Lung transplant rejection occurs when the immune system recognises a transplanted lung as foreign and begins to attack it. Because the immune system naturally tries to remove substances it considers foreign, rejection remains a possible complication even when a lung transplant is functioning well.
Rejection can develop at different stages after transplantation and may range from mild changes that are detected during routine monitoring to more significant lung dysfunction. Recognising changes early is important because many episodes of rejection can be treated when identified promptly.
If you or someone close to you has undergone a transplant, understanding lung transplant surgery and its potential complications can help you understand why regular follow-up, lung function monitoring and anti-rejection medicines are such an important part of long-term care.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
What Is Lung Transplant Rejection?
Lung transplant rejection happens when the recipient's immune system responds against the transplanted lung.
The transplanted lung contains cells and tissues that are genetically different from those of the recipient. The immune system can recognise these differences and activate an immune response against the transplanted organ.
To reduce this response, people who receive a lung transplant need immunosuppressive medicines. These medicines lower the activity of the immune system and help protect the transplanted lung.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
However, rejection can still occur even when anti-rejection medicines are being taken as prescribed. This is why ongoing monitoring remains necessary after transplantation.
What Are the Types of Lung Transplant Rejection?
Lung rejection can occur through different immune mechanisms and can present in different ways. Two important forms are cellular rejection and antibody-mediated rejection.
Acute Cellular Rejection
Acute cellular rejection occurs when immune cells, particularly T cells, respond against the transplanted lung. It can occur during the early period after transplantation but may also develop later.
Some episodes cause noticeable symptoms, while others are identified during routine testing before the person feels significantly unwell. Acute cellular rejection can often be treated by increasing or intensifying immunosuppressive treatment.
Antibody-Mediated Rejection
Antibody-mediated rejection occurs when antibodies target the transplanted lung. These antibodies may be directed against donor-specific human leukocyte antigens (HLA).
Antibody-mediated rejection can be more complex to diagnose and treat. The assessment may involve looking at changes in lung function, detecting donor-specific antibodies and examining lung tissue for characteristic findings.
Not every person with donor-specific antibodies will develop clinically significant rejection, so the results need to be interpreted together with the patient's clinical condition and other investigations.
Chronic Lung Allograft Dysfunction
Chronic lung allograft dysfunction, or CLAD, refers to a persistent decline in the function of a transplanted lung occurring after the early post-transplant period, once other potentially reversible causes have been considered.
CLAD is not simply another name for one specific type of rejection. It is an umbrella term describing chronic dysfunction of the transplanted lung and can have different patterns or phenotypes.
Previous episodes of rejection and other factors can contribute to long-term graft dysfunction, which is why preventing, detecting and treating rejection is an important part of long-term transplant care.
When Is Lung Transplant Rejection Most Likely to Occur?
Rejection can occur at any stage after a lung transplant. The risk is particularly important during the early months following transplantation, but the possibility does not disappear later.
This is one reason transplant recipients continue taking immunosuppressive medicines and attending regular follow-up appointments even when they feel well.
Long-term monitoring is also important because some forms of graft dysfunction may develop gradually rather than causing sudden symptoms.
What Are the Symptoms of Lung Transplant Rejection?
Symptoms can vary depending on the type and severity of rejection. In some cases, rejection may initially cause little or no noticeable change and may be detected through routine testing.
Possible symptoms include:
- Increasing shortness of breath
- Reduced ability to perform usual physical activities
- Persistent or increasing tiredness
- Changes in breathing
- Reduced lung function on testing
- Cough or other respiratory changes
These symptoms are not specific to rejection. Infection, airway problems, fluid accumulation and other complications after transplantation can cause similar changes.
Can Lung Transplant Rejection Occur Without Symptoms?
Yes. Some episodes of rejection may not cause obvious symptoms, particularly when they are detected through routine surveillance.
A person may feel relatively well while lung function testing, imaging, blood tests or other investigations show a change that requires further assessment. This is why regular transplant follow-up is important even when breathing feels normal.
How Is Lung Transplant Rejection Diagnosed?
There is no single test that identifies every episode of lung transplant rejection. Diagnosis usually involves combining the patient's symptoms, lung function, imaging, blood tests and, when appropriate, examination of lung tissue.
The transplant team may use several investigations to determine whether rejection is present and to distinguish it from other causes of declining lung function.
Lung Function Tests
Regular lung function testing is an important part of monitoring after transplantation. Spirometry measures how much air you can breathe out and how quickly you can exhale.
A decline from your established baseline can be an important warning sign that the transplanted lung is not functioning as well as before.
A change in lung function does not automatically mean rejection. Infection, airway narrowing, fluid around the lung and other conditions can also affect results. Further evaluation may therefore be necessary.
Home Spirometry and Lung Transplant Monitoring
Some transplant programmes use home spirometry so that patients can monitor their lung function between clinic visits.
Regular measurements can help identify a gradual change that might otherwise be difficult to notice. A significant or persistent decline should be reported to the transplant team rather than interpreted independently as rejection.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
Home monitoring does not replace scheduled clinical assessments, imaging, blood tests or other investigations when they are required.
Chest Imaging
Chest imaging may be performed when rejection is suspected or when lung function changes unexpectedly.
A chest X-ray or CT scan can show changes in the transplanted lung, but imaging findings are not always specific for rejection. Similar abnormalities can occur with infection, fluid accumulation and other causes of lung dysfunction.
