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Definition: The American Thoracic Society consensus statement 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, therefore, must be self-reported. In contrast, signs of increased work of breathing, such as tachypnea, accessory muscle use, and intercostal retraction, can be measured and reported by clinicians.
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Epidemiology: Dyspnea is a common, and it has been reported that up to one half of inpatients and one quarter of ambulatory patients experience dyspnea, with a prevalence of 9–13% in the community that increases to as high as 37% for adults aged ≥70 years. Dyspnea is a frequent cause for emergency room visits, accounting for as many as 3–4 million visits per year. Furthermore, it is increasingly appreciated that the degree of dyspnea may better predict outcomes in chronic obstructive pulmonary disease (COPD) than does the forced expiratory volume in 1 s (FEV1), and formal measures of dyspnea have been incorporated into the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 COPD severity assessment guidelines. Dyspnea may also predict outcomes in other chronic heart and lung diseases as well. Dyspnea can arise from a diverse array of pulmonary, cardiac, and neurologic underlying causes, and elucidation of particular symptoms may point toward a specific etiology and/or mechanism driving dyspnea (although additional diagnostic testing is often required as will be further discussed below).
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MECHANISMS UNDERLYING DYSPNEA
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The mechanisms underlying dyspnea are complex, as it can arise from different contributory respiratory sensations. While a large body of research has increased our understanding of mechanisms underlying particular respiratory sensations such as “chest tightness” or “air hunger” it is likely that a given disease state might produce the sensation of dyspnea via more than one underlying mechanism. Dyspnea can arise from a variety of pathways, including generation of afferent signals from the respiratory system to the central nervous system (CNS), efferent signals from the CNS to the respiratory muscles, and particularly when there is a mismatch in the integrative signaling between these two pathways, termed “efferent-reafferent mismatch” (Fig. 33-1).
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Afferent signals trigger the CNS (brainstem and/or cortex) and include primarily: (a) peripheral chemoreceptors in the carotid body and aortic arch and central chemoreceptors in the medulla that are activated by hypoxemia, hypercapnia, or acidemia, and might produce a sense of “air hunger”; and (b) mechanoreceptors in the upper airways, lungs (including stretch receptors, irritant receptors, and J receptors), and chest wall (including muscle spindles as stretch receptors and tendon organs that monitor force generation) that are activated in the setting of an increased work load from a disease state producing an increase in airway resistance that may be associated with symptoms of chest tightness (e.g., asthma or COPD) or decreased lung or chest wall compliance (e.g., pulmonary fibrosis). Other afferent signals that trigger dyspnea within the respiratory system can arise from pulmonary vascular receptor responses to changes in pulmonary artery pressure and skeletal muscle (termed metaboreceptors) that are believed to sense changes in the biochemical environment.
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Efferent signals are sent from the CNS (motor cortex and brainstem) to the respiratory muscles, and are also transmitted by corollary discharge to the sensory cortex that are believed to underlie sensations of respiratory effort (or “work of breathing”) and perhaps contribute to sensations of “air hunger,” especially in response to an increased ventilatory load in a disease state such as COPD. In addition, fear or anxiety may heighten the sense of dyspnea through exacerbating the underlying physiologic disturbance in response to an increased respiratory rate or disordered breathing pattern.
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While it is well appreciated that dyspnea is a difficult quality to reliably measure due to multiple relevant possible domains that can be measured (e.g., sensory-perceptual experience, affective distress, and symptom impact or burden), and there exist no uniformly agreed upon tools for dyspnea assessment, consensus opinion is that dyspnea should be formally assessed in a context most relevant and beneficial for patient management; furthermore, that the specific domains being measured are adequately described. There are a number of emerging tools that have been developed for formal dyspnea assessment. As an example, the GOLD 2017 criteria advocate use of a dyspnea assessment tool such as the Modified Medical Research Council Dyspnea Scale (MMRC, Table 33-1) to assess symptom/impact burden in COPD.
