Pulmonary emphysema, a progressive lung disease, is a form of chronic obstructive pulmonary disease (COPD). Global Initiative has defined COPD for chronic obstructive lung disease (GOLD) as "a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases" (http://goldcopd.org/wp-content/uploads/2016/12/wms-GOLD-2017-Pocket-Guide-1.pdf).
COPD is the third leading cause of death in the United States and fourth leading cause of the death worldwide. The World Health Organization (WHO) estimates suggest that it will rise to be the third most common cause of death worldwide by 2020. COPD includes patients with chronic bronchitis and emphysema. Although identified as separate entities, most patients with COPD have features of both. COPD often coexists with comorbidities, which affect the disease course.
Emphysema is primarily a pathological diagnosis which affects the air spaces distal to the terminal bronchiole. It is characterized by abnormal permanent enlargement of lung air spaces with the destruction of their walls without any fibrosis and destruction of lung parenchyma with loss of elasticity.
Emphysema is caused by chronic and significant exposure to noxious gases, of which, cigarette smoking remains the most common cause, and 80% to 90% of COPD patients are cigarette smokers identified, with 10% to 15% smokers developing COPD. However, in smokers, the symptoms also depend on the intensity of smoking, years of exposure, and baseline lung function. Symptoms usually begin after at least 20 pack per year of tobacco exposure.
Biomass fuels and other environmental pollutants such as sulfur dioxide and particulate matter are recognized as an important cause in developing countries affecting women and children greatly. A rare hereditary autosomal recessive disease, alpha one antitrypsin deficiency, can also lead to emphysema and liver abnormalities. However, it only contributes to 1% to 2% cases of COPD. It is a proven risk factor and can present with pan-acinar bibasilar emphysema early in life.
Other etiological factors are passive smoking, lung infections, allergies and low birth weight as a newborn makes one more prone to develop COPD later in life.
Emphysema, as a part of COPD, is an illness that affects a large number of people worldwide. In 2016, the Global Burden of Disease Study reported a prevalence of 251 million cases of COPD globally. Around 90% of COPD deaths occur in low and middle-income countries.
The prevalence of emphysema in the United States is approximately 14 million which includes 14% white male smokers and 3% white male nonsmokers. The prevalence is slightly less for white female smokers and African Americans.
It is slowly increasing in incidence primarily due to increase in cigarette smoking and environmental pollution. Another contributing factor is decreasing mortality from other causes such as cardiovascular and infectious diseases. Genetic factors also play a significant role in determining in which smoker’s airflow limitation will develop.
Emphysema severity is significantly higher in coal workers pneumoconiosis. This is independent of smoking status.
The clinical manifestations of emphysema are the consequence of damage to airways distal to terminal bronchiole which include respiratory bronchiole, alveolar sacs, alveolar ducts, and alveoli, known collectively as the acinus. There is abnormal permanent dilatation of the airspaces and destruction of their walls due to the action of the proteinases. This results in a decrease in alveolar and the capillary surface area which decreases the gas exchange. The part of the acinus affected determines the subtype.
It can be subdivided pathologically into:
After long-term exposure to noxious smoke, inflammatory cells such as macrophages, neutrophils, and T lymphocytes are recruited which play an important role in the development of emphysema. First, macrophages are activated which release the neutrophil chemotactic factors like leukotriene B4 and Interleukin-8. Once the neutrophils are recruited, these along with macrophages release multiple proteinases and lead to mucus hypersecretion.
Elastin is an important component of extracellular matrix that is required to maintain the integrity of lung parenchyma and small airways. Elastase/anti-elastase imbalance increases the susceptibility to lung destruction leading to airspace enlargement. Cathepsins and neutrophil-derived proteases (i.e., elastase and proteinase) act against elastin and destroy the connective tissue of the parenchyma of the lung. Cytotoxic T cells release TNF-a and perforins which destroy the epithelial cells of the alveolar wall.
Cigarette smoking not only causes mucus hypersecretion and release of neutrophilic proteolytic enzymes, but it also inhibits anti-proteolytic enzymes and alveolar macrophages. Genetic polymorphisms have a role in inadequate antiproteases production in smokers. All of these contribute to the development of the emphysema.
Lung parenchyma produces alpha one antitrypsin (AAT) which inhibits trypsinize and neutrophil elastase in the lung. AAT deficiency can lead to panacinar emphysema.
Most patients present with very nonspecific symptoms of chronic shortness of breath and cough with or without sputum production. As the disease process advances, the shortness of breath and cough progressively gets worse. Initially, there is exertional dyspnea with significant physical activity especially arm work at or above shoulder level with progression to dyspnea with simple daily activities and even rest. Some patients may present with wheezing because of the airflow obstruction.
