Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Bronchiolitis obliterans syndrome after lung transplantation

  Bronchiolitis obliterans syndrome remains the leading cause of late graft failure following lung transplantation, accounting for the majority of chronic lung allograft dysfunction diagnoses worldwide. Despite advances in donor selection, surgical technique, and immunosuppression, this fibroproliferative disorder of the small airways continues to limit long-term survival for recipients in every transplant program.

  For clinicians across Australia and the broader Asia-Pacific region, recognising risk factors, applying standardised diagnostic criteria, and initiating timely therapy are core responsibilities. The sections that follow summarise current understanding of pathogenesis, surveillance, and management, with attention to practical considerations relevant to the Australian healthcare context.

  Mechanisms driving chronic lung allograft dysfunction

  Bronchiolitis obliterans syndrome is now understood as the dominant obstructive phenotype of chronic lung allograft dysfunction. Histologically, the disease reflects concentric fibrosis of terminal and respiratory bronchioles, with submucosal collagen deposition and eventual luminal obliteration.

  The injury pattern is the final common pathway of repeated insults. Alloimmune triggers include HLA mismatch, donor-specific antibody formation, and recurrent acute cellular rejection. Non-alloimmune contributors encompass primary graft dysfunction, aspiration related to gastroesophageal reflux, and a wide range of microbial insults. Repair fails because the airway epithelium cannot regenerate a normal pseudostratified lining, and the result is irreversible obstruction.

  Recipient, donor, and environmental risk factors

  Recipient variables such as the underlying indication for transplantation, sensitisation history, and treatment adherence influence the trajectory of the graft. In Australia, indications mirror international patterns, with pulmonary fibrosis, cystic fibrosis, and COPD dominating the waiting lists at The Alfred Hospital in Melbourne and St Vincent's Hospital in Sydney.

  Donor-related risks include advanced age, smoking exposure, and prolonged mechanical ventilation before procurement. Extended-criteria donors are routinely used to address the persistent gap between demand and supply, and Australian retrieval teams coordinate across long distances to maximise utilisation.

  Environmental and infectious exposures add measurable risk. Episodes of poor air quality during Australia's bushfire seasons — most notably the 2019–2020 fires — increase particulate exposure for sensitised recipients, particularly those living in regional New South Wales and Victoria. Chronic airway colonisation with Pseudomonas aeruginosa, Aspergillus species, and community respiratory viruses further accelerates graft injury.

  Defining and staging the syndrome

  The International Society for Heart and Lung Transplantation standardises diagnosis through spirometric criteria. Bronchiolitis obliterans syndrome is defined as a sustained and otherwise unexplained decline in forced expiratory volume in one second of at least 20% from the post-transplant baseline.

  Staging ranges from potential disease (stage 0p, FEV1 81–90% of baseline) through stage 3 (FEV1 ≤ 50% of baseline). The restrictive allograft syndrome phenotype is now recognised separately, with a parallel staging system based on vital capacity decline. Establishing the baseline requires averaging the two best post-operative FEV1 values measured at least three weeks apart, a practical step that influences how Australian pulmonary function laboratories calibrate their quality-control protocols.

  Feature	Obstructive BOS	Restrictive allograft syndrome
  Spirometric pattern	Progressive obstructive decline	Restrictive decline in FVC and TLC
  Typical HRCT	Air trapping, mosaic attenuation	Pleural-based fibrosis, ground-glass opacities
  Azithromycin response	Favourable in a subset	Generally poor
  Median survival after onset	1.5–5 years	12–18 months
  Histology	Small airway fibrosis	Pleuroparenchymal fibroelastosis-like changes

  Surveillance and early detection

  Routine spirometry at each outpatient visit is supplemented in many Australian centres by home-based handheld devices that patients use between appointments. A consistent downward trend of more than 10% over four to six weeks typically triggers formal evaluation.

  High-resolution computed tomography with paired inspiratory and expiratory acquisitions identifies air trapping, bronchial thickening, and early fibrosis. Bronchoscopy with bronchoalveolar lavage remains essential to exclude acute rejection and infection when functional decline is sudden or atypical. Emerging imaging biomarkers such as parametric response mapping hold promise for earlier detection but are not yet part of routine care in most public hospitals.

  Pharmacological and procedural interventions

  After infection and acute rejection have been excluded, a typical first step is a short course of high-dose corticosteroids combined with augmented calcineurin inhibitor exposure. Azithromycin, usually given at 250 mg three times weekly, is widely prescribed for its anti-inflammatory and immunomodulatory properties, although response varies by phenotype.

  For disease that progresses despite first-line measures, options include extracorporeal photopheresis, total lymphoid irradiation, and the antifibrotic agents pirfenidone and nintedanib. Antireflux surgery, when indicated, reduces microaspiration. Retransplantation is the only definitive intervention for carefully selected recipients and is performed at The Alfred, St Vincent's, and The Prince Charles Hospital in Brisbane.

  Outcomes and prognosis

  Outcomes depend on the stage at diagnosis, the rate of FEV1 decline, and the underlying phenotype. Patients with obstructive disease detected at stage 1 and stabilised with treatment may survive several years with preserved functional capacity. Those who progress to stage 3 or who manifest a restrictive phenotype face substantially shorter survival.

  Quality of life, exercise tolerance, and mental health deteriorate in parallel with physiological decline, and transplant psychologists play an important role in long-term care. Early recognition combined with multimodal therapy appears to slow progression in a meaningful proportion of recipients, although reversal of established fibrosis remains uncommon.

  Integration with Australian transplant programs

  Australia's three adult lung transplant centres operate as a coordinated network supported by the Organ and Tissue Authority. The Alfred in Melbourne performs the highest volume nationally, while St Vincent's in Sydney and The Prince Charles Hospital in Brisbane provide complementary capacity and shared retrieval expertise.

  Recipients outside metropolitan areas are followed through shared-care arrangements with regional respiratory physicians, a model that supports continuity for patients travelling long distances from Western Australia, the Northern Territory, and far-western Queensland. Aboriginal and Torres Strait Islander recipients benefit from culturally safe care delivered with Aboriginal Liaison Officers, addressing disparities in referral and post-transplant outcomes.

  Funding through Medicare and the Pharmaceutical Benefits Scheme provides broad access to immunosuppression and antifibrotic agents. Practical barriers remain for families who relocate to capital cities for transplant evaluation and need affordable long-term accommodation, an area where hospital social workers and patient advocacy groups continue to provide essential support.

  What should remain clear is that bronchiolitis obliterans syndrome is a treatable but rarely curable complication, that early detection rests on rigorous spirometric surveillance, and that coordinated multidisciplinary care offers recipients the best chance of long graft survival and meaningful quality of life.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)