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DIFFERENTIAL DIAGNOSIS
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This chapter focuses largely on chronic dyspnea, which is defined as symptoms lasting longer than 1 month and can arise from a broad array of different underlying conditions, most commonly attributable to pulmonary or cardiac conditions that account for as many as 85% of the underlying causes of dyspnea. However, as many as one-third of patients may have multifactorial reasons underlying dyspnea. Examples of a wide array of conditions that underlie dyspnea with possible mechanisms underlying the presenting symptoms are described in Table 33-2.
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Respiratory system causes include diseases of the airways (e.g., asthma and COPD), diseases of the parenchyma (more commonly interstitial lung diseases are seen in the setting of chronic dyspnea, but alveolar filling processes, such as hypersensitivity pneumonitis or bronchiolitis obliterans organizing pneumonia [BOOP], can also present with similar symptoms), diseases affecting the chest wall (e.g., bony abnormalities such as kyphoscoliosis, or neuromuscular weakness conditions such as amyotrophic lateral sclerosis), and diseases affecting the pulmonary vasculature (e.g., pulmonary hypertension that can arise from a variety of underlying causes, or chronic thromboemolic disease). Diseases affecting the cardiovascular system that can present with dyspnea include processes affecting left heart function, such as coronary artery disease and cardiomyopathy, as well as disease processes affecting the pericardium, including restrictive pericarditis and cardiac tamponade. Other conditions underyling dyspnea that might not directly emanate from the pulmonary or cardiovascular systems include anemia (thereby potentially affecting oxygen-carrying capacity), deconditioning, and psychological processes such as anxiety. Distinguishing between the myriad of underlying processes that might present with dyspnea can be challenging. A graded approach that begins with a history and physical examination, followed by selected laboratory testing that might then advance to additional diagnostics and potentially subspecialty referral may help elucidate the underlying cause of dyspnea. However, a substantial proportion of patients may have persistent dyspnea despite treatment for an underlying process, or may not have a specific underlying process identified that is driving the dyspnea.
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APPROACH TO THE PATIENT
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APPROACH TO THE PATIENT Dyspnea OVERALL
For patients with a known prior pulmonary, cardiac, or neuromuscular condition and worsening dyspnea, the initial focus of the evaluation will usually address determining whether the known condition has progressed or whether a new process has developed that is causing dyspnea (See Fig. 33-2). For patients without a prior known potential cause of dyspnea, the initial evaluation will focus on determining an underlying etiology. Determining the underlying cause, if possible, is extremely important, as the treatment may vary dramatically based upon the predisposing condition. An initial history and physical examination remain fundamental to the evaluation followed by initial diagnostic testing as indicated that might prompt subspecialty referral (e.g., pulmonary, cardiology, neurology, sleep, and/or specialized dyspnea clinic) if the cause of dyspnea remains elusive (Fig. 33-2). As many as two-thirds of patients will require diagnostic testing beyond the initial clinical presentation.
HISTORY The patient should be asked to describe in his/her own words what the discomfort feels like as well as the effect of position, infections, and environmental stimuli on the dyspnea, as descriptors may be helpful in pointing toward an etiology. For example, symptoms of chest tightness might suggest the possibility of bronchoconstriction, and the sensation of inability to take a deep breath may correlate with dynamic hyperinflation from COPD. Orthopnea is a common indicator of congestive heart failure (CHF), mechanical impairment of the diaphragm associated with obesity, or asthma triggered by esophageal reflux. Nocturnal dyspnea suggests CHF or asthma. Acute, intermittent episodes of dyspnea are more likely to reflect episodes of myocardial ischemia, bronchospasm, or pulmonary embolism, while chronic persistent dyspnea is more typical of COPD, interstitial lung disease, and chronic thromboembolic disease. Information on risk factors for drug-induced or occupational lung disease and for coronary artery disease should be elicited. Left atrial myxoma or hepatopulmonary syndrome should be considered when the patient complains of platypnea—i.e., dyspnea in the upright position with relief in the supine position.
