It is not clear why some transplant recipients (those who receive a lung transplant) develop BOS sooner than others. Some of the factors that are thought to play a role are environmental irritants such as infection, air pollution, or tobacco smoke, stresses related to the transplant operation itself, and the recipient’s immune response to the transplanted lung(s). Some known risk factors for the development of BOS include:

Primary graft dysfunction—This is when the transplanted lung is injured during the process of retrieval from the donor and/or implantation into the recipient and does not function properly early after surgery. The injured lung(s) immediately after transplant generally need more support for a longer period of time than usual.

Lung rejection—Rejection can be caused by the immune cells in the recipient’s body or by antibodies that the body makes against the transplanted lung(s). Either form of rejection of the transplanted lung(s) leads to a higher risk of BOS. ( For more information on lung transplant rejection, see the ATS Patient Information Series “Rejection after lung transplantation“.)

Gastroesophageal reflux disease (GERD) –This is when fluid from the stomach (either acidic or non-acidic) comes back to the throat and gets into the lung. This is a common problem in people who have lung transplant and needs to be treated to reduce lung injury.

Certain infections increase the risk of BOS. These include:

• pseudomonas aeruginosa, a bacteria

• cytomegalovirus (CMV), a virus

• aspergillus, a fungus

• a number of common respiratory viruses, including respiratory syncytial virus (RSV), parainfluenza, and influenza

Early after the onset of BOS, a person may have no symptoms as he or she still has very good lung function. This is why it is so important to keep close follow-ups with the transplant team and get frequent lung function monitoring after the transplant. Transplant recipients become symptomatic from BOS because of decreased lung function. Common symptoms include:

• shortness of breath

• decreased exercise or activity tolerance and endurance

• fatigue

• cough, sometimes with increased mucus production

BOS is not an infection itself, but sometimes patients can have BOS and a respiratory infection at the same time. In that case, a person may also have fevers or chills. It is always important to look for other problems that can be treated.

In the period immediately after transplant, recipients undergo regular checkups to make sure that lung function is stable and there is no infection.

1. Lung function—One of the key lung function tests used in diagnosing BOS is the forced expiratory volume in 1 second (FEV1), which measures the amount of air you can blow out in the first second of a forced exhalation. The FEF25-75% is another measure of lung function test (called “spirometry”). Over the first several months after transplant, spirometry is measured at regular intervals to establish the baseline value for the new lung(s). After this time (usually about three months), any sustained drops in FEV1 raise the concern for BOS. When a drop in the FEV1 persists, several other tests will be done before the transplant physician will formally diagnose BOS.

2. Imaging—A chest x-ray or a CT is performed to rule out infection. Occasionally, certain patterns such as air-trapping or a new infiltrate (spot) may raise concern for rejection.

3. Bronchoscopy—Your transplant provider may decide to do this procedure to take samples from the lung. This procedure will include taking samples from the lung including fluid (bronchoalveolar lavage or BAL) and a tissue biopsy. The BAL involves squirting sterile fluid into the lung through the scope and suctioning it back out to send for tests. These tests mainly look for infection. The airway biopsies use a special forceps through the scope to get small pieces of airway tissue. These are looked at by a pathologist for any signs of rejection. It should be noted that biopsies obtained with bronchoscopy are not sensitive enough to always identify changes of BOS. The final decision about a diagnosis of BOS is based on the transplant physician’s judgment and the results of testing to exclude other potential causes of the decline in FEV1.

If there is no infection or acute rejection, the diagnosis is likely BOS and the severity of BOS is determined by comparing the FEV1 to the person’s usual (called baseline) FEV1.

The most important method for preventing the development or progression of BOS is to try to reduce risk factors as much as possible. It is also very important to act quickly when lung function starts to drop. Important steps include:

• Promptly treating any bacterial, viral, or fungal infections that may arise, including those that stem from dental problems. For more information on doing lung function testing, see the ATS Patient Information Series “Lung Function Testing”.

• Promptly treating any acute rejection episode with a short-term treatment, usually high doses of corticosteroids and other medications, as decided by your transplant team.

• If there is a concern for GERD that does not respond to medications, your health care provider may order specific tests for GERD and/or recommend an anti-reflux surgery to help prevent any further lung injury.

Some people may be prescribed long-term azithromycin, an antibiotic that may reduce inflammation, which may help slow or reverse the decline in lung function. All transplant patients receive immunosuppression therapy (the medications that help keep the recipient’s immune system from attacking the transplanted lung(s)). If a patient develops BOS on one immunosuppression medicine, sometimes switching or adding other immunosuppressive therapies may help prevent further loss of lung function. There are new treatments for BOS and research continues on how to prevent and treat BOS. Sometimes, despite doing all of the above, BOS continues to progress and lung function continues to decline. If BOS becomes severe enough and does not respond to any other therapies, the patient may have to be evaluated for a second lung transplant.