the neural activity that underlies it. Neuroimaging technologies, principally PET and functional magnetic resonance imaging, allow imaging of brain function associated with sensory, motor, and cognitive processes, and these have been applied to study the neural basis of dyspnea in healthy subjects. Different investigators have induced dyspnea in different ways, with varying degrees of “urge to breathe” and “sense of effort.” Despite this, a consistent pattern of neural activity associated with dyspnea perception is emerging from these studies. Of particular note is the activation of limbic and paralimbic structures, especially the anterior insular cortex, anterior cingulate gyrus, amygdala, and cerebellum. Activation of these phylogenically ancient regions of the brain has been seen in brain imaging studies of pain, thirst, and hunger and is consistent with the idea that dyspnea is a primal experience associated with behaviors intended to counteract a threat to survival. Such studies are difficult to interpret definitively and are not easily generalizable to clinical populations. Nonetheless, neuroimaging techniques are rapidly becoming more sophisticated, and future studies in symptomatic populations offer the potential of a clearer picture of the neural basis of clinical dyspnea.
There is good evidence that the “urge to breathe” component of the dyspnea sensation depends to a large extent on the degree to which respiratory-related neurons in the brain stem are stimulated. Stimulation of ventilation with exercise, hypoxia, hypercapnia, and metabolic acidosis induces dyspnea, whereas a voluntary increase in ventilation induces little dyspnea, even in patients with respiratory mechanical limitation. Moreover, dyspnea is felt strongly when the respiratory neurons are stimulated in the absence of a possible ventilatory response, as with spinal transection and experimental respiratory muscle paralysis. The role of afferent feedback from the lungs and chest wall in the genesis of dyspnea is complex. Conditions thought to activate lung irritant receptors and/or pulmonary C fibers (e.g., pulmonary edema, atelectasis, congestive heart failure) may well contribute to dyspnea via vagal nerve afferents either directly or by modulating other sensory inputs that give rise to dyspnea. Conversely, physiologic activation of slowly adapting stretch receptors during lung inflation may inhibit the central respiratory drive and in this way ameliorate dyspnea. When the desired ventilation and the achieved ventilation are not matched, based on feedback from mechanical and flow (temperature) receptors in the lungs, airways, and chest wall, the intensity of dyspnea increases. The immediate relief of dyspnea observed with thoracic movements following breath-holding but without improvements in blood gas status is consistent with this concept.
In their review of the roles of airway nerves in inflammatory airway disease, Undem and Nassenstein implicate vagal mechanisms in the production of dyspnea, both directly by neural signaling and indirectly by increasing the work of breathing via the release of acetylcholine (which stimulates airway smooth muscle contraction and mucus secretion). Nishino suggested that vagal mechanisms associated with coughing affected the sensation of dyspnea, although the author agreed that other neural mechanisms could play roles. Further support for this comes from the observation in quadriplegic patients, who lack afferent information from the chest wall, that increases in tidal volume reduce the dyspnea from carbon dioxide inhalation without any change in blood gas levels. Moreover, inhaled furosemide, which potentiates slowly adapting stretch receptor activity in an animal model, has been shown to ameliorate the sensation of experimental dyspnea in healthy subjects and exertional dyspnea in COPD patients. With respect to “sense of effort,” proprioceptive feedback from muscle, joint, and metaboreceptors (peripheral afferent nerves that respond to metabolic by-products of skeletal muscle metabolism) probably integrates with the motor cortical output in the genesis of this perception.
