Emphysema

Emphysema
Classification and external resources
A lateral chest x-ray of a person with emphysema. Note the barrel chest and flat diaphragm.
ICD-10	J43.
ICD-9	492
DiseasesDB	4190
MedlinePlus	000136
eMedicine	med/654
MeSH	D011656

Emphysema is a long-term, progressive disease of the lung that primarily causes shortness of breath. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. It is included in a group of diseases called chronic obstructive pulmonary disease or COPD (pulmonary refers to the lungs). Emphysema is called an obstructive lung disease because the destruction of lung tissue around smaller airways, called alveoli, makes these airways unable to hold their functional shape upon exhalation.

The term means swelling and comes from the Greek emhysan meaning inflate, itself composed of en meaning in and physa meaning breath, blast. ^[1]

Classification

Emphysema can be classified into primary and secondary color. However, it is more commonly classified by location.

Emphysema can be subdivided into panacinary and centroacinary (or panacinar and centriacinar,^[2] or centrilobular and panlobular).^[3]

• Panacinar (or panlobular) emphysema: The entire respiratory acinus, from respiratory bronchiole to alveoli, is expanded. Occurs more commonly in the lower lobes, especially basal segments, and anterior margins of the lungs.^[2]
• Centriacinar (or centrilobular) emphysema: The respiratory bronchiole (proximal and central part of the acinus) is expanded. The distal acinus or alveoli are unchanged. Occurs more commonly in the upper lobes.^[2]

Other types include distal acinar and irregular.^[2]

A special type is congenital lobar emphysema (CLE).

Congenital lobar emphysema

CLE results in overexpansion of a pulmonary lobe and resultant compression of the remaining lobes of the ipsilateral lung, and possibly also the contralateral lung. There is bronchial narrowing because of weakened or absent bronchial cartilage.^[4]

There may be congenital extrinsic compression, commonly by an abnormally large pulmonary artery. This causes malformation of bronchial cartilage, making them soft and collapsible.^[4]

CLE is potentially reversible, yet possibly life-threatening, causing respiratory distress in the neonate.^[4]

Signs and symptoms

Emphysema is a disease of the lung tissue caused by destruction of structures feeding the alveoli, in some cases owing to the action of alpha 1-antitrypsin deficiency. This causes the small airways to collapse during forced exhalation, as alveolar collapsibility has decreased. As a result, airflow is impeded and air becomes trapped in the lungs, in the same way as other obstructive lung diseases. Symptoms include shortness of breath on exertion, and an expanded chest. However, the constriction of air passages isn't always immediately deadly, and treatment is available. Most of the people who have emphysema are smokers. Damage caused by emphysema is permanent even after the person stops smoking. People with this disease do not get enough oxygen and cannot eradicate the carbon dioxide, so they always have a shortage of breath. Emphysema usually initially presents with dyspnea during physical activity. Eventually the person will notice that the dyspnea is occurring any time they are physically exerted. Finally, the person will be dyspneic all the time even when they are in a relaxed state. People with emphysema can have trouble coughing and lowered amounts of sputum. They can begin to lose weight and have tachypnea when they try to extend their expiration. Breathing is difficult and the patient must use accessory muscles to help them breathe. The patient can have an increase of the anteroposterior diameter of their chest which is sometimes referred as "barrel chest." The patient is often seen leaning forward with arms extended or leaning on something to help them breath. When lung auscultation and chest percussion is done there is a hyperresonant sound that is heard. (Mc Cance) Emphysema patients can have symptoms of cyanosis, lowered oxygen levels and increased carbon dioxide levels.

Causes

The primary cause of emphysema is the smoking of cigarettes. In some cases it may be due to alpha 1-antitrypsin deficiency. Severe cases of A1AD may also develop cirrhosis of the liver, where the accumulated A1AT leads to a fibrotic reaction. Some types of emphysema are considered a normal part of aging and are found in the elderly whose lungs have deteriorated due to age. At about 20 years of age, people stop developing new alveoli tissue. In the years following the cessation of the development of new alveoli, lung tissue can start to deteriorate. This is a normal, natural part of aging in healthy people. Alveoli will die, the amount of lung capillaries will decline and the elastin of the lungs will begin to break down causing a loss of pulmonary elasticity. As people age, they will also lose strength and mass in their chest muscles causing these muscles to become weaker. In addition, bones can start to deteriorate and a person’s posture can change. Together, all of these age-related manifestations can cause the development of emphysema. Though not all elderly people will develop emphysema, they are all at risk of having decreased respiratory function. Other causes of emphysema can be anything that causes the body to be unable to inhibit proteolytic enzymes in the lung. This could be exposure to air pollution, second hand smoke or other chemicals and toxins. However, the majority of all emphysema cases are secondary to smoking cigarettes, cigars or other nicotine products. This is why emphysema cases that are caused by these etiologies are referred to as secondary emphysema.

