Published: July 2015
Dyspnea is a symptom, not a discreet disease, and can be present in the absence of disease, or be the net result of multiple disease processes. It is an extremely common symptom. About 25% of patients seen by the physician in the ambulatory setting present with dyspnea. This number can be as high as 50% in the tertiary care setting.1
Despite its prevalence, the descriptions of dyspnea vary from patient to patient and no single definition encompasses all its qualitative aspects. Typically, it is defined as a feeling of shortness of breath or an inability to take a deep breath. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity." Many overlapping mechanisms account for descriptive terms used in the medical literature, such as "air hunger," "chest tightness," and many others.1
The mechanisms and pathophysiology of dyspnea involve interactions between the respiratory system (both the ventilatory function and gas exchange function), the cardiovascular system, neural responses, and oxygen carriers. A broad classification is key to realizing all important causes when faced with a dyspneic patient (Table 1).
Acute valvular disease
|Respiratory||Acute exacerbations of
obstructive lung diseases
Interstitial lung diseases
Malignancy (tumor related
obstructive lesions and
|Gastrointestinal/Hepatic||Acute liver failure
|Renal||Acute renal failure
|Neuromuscular||High cervical cord lesions
Trauma to phrenic nerves
ARDS = acute respiratory distress syndrome; COPD = chronic obstructive pulmonary disease.
The respiratory system includes a gas exchanger (the alveolar epithelium), a pump (the diaphragm and chest wall, both including skeletal muscle which may become deconditioned), a conduction system (the airways), and a central controller (the nervous system) that regulates its function. Abnormalities affecting any of these components can cause the subjective feeling of dyspnea.
Diseases such as pulmonary fibrosis affect the alveolar membrane as well as lung compliance, causing dyspnea through impairment of gas exchange and increased work of breathing to expand stiff lung tissue.2 Chronic obstructive pulmonary disease (COPD) and asthma are examples of diseases that primarily affect conduction of air through the airways, leading to dyspnea through increased work of breathing.3 These diseases of airflow obstruction also lead to air trapping and hyperinflation of the lungs, altering respiratory mechanics and further increasing the work of breathing.4 Deconditioning and neuromuscular diseases often involve an overlap of the mechanisms described above. For instance, in amyotrophic lateral sclerosis, the respiratory muscles become weak, which results in impaired ventilation due to failure of the respiratory pump. In obesity, the pump itself may require more energy to move air in and out, and yet still be unable to meet the demands of the body due to general deconditioning. The nervous system can be impaired by many disease states or sometimes by medications, leading to decreased respiratory drive or action, or even central apnea. The central nervous system also detects changes in body pH, which can be a powerful stimulus for a patient's dyspnea, even if the acidemia is not related to a respiratory abnormality.5
Cardiovascular disease is an important cause of dyspnea. Many of these mechanisms overlap with those of the respiratory system. For example, in low cardiac output states such as systolic heart failure, the low output is unable to meet the oxygen demands of the body causing ischemia due to inadequate tissue perfusion, resulting in lactate generation and acidemia. Patients with cardiac insufficiency often have pulmonary edema that impairs gas exchange as well as increasing the work of breathing, both of which add to the feeling of shortness of breath. Besides ischemic heart disease, other broad classes of cardiac disease can impair oxygen delivery by decreasing cardiac output, including arrhythmias, valvular insufficiency or stenosis, congenital structural heart disease or remodeling from infarction. or chronic heart failure. A commonly recognized anginal equivalent in patients with acute coronary syndromes is dyspnea, which may be the only symptom present.6
Defects in the oxygen carrying capacity are also important causes of dyspnea. The typical example would be anemia due to iron deficiency or other causes. This again is primarily due to a mismatch in oxygen supply capacity and demand. There is considerable overlap with other mechanisms here as well. When patients with severe anemia develop a high output state, cardiac failure can ensue causing them to have shortness of breath from cardiac causes as well.
Diseases in other organs, such as the kidneys and the liver, may cause dyspnea by a combination of the interactions we have discussed. In end stage renal disease, for example, dyspnea can be due to metabolic acidosis, volume overload causing pulmonary edema, and/or pleural effusions impairing lung expansion.
