Clinical Context and Manifestations

Bronchiolitis obliterans syndrome, or BOS, is due to a lesion called obliterative bronchiolitis, which is the fibrotic narrowing of small airways in the lungs. BOS is seen in other medical settings in addition to HCT. While BOS affects only 5-6% of patients who have received an allogeneic HCT, it can lead to progressive breathlessness and death. BOS is difficult to diagnose and treat: in many cases, lung function is very impaired by the time that patients develop symptoms of breathlessness and cough and seek medical attention. Once diagnosed, lung impairment generally does not recover, although we hypothesize that earlier diagnosis can lead to earlier treatments that stop the decline of lung function. Currently, the diagnosis is based on 2014 NIH consensus criteria, which relies on laboratory pulmonary function tests (PFTs) and do not encourage early detection. Other forms of lung disease, including organizing pneumonia, are also increasingly appreciated as potential manifestations of chronic GVHD. Treatment options for BOS are limited, and there are no agents that reliably recover lung function. Current approaches of immunosuppression (e.g., corticosteroids) put patients at risk for lung infections, which often lead to worsening of lung function. The only definitive treatment for end-stage lung disease due to BOS is lung transplantation, in which 50% of individuals also develop BOS within 5 years. 

Example of Obliterative Bronchiolitis Pathology

Resources

Bergeron A, Cheng GS. Bronchiolitis Obliterans Syndrome and Other Late Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation. Clin Chest Med. 2017 Dec;38(4):607-621. doi: 10.1016/j.ccm.2017.07.003. Epub 2017 Sep 19. Review. PubMed PMID: 29128013.

Scope of Scientific Inquiry

The Lung GVHD Consortium projects include clinical, translational, and bench research from multidisciplinary collaborations. The 2020 NIH Consensus Conference on Chronic GVHD Working Group 4, Highly Morbid Manifestation, Lung Group, provides a roadmap for our research direction and progress. One goal of the Consortium is to conduct a multi-center RCT to gain FDA approval of a novel agent for the BOS indication.