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)

• Managing chronic hypersensitivity pneumonitis with antifibrotic agents

  Chronic hypersensitivity pneumonitis is an immune-mediated interstitial lung disease triggered by repeated inhalation of antigens such as avian proteins, fungal spores or thermophilic actinomycetes. When exposure persists or remains unrecognised, the inflammatory infiltrate can evolve into a fibrotic phenotype resembling other progressive pulmonary fibrosing conditions. In Australia, where diverse climates support a wide range of microbial and avian reservoirs, the disease is increasingly encountered in both rural and metropolitan practice.

  Patients with fibrotic hypersensitivity pneumonitis experience exertional dyspnoea, dry cough and progressive loss of lung volumes, mirroring the trajectory seen in idiopathic pulmonary fibrosis. High-resolution computed tomography typically shows a combination of ground-glass opacities, mosaic attenuation, traction bronchiectasis and, in advanced cases, honeycombing. Lung function testing often reveals a restrictive pattern with reduced forced vital capacity and impaired diffusing capacity for carbon monoxide.

  Once a fibrotic phenotype is established, antigen avoidance alone may not halt disease progression. This recognition has shifted clinical attention toward pharmacotherapy that targets fibroproliferation, including the antifibrotic agents originally developed for idiopathic disease. Australian respiratory physicians are now integrating these therapies into multidisciplinary discussions alongside corticosteroids and immunosuppressants.

  The Therapeutic Goods Administration has approved both pirfenidone and nintedanib for progressive fibrosing interstitial lung disease, and listing on the Pharmaceutical Benefits Scheme makes them accessible in public hospitals from Perth to Brisbane. Local real-world cohorts, including patients from the wool-producing tablelands of New South Wales and the dairy belts of Victoria, have informed how these drugs are deployed outside the strict confines of registration trials.

  Recognising the shift from inflammation to fibrosis

  The pathological hallmark of chronic hypersensitivity pneumonitis is a triad of cellular interstitial pneumonia, bronchiolocentric fibrosis and poorly formed granulomas, often with a background of chronic bronchiolitis. Over time, the fibrotic component dominates and the disease enters a self-sustaining phase driven by fibroblast activation and extracellular matrix deposition. This transition marks the window when antifibrotic therapy offers the most tangible benefit.

  Identifying the offending antigen remains a cornerstone of management. In metropolitan areas such as Sydney and Melbourne, bird fancier's lung linked to cockatiels, budgerigars and feather bedding is a frequent culprit, while in inland Queensland and South Australia, thermophilic actinomycetes from mouldy hay or grain storage silos drive farmer's lung. When antigen avoidance is achieved early, inflammation may resolve; once fibrosis is established, structural lung damage tends to progress regardless.

  Diagnostic nuances for clinicians across Australia

  Diagnosing fibrotic hypersensitivity pneumonitis requires integration of exposure history, radiological pattern, bronchoalveolar lavage lymphocytosis and, when feasible, histopathological confirmation. Multidisciplinary discussion is considered the reference standard, particularly when features overlap with idiopathic pulmonary fibrosis or sarcoidosis. Lung Foundation Australia and the Thoracic Society of Australia and New Zealand have promoted standardised diagnostic pathways to support clinicians working outside tertiary centres.

  In rural and remote communities, telehealth-enabled multidisciplinary meetings hosted through services such as the Royal Flying Doctor Service have improved access to specialist input. Peripheral centres in places like Cairns, Launceston or Whyalla can now present imaging and pulmonary function data to metropolitan panels, ensuring that diagnostic uncertainty does not delay appropriate antifibrotic therapy.

  Choosing between the two licensed antifibrotics

  Two oral antifibrotic agents are available in Australia for progressive fibrosing disease. Their mechanisms, evidence base and tolerability profiles differ in clinically meaningful ways.

  Feature	Pirfenidone	Nintedanib
  Mechanism	Modulates TGF-β, TNF-α and collagen synthesis	Tyrosine kinase inhibitor targeting FGF, PDGF and VEGF receptors
  Pivotal evidence in fibrotic HP	Small randomised and open-label cohorts suggest FVC stabilisation	INBUILD trial subgroup and real-world data show slowing of FVC decline
  Common adverse effects	Photosensitivity, nausea, rash, fatigue	Diarrhoea, nausea, elevated liver enzymes, weight loss
  Typical daily dose	2403 mg in three divided doses	300 mg daily in two divided doses
  Liver function monitoring	Monthly for first six months, then periodically	Monthly for first three months, then periodically
  Pharmaceutical Benefits Scheme listing	Progressive fibrosing ILD including fibrotic HP	Progressive fibrosing ILD including fibrotic HP

  In Australian practice, choice often depends on comorbidity profile, pill burden tolerance and the patient's capacity to adhere to sun-protection measures. Those working outdoors in regions such as the Murray-Darling basin or the Pilbara are counselled about strict photoprotection with pirfenidone, while patients with a history of gastrointestinal disturbance may lean toward the alternative.

  Integrating antifibrotics into long-term care

  Before starting antifibrotics, baseline assessment should include full pulmonary function testing, six-minute walk distance, liver function tests and a comprehensive medication review. Nurses and pharmacists embedded in interstitial lung disease clinics in major hospitals such as the Royal Brisbane and Women's, The Alfred in Melbourne and Westmead in Sydney coordinate this workup and provide ongoing education.

  Adherence support is crucial. Patients are encouraged to take medications with food, manage gastrointestinal side effects proactively, and report any new symptoms such as jaundice or unexplained bruising. Smoking cessation, vaccination including annual influenza and pneumococcal immunisation, and pulmonary rehabilitation programs delivered through local health networks all complement antifibrotic therapy.

  Evolving evidence and future directions

  Several international trials are now specifically enrolling patients with fibrotic hypersensitivity pneumonitis, and Australian sites in Melbourne, Adelaide and Perth have contributed to recruitment. These studies aim to clarify whether antifibrotics alter mortality, hospitalisation rates and quality of life beyond the surrogate endpoint of forced vital capacity. Genomic and biomarker research is also progressing, with hopes of identifying which patients will derive the greatest benefit.

  Antifibrotic therapy should be viewed as one component of a broader management strategy that begins with meticulous antigen identification and continues with structured follow-up. For Australian clinicians, the practical message is to recognise the fibrotic phenotype early, refer promptly for multidisciplinary input, and initiate disease-modifying treatment before irreversible architectural distortion has occurred.

  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)