Chapter 39: Dyspnea¶

Alterations in Circulatory and Respiratory Functions · Part 2 – Cardinal Manifestations & Presentation

Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition

🔑 Key Clinical Points¶

The American Thoracic Society defines dyspnea as a 'subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.'
Dyspnea prevalence is 9–13% in the community, increasing to 37% in adults aged ≥70 years.
Dyspnea may predict outcomes in COPD better than FEV1 and is incorporated into GOLD guidelines.
Supplemental O2 is indicated if resting O2 saturation is ≤88% or if saturation drops to these levels with activity or sleep.
Platypnea (dyspnea in upright position with relief in supine) suggests left atrial myxoma or hepatopulmonary syndrome.
Pulsus paradoxus (>10 mmHg decrease in systolic pressure on inspiration) suggests COPD, acute asthma, or pericardial disease.
Clubbing of digits indicates interstitial pulmonary fibrosis or bronchiectasis.
Chronic breathlessness syndrome is defined as breathlessness persisting despite optimal treatment of underlying pathophysiology.
Opioids may reduce dyspnea symptoms but should be considered individually based on risk-benefit profile regarding respiratory depression.
Cardiopulmonary exercise testing (CPET) distinguishes respiratory from cardiovascular causes based on peak ventilation, dead space, and anaerobic threshold.

📑 Table of Contents¶

1. DEFINITION & OVERVIEW
1.1 Symptom vs. Sign
2. EPIDEMIOLOGY
3. ETIOLOGY & PATHOPHYSIOLOGY
3.1 Receptor Biology
4. CLINICAL FEATURES
4.1 Severity Grading
5. DIFFERENTIAL DIAGNOSIS
5.1 Pulmonary Causes
5.2 Cardiac Causes
5.3 Other Causes
6. INVESTIGATIONS & DIAGNOSIS
6.1 Diagnostic Algorithm
7. MANAGEMENT & TREATMENT
7.1 Pharmacologic Therapy
8. PROGNOSIS & COMPLICATIONS
9. SPECIAL CONSIDERATIONS
10. KEY PEARLS & CLINICAL TRAPS
Flowcharts & Algorithms
Figures & Illustrations

📋 Figures in This Chapter¶

#	Type	Description
1	🔀 Flowchart	Possible algorithm for the evaluation of the patient with dyspnea
1	🖼 Figure	Potential signaling pathways underlying the sensation of dyspnea

1. DEFINITION & OVERVIEW¶

📖 Harrison's defines this as:

'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.'

Dyspnea is a symptom perceived only by the person experiencing it and must be self-reported.
Signs of increased work of breathing (tachypnea, accessory muscle use, intercostal retraction) can be measured and reported by clinicians.
Dyspnea can arise from a diverse array of pulmonary, cardiac, and neurologic underlying causes.
Elucidation of particular symptoms may point toward a specific etiology and/or mechanism driving dyspnea, although additional diagnostic testing is often required.

1.1 Symptom vs. Sign¶

Symptom: Subjective experience of breathing discomfort.
Sign: Measurable indicators of increased work of breathing.
Examples of signs: Tachypnea, accessory muscle use, intercostal retraction.

2. EPIDEMIOLOGY¶

Prevalence: Up to one-half of inpatients and one-quarter of ambulatory patients experience dyspnea.
Community prevalence: 9–13%.
Elderly prevalence: Increases to as high as 37% for adults aged ≥70 years.
Emergency Department: Frequent cause of ER visits, accounting for as many as 3–4 million visits per year.
COPD Outcomes: Degree of dyspnea may better predict outcomes in COPD than forced expiratory volume in 1 s (FEV1).
Global Initiative: Formal measures of dyspnea incorporated into Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD severity assessment guidelines.
Other Diseases: Dyspnea may also predict outcomes in other chronic heart and lung diseases.
Post-COVID: Dyspnea incidence increased in the setting of the SARS-CoV-2 pandemic; persistent symptoms in many patients (Chap. 205).
Multifactorial: As many as one-third of patients may have multifactorial reasons underlying dyspnea.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