In light of the previous discussion, exertional dyspnea in patients with lung disease can be considered a manifestation of the increased central respiratory drive necessary to achieve adequate ventilation by a mechanically constrained respiratory apparatus. This concept fits with the observation that, in COPD patients, progressive hyperinflation is associated with increasing dyspnea because ventilatory demands require greater respiratory muscle activity to overcome increased elastic work at high lung volumes and to offset the foreshortening of inspiratory muscles that places them at a mechanical disadvantage. Furthermore, to the extent that inspiratory capacity is compromised by increases in end-expiratory lung volume in these patients, expected tidal volume and achieved tidal volume are not matched, and dyspnea intensity increases. Following from this, the lessening of dyspnea that follows successful lung volume-reduction surgery, as well as pharmacologic lung volume reduction, is consistent with improvement in both lung and respiratory muscle mechanics. Support of this concept comes from a study showing that a decrease in dyspnea after volume reduction was associated with alleviation of hyperinflation of the lungs and a decrease in neural drive to the diaphragm. Moreover, the concept is supported by the observation that noninvasive ventilatory support during exercise relieves dyspnea in patients with COPD, presumably by reducing the work of breathing and consequently the efferent neural activity to respiratory muscles.
The utility of this concept of dyspneogenesis extends to conditions in which lung disease is not the primary problem. In particular, the dyspnea of heart failure might be accounted for in terms of a heightened respiratory drive secondary to expiratory flow limitation or peripheral muscle dysfunction. A similar phenomenon may arise with deconditioning. The benefits of exercise training for those with dyspnea may be mediated in part by changes in peripheral muscle function. Other conditions in which dyspnea in the absence of lung disease could be accounted for by increased respiratory drive include motor neuron disease/respiratory muscle weakness, late-stage pregnancy, anemia, thyroid disorders, panic disorder, and anxiety.
The sensation of dyspnea, like pain, has a psychological dimension. An individual’s emotional state, personality, previous experience, and cognitive function are likely to influence the experience and reporting of dyspnea. Dyspnea is worse when it is unexpected, when it happens in inappropriate situations, and when it is perceived by the patient to be dangerous. Studies in healthy subjects and in patients with underlying disease have suggested that perception of the intensity of breathlessness may be influenced by prior experience of the sensation. Moreover, both auditory distraction and experimentally induced changes in mood have been shown to increase the unpleasantness of exertional dyspnea in COPD patients. Whether such observations are related to the frequency of prior experience of dyspnea (e.g., with exercise) or to some ill-defined psychological factor is unknown. In patients with the hyperventilation syndrome, both dyspnea and ventilation may dramatically increase in the absence of any known physiologic stimulus to breathe. Dyspnea is a particular problem in patients with panic attacks. An Internet-based survey found that 95% of the respondents reported breathing problems during panic attacks, and 68% reported “remarkable” dyspnea. An interesting example of clinically significant activity-related breathlessness in healthy human pregnancy is reported by Jensen and colleagues. They observed that variability in the perceptual response to exercise could not be explained by variation in central ventilatory drive or in respiratory mechanical/muscular factors, but ultimately reflected a difference in awareness of increased ventilation. The source of that variation in perception is not clear. O’Donnell and coworkers have reviewed the role of “higher center” neural processing on dyspnea perception and its relevance to self-management of this symptom.
In sum, dyspnea may develop when there is (1) increased central respiratory drive secondary to exercise, hypoxia, hypercapnia, or other afferent input; (2) augmented requirement for the respiratory drive to overcome mechanical constraints or weakness; and (3) altered central perception.
Assessment of Dyspnea
Clinicians generally rely on a combination of patients’ reports and physiologic measurements (e.g., forced expiratory volume in 1 second [FEV 1 ]) to evaluate the presence and intensity of dyspnea and its pathologic origins. By assessing the nature and severity of symptoms, such as dyspnea, physicians quickly gain an advantage in the decision-making process. With a better understanding of the physiologic basis of symptoms, physicians can target the types and extent of diagnostic testing as well as the urgency with which a diagnosis must be made. Understanding the mechanisms of dyspnea or the responses to interventions, however, requires objective measurement of the symptom. Although primarily used for clinical investigation, there is increasing interest in applying dyspnea measurements to clinical practice. For a review of factors that limit exercise performance in COPD and the identification of factors that contribute to the variability of dyspnea during exercise, see Stendardi and associates. O’Donnell and coworkers present a hypothetical model for exertional dyspnea based on current neurophysiologic concepts that were developed to explain the origins of “effort,” “air hunger,” and the accompanying affective “distress” response.