As COPD advances, patients can lose significant body weight due to systemic inflammation and increased energy spent in work of breathing. Also, there are frequent intermittent exacerbations as the obstruction of the airways increases. Episodes of COPD exacerbations may present with increased shortness of breath, increased severity of a cough, and increased sputum typically brought on by an infection or an environmental factor.
Smoking history is important with an emphasis on the age at which the person started smoking and the total pack years. If the person has quit smoking, then it is important to know how many years have passed since he/she last smoked. History of environmental and occupational exposure and family history of chronic respiratory conditions and COPD is essential.
In the early stages of the disease, the physical examination may be normal. Patients with emphysema are typically referred to as “pink puffers,” meaning cachectic and non-cyanotic. Expiration through pursed lips (increases airway pressure and prevent airway collapse during respiration) and use of accessory muscles of respiration are seen in advanced disease. Clubbing of the digits is not typical of COPD. Many other comorbidities may be possible. Current smokers may have an odor of smoke and nicotine staining of hands and fingernails.
Percussion may be normal early in the disease. It may range from prolonged expiration or wheezes on forced exhalation to increased resonance indicating hyperinflation as the airway obstruction increases. Distant breath sounds, wheezes, crackles at the lung bases, and/or distant heart sounds are heard on auscultation.
Emphysema is a pathological diagnosis. Accordingly, routine laboratory and radiographic studies are not indicated.
Pulmonary function testing (PFT), particularly spirometry, is the mainstay of diagnosis. A post-bronchodilator test may be done in those with abnormal values. COPD is only partially reversible or nonreversible with bronchodilator with post-bronchodilator FEV1/FVC less than 0.07, which is diagnostic.
GOLD staging based on the severity of airflow limitation is as follows:
The lung volume measurements indicative of air trapping in emphysema reveal increased residual volume and total lung capacity. Diffusing capacity for carbon monoxide is reduced due to the emphysematous destruction of the alveolar-capillary pulmonary membrane.
A chest x-ray is only helpful in diagnosis if emphysema is severe, but it is usually the first step when suspecting COPD to rule out other causes. Destruction of alveoli and air trapping causes hyperinflation of lungs with flattening of diaphragm and heart appears elongated and tubular shaped.
Arterial blood gases are usually not required in mild to moderate COPD. It is done when oxygen saturation goes below 92%, or there is severe airflow obstruction to access for hypercapnia.
A young person with symptoms of emphysema should be tested for alpha 1 antitrypsin deficiency (AATD).
There is no known, definitive treatment which can modify the disease process. However, risk-factor modification and management of symptoms have been proven effective in slowing the disease progression and optimizing the quality of living.
Based on the symptoms and number of exacerbations, we can divide the disease into 4 COPD GOLD stages and modify the treatment accordingly.
Treatment based on COPD GOLD ABCD Staging
Medical therapy includes using a bronchodilator alone or in combination with anti-inflammatory drugs (corticosteroids and phosphodiesterase four inhibitors).
The primary mechanisms of action can be divided into two categories: beta2 agonists and anticholinergic medications. They are first-line drugs for COPD and are administered by inhalation. They are known to improve FEV1 by altering the smooth muscle tone of the airways and thus improve exercise tolerance. Bronchodilators are usually given regularly to prevent and to reduce symptoms, exacerbations, and hospitalizations.
Short-acting beta2 agonists (SABA) and short-acting muscarinic antagonists (SAMA) are usually prescribed as needed for management of intermittent dyspnea. Long-acting beta2 agonists (LABA) and long-acting muscarinic antagonists (LAMA) are used especially with increasing dyspnea or more than occasional dyspnea. If the symptoms are persistent while on one bronchodilator, another bronchodilator should be added.
Beta2 agonists cause relaxation of airway smooth muscles. SABA like albuterol can be used with or without anticholinergics. SABA is the mainstay in COPD exacerbation. LABA includes formoterol, salmeterol, indacaterol, olodaterol, vilanterol, among others. The side effects are arrhythmias, tremors, and hypokalemia. Caution should be taken in heart failure as tachycardia may precipitate heart failure.
Anticholinergics inhibit acetyl-choline induced bronchoconstriction. SAMA includes ipratropium and oxitropium. LAMA such as tiotropium can be given once daily.
