Bronchiolitis obliterans secondary to chronic graft-versus-host disease

18-year-old male patient with acute myeloid leukemia was treated with induction therapy followed by consolidation therapy. Finally, he received allogeneic hematopoietic stem cell transplantation (HSCT).

Nine months later, routine Pulmonary Functional Tests (PFTs) revealed a FEV1 of 63% that pointed to an obstructive pulmonary disease.

Chest radiograph was normal in this case. The chest radiographic findings associated to BO are nonspecific and include mild hyperinflation, central bronchial wall thickening and reticulonodular markings.

Non-contrast low-dose inspiratory high-resolution CT (HRCT) chest with a 1.50 mm slice thickness demonstrated a bilateral patchy mosaic attenuation pattern with areas of low attenuation with paucity and reduced calibre of pulmonary vessels compared with the normal parenchyma. An expiratory CT was performed that showed persistence of the low attenuation areas, indicating air trapping.

Other CT features include bronchial wall thickening and bronchiectasis, absent in this patient.

Chronic graft-versus-host disease (cGVHD) is a multisystem disease with high morbidity and mortality that occurs as a complication in 30-70% of allogeneic HSCT [1].

The lungs are frequently affected after allogeneic HSCT, both in infectious and non-infectious complications. Bronchiolitis obliterans (BO), also known as constrictive bronchiolitis, is the most common pulmonary manifestation of cGVHD. BO is an irreversible obstructive disease that appears around 6-12 months after HSCT. The incidence is estimated at 2-5% in patients receiving allogeneic HSCT and at 6% in patients already diagnosed with cGVHD, although recent publications suggest a higher incidence [1,2].

After allogeneic HSCT, BO can be secondary to drug toxicity or cGVHD. Other less frequent causes of BO include toxic inhalation exposure, previous infection, small vessel vasculitis and collagen vascular disease [1,2].

Histologically, it is characterized by concentric stenosis of the bronchiolar lumen secondary to inflammation and fibrosis of the terminal bronchioles leading to airway obstruction and air trapping.

At an early stage, pulmonary cGVHD is asymptomatic in 20% of patients or could manifest with nonspecific symptoms such as dyspnea, exercise intolerance or non-productive cough [3]. This represents a challenge because reaching the diagnosis before the disease evolves into an advanced stage with irreversible structural changes is crucial for patient morbidity and mortality.

The detection of BO relies on PFTs and high resolution CT (HRCT) with inspiratory and expiratory images.

According to the 2015 National Institutes of Health (NIH) guidelines the diagnostic criteria for BO are [4]:

• Absence of active respiratory tract infection.
• Negative microbiological tests.
• FEV1<70 % in PFTs.
• Evidence of air trapping in PFT or one of the following findings on HRCT (air trapping, bronchiectasis, or small airway wall thickening).

Although diagnostic approaches remain challenging, early diagnosis may improve clinical outcome and regular post-transplant follow-up PFTs should be considered [5,6].

Systemic first-line treatment consists of high doses of corticosteroids and optional addition of azithromycin.

Take Home Messages

• Transplant-related complications are common after allogeneic HSCT, including GVHD.
• BO is a non-reversible obstructive lung disease with high morbidity and mortality that affects the terminal bronchioles, and it is the most frequent manifestation of pulmonary cGVHD.
• CT findings include mosaic attenuation pattern due to air trapping secondary to bronchiolar obstruction and bronchial wall thickening.
• Expiratory HRCT acquisition is required to demonstrate the evidence of air trapping when the diagnosis is suspected.
• Early treatment before structural irreversible changes have developed is crucial for patient morbidity and mortality.

All patient data have been completely anonymised throughout the entire manuscript and related files.