PHYSICAL EXAMINATION Initial vital signs might be helpful in pointing toward an underlying etiology in the context of the remainder of the evaluation. For example, the presence of fever might point toward an underlying infectious or inflammatory process; the presence of hypertension in the setting of a heart failure might point toward diastolic dysfunction; the presence of tachycardia might be associated with many different underlying processes including fever, cardiac dysfunction, and deconditioning; and the presence of resting hypoxemia suggests processes involving hypercapnia, ventilation-perfusion mismatch, shunt, or impairment in diffusion capacity might be involved. An exertional oxygen saturation should also be obtained as described below. The physical examination should begin during the interview of the patient. Inability of the patient to speak in full sentences before stopping to get a deep breath suggests a condition that leads to stimulation of the controller or impairment of the ventilatory pump with reduced vital capacity. Evidence of increased work of breathing (supraclavicular retractions; use of accessory muscles of ventilation; and the tripod position, characterized by sitting with the hands braced on the knees) is indicative of increased airway resistance or stiffness of the lungs and the chest wall. When measuring the vital signs, the physician should accurately assess the respiratory rate and measure the pulsus paradoxus (Chap. 265); if the systolic pressure decreases by >10 mmHg, the presence of COPD, acute asthma, or pericardial disease should be considered. During the general examination, signs of anemia (pale conjunctivae), cyanosis, and cirrhosis (spider angiomata, gynecomastia) should be sought. Examination of the chest should focus on symmetry of movement; percussion (dullness is indicative of pleural effusion; hyperresonance is a sign of emphysema); and auscultation (wheezes, rhonchi, prolonged expiratory phase, and diminished breath sounds are clues to disorders of the airways; rales suggest interstitial edema or fibrosis). The cardiac examination should focus on signs of elevated right heart pressures (jugular venous distention, edema, accentuated pulmonic component to the second heart sound); left ventricular dysfunction (S3 and S4 gallops); and valvular disease (murmurs). When examining the abdomen with the patient in the supine position, the physician should note whether there is paradoxical movement of the abdomen as well as the presence of increased respiratory distress in the supine position: inward motion during inspiration is a sign of diaphragmatic weakness, and rounding of the abdomen during exhalation is suggestive of pulmonary edema. Clubbing of the digits may be an indication of interstitial pulmonary fibrosis or bronchiectasis, and joint swelling or deformation as well as changes consistent with Raynaud’s disease may be indicative of a collagen-vascular process that can be associated with pulmonary disease.
Patients should be asked to walk under observation with oximetry in order to reproduce the symptoms. The patient should be examined during and at the end of exercise for new findings that were not present at rest (e.g., presence of wheezing), and for changes in oxygen saturation.
CHEST IMAGING After the history elicitation and the physical examination, a chest radiograph should be obtained if the diagnosis remains elusive. The lung volumes should be assessed: hyperinflation is consistent with obstructive lung disease, whereas low lung volumes suggest interstitial edema or fibrosis, diaphragmatic dysfunction, or impaired chest wall motion. The pulmonary parenchyma should be examined for evidence of interstitial disease, infiltrates, and emphysema. Prominent pulmonary vasculature in the upper zones indicates pulmonary venous hypertension, while enlarged central pulmonary arteries may suggest pulmonary arterial hypertension. An enlarged cardiac silhouette can point toward dilated cardiomyopathy or valvular disease. Bilateral pleural effusions are typical of CHF and some forms of collagen-vascular disease. Unilateral effusions raise the specter of carcinoma and pulmonary embolism but may also occur in heart failure or in the case of a parapneumonic effusion. CT of the chest is generally reserved for further evaluation of the lung parenchyma (interstitial lung disease) and possible pulmonary embolism if there remains diagnostic uncertainty.