Although the above pathophysiological model can help explain the interaction between organ systems and dyspnea, the real mechanism of dyspnea is much more nebulous and has to do with conscious perception and the how the signals produced by these mechanistic abnormalities are conveyed to the brain. Many of these sensations originate in various receptors throughout the respiratory system. Mechanoreceptors sense stretch or strain of lung tissue and have been linked to the cause of chest tightness in bronchoconstriction and lung fibrosis.7 Vascular mechanoreceptors convey a sense of dyspnea in diseases like pulmonary hypertension. Pulmonary edema activates J receptors which are sensitive to structural changes in the lung interstitium.8 Chest wall expansion and stretch, especially when combined with respiratory muscle fatigue, can give a sense of hyperinflation seen in emphysema.9 These peripheral receptors constitute the afferent limb of the central nervous system's interpretation of dyspnea. Chemoreceptors which detect changes in pH are also part of the afferent limb and contribute to the interpretation of dyspnea by the patient.10
The efferent limb of the central nervous system is also important in the sensation of dyspnea, linking the motor cortex and the muscles of the respiratory system. An increase in efferent neural discharge to meet ventilatory needs increases the work of the respiratory muscles and is perceived as dyspnea due to increased work of breathing. If the increased stimulation cannot result in an adequate increase in ventilation, the feeling of air hunger will persist and may become worse.11
Mismatch of the afferent and efferent signals may result in dyspnea. For example, in COPD, the cortex may be instructing the pump to work harder to increase ventilation. The rise in respiratory rate increases the work of breathing, and the obstructed outflow of air in COPD leads to worsening hyperinflation and heightened stimulation of mechanoreceptors. This results in more dyspnea, which may make the patient breath faster and worsen the hyperinflation still more.12
An exhaustive list of signs and symptoms is beyond the scope of this discussion although these often provide clues to the underlying organ system involved. In many respiratory disorders cough may be a common symptom, alerting to airway inflammation or irritation. Presence of fever may often point towards an infectious disease also contributing to dyspnea. Patients may misinterpret pleuritic chest pain as dyspnea, and this should be clarified in the history. History of allergies, pets, and rashes can point towards a diagnosis of asthma. In any suspected lung disorder the smoking history is essential, as are occupational and environmental exposures. Sputum analysis can also give clues to the underlying process, as can findings such as clubbing and cyanosis.
A detailed chest exam may reveal clues such as accessory respiratory muscle use, deviation of the trachea and kyphoscoliosis on inspection. Palpation and percussion can help localize the side of a unilateral abnormality. A wheeze on auscultation points towards obstructive pathologies. Inspiratory crackles often indicate edema or fibrosis.
Chest pain and pedal edema may indicate cardiac causes. A change in urine output with puffy eyes in the morning should point towards renal etiologies. Similarly presence of jaundice and ascites can point to underlying hepatic disease. Recognizing these patterns is usually not difficult, but the astute clinician must learn to link these various medical syndromes with the patient's dyspnea. Experience brings an appreciation that many times the cause of dyspnea does not originate in the respiratory system at all.
The most commonly employed initial test is the chest roentgenogram. A well performed posteroanterior and lateral view chest roentgenogram can be invaluable in the evaluation of dyspnea. Although primarily targeted at the lungs, it also helps in an evaluation of the cardiovascular system, the chest wall, pleura, mediastinum and upper abdomen.
Advanced modalities such as computed tomography (CT) assist in further delineating the nature and extent of disease, especially when an abnormality is suspected but not seen or seen but not clearly defined on the chest X-ray. Computed tomography is more sensitive than chest X-ray in detecting most pulmonary disorders. High resolution CT images can help in diagnosing interstitial lung disease and bronchiectasis. Computed tomography with contrast can evaluate pulmonary vascular disorders. Ventilation/perfusion scans are useful in diagnosing chronic thromboembolic disease as a cause of dyspnea.
Thoracic magnetic resonance imaging (MRI) has not proved as useful in the evaluation of dyspnea. However, some progress is being made in cardiac MRI and thoracic MRI for diagnosis of vascular disorders. Magnetic resonance imaging also shows better images of the chest with regard to soft tissue masses and mediastinal structures. Magnetic resonance imaging's shortcoming is in imaging air-filled lung tissue, where it is not as good as other modalities.
Pulmonary function testing includes spirometry (measurement of air flow and functional respiratory volumes), lung volume measurement, and gas exchange properties of the lung (also called DLCO, for diffusing capacity of the lung for carbon monoxide) can help the physician understand the functional quality of the respiratory system. Pulmonary function tests can also help to grade the severity of diagnosed disease conditions. Six-minute walk protocols and other functional performance tests, as well as cardiopulmonary exercise testing, represent more involved methods of testing, which can often help distinguish the principle etiology in patients who have more than one possible factor for their dyspnea.
An echocardiogram and an electrocardiogram are standard in the workup of dyspnea that may be due to cardiac disease. Further cardiac testing such as stress testing and cardiac catheterization (right and left) can be considered based on history and other testing.
Polysomnograms (multichannel physiologic testing performed during sleep) are the gold standard for diagnosis of obstructive sleep apnea and other sleep disorders which can contribute significantly to dyspnea.
Arterial blood gas measurement can reveal respiratory and metabolic disorders with respect to acid-base balance and assessment of hypoxia related to a suspected cause of dyspnea.
