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 Drug-Induced Interstitial Lung Disease in Clinical Practice

  Drug-induced interstitial lung disease sits firmly on the agenda of every respiratory physician because its presentation often mimics infection, heart failure, or progression of an underlying connective tissue disorder. The list of causative agents keeps growing as targeted oncology therapies, biologic immunomodulators, and even commonly prescribed cardiovascular drugs continue to demonstrate pulmonary toxicity. Clinicians working in thoracic medicine therefore need a structured approach that combines vigilance, early imaging, and a clear dechallenge pathway.

  In Australia, management is shaped by national pharmacovigilance frameworks and by clinical guidelines published through the Thoracic Society of Australia and New Zealand. The Therapeutic Goods Administration maintains the Adverse Drug Reaction Reporting System, while the Pharmaceutical Benefits Scheme subsidises many of the agents most often implicated in interstitial injury. Patients in metropolitan centres such as Sydney, Melbourne, Brisbane, and Perth generally have access to multidisciplinary interstitial lung disease meetings, although rural and remote consumers often rely on telehealth links and outreach respiratory services.

  This overview outlines a practical pathway for recognising drug-induced pulmonary toxicity, establishing causality, withdrawing the offending agent, and coordinating ongoing care. It draws on Australian prescribing patterns, locally available imaging and laboratory resources, and the regulatory environment that surrounds adverse event reporting in this country.

  Recognising the Spectrum of Drug-Induced Lung Injury

  Drug-induced interstitial lung disease does not present as a single entity. Instead, the histopathological and radiographic patterns vary widely, ranging from acute hypersensitivity pneumonitis and organising pneumonia through non-specific interstitial pneumonia and diffuse alveolar damage to patterns resembling pulmonary alveolar proteinosis. Latency also differs: some reactions occur within days of the first dose, while others emerge only after months or years of cumulative exposure. Recognising this heterogeneity is the first step toward avoiding diagnostic anchoring on a single disease label.

  A careful drug history remains the cornerstone of clinical assessment. Patients should be asked about prescription items, over-the-counter products, complementary medicines, and recreational substances, because products available through Australian compounding pharmacies or imported under the Special Access Scheme are not always captured in routine medication reconciliation. Linking the temporal relationship between exposure and symptom onset to a compatible imaging pattern is what separates a credible diagnosis from a coincidental finding.

  High-Risk Medication Classes Frequently Prescribed in Australia

  Several medication classes dominate Australian case series of drug-induced interstitial lung disease. Amiodarone, still widely used for atrial fibrillation in older patients, can produce both acute inflammatory pneumonitis and chronic interstitial fibrosis, often after cumulative doses exceeding 400 milligrams per day for prolonged periods. Nitrofurantoin, commonly prescribed in primary care for recurrent urinary tract infections, classically produces an acute hypersensitivity reaction that may be mistaken for community-acquired pneumonia.

  Oncology agents create a particularly heavy burden. Immune checkpoint inhibitors approved through the Pharmaceutical Benefits Scheme for melanoma, non-small cell lung cancer, and renal cell carcinoma carry well-recognised risks of immune-related pneumonitis. Bleomycin, methotrexate, and certain tyrosine kinase inhibitors remain part of Australian treatment protocols and continue to surface in respiratory referrals. More recently, antibody-drug conjugates and combination regimens used in haematology have added new patterns of pulmonary toxicity that Australian pharmacists are now encouraged to flag during medication review.

  Diagnostic Pathways and Imaging

  High-resolution computed tomography of the chest forms the backbone of investigation. Ground-glass opacification, consolidation, reticulation, and traction bronchiectasis appear in different combinations depending on the pattern of injury, and distribution can offer clues to specific agents. Bronchoalveolar lavage is performed selectively, particularly when infection must be excluded, while transbronchial or surgical lung biopsy is reserved for cases where imaging and drug history leave real diagnostic doubt.

  Australian respiratory laboratories typically report lymphocyte subsets, CD4/CD8 ratios, and microbiological panels that help differentiate drug-induced pneumonitis from sarcoidosis, hypersensitivity pneumonitis from environmental triggers, and organising pneumonia from cryptogenic disease. Pulmonary function testing with serial transfer factor for carbon monoxide provides an objective marker of disease activity and is widely available across tertiary centres such as the Royal Prince Alfred, The Alfred, and The Prince Charles Hospital.