LABORATORY STUDIES Initial laboratory testing should include a hematocrit to exclude occult anemia as an underlying cause of reduced oxygen-carrying capacity contributing to dyspnea, and a basic metabolic panel may be helpful to exclude a significant underlying metabolic acidosis (and conversely, an elevated bicarbonate might point toward the possibility of carbon dioxide retention that might be seen in chronic respiratory failure—in such a setting, an arterial blood gas may provide useful additional information). Additional laboratory studies should include electrocardiography to seek evidence of ventricular hypertrophy and prior myocardial infarction and spirometry that can be diagnostic of the presence of an obstructive ventilatory defect, and suggest the possibility of a restrictive ventilatory defect (that then might prompt additional pulmonary function laboratory testing, including lung volumes, diffusion capacity, and possible tests of neuromuscular function). Echocardiography is indicated when systolic dysfunction, pulmonary hypertension, or valvular heart disease is suspected. Bronchoprovocation testing and/or home peak-flow monitoring may be useful in patients with intermittent symptoms suggestive of asthma who have a normal physical examination and spirometry; up to one-third of patients with the clinical diagnosis of asthma do not have reactive airways disease when formally tested. Measurement of brain natriuretic peptide levels in serum is increasingly used to assess for CHF in patients presenting with acute dyspnea but may be elevated in the presence of right ventricular strain as well.
DISTINGUISHING CARDIOVASCULAR FROM RESPIRATORY SYSTEM DYSPNEA If a patient has evidence of both pulmonary and cardiac disease that is either not responsive to treatment, or it remains unclear what factors are primarily driving dyspnea, a cardiopulmonary exercise test (CPET) can be carried out to determine which system is responsible for the exercise limitation. CPET includes incremental symptom-limited exercise (cycling or treadmill) with measurements of ventilation and pulmonary gas exchange, and in some cases includes non-invasive and invasive measures of pulmonary vascular pressures and cardiac output. If, at peak exercise, the patient achieves predicted maximal ventilation, demonstrates an increase in dead space or hypoxemia, or develops bronchospasm, the respiratory system may be the cause of the problem. Alternatively, if the heart rate is >85% of the predicted maximum, if the anaerobic threshold occurs early, if the blood pressure becomes excessively high or decreases during exercise, if the O2 pulse (O2 consumption/heart rate, an indicator of stroke volume) falls, or if there are ischemic changes on the electrocardiogram, an abnormality of the cardiovascular system is likely the explanation for the breathing discomfort. Additionally, a CPET may also help point toward a peripheral extraction deficit, or metabolic/neuromuscular disease as potential underlying processes driving dyspnea.
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TREATMENT Dyspnea
The first goal is to correct the underlying condition(s) driving dyspnea and address potentially reversible causes with appropriate treatment for the particular condition. Multiple different interventions may be necessary, given that dyspnea often arises from multifactorial causes. If relief of dyspnea with treatment of the underlying condition(s) is not fully possible, an effort is made to lessen the intensity of the symptom and its effect on the patient’s quality of life. Despite an increased understanding of the mechanisms underlying dyspnea, there has been limited progress in treatment strategies for dyspnea. Supplemental O2 should be administered if the resting O2 saturation is ≤88% or if the patient’s saturation drops to these levels with activity or sleep. In particular, for patients with COPD, supplemental oxygen for those with hypoxemia has been shown to improve mortality, and pulmonary rehabilitation programs have demonstrated positive effects on dyspnea, exercise capacity, and rates of hospitalization. Opioids have been shown to reduce symptoms of dyspnea, largely through reducing air hunger, thus, likely suppressing respiratory drive and influencing cortical activity. However, opioids should be considered for each patient individually based upon the risk-benefit profile as regards the effects of respiratory depression. Studies of anxiolytics for dyspnea have not demonstrated consistent benefit. Additional approaches are under study for dyspnea, including inhaled furosemide that might alter afferent sensory information.
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ACKNOWLEDGMENT
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With prior contributions from Richard M. Schwartzstein.