A complete blood count and other basic biochemical tests such as liver and kidney function tests can be helpful in looking for other organ systems involved, including anemia.
Biomarkers such as troponin and brain natriuretic peptide measurements can be used to diagnose and prognosticate many respiratory and cardiovascular disorders.
Management of dyspnea generally involves two fundamental aspects: correction of the underlying disorder and relief of symptoms. Symptomatic care includes supporting oxygenation and ventilation until the cause is diagnosed and possibly reversed. Symptomatic care also alleviates the feeling of dyspnea, which is recognized as a significant source of the burden of suffering associated with many diseases.
Empiric pharmacological therapy for the dyspneic patient may focus on alleviating obstruction, clearing mucus, reducing airway inflammation, and palliation of air hunger itself. Sometimes treatment of obstruction also treats the underlying condition. For example, treating asthma with bronchodilators and steroids is specific for the disease but also helps the patient with symptom relief.
Drugs to improve mucous clearance, such as N-acetylcysteine13 and guaifenesin14, do improve clearance but have not been associated with improved outcomes, probably because they do not alter any known underlying etiology. Steroids are often used for their broad spectrum anti-inflammatory effects in a wide variety of inflammatory lung diseases. Whenever possible, their use should be limited to a short time frame due to their significant long-term toxicity.
Palliative treatment of dyspnea is important, and may be the principle component of end-of-life care, discussed below in the section on special populations.
Organ support for conditions associated with dyspnea includes interventions with various levels of invasiveness (noninvasive ventilation, mechanical ventilation via endotracheal tube or tracheostomy, extra-corporeal membrane oxygenation, hemodialysis). Despite the availability of devices, the most common initial treatment offered is supplemental oxygen delivery. Increasing the fraction of inspired oxygen may alleviate the sensation of inadequate breathing, resulting in relief of dyspnea.15 Supplemental oxygen also helps reverse the systemic consequences of hypoxia such as anaerobic metabolism and pulmonary hypertension. Adding helium to the inspired gas mixture can reduce the work of breathing in obstructive lung diseases due to the density and laminar flow properties of helium.16,17
Beginning with less invasive therapies may avoid the need to use more invasive, expensive, or risky interventions. For example, noninvasive positive pressure ventilation has a special role in patients with COPD as a potential means to avoid invasive mechanical ventilation.
Nonpharmacological approaches to dyspnea, such as pulmonary rehabilitation, play an important role in the treatment of patients with chronic lung diseases where the goal is to improve symptoms and increase exercise tolerance. Patients with COPD may particularly benefit from the reconditioning training of pulmonary rehabilitation, but also from other integrated strategies like inspiratory muscle training and pursed lip breathing techniques to improve expiratory airflow.18
Lifestyle modifications can affect dyspnea significantly in some cases, such as weight loss for those with dyspnea related to obesity hypoventilation and sleep apnea, or smoking cessation for those with smoking related disease. Surgical techniques, such as lung volume reduction surgery, are useful in a highly selected subset of patients and should be reserved for those cases where they are recommended by specialists.19
During pregnancy the respiratory system undergoes important and predictable changes. The functional residual capacity of the lungs declines by 18% to 20% as does the residual volume. The tidal volume of resting breaths increases by about 0.2 L, and the volume of air exchanged in each minute increases by about 40%. These factors must be taken into account when assessing a pregnant woman with dyspnea, which is a common but usually mild symptom. Importantly during pregnancy, the respiratory rate typically does not change.20,21
Advanced lung diseases are often incurable and the focus shifts towards comfort and alleviation of dyspnea. Opiates have played an important role in this regard in reducing breathlessness and providing relief and comfort to these patients.22 Use of opiates must be weighed against their side effects such as constipation and delirium. Opiates can be given through many delivery routes, including intravenous, oral, transdermal, rectal, or inhaled.23
Benzodiazepines are used but extreme caution is needed, especially when combined with opiates, which can worsen the risk of respiratory depression and cause unintended hypercarbia. Therefore one must be careful when using these drugs and therapy must be individualized and closely monitored.24
Inhaled furosemide is a promising emerging therapy in the treatment of severe dyspnea. Inhaled furosemide has been shown to decrease breathlessness and avoids the adverse effects of benzodiazepines and opiates. Professional societies do not yet endorse its use. Further studies are needed to clarify its position in the treatment of dyspnea.25, 26
The evaluation and management of patients with dyspnea is an important skill and involves a comprehensive understanding of pathophysiology, thorough history taking and focused physical examination. Providers seeking to understand the etiology of a patient's dyspnea must consider non-pulmonary causes and indirect effects of seemingly unrelated disease states or conditions. The correct and timely diagnosis of the cause of dyspnea can often be lifesaving given the critical importance of ventilation and oxygenation to survival of the patient.