Imaging therefore forms part of the overall assessment rather than providing a diagnosis on its own.
What Is a Bronchoscopy?
Bronchoscopy allows the transplant team to examine the airways using a thin, flexible camera passed through the nose or mouth into the lungs.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
During the procedure, doctors can inspect the airways and may collect samples for laboratory testing. These samples can help investigate infection as well as possible rejection.
Bronchoscopy may therefore be particularly useful when the cause of a change in lung function is not immediately clear.
Why Is Infection Ruled Out Before Diagnosing Rejection?
Infection and rejection can cause similar symptoms and changes in lung function after transplantation. Both may cause breathing difficulties, fatigue, cough or changes on imaging.
This makes it important to investigate possible infection when a transplanted lung begins functioning less well. The distinction matters because treatment for rejection usually involves increasing immunosuppression, while an infection may require antimicrobial treatment.
Increasing immunosuppression in someone with an active infection can create additional concerns. The transplant team therefore considers infection and other potential causes as part of the diagnostic process.
How Is Lung Transplant Rejection Treated?
Treatment depends on the type, severity and timing of rejection and on the patient's overall condition. The main approach is to adjust or intensify immunosuppressive treatment to reduce the immune response against the transplanted lung. Treatment decisions are individualised because different forms of rejection can require different approaches.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
How Is Acute Cellular Rejection Treated?
Acute cellular rejection is commonly treated with stronger immunosuppression, often using corticosteroids. More significant episodes may require high-dose steroids administered intravenously and treatment in hospital.
If rejection does not respond adequately, the transplant team may consider additional immunosuppressive therapies. The specific treatment depends on the severity of rejection and how the patient responds to therapy.
How Is Antibody-Mediated Rejection Treated?
Antibody-mediated rejection can be more difficult to manage because treatment needs to address the antibody-driven immune response.
Depending on the patient's findings, the transplant team may use combinations of therapies intended to reduce harmful antibodies or modify the immune response.
Because antibody-mediated rejection is a complex condition, treatment is individualised according to the clinical and laboratory findings.
What Happens After Rejection Treatment?
Patients are monitored closely after treatment to determine whether lung function and other findings improve. Follow-up may include repeated spirometry, blood tests, imaging and, when necessary, bronchoscopy or biopsy.
The transplant team may also review immunosuppressive medicine levels and adjust the long-term medication plan according to the patient's response and risk of further rejection.
Can Lung Transplant Rejection Be Prevented?
Rejection cannot always be completely prevented, but several measures can reduce the risk and help detect it early.
- Take immunosuppressive medicines exactly as prescribed.
- Do not stop or change anti-rejection medicines without speaking with the transplant team.
- Attend scheduled transplant appointments.
- Complete recommended lung function monitoring.
- Report new or worsening symptoms promptly.
- Follow the transplant team's recommendations for infection prevention and general care.
What Happens If Rejection Is Not Treated?
Untreated rejection can cause progressive damage to the transplanted lung. Severe rejection can lead to significant loss of lung function and, in some cases, graft failure.
Repeated or persistent injury to the transplanted lung may also contribute to chronic lung allograft dysfunction. Early identification gives the transplant team an opportunity to investigate the cause and begin treatment before more extensive damage occurs.
Can Rejected Lungs Recover?
Many episodes of acute rejection can respond to treatment, particularly when they are detected early. The response depends on the type and severity of rejection, how quickly treatment begins and the condition of the transplanted lung.
Some episodes may resolve with treatment, while more severe or repeated injury can result in lasting impairment. This is why monitoring does not stop after symptoms improve. Continued follow-up is important for assessing long-term lung function.
What Is Chronic Lung Allograft Dysfunction?
Chronic lung allograft dysfunction, or CLAD, is a major long-term complication following lung transplantation. It describes a persistent decline in the function of the transplanted lung after other potentially reversible causes have been considered.
CLAD can have different clinical patterns. One important phenotype is bronchiolitis obliterans syndrome, while another is restrictive allograft syndrome. The condition may develop gradually, and a persistent decline in lung function is an important part of its assessment.
How Is Chronic Rejection Different From Acute Rejection?
| Feature | Acute rejection | Chronic lung allograft dysfunction |
|---|---|---|
| Pattern | May develop over a relatively short period | Persistent or progressive decline in transplanted lung function |
| Symptoms | May include increasing breathlessness or fatigue, but can sometimes be detected before symptoms appear | Often associated with gradually worsening respiratory function |
| Assessment | Lung function, imaging, bronchoscopy, biopsy and other tests may be used | Serial lung function testing, imaging and evaluation for other causes are important |
| Treatment | Usually involves intensifying immunosuppression when rejection is confirmed | Management depends on the phenotype, cause, severity and individual clinical situation |
The Bottom Line
Lung transplant rejection occurs when the immune system attacks the transplanted lung. It can be acute or contribute to longer-term problems affecting graft function, and it may occur even when anti-rejection medicines are taken correctly.
Increasing breathlessness, fatigue or a decline in lung function can be warning signs, but rejection cannot be diagnosed from symptoms alone. Lung function testing, imaging, blood tests, bronchoscopy and sometimes lung biopsy may all play a role in finding the cause.
Treatment generally involves adjusting or strengthening immunosuppressive therapy according to the type and severity of rejection. Regular follow-up, careful medication adherence and prompt reporting of new symptoms are important parts of protecting the transplanted lung over the long term.
