Abstract
Lung transplantation is currently considered as an ultimate live-saving treatment
for selected patients suffering from end-stage pulmonary disease. Long-term survival,
however, is hampered by chronic rejection, or chronic lung allograft dysfunction (CLAD).
Recently, various phenotypes within CLAD have been identified, challenging the established
clinical definition of bronchiolitis obliterans syndrome (BOS). Some patients with
presumed BOS, for instance, demonstrate an important improvement in forced expiratory
volume in the first second of expiration (FEV1) after treatment with azithromycin. These patients are characterized by the presence
of excess (≥15%) bronchoalveolar lavage (BAL) neutrophils, in absence of concurrent
infection. This phenotype of CLAD has been redefined as neutrophilic reversible allograft
dysfunction (NRAD), and these patients generally have a very good prognosis after
diagnosis. Another group of patients with CLAD develop a restrictive rather than an
obstructive pulmonary function defect (defined as a decline in total lung capacity
of at least 10%) and demonstrate persistent interstitial and ground-glass opacities
on chest computed tomographic (CT) scan. This phenotype is called restrictive allograft
syndrome (RAS), and patients with RAS have a much worse prognosis after diagnosis.
This review further discusses both of these CLAD phenotypes that do not fit the classical
definition of BOS. Potential pathophysiological mechanisms, etiology, diagnosis, prognosis,
and treatments are discussed.
Keywords
neutrophilic reversible allograft dysfunction (NRAD) - restrictive allograft syndrome
(RAS) - chronic lung allograft dysfunction - lung transplantation
