Graft-versus-Host Disease (GVHD) is a complication that occurs after an allogeneic stem cell transplant, a procedure used to treat certain cancers and blood disorders. The transplant introduces healthy donor immune cells into the recipient’s body. In GVHD, these donor cells recognize the patient’s tissues as foreign and launch an immune attack. This reaction can target organs such as the skin, liver, and gastrointestinal tract. When this immune response specifically targets the respiratory system, it results in lung GVHD, which requires specialized diagnosis and long-term management.
Defining Graft-versus-Host Disease in the Lungs
Lung GVHD is a manifestation of chronic GVHD, typically developing more than 100 days after the stem cell transplant. This pulmonary form of the disease is almost exclusively identified as Bronchiolitis Obliterans Syndrome (BOS). BOS is characterized by donor T-cells attacking the epithelial lining of the smallest airways, called the bronchioles.
This immune attack causes persistent inflammation and subsequent scarring (fibrosis) within the walls of the bronchioles. Over time, this scarring thickens the airway walls, leading to progressive narrowing and eventual blockage of the small air passages. The resulting fixed obstruction traps air within the distal parts of the lung, making it difficult for the patient to exhale completely. Chronic GVHD can affect nearly any organ, with the lungs being a particularly vulnerable site.
Common Symptoms and Clinical Presentation
The clinical presentation of lung GVHD is often subtle at first. Patients frequently report a persistent, dry cough that does not produce mucus and is unresponsive to common cough suppressants. Shortness of breath (dyspnea) is a key symptom, initially noticeable only during physical exertion.
As the disease progresses and more small airways become obstructed, dyspnea can occur even with minimal activity or at rest. Wheezing is common, but it is often resistant to conventional bronchodilator medications, unlike typical asthma. Patients may also describe chest tightness or the inability to take a satisfyingly deep breath. Because the onset is insidious, these symptoms may be mistakenly attributed to other post-transplant complications, delaying diagnosis.
Diagnostic Procedures
Confirming lung GVHD requires objective testing to measure and visualize the characteristic airway obstruction. Pulmonary Function Tests (PFTs) are the most important tool for diagnosis and ongoing monitoring. PFTs typically reveal a fixed obstructive pattern, notably a forced expiratory volume in one second (FEV1) less than 75% of the predicted value, along with a reduced FEV1 to forced vital capacity (FEV1/FVC) ratio.
High-Resolution Computed Tomography (HRCT) scans of the chest are routinely performed to visualize the lung structure. HRCT can show signs of air trapping, especially on expiratory images, due to the blocked bronchioles. Imaging may also show evidence of bronchial wall thickening or bronchiectasis. In specific cases, a bronchoscopy with bronchoalveolar lavage or transbronchial biopsy may be used to rule out active infection or other causes of lung injury.
Managing Lung GVHD
The management of lung GVHD focuses on controlling immune-mediated inflammation and stopping progressive fibrotic damage to the airways. Initial treatment relies on systemic immunosuppression, using high-dose corticosteroids like prednisone as first-line therapy. These medications suppress the attacking donor T-cells, but they must be tapered slowly to avoid disease flares.
For patients who do not respond adequately to corticosteroids, or as part of a sequential strategy, other systemic agents are introduced. Second-line therapies can include targeted drugs like ruxolitinib, or procedures such as Extracorporeal Photopheresis (ECP). ECP involves treating a portion of the patient’s white blood cells with a light-activated drug before returning them to the body. Many patients also receive topical treatments delivered directly to the airways, such as inhaled corticosteroids and long-acting bronchodilators.
A regimen known as “FAM” therapy combines the inhaled corticosteroid fluticasone with the anti-inflammatory agents azithromycin and montelukast. This is a common strategy used to slow the decline in lung function. Supportive care is also important for improving quality of life and functional capacity, including rigorous pulmonary rehabilitation programs. Because of the necessary immunosuppression, patients are at high risk for infection, requiring prophylactic antibiotics and vigilance against respiratory viruses and bacteria.