Pathophysiology

Pathology of lung showing centrilobular emphysema characteristic of smoking. Closeup of fixed, cut surface shows multiple cavities lined by heavy black carbon deposits. (CDC/Dr. Edwin P. Ewing, Jr., 1973)

In normal breathing, air is drawn in through the bronchi and into the alveoli, which are tiny sacs surrounded by capillaries. Alveoli absorb oxygen and then transfer it into the blood. When toxicants, such as cigarette smoke, are breathed into the lungs, the harmful particles become trapped in the alveoli, causing a localized inflammatory response. Chemicals released during the inflammatory response (e.g., elastase) can eventually cause the alveolar septum to disintegrate. This condition, known as septal rupture, leads to significant deformation of the lung architecture.^[5] The large cavities left by the septal degeneration are known as bullae (sin. = bulla). These deformations result in a large decrease of alveoli surface area used for gas exchange. This results in a decreased Transfer Factor of the Lung for Carbon Monoxide (TLCO). To accommodate the decreased surface area, thoracic cage expansion (barrel chest) and diaphragm contraction (flattening) take place. Expiration increasingly depends on the thoracic cage and abdominal muscle action, particularly in the end expiratory phase. Due to decreased ventilation, the ability to exude carbon dioxide is significantly impaired. In the more serious cases, oxygen uptake is also impaired.

As the alveoli continue to break down, hyperventilation is unable to compensate for the progressively shrinking surface area, and the body is not able to maintain high enough oxygen levels in the blood. The body's last resort is vasoconstricting appropriate vessels. This leads to pulmonary hypertension, which places increased strain on the right side of the heart, the side responsible for pumping deoxygenated blood to the lungs. The heart muscle thickens in order to pump more blood. This condition is often accompanied by the appearance of jugular venous distension. Eventually, as the heart continues to fail, it becomes larger and blood backs up in the liver.

Patients with alpha 1-antitrypsin deficiency (A1AD) are more likely to suffer from emphysema. A1AT inhibits inflammatory enzymes (such as elastase) from destroying the alveolar tissue. Most A1AD patients do not develop clinically significant emphysema, but smoking and severely decreased A1AT levels (10-15%) can cause emphysema at a young age. The type of emphysema caused by A1AD is known as panacinar emphysema (involving the entire acinus) as opposed to centrilobular emphysema, which is caused by smoking. Panacinar emphysema typically affects the lower lungs, while centrilobular emphysema affects the upper lungs. A1AD causes about 2% of all emphysema. Smokers with A1AD are at the greatest risk for emphysema. Mild emphysema can often develop into a severe case over a short period of time (1–2 weeks).

While A1AD provides some insight into the pathogenesis of the disease, hereditary A1AT deficiency only accounts for a small proportion of the disease. Studies for the better part of the past century have focused mainly upon the putative role of leukocyte elastase (also neutrophil elastase), a serine protease found in neutrophils, as a primary contributor to the connective tissue damage seen in the disease. This hypothesis, a result of the observation that neutrophil elastase is the primary substrate for A1AT, and A1AT is the primary inhibitor of neutrophil elastase, together have been known as the "protease-antiprotease" theory, implicating neutrophils as an important mediator of the disease. However, more recent studies have brought into light the possibility that one of the many other numerous proteases, especially matrix metalloproteases might be equally or more relevant than neutrophil elastase in the development of non-hereditary emphysema.