Inhaled corticosteroid (ICS) is an add-on therapy to bronchodilator in a step-up therapy. ICS includes beclomethasone, budesonide, fluticasone, etc. The common side effects are a local infection, cough, and pneumonia. Oral systemic corticosteroids are used for all patients with COPD exacerbation and avoided in stable patients due to more adverse effects.
Oral Phosphodiesterase-4 inhibitors like Roflumilast act by reducing inflammation and can be added if there is severe airflow obstruction with no improvement with above medications.
Triple inhaled therapy (LABA+ LAMA+ ICS) has been recently approved by the FDA and is taken only once a day.
Intravenous aloha1 antitrypsin augmentation therapy for AATD patients. The high cost and lack of availability is the main limitation of this therapy.
Supportive therapy includes oxygen therapy and ventilatory support, pulmonary rehabilitation, and palliative care.
Routine supplemental oxygen does not improve the quality of life or clinical outcomes in stable patients. Continuous long-term, i.e., longer than 15 hours of supplemental oxygen is recommended in COPD patients with PaO2 less than 55 mmHg (or oxygen saturation less than 88%) or PaO2 less than 59 mm Hg in case of cor pulmonale. Oxygen therapy has shown to increase survival these patients with severe resting hypoxemia. For those who desaturate with exercise, intermittent oxygen will help. The goal is to maintain oxygen saturation greater than 90%.
A major cause of hypoxemia in COPD is due to ventilation-perfusion mismatch (V/Q Mismatch), particularly in low V/Q areas. Hypoxic vasoconstriction of pulmonary arteries is to improve overall gas exchange efficiency. Supplemental oxygen can successfully reach the alveoli in these lungs, which prevent this vasoconstriction and thereby increasing perfusion and improving gas exchange thus resulting in improvement of hypoxemia.
Noninvasive positive pressure ventilation (NPPV) is known to decrease morbidity and mortality in patients with acute respiratory failure and hospitalized for COPD exacerbation. It should be tried as the first mode of ventilation in patients with COPD exacerbation with respiratory failure who otherwise have no absolute contraindication as it improves gas exchange, decreases hospitalization duration, reduces work of breathing, improves VQ matching, and improves survival. If NPPV doesn’t work in in a COPD patient in a hospital setting, then the patient should be intubated and put on a ventilator.
Pulmonary rehabilitation for patients with severe symptoms and multiple exacerbations reduces dyspnea and hospitalizations and is recommended for GOLD stages B, C, and D.
Although available from the time the person is diagnosed with COPD, palliative care is typically recommended for GOLD stage D. It is additional care to the patient's current treatment plan. The goal is to provide the best quality of life possible. Not only does it play a role in assessment and management of the symptoms, but it also helps patients understand their illness and prognosis and facilitates a discussion about the patient’s goal of care, advance care, and end of life care plans. Advance care planning involves communication between patients, their families, and the physician and helps patients formulate their treatment preferences. Reassuring the patients of a clear plan to deal with dyspnea in advanced disease and management of depression and anxiety is an important component of palliative care. These can be managed with low dose opioids, lifestyle modification, and relaxation techniques respectively. Most patients underestimate the disease, so it is important to look for transition time and discuss advance care early in the disease. It is also important to explore where the patients want to spend their last days (e.g., home or hospital) and help provide them with whatever they are most comfortable.
Management of a Patient with COPD Exacerbation
Beta blockers and anticholinergics are used simultaneously. Initially with nebulizers and later switched to MDI. Systemic Corticosteroids (intravenous or oral) shown to hasten recovery and decrease hospital stay. Antibiotics are beneficial especially if productive, purulent cough. Second generation macrolides, extended spectrum fluoroquinolones, cephalosporins and amoxicillin-clavulanate. NIPPV can be beneficial in patients who can protect their airway and does not have a major acid-base disorder on the ABG. Very often end-stage COPD patients with exacerbations are intubated and are put on a ventilator. Ventilated patients should be watched for development of auto-PEEP and its related complications.
The disease presents with nonspecific symptoms, and hence, it has broad differential diagnoses. These include:
The management of emphysema is by a multidisciplinary team that consists of a pulmonologist, internist, pharmacist, dietitian, social worker, respiratory therapist, primary care provider, and a thoracic surgeon. There is no cure for emphysema and the primary cause needs to be treated. In North America, this means educating the patient about the harms of smoking and getting the annual flu vaccine. The outlook for most patients is guarded and the quality of life is poor, marked by frequent exacerbations and remissions of acute respiratory distress. Some may develop repeated pneumothoraces which may need to be managed by a thoracic surgeon. Several types of lung volume reduction procedures are available but they are high risk, associated with serious complications and require prolonged intensive care. (Level V)