Emphysema

Emphysema is primarily a pathological diagnosis that 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.

(A) Changes in the alveoli as the disease progresses. (B) Lateral x-ray showing lung enlargement and abnormal barrel chest in emphysema. (Note: the short white lines shown in the x-ray are surgical clips.)

Pulmonary emphysema, a progressive lung disease, is a form of chronic obstructive pulmonary disease (COPD). Global Initiative for chronic obstructive lung disease (GOLD) has defined COPD 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."

COPD is the third leading cause of death in the United States and the fourth leading cause of 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.

📖 Interventions in Pulmonary Medicine 2nd ed.

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 patients with COPD 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. oms usually begin after at least 20 packs 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% of 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, and allergies. Moreover, low birth weight as a newborn makes one more prone to develop COPD later in life.

Image is of H&E (haematoxylin and eosin) stained lung tissue sample taken from an end-stage emphysema patient.
Cell nuclei are blue-purple, red blood cells are red, other cell bodies and extracellular material are pink, and air spaces are white. 

The clinical manifestations of emphysema are the consequences of damage to airways distal to terminal bronchiole, which include respiratory bronchiole, alveolar sacs, alveolar ducts, and alveoli, collectively known 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 the 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 the following:

• 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 the above two. When it occurs alone, the usual association is a 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 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 the 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 emphysema.

Lung parenchyma produces alpha one antitrypsin (AAT), which inhibits trypsinize and neutrophil elastase in the lung. AAT deficiency can lead to panacinar emphysema.

References

1: Shah PL, Herth FJ, van Geffen WH, Deslee G, Slebos DJ. Lung volume reduction
for emphysema. Lancet Respir Med. 2017 Feb;5(2):147-156. doi:
10.1016/S2213-2600(16)30221-1. Epub 2016 Sep 29. Erratum in: Lancet Respir Med.
2016 Nov;4(11):e55. PMID: 27693408.

2: Busarova GA, Vorob'ev LP. Emfizema legkikh [Pulmonary emphysema]. Ter Arkh.
1991;63(7):142-7. Russian. PMID: 1788796.

3: ROSSIER PH. [Emphysema]. Medicina (B Aires). 1959 May-Jun;19:149-62. Spanish.
PMID: 14439292.

4: MAYER E, RAPPAPORT I, SCHEPERS GW. Emphysema. J Am Med Assoc. 1956 Jan
21;160(3):230-1. doi: 10.1001/jama.1956.02960380078022. PMID: 13278180.

5: MORLEDGE W. Emphysema. J Okla State Med Assoc. 1953 Mar;46(3):60-2. PMID:
13035550.

6: DOUGLAS RA. Emphysema. Med J Aust. 1959 Aug 29;46(2):279-81. doi:
10.5694/j.1326-5377.1959.tb89401.x. PMID: 13817833.

7: O'BRIEN B. Emphysema. Practitioner. 1952 Dec;169(1014):613-19. PMID:
13003793.

8: KNUDSON RJ, GAENSLER EA. SURGERY FOR EMPHYSEMA. Ann Thorac Surg. 1965
May;1:332-62. doi: 10.1016/s0003-4975(10)66764-1. PMID: 14301435.

9: Furuya Y, Wakahara T, Furuya A, Yanagie H, Yasuhara H. Rare bowel emphysema
with superior mesenteric artery syndrome after surgery. Ann R Coll Surg Engl.
2020 Feb;102(2):e26-e28. doi: 10.1308/rcsann.2019.0114. Epub 2019 Aug 16. PMID:
31418283; PMCID: PMC6996434.

10: WIMPFHEIMER F, SCHNEIDER L. Familial emphysema. Am Rev Respir Dis. 1961
May;83:697-703. doi: 10.1164/arrd.1961.83.5.697. PMID: 13785747.