Primary spontaneous pneumothorax is an abnormal accumulation of air in the space between the lungs and the chest cavity (called the pleural space) that can result in the partial or complete collapse of a lung. This type of pneumothorax is described as primary because it occurs in the absence of lung disease such as emphysema. Spontaneous means the pneumothorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely due to the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. Air in the pleural space creates pressure on the lung and can lead to its collapse. A person with this condition may feel chest pain on the side of the collapsed lung and shortness of breath.

Blebs may be present on an individual's lung (or lungs) for a long time before they rupture. Many things can cause a bleb to rupture, such as changes in air pressure or a very sudden deep breath. Often, people who experience a primary spontaneous pneumothorax have no prior sign of illness; the blebs themselves typically do not cause any symptoms and are visible only on medical imaging. Affected individuals may have one bleb to more than thirty blebs. Once a bleb ruptures and causes a pneumothorax, there is an estimated 13 to 60 percent chance that the condition will recur.

Mutations in the FLCN gene can cause primary spontaneous pneumothorax, although these mutations appear to be a very rare cause of this condition. The FLCN gene provides instructions for making a protein called folliculin. In the lungs, folliculin is found in the connective tissue cells that allow the lungs to contract and expand when breathing. Folliculin is also produced in cells that line the small air sacs (alveoli). Researchers have not determined the protein's function, but they believe it may help control the growth and division of cells. Folliculin may play a role in repairing and re-forming lung tissue following damage. Researchers have not determined how FLCN gene mutations lead to the formation of blebs and increase the risk of primary spontaneous pneumothorax. One theory is that the altered folliculin protein may trigger inflammation within the lung tissue that could alter and damage the tissue, causing blebs.

Primary spontaneous pneumothorax most often occurs in people without an identified gene mutation. The cause of the condition in these individuals is often unknown. Tall young men are at increased risk of developing primary spontaneous pneumothorax; researchers suggest that rapid growth of the chest during growth spurts may increase the likelihood of forming blebs. Long-term smoking also greatly increases the risk of developing primary spontaneous pneumothorax in both men and women.

Normal Function

The FLCN gene provides instructions for making a protein called folliculin. Researchers have not determined the protein's function, but they believe it may act as a tumor suppressor. Tumor suppressors help control the growth and division of cells.

The folliculin protein is present in many of the body's tissues, including the brain, heart, placenta, testis, skin, lung, and kidney. Researchers have proposed several possible roles for the protein within cells. Folliculin may be important for cells' uptake of foreign particles (endocytosis or phagocytosis). The protein may also play a role in the structural framework that helps to define the shape, size, and movement of a cell (the cytoskeleton) and in interactions between cells. In the lung, it is thought that folliculin plays a role in repairing and re-forming lung tissue following damage.

Health Conditions Related to Genetic Changes

Birt-Hogg-Dubé syndrome

Several mutations in the FLCN gene have been identified in people with Birt-Hogg-Dubé syndrome, a condition characterized by multiple noncancerous (benign) skin tumors, an increased risk of other tumors, and lung cysts. Most of these mutations insert or delete one or more protein building blocks (amino acids) in the folliculin protein. These mutations lead to the production of an abnormally small, nonfunctional version of this protein. Without folliculin, researchers believe that cells can grow and divide uncontrollably to form cancerous or noncancerous tumors. They have not determined how a loss of folliculin increases the risk of lung abnormalities that are often associated with Birt-Hogg-Dubé syndrome.

Primary spontaneous pneumothorax

At least eight mutations in the FLCN gene have been found to cause primary spontaneous pneumothorax. This condition occurs when air builds up abnormally in the space between the lungs and the chest cavity (plural space), potentially leading to a partial or complete collapse of the lung. Many of these mutations result in the production of a folliculin protein that is abnormally short and nonfunctional. Researchers have not determined how FLCN gene mutations lead to the development of primary spontaneous pneumothorax. One theory is that the altered folliculin protein may trigger inflammation within lung tissue that could lead to the formation of small sacs of air (blebs) in the tissue. These blebs can rupture, causing air to leak into the pleural space. People who have an FLCN gene mutation associated with primary spontaneous pneumothorax all appear to develop blebs, but it is estimated that only 40 percent of those individuals go on to have a primary spontaneous pneumothorax.

Other cancers

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, called somatic mutations, are not inherited. Somatic mutations in the FLCN gene are probably associated with several types of nonhereditary (sporadic) tumors. Specifically, somatic FLCN mutations have been identified in some cases of clear cell renal cell carcinoma (a type of kidney cancer) and in some colon cancers. These mutations may change the structure of the folliculin protein, disrupting its tumor suppressor function. Researchers do not know how FLCN mutations lead to these particular forms of cancer.

Other Names for This Gene

• BHD
• FLCL
• FLCN_HUMAN
• MGC17998
• MGC23445

Genomic Location

When this condition is caused by mutations in the FLCN gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, a person inherits the FLCN gene mutation from an affected parent. People who have an FLCN gene mutation associated with primary spontaneous pneumothorax all appear to develop blebs, but it is estimated that only 40 percent of those individuals go on to have a primary spontaneous pneumothorax.

Treatment for your pneumothorax will be guided by:

• your symptoms
• the type of pneumothorax
• the size of the pneumothorax

Observation

If you have a primary spontaneous pneumothorax and only minor symptoms, your pneumothorax might clear up on its own. Symptoms usually get better within 1-2 days without specific treatment.

Your doctor may recommend:

• observation in hospital
• oxygen (if needed)
• pain relievers

You might need to have a repeat chest x-ray after a couple of weeks.

Tension pneumothorax is very rare in people with a primary spontaneous pneumothorax.

Removal of trapped air

You may need to have the trapped air removed from the pleural space if you have:

• ongoing symptoms
• an underlying lung condition

‘Catheter aspiration’ involves inserting a thin tube into your chest wall. Local anaesthetic is used to numb your skin beforehand.

Catheter aspiration treatment involves inserting a thin tube into the chest wall. A syringe is used to suck air out of the pleural space.

A syringe is attached to the tube. The syringe sucks the air out from inside the chest wall.

Some people need a chest tube to release the air from the pleural space.

Primary spontaneous pneumothorax is more common in men than in women. This condition occurs in 7.4 to 18 per 100,000 men each year and 1.2 to 6 per 100,000 women each year.