Exercise Performance as an Indication of Dyspnea
Exercise testing is commonly used to understand dyspnea better, although there are discrepancies in the available diagnostic algorithms. This form of testing focuses more on physiologic limitations than on the symptoms that limit exercise and might not be necessary for all patient groups. Two widely used field tests are the 6-minute walk distance and shuttle walking tests, which are easy to perform and require minimal equipment; more sophisticated cardiopulmonary exercise testing can be particularly helpful when it is unclear whether the patient is limited by the respiratory or the cardiovascular system. When an exercise test is limited by symptoms, it is important to ask the patient the exact reason for stopping. Although the patient may appear to be in respiratory distress, it is not uncommon that joint pain, leg fatigue or discomfort, or generalized weakness is the actual limiting factor.
Exercise Limitation Due to Dyspnea
Early attempts to evaluate the severity of dyspnea involved patient assessments of their own exercise tolerance (e.g., the five-point Medical Research Council scale and its modified version, the American Thoracic Society scale). Although such scales are simple, they are insensitive, require individuals to make comparisons with others, and cannot readily measure changes following therapeutic interventions. The Baseline Dyspnea Index, a rater-administered test, was developed to rate patients with regard not only to the “magnitude of the task” that elicits dyspnea (e.g., hills compared with level ground) but also to the impact of dyspnea on activities of daily living and the effort required to produce dyspnea. Measurements can be repeated over time or in response to interventions. A number of easy-to-use self-administered questionnaires to assess functional limitation due to dyspnea have been developed but in general have not found widespread use.
Quality of Life and Dyspnea
The negative impact of dyspnea on an individual’s quality of life has been increasingly recognized since the mid-1980s and now is an important outcome measure in studies of therapeutic intervention for COPD/dyspnea. Two questionnaires, the Chronic Respiratory Disease Questionnaire and the St. George’s Respiratory Questionnaire, are used most often. The Chronic Respiratory Disease Questionnaire is a rater-administered questionnaire with 20 items that focus on four aspects of illness: dyspnea, fatigue, emotional function, and the patient’s feeling of control over the disease. Dyspnea is evaluated on a seven-point scale in relation to the five most important activities provoking dyspnea during the previous 2 weeks. In effect, the Chronic Respiratory Disease Questionnaire assesses how breathing sensations alter the quality of the patient’s life. The St. George’s Respiratory Questionnaire is a self-administered questionnaire with 76 items addressing symptoms, activity, and the impact of disease on daily life. Dyspnea is not evaluated specifically but is included with other respiratory symptoms such as cough, sputum, and wheezing. These instruments have been shown to be reproducible, to correlate with each other, and to relate appropriately to physiologic measurements. Although important for clinical investigation, these tools are somewhat demanding to use, often requiring trained health personnel, and are of unproven value for routine clinical care.
Psychometric Measurement of Dyspnea
Several instruments are available for rating the symptom dyspnea directly; they allow reasonably reproducible rating of the intensity of dyspnea on a simple linear or numeric scale during exercise or in response to specific questions. The visual analogue scale (VAS) is a horizontal or vertical line, usually 10 cm long, anchored at either end with words such as “no dyspnea” and “maximal dyspnea” ( Fig. 29-2 ). In response to a question (e.g., “How short of breath are you?”), the subject marks a point along the line so the length reflects the intensity of the sensation. The Borg scale is a 10-point scale with extremes of “nothing at all” and “maximal.” Unlike the visual analogue scale, the Borg scale ( Table 29-1 ) includes verbal descriptors (e.g., “slight,” “severe”) to assist in rating the symptom. Both scales demonstrate good reproducibility, but the proximity of the terms “slight” and “severe” on the Borg scale may reduce its sensitivity and discourage subjects from using the whole scale as they do with the visual analogue scale. A valid approach, which has perhaps better clinical utility, has been to employ a simple numeric rating scale ranging from 0 to 10. Additional scales continue to be developed. Any of these validated instruments may be appropriate when designing research studies, but it is critical that they be administered in a standardized way.
