A new classification system for chronic lung allograft dysfunction

Chronic lung allograft dysfunction phenotypes and treatment

“…In some patients, this FEV 1 improvement was so pronounced that criteria for BOS were no longer fulfilled. This was confirmed by several other groups (8,9) and led to the first proposition of phenotypes of chronic rejection, leading to a novel phenotype called neutrophilic reversible allograft dysfunction or azithromycin responsive allograft dysfunction (10), which is nowadays considered as a reversible cause of CLAD and therefore is no longer thought to be a manifestation of chronic rejection (11). It was only in 2010 that a restrictive pulmonary function defect came apparent when Woodrow and colleagues defined a group of patients with so called 'restrictive BOS' (12).…”

Mast Cell Phenotypes in the Allograft After Lung Transplantation.

“…23 Diagnosis of CLAD was based upon persistent (at least 3 months), unexplained allograft dysfunction defined by FEV 1 and/or FVC <90% from baseline. 5 Baseline lung function was defined as the average of two best post-transplant values for FEV 1 and FVC obtained at least 3 weeks apart.…”

“…4 However, it has been recognized that diverse clinical entities (or phenotypes) may lead to a decline in allograft function and the use of an umbrella term, chronic lung allograft dysfunction (CLAD), has been recommended by the International Society for Heart and Lung Transplantation (ISHLT). 5 There is growing evidence implicating the innate immune system in causing allograft injury. In this context, mast cells (MCs) modulate the adaptive immune response through release of cytokines such as tumor necrosis factor-α, facilitate the recruitment T cells to sites of inflammation, and enhance interactions with antigen presenting cells.…”

Diagnosis and management of bronchiolitis obliterans syndrome following lung or hematopoietic cell transplantation

“…[2] In contrast to HCT, BOS in LTX recipients is attributed to a host-versus-graft reaction to lung antigens, affects ≥50% of patients who survive beyond 5 years post-LTX, and is the leading cause of death for those who survive beyond one year post-LTX. [3] A more recent examination of LTX-BOS reveals that different phenotypes exist, [5] and use of the term chronic lung allograft dysfunction (CLAD) has been proposed as an overarching term for chronic lung allograft rejection that encompasses the subsets/phenotypes of (i) obstructive BOS, which typically lacks significant lung parenchymal changes on thoracic imaging and is characterized by obstructive physiology, and (ii) restrictive allograft syndrome (RAS), which is characterized by a restrictive pattern of lung physiologic impairment accompanied by parenchymal infiltrates (both CONTACT Keith C. Meyer kcm@medicine.wisc.edu entities were historically identified as BOS). Recent investigations indicate that RAS has a worse prognosis than the more prevalent obstructive BOS phenotype, and responses to therapy may also differ.…”

“…[3] It should be noted that newer views on classification of CLAD suggest that the term azithromycinresponsive allograft dysfunction may be a more precise and preferred term for graft dysfunction that reverses or at least improves significantly in response to AZI therapy. [5] Prophylactic AZI has also been evaluated as an intervention to prevent BOS in both LTX and HCT recipients. Vos et al [13] published a placebo-controlled RCT that demonstrated significantly improved, BOS-free survival and significantly better preservation of FEV1 in the AZI treatment arm when AZI started prior to hospital discharge following LTX.…”