Noninvasive Early Detection of Lung Allograft Dysfunction After Lung Transplantation With Multiple Breath Washout Test: Lung Clearance Index as an Early Marker

Lung transplantation is a treatment option for patients with advanced lung disease or irreversible pulmonary failure. Despite advancements in surgical techniques, lung preservation, immunosuppression, and management of ischemia/reperfusion injury and infections, chronic allograft rejection continue to be a major problem. Chronic rejection, more commonly called bronchiolitis obliterans syndrome (BOS), is the leading cause of death beyond the first year post lung transplantation.

BOS affects 50% or more of recipients who survive beyond 5 years and accounts for a considerable proportion of cases of lung allograft loss and recipient death beyond 3 months post-transplant. It is the leading cause of death for recipients who survive beyond 1 year post-transplant, and it is widely perceived as the physiological surrogate of immunologically-mediated phenomena due to many observations that include its association with acute cellular rejection, the tendency of recipients who develop BOS to have greater degrees of human leukocyte antigen mismatch, and accumulating evidence of the involvement of autoimmune pathways. Furthermore, there are striking similarities to obliterative bronchiolitis that can occur in allogeneic bone marrow or stem cell transplant recipients as well as in patients with connective tissue diseases, which are also perceived as alloimmune or autoimmune disorders, respectively. Therefore, BOS is frequently equated with the term chronic rejection.

The diagnosis of BOS is typically made by clinical, physiological, and radiographic parameters. Early detection would be desirable since it allows treatment modification to stop or delay the process. Due to the sporadic or patchy involvement of obliterative bronchiolitis, pathologic diagnosis can be missed by transbronchial biopsies (TBB), which are often performed to exclude other diagnoses including acute rejection or infection. Histologically, early lesions of BOS demonstrate partial or complete obstruction of the small airways.

Currently, radiographic imaging is not used as a diagnostic tool in transplant recipients when evaluating for BOS; however, high resolution computed tomography (HRCT) imaging with inspiratory and expiratory views may be helpful when considering the diagnosis.

In the last few years there has been a growing interest in lung clearance index (LCI), a measure of lung physiology derived from multiple breath washout tests. LCI is derived from Multiple Breath Washout (MBW) tests. The test involves following the washout of an inert tracer gas from the lungs during relaxed tidal breathing. The tracer gas can be nitrogen that is normally resident in the lungs, washed out when the participant is switched to breathing 100% oxygen.