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Emphysema

Chapter · January 2018

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Emphysema
Parul Pahal; Sandeep Sharma1.

1 Baptist Regional Medical Center

Last Update: January 19, 2018.

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Introduction
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.
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Etiology
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.
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Epidemiology
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.
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Pathophysiology
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:
• Centrilobular (Proximal Acinar) is the most common type and is
commonly associated with smoking. It can also be seen in coal workers
pneumoconiosis.
• Panacinar is most commonly seen with alpha one antitrypsin
deficiency.
• Paraseptal (Distal acinar) may occur alone or in association with above
2. When it occurs alone, the usual association is spontaneous
pneumothorax in a young adult.
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.
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History and Physical

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.
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Evaluation
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:
• Mild with FEV1 greater or equal to 80% predicted
• Moderate with FEV1 less than 80%predicted
• Severe with FEV1 less than 50% predicted
• Very severe with FEV1 less than 30 % predicted
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).
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Treatment / Management
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.
(See Figure-1)
Treatment based on COPD GOLD ABCD Staging
(See Figure-2)
Medical Therapy
Medical therapy includes using a bronchodilator alone or in combination with
anti-inflammatory drugs (corticosteroids and phosphodiesterase four
inhibitors).
Bronchodilator
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
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.
Interventional Therapy
• Lung volume reduction surgery reduces hyperinflation and improves
elastic recoil
• Lung transplantation when FEV1 and or DLCO is less than 20%.
Additional Interventions
1. Identification and reduction of exposure to risk factors. Counseling
about smoking cessation, as it is the single most important intervention
that slows the progression of the disease Reduce the exposure to open
cooking fires and promote efficient ventilation.
2. Daily oral opioids for severe COPD symptoms refractory to medical
therapy. Nutritional supplementation in malnourished COPD patients
3. Pneumococcal vaccine 23 valent every 5 year years for COPD patients
older than 65 or with other cardiopulmonary disease and Influenza
vaccine for all COPD patients every year
4. Readmission rates can be reduced with counseling on the optimal use
of metered dose inhalers (MDI)
5. Exercise for all COPD patients
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.
Prevention
• Smoking cessation
• Vaccination against Pneumococcus and Influenza
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Differential Diagnosis
The disease presents with nonspecific symptoms, and hence, it has broad
differential diagnoses. These include:
• Chronic obstructive asthma
• Chronic bronchitis with normal spirometry
• Cystic Fibrosis
• Bronchopulmonary mycosis
• Central airway obstruction
• Bronchiectasis
• Heart Failure
• Tuberculosis
• Constrictive bronchiolitis
• Anemia
• Complications
• Pulmonary hypertension
• Cor Pulmonale
• Chronic respiratory failure
• Spontaneous Pneumothorax
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Pearls and Other Issues

• Primary pulmonary hypertension drugs are not recommended for
patients with pulmonary hypertension secondary to COPD.
• Depression and anxiety are very common in end-stage lung disease,
and pharmacological agents can be used accordingly.
• Statin therapy does not reduce exacerbation.
 • Long-term oral corticosteroids are not recommended.
• ICS alone is not recommended.
• Combination treatment LABA and LAMA is more effective in
reducing exacerbations as compared to monotherapy.
• Combination of SAMA and SABA improves symptoms and FEV-1.
• Theophylline has a small bronchodilator effect in stable COPD and is
associated with modest symptomatic benefits.
• Assessment and appropriate management for comorbidities in a COPD
patient independently influence mortality and hospitalizations.
• Excessive correction of hypoxia in a patient with longstanding COPD
can sometimes lead to hypercapnia. This is due to loss of compensatory
vasoconstriction with an ineffective gas exchange as there is a loss of
hypoxic drive for ventilation. Also, increased oxyhemoglobin decreases
the uptake of carbon dioxide due to Haldane effect.
• The only interventions that decrease the mortality of COPD are
smoking cessation and continuous home oxygen.
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Questions
To access free multiple choice questions on this topic, click here.
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