Lung problems from infections or graft-versus-host disease (GVHD) occur in up to 70 percent of people who’ve had an allogeneic stem cell transplant. GVHD happens when donor cells (the graft) attack healthy tissue in the recipient’s body (the host). When this affects the lungs’ airways, it’s sometimes called pulmonary GVHD or GVHD of the lungs.

Recognizing lung-related symptoms can help you get the right treatment. This article explains how GVHD can affect your lungs so you know what to expect.

Types of Lung Problems After a Stem Cell Transplant

Research shows that lung complications can be fatal in over 60 percent of people who need a breathing machine after undergoing an autologous hematopoietic stem cell transplant, a procedure in which they receive their own stem cells. In the first 100 days after the transplant, lung problems may be caused by several factors, including:

• Infections due to a weakened immune system
• Fluid buildup from large amounts of IV fluids during chemotherapy
• Side effects of the conditioning regimen used to prepare for the transplant

After 100 days, lung problems are often linked to chronic GVHD or other lung diseases that decrease the amount of air the lungs can hold. These conditions, known as late-onset noninfectious pulmonary complications, affect up to 20 percent of people within two years of a stem cell transplant.

People with chronic GVHD may also have a higher risk of infection because of medications that suppress the immune system.

How Does Graft-Versus-Host Disease Affect the Lungs?

When donor T cells attack healthy tissues in the host, it can trigger chronic (long-term) inflammation that damages lung tissue. Over time, the inflammation and tissue damage can lead to pulmonary fibrosis, in which scar tissue narrows and obstructs the small airways. This makes breathing more difficult.

About 14 percent of people with chronic GVHD may develop a lung disease called bronchiolitis obliterans syndrome (BOS). According to the Leukemia & Lymphoma Society, risk factors for pulmonary GVHD include:

• Having a donor tissue-type mismatch
• Being older at the time of transplant
• Receiving cells from an older donor
• Being a male recipient of female donor cells
• Using peripheral (circulating) stem cells instead of bone marrow or umbilical cord blood stem cells
• Having a respiratory infection within the first 100 days after transplant

BOS is the most common lung complication in chronic GVHD, but other late-onset noninfectious pulmonary conditions can occur, including organizing pneumonia and interstitial lung disease.

What Are the Symptoms of GVHD of the Lungs?

People with BOS may not notice symptoms right away. In fact, about 20 percent of people diagnosed with BOS have no symptoms at first. As the disease progresses, symptoms can gradually get worse and may include:

• A cough lasting more than two to four weeks
• A dry cough (doesn’t produce mucus)
• Shortness of breath
• Chest tightness or difficulty breathing deeply
• Wheezing

If you notice any new lung symptoms, contact your healthcare team right away. An oncologist (cancer specialist) may refer you to a lung specialist for further evaluation.

How Is GVHD of the Lungs Diagnosed?

BOS can be difficult to diagnose because its symptoms are similar to those of other lung diseases. Doctors use several tests to diagnose BOS, including pulmonary function tests (PFTs), imaging tests, and bronchoscopy.

Pulmonary Function Tests

Regular PFTs can detect lung problems early, sometimes before symptoms appear. If you start experiencing breathing issues, you may need more frequent testing.

Spirometry is a common PFT that measures how much air you move in and out of your lungs. Key measurements include:

• Forced expiratory volume in 1 second (FEV1) — The volume of air you forcefully exhale in one second
• Forced vital capacity (FVC) — The full volume of air you can exhale after taking a deep breath
• FEV1/FVC ratio — The percentage of a forced exhale that you push out in the first second

These tests can also help your healthcare team track disease progression and monitor how well treatments are working.

Imaging Tests

Imaging tests provide detailed pictures of the lungs. The two main types of imaging tests used for diagnosing BOS are:

Chest X-rays — Use radiation to create lung images but may not always detect BOS-related changes

CT scans — Preferred for diagnosing BOS because they provide more detailed cross-sectional images using multiple X-rays and a computer

Bronchoscopy

A bronchoscopy is a procedure in which a thin tube with a camera is inserted into the airways to examine the lungs and perform a biopsy (collect tissue samples to be examined in a lab). This test helps rule out other possible causes of lung symptoms, such as infection or acute rejection (immune system attack).

How Is GVHD of the Lungs Treated?

Chronic GVHD affecting the lungs is usually treated by a team of healthcare professionals, including an oncologist, a GVHD specialist, and a pulmonologist (lung disease specialist). The team will work together to prevent lung function from worsening and manage your symptoms.

There isn’t one standard treatment for chronic GVHD of the lungs. Additionally, BOS usually isn’t the only symptom. Your healthcare team will consider other affected parts of your body when creating a treatment plan.

Systemic Treatments

Systemic treatments work throughout the body because they’re absorbed into the bloodstream after being taken orally (by mouth) or by injection. Chronic GVHD is usually first treated with corticosteroids (steroids), such as prednisone (Rayos) or methylprednisolone (Medrol). Steroids are immunosuppressants that treat chronic GVHD by holding back the immune system and reducing inflammation.

Other commonly used treatments for chronic GVHD of the lungs include:

• Belumosudil (Rezurock)
• Ibrutinib (Imbruvica)
• Imatinib (Gleevec, Imkeldi), used off-label (not for the officially approved use)
• Ruxolitinib (Jakafi)

Additional treatments may be recommended to help manage symptoms. When combined with an inhaled corticosteroid, azithromycin (Zithromax) and montelukast (Singulair) may help prevent BOS from getting worse.

Inhaled Treatments

Inhaled treatments work directly in the lungs to help improve symptoms and reduce inflammation. Your healthcare team may recommend using an inhaler with a corticosteroid, which can be combined with long-acting beta-agonist drugs to help open the airways. Inhaled treatments are usually added alongside systemic treatments for better symptom control.

Extracorporeal Photopheresis

Extracorporeal photopheresis (ECP) is a nonsurgical procedure that’s thought to reduce inflammation by exposing white blood cells to ultraviolet light. Clinical studies have found that people with BOS often respond well to ECP, which may also help people with severe lung involvement live longer.

Lung Transplant

A lung transplant is a surgical procedure in which a diseased lung is replaced with a healthy lung from a donor. This procedure may be an option for people with life-threatening lung failure from chronic GVHD when other treatments aren’t effective.

What’s the Outlook for GVHD of the Lungs?

Chronic GVHD of the lungs often has a poor prognosis (outlook), and BOS can be challenging to treat. Less than half of people with BOS respond to the initial treatments, and about 50 percent of those diagnosed have a five-year life expectancy. This means that about half of people with BOS are still alive five years after diagnosis.

To help find BOS early, bone marrow transplant experts recommend starting PFTs six months after the transplant and then repeating them at least once per year, with more frequent testing if symptoms develop.

Talk With Others Who Understand

On myGVHDteam, the site for people with graft-versus-host disease and their loved ones, people come together to ask questions, give advice, and share their stories with others who understand life with this condition.

Are you living with GVHD of the lungs? What treatments have helped manage your symptoms? Share your experience in the comments below.