Mechanisms: Complex, can arise from different contributory respiratory sensations.
Disease State: Might produce the sensation of dyspnea via more than one underlying mechanism.
Pathways: 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.
Afferent Signals: Trigger the CNS (brainstem and/or cortex).
Chemoreceptors: Peripheral chemoreceptors in the carotid body and aortic arch and central chemoreceptors in the medulla activated by hypoxemia, hypercapnia, or acidemia; might produce a sense of 'air hunger'.
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).
Mechanoreceptor Activation: Activated in the setting of an increased workload 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).
Metaboreceptors: In skeletal muscle; believed to sense changes in the biochemical environment.
Pulmonary Vascular Receptors: Responses to changes in pulmonary artery pressure.
Efferent Signals: Sent from the CNS (motor cortex and brainstem) to the respiratory muscles and are also transmitted by corollary discharge to the sensory cortex.
Efferent Function: 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.
Psychological Factors: Fear or anxiety may heighten the sense of dyspnea by exacerbating the underlying physiologic disturbance in response to an increased respiratory rate or disordered breathing pattern.

3.1 Receptor Biology¶

Peripheral chemoreceptors: Carotid body and aortic arch.
Central chemoreceptors: Medulla.
Mechanoreceptors: Upper airways, lungs, chest wall.
Metaboreceptors: Skeletal muscle.
Pulmonary vascular receptors: Pulmonary artery pressure.

4. CLINICAL FEATURES¶

Symptoms: Chest tightness, air hunger, inability to get a deep breath, tachypnea, increased work of breathing (WOB), exertional hypoxemia.
Signs: Wheezing, accessory muscle use, supraclavicular retractions, use of accessory muscles of ventilation, tripod position, wet crackles on lung examination, dry end-inspiratory crackles, clubbing.
Temporal Course: Chronic dyspnea defined as symptoms lasting longer than 1 month.
Acute Episodes: More likely to reflect episodes of myocardial ischemia, bronchospasm, or pulmonary embolism.
Positional: Orthopnea (indicator of CHF, mechanical impairment of diaphragm associated with obesity, or asthma triggered by esophageal reflux).
Nocturnal: Suggests CHF or asthma.
Platypnea: Dyspnea in the upright position with relief in the supine position.
Severity Grading: Modified Medical Research Council Dyspnea Scale (Table 39-1).
Speech: Inability 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.

Table 1 — Table 39-1 An Example of a Clinical Method for Rating Dyspnea: The Modified Medical Research Council Dyspnea Scale¶

GRADE OF DYSPNEA	DESCRIPTION
0	Not troubled by breathlessness, except with strenuous exercise
1	Shortness of breath walking on level ground or with walking up a slight hill
2	Walks slower than people of similar age on level ground due to breathlessness, or has to stop to rest when walking at own pace on level ground
3	Stops to rest after walking 100 m or after walking a few minutes on level ground
4	Too breathless to leave the house, or breathless with activities of daily living (e.g., dressing/undressing)

4.1 Severity Grading¶

Modified Medical Research Council Dyspnea Scale (Table 39-1).
Grade 0: Not troubled by breathlessness, except with strenuous exercise.
Grade 1: Shortness of breath walking on level ground or with walking up a slight hill.
Grade 2: Walks slower than people of similar age on level ground due to breathlessness, or has to stop to rest when walking at own pace on level ground.
Grade 3: Stops to rest after walking 100 m or after walking a few minutes on level ground.
Grade 4: Too breathless to leave the house, or breathless with activities of daily living (e.g., dressing/undressing).
Integration: This scale has been integrated into the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines clinical classification scheme.

5. DIFFERENTIAL DIAGNOSIS¶

Distinguishing among the myriad of underlying processes that might present with dyspnea can be challenging.
Graded approach: History and physical examination, followed by initial diagnostic testing that might prompt subspecialty referral if the cause of dyspnea remains elusive.
Underlying Causes: Pulmonary or cardiac conditions that account for as many as 85% of the underlying causes of dyspnea.
Multifactorial: As many as one-third of patients may have multifactorial reasons underlying dyspnea.
Post-COVID: Increasing number of individuals suffering from dyspnea as part of a post-COVID syndrome.
Table 39-2: Differential Diagnosis of Disease Processes Underlying Dyspnea.