|Rating||Intensity of Sensation|
|0||Nothing at all|
|0.5||Very, very slight (just noticeable)|
|9||Very, very severe (almost maximal)|
Multidimensional Assessment of Dyspnea
There has been a growing focus on extending the assessment of dyspnea beyond the intensity domain to include the qualitative and affective components of this complex symptom. Using a multidimensional approach (modeled on those widely used in pain research), there are now a number of validated instruments that are being used in research and clinical studies. A number of these are referenced in the “Language of Dyspnea” section and have been comprehensively reviewed, in the overall context of dyspnea assessment.
Diagnostic Approach to the Patient with Dyspnea
Overview: Physiologic Categories of Dyspnea
The differential diagnosis of dyspnea includes neuromuscular, renal, endocrine, rheumatologic, hematologic, and psychiatric diseases, as well as diseases of the lungs, heart, and chest wall. The diagnostic approach is determined by the acuity of the problem. For acute dyspnea, the differential diagnosis is relatively narrow, and the cause is generally easily identified (e.g., pneumonia, pulmonary embolism, congestive heart failure, asthma), although psychogenic dyspnea or hyperventilation syndrome can pose a diagnostic challenge. For subacute or chronic dyspnea, a systematic, physiologically based approach enables one to make sense of what otherwise becomes a long list of potential diagnoses.
At its core, the goal of the respiratory and cardiovascular systems is to take oxygen from the air we breathe, transfer it to hemoglobin, deliver it to metabolically active tissue, and transport carbon dioxide, the primary product of metabolism, back to the lung, where it can be eliminated. Dyspnea arises (1) when this goal has not been met and the patient becomes hypoxemic, hypercapnic, and/or acidemic with consequent stimulation of the chemoreceptors; (2) when achieving this goal produces stress within the cardiorespiratory system (e.g., increased work of breathing, inappropriately small tidal volume for a given level of respiratory drive, or elevated left ventricular and pulmonary capillary pressures, secondary to pathologic abnormalities); or (3) when pulmonary receptors (e.g., irritant receptors, again resulting from a pathologic process) are stimulated. Ultimately, one can consider dyspnea as originating from the respiratory or cardiovascular systems, which includes derangements in oxygen delivery, such as in anemia, and problems with uptake and utilization of oxygen, such as in mitochondrial disorders.
To facilitate a systematic approach to this problem, one can divide the process of respiration into three components ( Table 29-2 ):
A controller, which determines the rate and depth of breathing;
A ventilatory pump, which facilitates the movement of gas into and out of the alveolus; and
A gas exchanger, which consists of the pulmonary vasculature and the alveolus.
