Dyspnea on Exertion

Etiology

Dyspnea on exertion is a symptom of various diseases rather than a disease itself. As such, its etiology can be designated as arising from two primary organ systems: the respiratory system and the cardiac system. Other systemic illnesses may be culprits as well as a combination of different etiologies.

Respiratory causes may include asthma, acute exacerbation of chronic obstructive pulmonary disorder (COPD), pneumonia, pulmonary embolism, lung malignancy, pneumothorax, or aspiration.[1]

Cardiovascular causes may include congestive heart failure, pulmonary edema, acute coronary syndrome, pericardial tamponade, valvular heart defect, pulmonary hypertension, cardiac arrhythmia, or intracardiac shunting.

Other systemic illnesses, such as anemia, acute renal failure, metabolic acidosis, thyrotoxicosis, cirrhosis of the liver, anaphylaxis, sepsis, angioedema, and epiglottitis, may also cause dyspnea on exertion.

Epidemiology

The epidemiology of dyspnea on exertion is highly variable depending on etiology.[1] The most common cause of dyspnea on exertion is congestive heart failure. According to 2017 American heart association (AHA) data, heart failure affects 6.5 million Americans aged 20 years or older.[3] Similarly, about 6.3% of the US adult population has COPD.

Pathophysiology

Dyspnea on exertion is the sensation of running out of the air and of not being able to breathe fast or deeply enough during physical activity. It results from multiple signal interactions with receptors in the central nervous system (CNS), peripheral chemoreceptors, and mechanoreceptors in the respiratory tract and chest wall.

The respiratory center is comprised of three neuron groupings in the brain: the dorsal and ventral medullary groups and the pontine grouping. The pontine grouping further classifies into the pneumotaxic and apneustic centers. Inhalation is managed by the dorsal group, and the ventral medulla accounts for exhalation. The pontine groupings play their part in modulating the intensity and frequency of the medullary signals where the pneumotaxic groups limit inhalation, and the apneustic centers prolong and encourage inhalation. Each of these groups communicates with one another to unify the efforts as the pace-making potential of respiration.

Sensory information to the respiratory center regarding the volume of the lung space is provided by mechanoreceptors located in the airways, trachea, lung, and pulmonary vessels. There are two primary types of thoracic sensors: slow adapting stretch spindles and rapid adapting irritant receptors. Slow-acting spindle sensors convey only volume information.

However, the rapid-acting receptors respond to both the volume of the lungs and chemical triggers, such as foreign agents that may be harmful. Both kinds of mechanoreceptors signal through the tenth cranial nerve to the brain to escalate the rate of breathing, the volume of breaths, or to stimulate coughing patterns of breathing because of irritants present in the airway.

Peripheral chemoreceptors comprise the carotid and aortic bodies. Both receptors function to monitor the partial pressure of oxygen in the arterial blood. However, hypercapnia and acidosis enhance the sensitivity of these sensors and play a partial role in the functioning of receptors. Once stimulated by hypoxia, carotid and aortic bodies send a signal via the ninth cranial nerve (the glossopharyngeal nerve) to the nucleus tractus solitarius in the brain, which then, stimulates excitatory neurons to increase the rate of ventilation. It has been postulated that the carotid bodies comprise 15% of the total driving force of respiration.[4]

Central chemoreceptors manage the majority of control over the respiratory drive. They function by sensing pH changes in the CNS. Prime locations within the brain include the ventral surface of the medulla and the retrotrapezoid nucleus. pH changes within the brain, and surrounding cerebrospinal fluid is derived primarily from increases or decreases in carbon dioxide levels. Carbon dioxide is a lipid-soluble molecule that freely diffuses across the blood-brain barrier. This characteristic proves to be useful in that rapid changes in pH within the cerebrospinal fluid are possible. Chemoreceptors responsive to pH change are located on the ventral surface of the medulla. As these areas become more acidic, sensory input is generated to stimulate hyperventilation, and carbon dioxide within the body is reduced through increased ventilation. When pH rises to more alkalotic levels, hypoventilation occurs, and carbon dioxide levels increase secondary to decreased ventilation.