Table 2 — Table 39-2 Differential Diagnosis of Disease Processes Underlying Dyspnea¶

SYSTEM	TYPE OF PROCESS	EXAMPLE OF DISEASE PROCESS	POSSIBLE PRESENTING DYSPNEA SYMPTOMS	POSSIBLE PHYSICAL FINDINGS	POSSIBLE MECHANISMS UNDERLYING DYSPNEA	INITIAL DIAGNOSTIC STUDIES (AND POSSIBLE FINDINGS)
Pulmonary	Airways disease	Asthma, COPD, upper airway obstruction	Chest tightness, tachypnea, increased WOB, air hunger, inability to get a deep breath	Wheezing, accessory muscle use, exertional hypoxemia (especially with COPD)	Increased WOB, hypoxemia, hypercapnia, stimulation of pulmonary receptors	Peak flow (reduced); spirometry (OVD); CXR (hyperinflation; loss of lung parenyma in COPD), chest CT and airway examination for upper airway obstruction
Pulmonary	Parenchymal disease	Interstitial lung disease	Air hunger, inability to get a deep breath	Dry end-inspiratory crackles, clubbing, exertional hypoxemia	Increased WOB, increased respiratory drive, hypoxemia, hypercapnia, stimulation of pulmonary receptors	Spirometry and lung volumes (RVD); CXR and chest CT (interstitial lung disease)
Pulmonary	Chest wall disease	Kyphoscoliosis, neuromuscular (NM) weakness	Increased WOB, inability to get a deep breath	Decreased diaphragm excursion; atelectasis	Increased WOB; stimulation of pulmonary receptors (if atelectasis is present)	Spirometry and lung volumes (RVD); MIP and MEPs (reduced in NM weakness)
Pulmonary	Pulmonary vasculature	Pulmonary hypertension	Tachypnea	Elevated right heart pressures, exertional hypoxemia	Increased respiratory drive, hypoxemia, stimulation of vascular receptors	Diffusion capacity (reduced); ECG; ECHO, RHC (to evaluate pulmonary artery pressures)
Cardiac	Left heart failure	Coronary artery disease, cardiomyopathy	Chest tightness, air hunger	Elevated left heart pressures; wet crackles on lung examination; pulsus paradoxus (pericardial disease)	Increased WOB and drive, hypoxemia, stimulation of vascular and pulmonary receptors	Consider BNP testing, especially in the acute setting; ECG, ECHO, may need stress testing and/or LHC
Cardiac	Pericardial disease	Constrictive pericarditis; cardiac tamponade	Chest tightness, air hunger	Elevated left heart pressures; wet crackles on lung examination; pulsus paradoxus (pericardial disease)	Increased WOB and drive, hypoxemia, stimulation of vascular and pulmonary receptors	Consider BNP testing, especially in the acute setting; ECG, ECHO, may need stress testing and/or LHC
Other	Variable	Anemia	Exertional breathlessness	Variable	Metaboreceptors (anemia, poor fitness)	Hematocrit for anemia; laboratory studies (e.g., metabolic panel, thyroid hormone testing for metabolism from poor fitness); consider upper gastrointestinal endoscopy and/or esophageal pH probe testing for GERD and concerns for aspiration; consider referral to post-COVID care center for persistent symptoms after COVID infection; exclude other causes
Other	Variable	Deconditioning	Poor fitness	Variable	Chemoreceptors (anaerobic metabolism from poor fitness)	Hematocrit for anemia; laboratory studies (e.g., metabolic panel, thyroid hormone testing for metabolism from poor fitness); consider upper gastrointestinal endoscopy and/or esophageal pH probe testing for GERD and concerns for aspiration; consider referral to post-COVID care center for persistent symptoms after COVID infection; exclude other causes
Other	Variable	Psychological	Anxiety	Variable	Chemoreceptors (anaerobic metabolism from poor fitness)	Hematocrit for anemia; laboratory studies (e.g., metabolic panel, thyroid hormone testing for metabolism from poor fitness); consider upper gastrointestinal endoscopy and/or esophageal pH probe testing for GERD and concerns for aspiration; consider referral to post-COVID care center for persistent symptoms after COVID infection; exclude other causes
Other	Variable	Metabolic disturbances	Variable	Variable	Metaboreceptors (anemia, poor fitness); chemoreceptors (anaerobic metabolism from poor fitness)	Hematocrit for anemia; laboratory studies (e.g., metabolic panel, thyroid hormone testing for metabolism from poor fitness); consider upper gastrointestinal endoscopy and/or esophageal pH probe testing for GERD and concerns for aspiration; consider referral to post-COVID care center for persistent symptoms after COVID infection; exclude other causes
Other	Variable	Gastrointestinal (e.g., gastroesophageal reflux disease [GERD], aspiration pneumonitis)	Variable	Variable	Metaboreceptors (anemia, poor fitness); chemoreceptors (anaerobic metabolism from poor fitness)	Hematocrit for anemia; laboratory studies (e.g., metabolic panel, thyroid hormone testing for metabolism from poor fitness); consider upper gastrointestinal endoscopy and/or esophageal pH probe testing for GERD and concerns for aspiration; consider referral to post-COVID care center for persistent symptoms after COVID infection; exclude other causes
Other	Variable	Post-COVID syndrome	Variable	Variable	Metaboreceptors (anemia, poor fitness); chemoreceptors (anaerobic metabolism from poor fitness)	Hematocrit for anemia; laboratory studies (e.g., metabolic panel, thyroid hormone testing for metabolism from poor fitness); consider upper gastrointestinal endoscopy and/or esophageal pH probe testing for GERD and concerns for aspiration; consider referral to post-COVID care center for persistent symptoms after COVID infection; exclude other causes