|VENTILATORY CONTROLLER AND GAS EXCHANGE—INCREASED RESPIRATORY DRIVE|
|Simulation of Chemoreceptors|
|Conditions leading to acute hypoxemia|
|Impaired gas exchange (e.g., asthma, pulmonary embolism, pneumonia, congestive heart failure † )|
|Environmental hypoxia (e.g., altitude, contained space with fire) |
Conditions leading to increased dead space and/or acute hypercapnia
|Impaired gas exchange (e.g., acute, severe asthma, exacerbations of COPD, severe pulmonary edema)|
|Impaired ventilatory pump (see below) (e.g., muscle weakness, airflow obstruction)|
|Renal disease (renal failure, renal tubular acidosis)|
|Decreased oxygen-carrying capacity (e.g., anemia)|
|Decreased release of oxygen to tissues (e.g., hemoglobinopathy)|
|Decreased cardiac output|
|Stimulation of Pulmonary Receptors (Irritant, Mechanical, Vascular) ‡|
|Interstitial lung disease|
|Pleural effusion (atelectasis)|
|Pulmonary vascular disease (e.g., thromboembolism, idiopathic pulmonary hypertension)|
|Congestive heart failure|
|Mild asthma |
Inhalation of toxic gases
|Hyperventilation syndrome, anxiety disorders, panic attacks|
|VENTILATORY PUMP—INCREASED EFFORT OR WORK OF BREATHING|
|Myasthenia gravis, Guillain-Barré syndrome, spinal cord injury, myopathy, postpoliomyelitis syndrome|
|Decreased Compliance of the Chest Wall|
|Severe kyphoscoliosis, obesity, pleural effusion|
|Airflow Obstruction (Includes Increased Resistive Load from Narrowing of Airways and Increased Elastic Load from Hyperinflation)|
|Asthma, COPD, laryngospasm, aspiration of foreign body, bronchitis|
† Heart failure includes both systolic and diastolic dysfunction. Systolic dysfunction may produce dyspnea at rest and with activity. Diastolic dysfunction typically leads to symptoms primarily with exercise. In addition to the mechanisms noted above, systolic heart failure may also produce dyspnea via metaboreceptors; these are receptors that are postulated to lie in muscles and are stimulated by changes in the metabolic milieu of the tissue that result when oxygen delivery does not meet oxygen demand.
Abnormalities in any one of these elements can lead to dyspnea. Similarly, one can consider the derangements of the cardiovascular system within three categories: conditions characterized by high cardiac output, normal cardiac output, and low cardiac output.
Abnormalities of the controller, such as any stimulus of ventilation (e.g., exercise, hypoxia, acidosis, interstitial edema, pulmonary hypertension), may provoke the sensation of dyspnea. Diseases that interfere with the ventilatory pump increase the effort of breathing, whether because of narrowing of the airway or because of a change in the elastic properties of the lungs or chest wall. If the respiratory muscles are weakened, the effort of breathing seems greater because a larger fraction of maximal available muscle force is required. (This is analogous to peripheral muscle function, in which, for example, it would be more difficult to lift a weight after an arm has just been liberated from being in a cast.) Mechanical derangements of the pump also frequently result in inappropriately small tidal volumes. Patients with reduced chest wall compliance or dynamic hyperinflation, which reduces inspiratory capacity as end-expiratory lung volume approaches total lung capacity, commonly complain of air hunger or an unsatisfied inspiration as a consequence of the limited tidal volume. One study described a change in the qualitative descriptors used by patients with COPD from “work and effort” to “unsatisfied inspiration” as dynamic hyperinflation led to increasingly small tidal volume. Abnormalities in the gas exchange functions can lead to increased respiratory drive and resultant dyspnea. Psychological dysfunction may cause or exaggerate dyspnea and is thought to be an alteration in behavioral control of breathing. In many conditions the origin of dyspnea is only partially understood (e.g., pulmonary embolism without hypoxemia) or is due to multiple factors (e.g., abnormalities of the ventilatory pump and gas exchange in a patient with COPD).
A comprehensive medical history is important for uncovering the diagnosis responsible for dyspnea. It is important to identify activities that precipitate it and to understand its impact on the patient’s life. Because decreased exercise tolerance may go unrecognized by the patient owing to alterations in lifestyle that do not tax the respiratory and cardiovascular systems (e.g., a patient who develops dyspnea climbing stairs may move from a two-story house to a single-level apartment), input from close acquaintances may be helpful. Although most patients with severe lung disease report that their activities are limited by dyspnea, some patients are actually more limited by fatigue, weakness, joint pain, or chest pain than by dyspnea. Key questions to ask your patient to localize the cause of exercise limitation include the following: “At the moment you feel you need to stop (walking, jogging, etc.), what is making you stop?” or “If I could fix one thing to enable you to walk more, what would that be?”