The better part of the past few decades of research into the pathogenesis of emphysema involved animal experiments where various proteases were instilled into the trachea of various species of animals. These animals developed connective tissue damage, which was taken as support for the protease-antiprotease theory. However, just because these substances can destroy connective tissue in the lung, as anyone would be able to predict, doesn't establish causality. More recent experiments have focused on more technologically advanced approaches, such as ones involving genetic manipulation. One particular development with respect to our understanding of the disease involves the production of protease "knock-out" animals, which are genetically deficient in one or more proteases, and the assessment of whether they would be less susceptible to the development of the disease. Often individuals who are unfortunate enough to contract this disease have a very short life expectancy, often 0–3 years at most.

Diagnosis

A severe case of emphysema.

The diagnosis is usually confirmed by pulmonary function testing (e.g. spirometry); however, X-ray radiography may aid in the diagnosis.

Prognosis and treatment

Emphysema is an irreversible degenerative condition. The most important measure to slow its progression is for the patient to stop smoking and avoid all exposure to cigarette smoke and lung irritants. Pulmonary rehabilitation can be very helpful to optimize the patient's quality of life and teach the patient how to actively manage his or her care. Patients with emphysema and chronic bronchitis can do more for themselves than patients with any other disabling disease.

Emphysema is also treated by supporting the breathing with anticholinergics, bronchodilators, steroid medication (inhaled or oral), effective body positioning (High Fowlers), and supplemental oxygen as required. Treating the patient's other conditions including gastric reflux and allergies may improve lung function. Supplemental oxygen used as prescribed (usually more than 20 hours per day) is the only non-surgical treatment which has been shown to prolong life in emphysema patients. There are lightweight portable oxygen systems which allow patients increased mobility. Patients can fly, cruise, and work while using supplemental oxygen. Other medications are being researched.

Lung volume reduction surgery (LVRS) can improve the quality of life for certain carefully selected patients. It can be done by different methods, some of which are minimally invasive. In July 2006 a new treatment, placing tiny valves in passages leading to diseased lung areas, was announced to have good results, but 7% of patients suffered partial lung collapse. The only known "cure" for emphysema is lung transplant, but few patients are strong enough physically to survive the surgery. The combination of a patient's age, oxygen deprivation and the side-effects of the medications used to treat emphysema cause damage to the kidneys, heart and other organs. Surgical transplantation also requires the patient to take an anti-rejection drug regimen which suppresses the immune system, and can lead to microbial infection of the patient. Patients who think they may have contracted the disease are recommended to seek medical attention as soon as possible.

Research

A study published by the European Respiratory Journal suggests that tretinoin (an anti-acne drug commercially available as Retin-A) derived from vitamin A can reverse the effects of emphysema in mice by returning elasticity (and regenerating lung tissue through gene mediation) to the alveoli.^[6][7]

While vitamin A consumption is not known to be an effective treatment or prevention for the disease, this research could in the future lead to a cure. A follow-up study done in 2010 found inconclusive results ("no definitive clinical benefits") using Vitamin A (retinoic acid) in treatment of emphysema in humans and stated that further research is needed to reach conclusions on this treatment.^[8]

Notable cases

Notable cases of emphysema have included Ava Gardner, Don Cornell, Spencer Tracy,^[9] Leonard Bernstein, Eddie Dean,^[10] Dean Martin, Norman Rockwell, Samuel Beckett, Johnny Carson, Al Capp, T. S. Eliot, Tallulah Bankhead, Dick York, James Franciscus, R. J. Reynolds, R. J. Reynolds Jr., R. J. Reynolds, III,^[11] Don Imus,^[12] Ike Turner, Charlie Simpson, Yosef Hayim Yerushalmi, Elizabeth Dawn, Jerry Reed, Boris Karloff, Leonid Brezhnev and Paul Avery.^[13]

Additional images

H&E (haematoxylin and eosin) stained lung tissue sample from an end-stage emphysema patient. RBCs are red, nuclei are blue-purple, other cellular and extracellular material is pink, and air spaces are white.

Micrograph demonstrating emphysema (left of image - large empty spaces) and lung tissue with relative preservation of the alveoli (right of image). H&E stain.

See also

• Paraseptal emphysema
• Subcutaneous emphysema

Footnotes

External links

• https://health.google.com/health/ref/Chronic+obstructive+pulmonary+disease
• Images of Emphysema http://www.radrounds.com/photo/paraseptal-and-centrilobular-1