5.1 Pulmonary Causes¶

Airways disease: Asthma, COPD, upper airway obstruction.
Parenchymal disease: Interstitial lung disease.
Chest wall disease: Kyphoscoliosis, neuromuscular (NM) weakness.
Pulmonary vasculature: Pulmonary hypertension.

5.2 Cardiac Causes¶

Left heart failure: Coronary artery disease, cardiomyopathy.
Pericardial disease: Constrictive pericarditis; cardiac tamponade.

5.3 Other Causes¶

Variable: Anemia, Deconditioning, Psychological, Metabolic disturbances, Gastrointestinal (e.g., gastroesophageal reflux disease [GERD], aspiration pneumonitis), Post-COVID syndrome.
Anemia: Exertional breathlessness.
Deconditioning: Poor fitness.
Psychological: Anxiety.
Metabolic: Anaerobic metabolism from poor fitness.
Gastrointestinal: Increased sensitivity to hypercapnia.

6. INVESTIGATIONS & DIAGNOSIS¶

History: Patient should be asked to describe in their own words what the discomfort feels like as well as the effect of position, infections, and environmental stimuli on the dyspnea.
Physical Exam: Inability 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.
Work of Breathing: 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.
Vital Signs: Accurately assess the respiratory rate and measure the pulsus paradoxus.
Pulsus Paradoxus: If the systolic pressure decreases by >10 mmHg on inspiration, the presence of COPD, acute asthma, or pericardial disease should be considered.
General Exam: Signs of anemia (pale conjunctivae), cyanosis, and cirrhosis (spider angiomata, gynecomastia) should be sought.
Chest Exam: Symmetry of movement; percussion (dullness is indicative of pleural effusion; hyperresonance is a sign of pneumothorax and emphysema); auscultation (wheezes, rhonchi, prolonged expiratory phase, and diminished breath sounds are clues to disorders of the airways; rales suggest interstitial edema or fibrosis).
Cardiac Exam: 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).
Abdomen: 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.
Digits: 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.
Walking Oximetry: Patients should be asked to walk under observation with oximetry in order to reproduce the symptoms.
Exercise Exam: Patients 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: Chest radiograph should be obtained if the diagnosis remains elusive.
Lung Volumes: Hyperinflation is consistent with obstructive lung disease, whereas low lung volumes suggest interstitial edema or fibrosis, diaphragmatic dysfunction, or impaired chest wall motion.
Parenchyma: Examine for evidence of interstitial disease, infiltrates, and emphysema.
Vasculature: Prominent pulmonary vasculature in the upper zones indicates pulmonary venous hypertension, while enlarged central pulmonary arteries may suggest pulmonary arterial hypertension.
Cardiac Silhouette: Enlarged cardiac silhouette can point toward dilated cardiomyopathy or valvular disease.
Pleural Effusions: 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: CT of the chest is generally reserved for further evaluation of the lung parenchyma (e.g., interstitial lung disease) and possible pulmonary embolism (with CT angiography) if diagnostic uncertainty remains.
Laboratory: Initial laboratory testing should include a hematocrit to exclude occult anemia as an underlying cause of reduced oxygen-carrying ability 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).
ECG: Additional laboratory studies should include electrocardiography to seek evidence of ventricular hypertrophy and prior myocardial infarction.
Spirometry: Spirometry, which 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: Indicated when systolic dysfunction, pulmonary hypertension, or valvular heart disease is suspected.
BNP: 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.
Bronchoprovocation: 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.
Algorithm: Possible algorithm for the evaluation of the patient with dyspnea (Fig. 39-2).
CPET: If a patient has evidence of both pulmonary and cardiac disease that is not responsive to treatment or it remains unclear what factors are primarily driving the dyspnea, a cardiopulmonary exercise test (CPET) can be conducted to determine which system is responsible for the exercise limitation.
CPET Criteria: CPET includes incremental symptom-limited exercise (cycling or treadmill) with measurements of ventilation and pulmonary gas exchange and, in some cases, includes noninvasive and invasive measures of pulmonary vascular pressures and cardiac output.
Respiratory Cause: 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.
Cardiovascular Cause: 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.
Other Causes: Additionally, a CPET may also help point toward a peripheral extraction deficit or metabolic/neuromuscular disease as potential underlying processes driving dyspnea.

