Table 8– Key unanswered questions and research needs
Unanswered questions
 1) What are the roles and mechanisms of alloimmune and autoimmune responses in BOS pathogenesis?
 2) Does antibody-mediated rejection play a role in BOS onset and progression?
 3) What is the significance of the appearance of de novo anti-HLA antibodies in BOS pathogenesis, and when and how should screening and treatment for anti-HLA antibodies be performed?
 4) Can specific biomarkers identify and reliably predict increased risk for the development of BOS, and can such biomarkers be used to detect the early (subclinical) onset of BOS?
 5) Can specific BOS phenotypes be identified that are useful for predicting prognosis and response to therapy?
 6) Which specific agent or combinations of post-transplant immunosuppressive agents are most likely to prevent BOS and improve allograft and patient survival?
 7) Does any early, specific therapy significantly alter the natural history of BOS?
 8) When lung retransplantation is performed for end-stage BOS, is the retransplanted lung at increased risk for the development of rejection and/or OB?
 9) Can patients who are more tolerant to their grafts and, therefore, require less intense immunosuppression be identified?
 10) Can induction of tolerance to self-antigens (e.g. collagen V) or strategies to augment regulatory T- or B-cells to promote and maintain tolerance diminish risk for BOS?
 11) Will the use of ex vivo lung perfusion (EVLP) techniques to condition the lung allograft diminish the risk of developing BOS?
 12) What is the optimal frequency for obtaining spirometry to assist in the early detection of evolving BOS?
Research needs
 1) Multi-centre clinical investigations are needed to identify and assess risk factors for BOS.
 2) Multi-centre clinical trials are needed to evaluate potential therapeutic interventions to treat BOS as well as strategies to prevent its onset.
 3) Additional studies of mechanisms and phenotypes (animal models and lung allograft recipients) are needed.
 4) Guidelines for optimal testing for abnormal GOR and the selection of patients (and procedure) for anti-reflux surgery to prevent or treat BOS.
 5) Identification of optimal approaches to allograft surveillance (e.g. the role of bronchoscopy with transbronchial biopsies in clinically stable lung transplant recipients, screening for de novo anti-HLA antibodies and the presence of humoral rejection).
 6) Improved animal and other laboratory models of OB to better understand its pathogenesis and identify key mediators of airway inflammation and fibrosis.
  • BOS: bronchiolitis obliterans syndrome; HLA: human leukocyte antigen; OB: obliterative bronchiolitis; GOR: gastro-oesophageal reflux.