Respiratory centers located within the medulla oblongata and pons of the brainstem are responsible for generating the baseline respiratory rhythm. However, the rate of respiration is modified by allowing for aggregated sensory input from the peripheral sensory system, which monitors oxygenation, and the central sensory system, which monitors pH and indirectly carbon dioxide levels along with several other portions of the cerebellar brain modulate to create a unified neural signal. The signal is then sent to the primary muscles of respiration, the diaphragm, external intercostals, and scalene muscles along with other minor muscles of respiration.[5]

History and Physical

The history and physical exam should ascertain whether there are any chronic underlying cardiovascular or pulmonary illnesses. Key components of history include onset, duration, aggravating factors, and alleviating factors. The presence of cough may indicate the presence of asthma, chronic obstructive pulmonary disease (COPD), or pneumonia. A severe sore throat could indicate epiglottitis. Pleuritic quality chest pain may indicate pericarditis, pulmonary embolism, pneumothorax, or pneumonia. Orthopnea, paroxysmal nocturnal dyspnea, and edema suggest a possible diagnosis of congestive heart failure. Tobacco use is a common history finding that increases the likelihood of COPD, congestive heart failure, and pulmonary embolism. If indigestion or dysphagia is present, consider gastroesophageal reflux disease or gastric secretion aspiration in the lungs. A barking quality cough, especially in children, may suggest croup. The presence of fever strongly suggests an infectious etiology.

The physical exam should begin with a rapid assessment of the ABCs (airway, breathing, and circulation). Once determined to be stable, a full physical exam can be done. To determine the severity of dyspnea, one needs to observe respiratory effort, use of accessory muscles, mental status, and ability to speak. Engorgement of the neck veins may imply cor pulmonale caused by severe COPD, congestive heart failure, or cardiac tamponade. Thyromegaly may indicate hyperthyroidism or hypothyroidism. Percussion of the lung lobes for dullness can determine the presence or absence of consolidation and effusion. Hyperresonance on percussion is a worrisome finding that indicates possible pneumothorax or severe bullous emphysema. Lung auscultation may reveal absent breath sounds indicating the presence of region occupying mass, such as pleural effusion or malignancy. The presence of wheezing is highly consistent with the diagnosis of obstructive lung diseases such as asthma or COPD. However, wheezing may be associated with pulmonary edema or pulmonary embolism. Pulmonary edema and pneumonia may present with rales on auscultation. Auscultation of the heart may reveal the presence of dysrhythmia, cardiac murmurs, or aberrant heart gallops. An S3 gallop indicates cardiac overfilling seen in left ventricular systolic dysfunction and congestive heart failure (CHF). An S4 gallop suggests left ventricular dysmotility and dysfunction. A loud P2 indicates possible pulmonary hypertension. Murmurs may indicate valvular dysfunction. Diminished heart sounds may indicate cardiac tamponade. Pericarditis may present with a rubbing cardiac sound on auscultation. On abdominal examination, hepatomegaly, ascites, positive hepatojugular reflux may suggest a diagnosis of CHF. Lower extremity edema is associated with CHF, and extreme swelling of the extremities suggests possible deep venous thrombosis that can lead to a pulmonary embolism. Digital clubbing is present in some forms of lung malignancy or severe chronic hypoxia. Cyanosis of the extremities indicates hypoxia.[6]

Evaluation

Every evaluation should begin with a rapid assessment of the ABC status of the patient. Once these are determined to be stable and no life-threatening status present, a complete history, and physical exam can be collected. Vital signs should be assessed for heart rate, respiratory rate, body temperature, body mass index (BMI), and oxygen saturation. Oxygen saturation may be normal at rest, so oxygen saturation with physical exertion should be obtained. In normal physiological conditions, the pulse oximetry improves as V/Q matching improves. Fever may indicate an infectious etiology. A chest x-ray is the first diagnostic test that should be utilized in evaluating dyspnea on exertion. If abnormal, the disease process is likely cardiac or a primary pulmonary process. An echocardiogram is needed to evaluate cardiac function, pericardial space, and valvular function.

Additionally, an electrocardiogram should be obtained to evaluate for myocardial infarction or right-sided heart strain pattern. Elevated pro-brain natriuretic peptide (BNP) levels can further a congestive heart disease diagnosis. Exercise stress testing is also beneficial to determine cardiac function along with exercise oxygenation. If the chest x-ray is normal, then spirometry is needed to determine lung function. Abnormal spirometry can indicate either an obstructive pathology such as asthma, COPD, or physical airway obstruction or restrictive disease processes such as interstitial fibrosis. Spirometry can also indicate the presence of respiratory muscle weakness from muscular or neurological abnormalities. Normal spirometry indicates a need to evaluate for hypoxia as a source of dyspnea. The restrictive pathology can be confirmed with lung volumes, which will show reduced total lung capacity (TLC). In obstructive lung disease, the TLC is increased, and the RV/TLC ratio is increased. Diffusion capacity is reduced in disease processes that affect the alveolar membrane area and or thickness. For example, it will be reduced with interstitial lung disease (ILD), emphysema, pulmonary embolism (PE), CHF, and obesity.