6.1 Diagnostic Algorithm¶

Step 1: History and physical examination.
Step 2: Walking oximetry, Peak flow assessment.
Step 3: Diagnosis obtained? Treat.
Step 4: If No -> Further testing ('Phase 1'): Chest x-ray, Initial vital signs, CBC, basic metabolic panel, ECG, Spirometry.
Step 5: Diagnosis obtained? Treat.
Step 6: If No -> Further testing ('Phase 2'): Chest CT (consider angiography for thromboembolic disease), Lung volumes, DLCO, tests of neuromuscular function, Echocardiogram, cardiac stress testing.
Step 7: Diagnosis obtained? Treat.
Step 8: If No -> Further testing ('Phase 3'): Consider cardiopulmonary exercise testing (and subspecialty referral).
Note: As many as two-thirds of patients will require diagnostic testing beyond the initial clinical presentation.

7. MANAGEMENT & TREATMENT¶

Goal: Correct the underlying condition(s) driving dyspnea and address potentially reversible causes with appropriate treatment for the particular condition.
Multifactorial: Multiple different interventions may be necessary, given that dyspnea often arises from multifactorial causes.
Refractory: 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.
Chronic Breathlessness Syndrome: In 2017, an international group of experts defined 'chronic breathlessness syndrome' as 'the experience of breathlessness that persists despite optimal treatment of the underlying pathophysiology and results in disability for the patient.'
Supplemental Oxygen: 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.
COPD: For patients with COPD, supplemental oxygen for those with hypoxemia has been shown to improve mortality.
Pulmonary Rehabilitation: Pulmonary rehabilitation programs (including some home and community-based exercise programs such as yoga and Tai Chi) have demonstrated positive effects on dyspnea, exercise capacity, and rates of hospitalization.
Post-COVID: More recent studies have suggested that supervised exercise programs similarly improved outcomes in post-COVID conditions.
Opioids: Opioids have been shown in some studies to reduce symptoms of dyspnea, largely through reducing air hunger, thus likely suppressing respiratory drive and influencing cortical activity.
Opioid Dosing: However, a recent study did not support the benefit of two different doses of daily low-dose extended-release morphine in COPD, for which reason opioids should be considered for each patient individually based on the risk-benefit profile in regard to respiratory depression.
Anxiolytics: Studies of anxiolytics for dyspnea have not demonstrated consistent benefit.

7.1 Pharmacologic Therapy¶

Opioids: Reduce symptoms of dyspnea, largely through reducing air hunger.
Mechanism: Suppressing respiratory drive and influencing cortical activity.
Risk: Respiratory depression.
Recommendation: Consider for each patient individually based on the risk-benefit profile.
Anxiolytics: Not demonstrated consistent benefit.

