<p>Bronchiolitis obliterans syndrome (BOS) is a potential manifestation of chronic graft-versus-host disease (cGVHD) that may cause substantial morbidity and mortality. As BOS is progressive and may present subtly, a heightened awareness of BOS, early detection, and prompt treatment are crucial.</p>

BOS usually develops 3 months to 2 years following transplantation, but it can be triggered later. Unfortunately, BOS is often not recognized until patients have clinical manifestations such as shortness of breath or severe deterioration in exercise tolerance. BOS is characterized by a substantial decline in the patient’s forced expiratory volume in 1 second (FEV1). Risk factors for BOS include having lung impairment prior to transplant or shortly afterward, receiving a busulfan-containing myeloablative conditioning regimen, being cytomegalovirus positive, and having had a female donor or acute GVHD.

 

Many centers are piloting the use of the in-house monitoring of patient pulmonary function with portable spirometers. Patients can monitor their own FEV1, and, if they detect longitudinal deterioration, they connect with their transplant center, where they can receive a full pulmonary function test and see a pulmonologist to determine if they have BOS.

 

Patients with BOS may initially present with a persistent cough. So, those with an unexplained chronic cough should be seen by their transplant center and should get a pulmonary function test to evaluate for potential early BOS. We do not want to wait until a patient starts having chronic cough and shortness of breath before evaluating them. If we see that a patient has deterioration in their FEV1, we monitor them more carefully and, in many cases, add steroids early to prevent further deterioration. Once we believe that a patient has early BOS, they are treated aggressively, initially with systemic steroids and also with inhaled steroids.

 

Clinicians should continue carefully monitoring the pulmonary function of their patients to see if it improves with steroids. If pulmonary function does not improve with steroids, or if a patient’s steroids cannot be adequately tapered, you should think about adding a second agent such as belumosudil or ruxolitinib. There are limited data for these agents, but both have been reported to have some efficacy. The combination of the inhaled steroid fluticasone with oral azithromycin and montelukast has been suggested, but many clinicians have decided that azithromycin should not be included due to a potentially increased risk of relapse. Therefore, we currently recommend using an inhaled steroid and systemic steroids.

 

Ultimately, the best way to prevent BOS is to prevent cGVHD. Post-transplant cyclophosphamide-containing regimens with tacrolimus and mycophenolate mofetil may significantly reduce the incidence of cGVHD, as may abatacept.