Arterial blood gas testing is used for this purpose as well as to calculate the A-a gradient and assess for an acidotic state. If PaO2 is low with a normal chest x-ray, then pulmonary embolism (PE) should be considered. The pH is mostly alkalotic in the setting of PE. This is to blow carbon dioxide to relatively increase the partial pressure of oxygen. In a pregnant female, a d-dimer with leg ultrasound and V/Q scan should be ordered first. Detection of a mismatch in two or more areas indicates pulmonary embolism. D-dimer testing has low specificity and high sensitivity. Spiral CT of the chest is an alternative to V/Q scanning. In acute settings, the CT chest with PE protocol is the gold standard. If the dyspnea on exertion is chronic, then chronic thromboembolic pulmonary hypertension (CTEPH) should be considered, and the VQ scan is the test of choice and is considered the gold standard. The VQ scan in this setting has a “moth-eaten” appearance.

A normal scan necessitates cardiac catheterization to determine pulmonary hypertension, intracardiac shunting, or coronary artery disease. A normal cardiac catheterization diagnoses idiopathic dyspnea. If hypoxia is not present with a PaO2 greater than 70 mm Hg, correlation with oxygen saturation is needed. Abnormal oxygen saturation indicates possible carbon monoxide poisoning, methemoglobinemia, or an abnormal hemoglobin molecule.

Normal oxygen saturation requires a complete blood count (CBC) to evaluate hemoglobin content and hematocrit values. The white blood count also assesses for an immune response to possible infection. Hematocrit less than 35% is anemia.

• Oxygen Delivery:  Hb x 1.39 x SaO2 x Cardiac Output + 0.003 x Pao2

If one cannot determine the etiology of dyspnea, then we should order a cardiopulmonary exercise test (CPET). If the CPET does not show any cardiac or pulmonary etiology, then the likely diagnosis for dyspnea on exertion is physical deconditioning.

All testing modalities should target clinical suspicion and the history and physical exam to avoid overtesting and minimize the cost to the patient.[7]

Treatment / Management

Treatment for dyspnea on exertion depends on its underlying etiology. The first intervention is to determine that there are no life-threatening etiologies present on an acute presentation by monitoring the ABCs (airway, breathing, and circulation) of the patient. Once determined to be stable and that no immediate lifesaving interventions are necessary, an assessment for further treatment can be made. If a patient is a tobacco smoker, this should be discontinued. Various inhaler therapies may be used in respiratory disease, including short-acting or long-acting bronchodilators, inhaled antimuscarinics, and inhaled corticosteroids. Continuous supplemental oxygen therapy is used to ease discomfort associated with dyspnea on exertion if oxygen saturation is shown to decrease with exercise. [8] Cardiac function should be optimized when a cardiac illness is identified. If myocardial infarction is suspected based on ST changes on electrocardiogram or troponin marker evaluation, rapid percutaneous intervention should be performed by a cardiologist. Therapy with aspirin, statin, ACE inhibitor, beta-blocker, heparin, and nitrates should be initiated immediately if no contraindications. Occasionally, medications such as beta-blockers and calcium-channel blockers can induce dyspnea on exertion by decreasing cardiac function, which can be picked up on a CPET. These should be decreased or discontinued when possible. In CHF, diuretic medications should be used to decrease vascular congestion from fluid overloading. If the dyspnea on exertion is due to obesity or deconditioning physical therapy, an exercise regimen should be pursued. If psychological problems are causing dyspnea on exertion, a selective serotonin receptor inhibitor can be tried along with counseling sessions.[9] Weight loss in obese patients, especially women, will improve outcomes.[10]

Differential Diagnosis

Acute dyspnea on exertion is most likely caused by:

• Acute myocardial ischemia
• Heart failure
• Cardiac tamponade
• Pulmonary embolism
• Pneumothorax
• Pulmonary infection in the form of bronchitis or pneumonia
• Upper airway obstruction by aspiration or anaphylaxis

Chronic dyspnea is most likely caused by:

• Asthma
• Chronic obstructive pulmonary disease
• Congestive heart failure
• Interstitial lung disease
• Myocardial dysfunction
• Obesity
• Deconditioning

The most common diagnosis underlying dyspnea on exertion is CHF.

Prognosis

In itself, dyspnea on exertion is harmless and a normal physiological finding; however, as it is a symptom and not an illness, it may indicate an underlying disease. The prognosis is highly variable and depends on the underlying etiology and comorbidities.

Complications

If left untreated, dyspnea on exertion can progress to acute respiratory failure with hypoxia or hypercapnia, further leading to life-threatening respiratory or cardiac arrest or both.