8. PROGNOSIS & COMPLICATIONS¶

COPD: Degree of dyspnea may better predict outcomes in COPD than FEV1.
Persistent Dyspnea: As many as one-third of patients may have multifactorial reasons underlying dyspnea, with an increasing number of individuals suffering from dyspnea as part of a post-COVID syndrome.
Chronic Breathlessness Syndrome: Defined as breathlessness persisting despite optimal treatment of the underlying pathophysiology and results in disability.
Hospitalization: Pulmonary rehabilitation programs have demonstrated positive effects on rates of hospitalization.

9. SPECIAL CONSIDERATIONS¶

Post-COVID: Increasing number of individuals suffering from dyspnea as part of a post-COVID syndrome.
Rehabilitation: Pulmonary rehabilitation programs (including some home and community-based exercise programs such as yoga and Tai Chi) have demonstrated positive effects on dyspnea, exercise capacity, and rates of hospitalization.
Post-COVID Exercise: More recent studies have suggested that supervised exercise programs similarly improved outcomes in post-COVID conditions.

10. KEY PEARLS & CLINICAL TRAPS¶

Platypnea: Dyspnea in the upright position with relief in the supine position suggests left atrial myxoma or hepatopulmonary syndrome.
Pulsus Paradoxus: Systolic pressure decreases by >10 mmHg on inspiration suggests COPD, acute asthma, or pericardial disease.
Clubbing: Digits may be an indication of interstitial pulmonary fibrosis or bronchiectasis.
Orthopnea: 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 Episodes: More likely to reflect episodes of myocardial ischemia, bronchospasm, or pulmonary embolism.
Vital Signs: 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.
CXR Findings: Hyperinflation is consistent with obstructive lung disease, whereas low lung volumes suggest interstitial edema or fibrosis, diaphragmatic dysfunction, or impaired chest wall motion.
Pleural Effusions: 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.
CPET Interpretation: 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 falls, or if there are ischemic changes on the electrocardiogram, an abnormality of the cardiovascular system is likely the explanation for the breathing discomfort.

Flowcharts & Algorithms¶

Reproduced from Harrison's 22nd Edition.

Flowchart 1¶

Possible algorithm for the evaluation of the patient with dyspnea

Caption: FIGURE 39-2 Possible algorithm for the evaluation of the patient with dyspnea. As described in the text, the approach should begin with a detailed history and physical examination, followed by progressive testing and ultimately more invasive testing and subspecialty referral as is indicated to determine the underlying cause of dyspnea. CBC, complete blood count; DLCO, diffusing capacity of the lungs for carbon monoxide; ECG, electrocardiogram. (Adapted from NG Karnani et al: Am Fam Physician 71:1529, 2005.)

Figures & Illustrations¶

Reproduced from Harrison's 22nd Edition.

Figure 1¶

Potential signaling pathways underlying the sensation of dyspnea

Caption: FIGURE 39-1 Potential signaling pathways underlying the sensation of dyspnea. (examples in pink boxes include hypoxemia, hypercapnia, acidemia, increase in airway are mediated via relevant receptors (examples in yellow boxes include central arch; mechanoreceptors in upper airways, lungs, and chest wall; and metaboreceptors Efferent signals are sent from the brainstem and motor cortex to the respiratory generated by these signals are indicated in italics. — FIGURE 39-1 Potential signaling pathways underlying the sensation of dyspnea. Dyspnea is a complex sensation that can arise from a variety of physiologic stimuli (examples in pink boxes include hypoxemia, hypercapnia, acidemia, increase in airway resistance, and decrease in lung and/or chest wall compliance). Physiologic signals are mediated via relevant receptors (examples in yellow boxes include central chemoreceptors in the medulla; peripheral chemoreceptors in the carotid body and aortic arch; mechanoreceptors in upper airways, lungs, and chest wall; and metaboreceptors in skeletal muscle) that send afferent signals to the brainstem and sensory cortex. Efferent signals are sent from the brainstem and motor cortex to the respiratory muscles and sensory cortex. Potential symptoms associated with dyspnea that may be generated by these signals are indicated in italics.

Generated from Harrison's Principles of Internal Medicine, 22nd Edition.