Background: Long-term survival in pediatric lung transplantation is limited by bronchiolitis obliterans (BO), but varieties of chronic lung allograft dysfunction (CLAD) are poorly understood. Restrictive allograft syndrome (RAS) is a recently proposed form of chronic lung rejection typified by restrictive physiology and interstitial infiltrates on CT scan. Few studies have sought associations between clinical criteria and characteristic lung pathology in these patients.

Methods: We retrospectively analyzed a total of 54 pediatric lung transplant recipients who developed BO or BO syndrome and underwent a lung biopsy between 1991 and 2010. Restrictive physiology was identified as a drop in total lung capacity (TLC) of at least 10%. Only open lung biopsies were considered, and transbronchial biopsy results, retransplanted patients, and patients with insufficient pulmonary function testing data were excluded. We used exact chi-square testing to identify whether diffuse alveolar damage and airway fibrosis were more likely to be identified in patients with RAS than in those patients with non-restrictive CLAD.

Results: Restrictive physiology was present in 22 of the 54 patients (41%) who underwent open lung biopsy. Among all patients, airways were more commonly affected than alveoli, and only 2 of 54 patients (4%) had a pattern identified as diffuse alveolar damage. Lung fibrosis was almost always present in patients with restrictive physiology (21/22, 95%), and was significantly less frequent (p=0.02) in those patients without restrictive physiology (22/32, 69%). Airway fibrosis was the most common finding in patients with RAS, with pleural or generalized interstitial fibrosis appearing less frequently.

Conclusion: RAS, while defined clinically, is also associated with a distinct set of pathologic findings, most notably airway fibrosis. Alveolar damage and generalized interstitial fibrosis were found in these patients as well, although these sites were less commonly affected. Future study will be needed to identify the mechanism by which airway fibrosis occurs in this subset of patients, who are thought to have poorer prognosis with shortened graft survival.

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