Guideline sources The following summarized guidelines for the management of bronchiolitis obliterans syndrome (BOS) are prepared by our editorial team based on guidelines from the British Thoracic Society (BTS 2020) and the European Respiratory Society (ERS/ATS/ISHLT 2014). 1 2 3 3 4 5 Definition BOS is a form of chronic lung allograft dysfunction characterized by progressive airflow obstruction in the absence of acute rejection, infection, or other coexistent conditions. 3 Epidemiology BOS is caused by immune-mediated injury (alloimmune T-cell reactivity, humoral immunity, autoimmunity, pulmonary innate immunity) and environmental insults. 3 Disease course BOS manifests as progressive dyspnea and cough, with imaging features of constrictive bronchiolitis, airway distortion, and subepithelial fibrosis. 4 Prognosis and risk of recurrence Severe BOS is associated with a mortality of 66.6%. 5 https://web.pathway.md/diseases/recIgNOy9NrPRdTwU 1/3 6/29/23, 3:21 AM Bronchiolitis obliterans syndrome Pathway Guidelines 1. Medical management High-dose corticosteroids: consider avoiding long-term, high-dose corticosteroids for lung transplant recipients who develop a decline in FEV in 1 second consistent with the onset of BOS. D Tacrolimus: consider switching from cyclosporine to tacrolimus in lung transplant recipients who develop BOS while receiving chronic immunosuppression with a regimen that includes cyclosporine. C Azithromycin: As per ERS 2020 guidelines, consider offering low-dose azithromycin (250 mg alternate days for a trial period of 3 months) for the treatment of bronchiolitis obliterans in lung transplant recipients. C As per ISHLT 2014 guidelines, consider a trial of azithromycin for lung transplant recipients who develop a decline in FEV in 1 second consistent with the onset of BOS. C 2. Surgical interventions Fundoplication: consider referral to an experienced surgeon to evaluate for potential fundoplication of the gastro-oesophageal junction in lung transplant recipients who develop a decline in FEV in 1 second consistent with the onset of BOS and have confirmed gastro- oesophageal reflux. C Re-transplantation: refer lung transplant recipients with refractory, end-stage BOS to a transplant surgeon to be evaluated for re-transplantation. B 3. Preventative measures Primary prevention: As per ERS 2020 guidelines, consider offering low-dose, long-term azithromycin (250 mg thrice weekly) for the prevention of BOS after lung transplantation. C As per ISHLT 2014 guidelines, consider augmented immunosuppression with a course of systemic steroids to prevent the development of BOS in lung transplant recipients who have non-minimal acute cellular rejection (grade 2) or lymphocytic bronchitis on transbronchial lung biopsy specimens. C Clinical findings Symptoms Past medical history https://web.pathway.md/diseases/recIgNOy9NrPRdTwU 2/3 6/29/23, 3:21 AM Bronchiolitis obliterans syndrome Pathway Asymptomatic Chronic disease Dry cough Inflammation Dyspnea No asthma Fatigue Imaging findings Flu-like symptoms Infection Lung consolidation No cold Symptoms flare up with exercising Respiratory exam Dyspnea Wheezing References 1. Meyer KC, Raghu G, Verleden GM et al. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014 Dec;44 6 1479 503. Open 2. David Smith, Ingrid Du Rand, Charlotte Louise Addy et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease. Thorax. 2020 May;75 5 370 404. Open 3. Jamie L Todd, Scott M Palmer. Bronchiolitis obliterans syndrome: the final frontier for lung transplantation. Chest. 2011 Aug;140 2 502 508. Open 4. Patrick R Aguilar, Andrew P Michelson, Warren Isakow. Obliterative Bronchiolitis. Transplantation. 2016 Feb;100 2 272 83.2016 Feb;100 2 272 83. Open 5. M T Parada, A Alba, C Sep lveda. Bronchiolitis obliterans syndrome development in lung transplantation patients. Transplant Proc. Jan-Feb 2010;42 1 331 2. Open 6. Patrick R Aguilar, Andrew P Michelson, Warren Isakow. Obliterative Bronchiolitis. Transplantation. 2016 Feb;100 2 272 83. Open 7. Jamie L Todd, Scott M Palmer. Bronchiolitis obliterans syndrome: the final frontier for lung transplantation. Chest. 2011 Aug;140 2 502 508.2011 Aug;140 2 502 508. Open 8. M T Parada, A Alba, C Sepulveda. Bronchiolitis obliterans syndrome development in lung transplantation patients. Transplant Proc. Jan-Feb 2010;42 1 331 2.Jan-Feb 2010;42 1 331 2. Open 9. Anand Padmanabhan, Laura Connelly-Smith, Nicole Aqui et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019 Jun;34 3 171 354. Open https://web.pathway.md/diseases/recIgNOy9NrPRdTwU 3/3