  Causality Assessment Tools

  Formal scoring systems support clinical judgement. The Naranjo algorithm and the World Health Organization-Uppsala Monitoring Centre categories offer structured frameworks, although both were designed for broader adverse drug reactions and require adaptation for pulmonary events. Modified pulmonary-specific criteria assign weight to latency, dechallenge response, rechallenge behaviour, and the presence of competing diagnoses.

  Practical application involves documenting the timeline carefully, recording baseline imaging or lung function where available, and seeking consensus through a multidisciplinary interstitial lung disease meeting. Australian centres increasingly embed pharmacists in these discussions to capture dispensing data and to verify adherence, particularly when patients are managed across both public and private healthcare settings.

  Pharmacovigilance and Adverse Event Reporting

  Reporting suspected adverse drug reactions to the Therapeutic Goods Administration is a professional obligation and a critical safeguard. Under-reporting remains a recognised weakness, particularly for delayed toxicities that emerge after discharge from oncology or cardiology services. Embedding a simple reporting prompt into electronic prescribing systems, discharge summaries, and outpatient letters can lift reporting rates substantially.

  Collaboration with the Thoracic Society of Australia and New Zealand supports educational outreach and the development of position statements on emerging toxicities. Regional adverse drug reaction committees, often coordinated through state pharmacovigilance centres, provide a forum for discussing complex cases and for sharing deidentified data with international registries.

  Treatment Strategies After Drug Withdrawal

  Stopping the offending drug is non-negotiable and should occur as soon as a plausible alternative explanation has been excluded. Corticosteroids are the mainstay of pharmacological treatment, with typical starting doses of 0.75 to 1 milligram per kilogram of prednisone equivalent tapered over weeks to months according to clinical and physiological response. In steroid-refractory checkpoint inhibitor pneumonitis, additional immunosuppression with infliximab, mycophenolate, or intravenous immunoglobulin may be required.

  Supportive care includes supplemental oxygen, pulmonary rehabilitation referral, and vaccination updates to reduce the risk of subsequent respiratory infection. Antifibrotic therapy, originally approved through the Pharmaceutical Benefits Scheme for idiopathic pulmonary fibrosis, is now studied in progressive fibrosing interstitial lung disease and may have a role in selected drug-induced cases with established fibrosis.

  Multidisciplinary Care Across Australian Centres

  Coordination between respiratory physicians, oncologists, cardiologists, pharmacists, and primary care practitioners is essential, particularly when a vital therapy cannot simply be discontinued. Regular case conferences, accessible through the Royal Australasian College of Physicians continuing professional development network, allow clinicians in Hobart, Darwin, and regional New South Wales to present cases to metropolitan expert panels. This model reduces professional isolation and shortens time to diagnosis for patients living outside major teaching hospitals.

  Practical Treatment Comparison

  Strategy	Typical Indication	Australian Access Considerations
  Corticosteroid taper	Acute inflammatory DILD, organising pneumonia	PBS-subsidised; outpatient taper protocols established
  Antifibrotic therapy	Progressive fibrosing phenotype post-injury	PBS-listed for IPF; access for post-DILD fibrosis varies by indication
  Infliximab or mycophenolate	Steroid-refractory checkpoint inhibitor pneumonitis	Hospital-based infusion; requires specialist approval
  Supportive oxygen and rehabilitation	Persistent hypoxaemia, functional decline	Available through community and rural services

  Recommendations for Australian Clinicians

  • Document a structured drug timeline at the first suspicion of drug-induced interstitial lung disease, including complementary and compounded products.
  • Arrange baseline and serial transfer factor measurements whenever feasible to track physiological decline or recovery.
  • Report all suspected cases to the Therapeutic Goods Administration, even when causality seems certain, to strengthen pharmacovigilance data.
  • Engage a multidisciplinary interstitial lung disease meeting before initiating steroid-sparing immunosuppression or considering rechallenge.
  • Provide patients with a written action plan listing the implicated drug, warning symptoms, and emergency contact details.

  Embedding a five-minute drug-induced interstitial lung disease review into every outpatient consultation for a patient on a known high-risk agent is a single concrete change that can shift detection earlier and reduce irreversible fibrosis.

  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)