The key areas of inquiry are (1) quality of the symptom, (2) persistence or variability of the symptom, and (3) aggravating or precipitating factors leading to the symptom. As noted previously (in “Mechanisms of Dyspnea”), the sensation of “chest tightness” is commonly associated with bronchoconstriction, an increased sense of “effort or work of breathing” is typical of derangements of the ventilatory pump, and a sense of “air hunger” or “urge to breathe” is characteristic of problems that stimulate the respiratory controller (often exacerbated by inappropriately small tidal volume). The sense of difficulty getting a deep breath may be associated with hyperinflation due to obstructive lung disease or with the hyperventilation syndrome.
Intermittent dyspnea is probably due to reversible conditions (e.g., bronchoconstriction, congestive heart failure, pleural effusion, acute pulmonary embolism, hyperventilation syndrome), whereas persistent or progressive dyspnea is more characteristic of chronic conditions (e.g., COPD, interstitial fibrosis, chronic pulmonary embolism, dysfunction of the diaphragm or chest wall). Nocturnal dyspnea may be brought on by asthma, congestive heart failure, gastroesophageal reflux, obstructive sleep apnea, or even nasal obstruction. Dyspnea in the recumbent position (i.e., orthopnea) is classically associated with left ventricular failure but may also be seen with abdominal processes (e.g., ascites) or diaphragmatic dysfunction. Dyspnea that worsens in the upright position (i.e., platypnea) may be related to orthodeoxia, a decrease in arterial P o 2 in the upright position, seen with cirrhosis, pulmonary arteriovenous malformations, or interatrial shunts. Physical activity generally accentuates dyspnea of physiologic origin, as when ventilation is stimulated by lactic acid production at relatively low levels of exercise (e.g., anemia, cardiac disease, deconditioning). Dyspnea after exercise may be affected by a number of factors (e.g., activity, time of day, position, exposures, meals, medications). To the extent that postexercise dyspnea may be mitigated by warm-up activities or use of inhaled bronchodilators, exercise-induced asthma should be considered. Although emotional states may affect dyspnea of any cause, psychogenic dyspnea should be suspected when dyspnea varies on a daily or hourly basis, especially when it is unrelated to exertion or if litigation is involved.
Recognition of factors that may precipitate (e.g., cigarettes, allergens, smog) or relieve (e.g., position, medications) breathlessness is helpful. Obesity may aggravate dyspnea because of increased metabolic and ventilatory demands as well as mechanical interference with chest movement. Severe weight loss may weaken the respiratory muscles. Symptoms of right ventricular failure (e.g., abdominal swelling, edema of the extremities) suggest hypoxemia, pulmonary vascular problems (e.g., pulmonary hypertension of any cause, obstructive sleep apnea), or left ventricular failure. Neuromuscular diseases, such as amyotrophic lateral sclerosis, may present with dyspnea as a result of respiratory muscle weakness. Raynaud phenomenon alone or in combination with skin, joint, or swallowing problems suggests collagen vascular disease.
Pattern of breathing (e.g., splinting, use of pursed lips or accessory muscles), body habitus (e.g., cachexia, obesity), posture (e.g., leaning forward on elbows to recruit pectoralis muscles as ventilatory muscles, as in COPD), skeletal deformity, and emotional state may be important clues to the underlying diagnosis. Cough on deep inspiration or expiration suggests asthma or interstitial lung disease. A generalized decrease in the intensity of breath sounds suggests emphysema or moderate to severe bronchoconstriction, whereas a localized decrease may result from pneumothorax, pleural effusion, localized airway obstruction, or elevated hemidiaphragm of any cause. Forced expiratory maneuvers may elicit focal or diffuse wheezing. Cardiac examination may suggest pulmonary hypertension (e.g., right ventricular heave or prominent P 2 ) or right ventricular failure (e.g., jugular venous distention, right-sided S 3 gallop). Clubbing of the digits is an easily overlooked sign of many processes, notably cancer or purulent lung disease (e.g., bronchiectasis). Cyanosis, a bluish coloration of the perioral region or nails, indicates there are at least 5 g of deoxygenated hemoglobin per 100 mL of blood (note: hypoxemia in the presence of significant anemia may not cause cyanosis because of insufficient hemoglobin). Edema of the lower extremities suggests congestive heart failure if symmetrical and thromboembolic disease if asymmetrical. Assessment of the patient’s emotional status may be helpful.
