Pulmonary causes
Shortness of breath is common with most pulmonary diseases, although it may not be an initial symptom and may have an insidious onset. It occurs once oxygenation of blood becomes inadequate, resulting in peripheral nervous system activation and neurochemical dissociation. Most patients with a pulmonary infection, asthma exacerbation, or COPD will have dyspnea. Once infection, asthma, and COPD have been ruled out, other pathologic processes that interrupt oxygenation should be considered. Unlike COPD and infections, patients with lung cancer may not have dyspnea until the end stages of their disease.11 The following entities should be considered in patients with dyspnea when more common causes have been eliminated.
Restrictive lung diseases
Restrictive lung disease occurs when functional lung volume is decreased, either by an intrinsic or extrinsic source. As a result, these lung diseases cover a wide variety of pathologies and disease processes including interstitial lung diseases (which we’ll discuss here), environmental exposures, neuromuscular diseases, and other forms of chest wall dysfunction.
Interstitial lung disease occurs in the presence of lung parenchymal scarring or thickening, which can have many causes including pulmonary fibrosis, connective tissue diseases (eg, sarcoidosis or rheumatoid arthritis), and inflammatory processes (eg, hypersensitivity pneumonitis and coal worker's pneumoconiosis). Dyspnea results because parenchymal thickening decreases oxygen diffusion between the alveolar and capillary endothelium. Additionally, the lung’s ability to exchange air is restricted by parenchymal stiffness and decreased total lung and functional lung capacity. Treatment is disease specific.
Idiopathic pulmonary fibrosis is the most common interstitial pneumonia with a prevalence of 13 to 20 per 100,000 people.12 It commonly affects men between the ages of 50 and 75 years. Risk factors include cigarette smoking, dust exposure (to metals, woods, vegetables), and exposure to livestock or other animals.12 Suspect it when you have a middle-aged farmer or mill worker who complains of shortness of breath.
Treatment recommendations have changed recently and now consist of using only nintedanib (a tyrosine-kinase inhibitor), antacid medication, and pirfenidone. Anticoagulation (with warfarin), steroids, other immunologic agents including azathioprine, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors are not recommended.13
Pulmonary arterial hypertension and cor pulmonale
Pulmonary arterial hypertension (PAH) is defined as a mean resting precapillary pulmonary artery pressure >25 mm Hg or >30 mm Hg with activity. It can be idiopathic or caused by a variety of agents, diseases, and conditions (TABLE 314). PAH is rare (15 in one million adults) and underdiagnosed, and more often occurs in 20- to 30-year-old black women.14
Suspect PAH in younger, otherwise healthy patients who complain of exertional dyspnea, fatigue, chest pain, or palpitations who do not have any other heart or lung disease signs or symptoms. A diagnosis of PAH is often delayed because patients are worked up for other etiologies such as CHF, coronary artery disease, PE, and COPD.
Diagnosis. When PAH is suspected, the initial work-up should include:
- an echocardiogram with a possible bubble study,
- arterial blood gas measurements,
- complete blood count,
- complete metabolic panel,
- human immunodeficiency virus (HIV) testing,
- thyroid-stimulating hormone levels,
- chest x-ray (which is abnormal in 90% of patients and shows right ventricular enlargement, a prominent central pulmonary artery, or peripheral hypovascularity),14
- electrocardiogram (to rule out other acute cardiac etiologies, but not to diagnosis PAH because of poor sensitivity and specificity),
- liver ultrasound, and
- pulmonary function tests.
If clinically suggested, tests for anticentromere antibody, antinuclear antibodies, anti-Scl-70 antibodies, and ribonucleoprotein antibodies should be ordered, as well as sickle cell screening, cardiac magnetic resonance imaging, and chest computed tomography. A right heart catheterization is required to confirm PAH and determine disease severity.
Vasoreactivity testing helps guide treatment because it identifies which patients will benefit from calcium channel blockers. The 6-minute walk test is the best way to estimate prognosis and disease severity. It is a simple test you can perform in the office by measuring how far your patient can walk in 6 minutes. Miyamoto et al showed the test to be predictive of survival in idiopathic PAH.15 A lung biopsy is never indicated or needed for diagnosis, disease severity classification, or prognosis.