If a patient’s history includes a report that he or she develops dyspnea walking a short distance (e.g., <200 yards), one should consider walking the patient in a corridor or up a flight of stairs near the examination room to provoke his or her symptoms. When the patient becomes dyspneic, observe the patient, repeat the vital signs, reexamine the chest and heart, and check the oxygen saturation with pulse oximetry. The development of an abrupt increase in heart rate and blood pressure (e.g., pulse pressure product) or onset of basilar crackles or acute wheezing suggests a rapid increase in pulmonary capillary pressure and interstitial edema. Rapid shallow breathing may be a sign of stiff lungs or chest wall. Occasionally the patient will walk farther than one would expect from the history; motivation and the inability of the patient to tolerate any respiratory discomfort may, in fact, be the cause of the patient’s limitation. It is not uncommon for patients who lead extremely sedentary lives, especially if they have been told they have a condition that may cause shortness of breath, to interpret any increase in ventilation as pathologic.
The laboratory is only occasionally of help in the diagnosis of dyspnea. Anemia of any cause may contribute to dyspnea. Polycythemia may be the only clue to chronic hypoxemia. Elevation of the erythrocyte sedimentation rate may suggest occult infection or autoimmune disease. A chemistry panel may reveal occult renal disease or acid-base derangement; elevated serum bicarbonate level may be a clue to the presence of hypercapnia. More elaborate screening may uncover collagen vascular or thyroid disease. Measurement of B-type natriuretic peptide level is finding wide acceptance in refining the differential diagnosis of acute dyspnea, primarily in the emergency department setting, where its use has been shown in a meta-analysis to reduce the duration of hospitalization but not to change other clinical outcomes. The ventricle secretes B-type natriuretic peptide in response to elevated pressure. Therefore it is usually elevated in patients with left ventricular failure or cor pulmonale but not in patients with exacerbations of obstructive lung disease. It has been shown to be more accurate than echocardiography in recognizing left ventricular dysfunction as a cause of acute dyspnea.
The clinical database should include chest radiography, spirometry, and possibly electrocardiography. Chest radiographs are useful when abnormal but are insensitive for detecting early obstructive and interstitial diseases; approximately 10% of patients with interstitial disease will have a normal chest radiograph. Computed tomography pulmonary angiography (CTPA) has become the standard modality for assessment of suspected thromboembolic disease. Although it is not recommended as a general screening test, it can be used to assess for both occult interstitial lung disease and thromboembolic disease in patients with evidence of gas-exchange abnormalities, for example, low diffusing capacity and/or hypoxemia at rest or with exercise (desaturation on exercise oximetry), or pulmonary hypertension on echocardiography.
Spirometry is a useful screening test for both airway and parenchymal disease. Because airway obstruction in asthma may be intermittent, monitoring peak flow at home or in the workplace may be productive. The yield of routine electrocardiography is low, although it may reveal previously unsuspected coronary artery disease, occult valvular disease, or diastolic dysfunction and can suggest pulmonary hypertension (i.e., if signs of right ventricular hypertrophy or tricuspid regurgitation are present). As ultrasound technology has advanced, small hand-held ultrasound machines are increasingly being employed by nonradiologists at the bedside, particularly to assess left ventricular function, central venous pressure, alveolar filling, and pleural effusion.
Special Studies (Including Pulmonary Function Tests)
An array of special studies may be required for the diagnosis of conditions causing dyspnea ( Table 29-3 ). Pulmonary function tests are useful but correlate only moderately with the severity of the dyspnea. In the patient with episodic dyspnea but with normal spirometry results, methacholine inhalation testing can aid in the diagnosis of asthma. Patients who characterize their dyspnea as “chest tightness” are most likely to have positive study results.