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)

• Radiological Patterns of Drug-Induced Pulmonary Injury in Practice

  Drug-induced pulmonary injury remains one of the most demanding diagnostic puzzles in respiratory medicine. When a patient develops new respiratory symptoms while on medication, distinguishing between infection, disease progression, and an adverse drug reaction requires careful integration of clinical history, laboratory findings, and imaging characteristics. The lungs respond to drug toxicity through a limited repertoire of patterns, yet the underlying causes range from common cardiovascular medications to modern cancer immunotherapies.

  Radiology sits at the centre of this process. High-resolution computed tomography (HRCT) offers a window into parenchymal changes invisible on plain radiographs, allowing clinicians to identify patterns such as ground-glass opacities, consolidation, or reticulation. When interpreted alongside the timing of drug exposure, these patterns often point toward a specific class of culprit medication. Without systematic imaging review, drug-induced lung disease can progress to irreversible fibrosis before the connection is recognised.

  In Australia, the clinical relevance of this topic continues to grow. An ageing population in cities like Sydney and Melbourne is increasingly prescribed amiodarone for atrial fibrillation, methotrexate for autoimmune arthritis, and immune checkpoint inhibitors for lung cancer and melanoma. The Pharmaceutical Benefits Scheme subsidises many of these agents, widening their use across metropolitan and regional centres. Pulmonologists at institutions such as Royal Prince Alfred Hospital and the Royal Melbourne Hospital frequently encounter complex cases demanding precise radiological interpretation.

  This overview examines the radiological patterns that characterise drug-induced pulmonary injury, the medications most commonly implicated in Australian practice, and the practical steps clinicians can take when imaging raises suspicion of an adverse drug reaction.

  Imaging Modalities and the Australian Context

  Selecting the right imaging modality is the first step toward identifying drug-related lung injury. Chest radiography remains the initial investigation in most Australian emergency departments and general practice clinics, but its sensitivity for early parenchymal change is limited. HRCT has become the cornerstone of evaluation because it captures fine architectural detail that plain films miss, particularly subtle ground-glass change and early fibrosis. Teleradiology networks now extend specialist interpretation to regional towns such as Broome and Mount Isa.

  Modality	Strengths	Limitations	Best Use Case
  Chest radiography	Widely available, low radiation, inexpensive	Low sensitivity for early interstitial change	Initial screening, monitoring known disease
  HRCT	High spatial resolution, pattern recognition	Higher radiation, cost, need for specialist interpretation	Suspected drug-induced lung injury with normal or equivocal radiograph
  FDG-PET/CT	Functional assessment, distinguishes active inflammation from fibrosis	Limited availability, high cost, radiation burden	Oncology patients on immune checkpoint inhibitors with equivocal HRCT

  In Australian practice, the decision to proceed from chest radiography to HRCT is guided by Lung Foundation Australia pathways and local multidisciplinary discussion. Embedding imaging review within a team of respiratory physicians, radiologists, and pharmacists shortens time to diagnosis and reduces missed drug-related events. For patients with chronic suppurative lung conditions, recent commentary on airway clearance techniques underscores how integrated respiratory care complements imaging-based assessment.

  Common Culprit Medications in Practice

  Drug-induced pulmonary injury arises from agents encountered across nearly every medical specialty. Australian prescribers should remain alert to lung toxicity from medications used in cardiology, oncology, rheumatology, and infectious disease.

  Among cardiovascular agents, amiodarone remains a leading cause, particularly in older patients. Its lipophilic nature leads to lung accumulation, producing patterns ranging from organising pneumonia to established fibrosis. Bleomycin, used in current regimens for Hodgkin lymphoma and germ cell tumours, causes dose-dependent pneumonitis. Immune checkpoint inhibitors such as nivolumab and pembrolizumab, widely subsidised through the Pharmaceutical Benefits Scheme, trigger immune-related pneumonitis that mimics infection or disease progression.

  The most frequently implicated drug classes in Australian practice include:

  • Antiarrhythmics, particularly amiodarone, with risk rising after prolonged high cumulative doses
  • Cytotoxic agents including bleomycin, methotrexate, and cyclophosphamide
  • Biologic therapies such as immune checkpoint inhibitors and TNF inhibitors
  • Antimicrobial agents including nitrofurantoin, often prescribed for recurrent urinary tract infections in older women

  Key HRCT Patterns and Their Signatures

  Although drug-induced pulmonary injury produces overlapping appearances, certain HRCT patterns are encountered more often with specific drug classes. Recognising these signatures allows the radiologist to suggest a drug-related cause even when the clinical history is incomplete.

  Ground-glass opacity is the most frequently observed pattern and appears with hypersensitivity reactions to methotrexate, nitrofurantoin, and checkpoint inhibitors. Consolidation typically signals organising pneumonia, classically linked to amiodarone but also reported with bleomycin. Reticulation with traction bronchiectasis suggests established fibrosis, often the consequence of delayed recognition of earlier injury.

  Patterns useful for narrowing the differential include:

  • Diffuse alveolar damage, producing widespread ground-glass opacity and dependent consolidation, typically seen with cytotoxic agents and severe immune-related pneumonitis
  • Eosinophilic pneumonia, presenting as peripheral consolidation with upper lobe predominance, associated with dapsone, sulfonamides, or nitrofurantoin
  • High-attenuation parenchymal opacities, a distinctive feature of amiodarone toxicity due to iodine deposition, visible on non-contrast CT
  • Pleural effusion or lymphadenopathy, which may point toward drug-induced lupus-like reactions from hydralazine or procainamide

  Pathophysiology and Risk Factors

  The mechanisms underlying drug-induced pulmonary injury reflect the molecular targets of each agent. Direct cytotoxicity, immune-mediated inflammation, and oxidative stress are the three dominant pathways, with overlap common.

  Patient-related risk factors significantly modify the likelihood of pulmonary toxicity. Older age, pre-existing lung disease, renal impairment, and concurrent thoracic irradiation increase vulnerability. In Australia, the high prevalence of cigarette smoking among older adults compounds the risk for those starting amiodarone or bleomycin. Aboriginal and Torres Strait Islander patients, who experience higher rates of chronic respiratory disease, may be disproportionately affected, although robust Australian data on this specific question remain limited.

  Diagnostic Approach and Differential Diagnosis

  A structured diagnostic approach improves recognition of drug-induced lung injury. This includes establishing a clear timeline of drug exposure relative to symptom onset, excluding infection through sputum culture and serum biomarkers, and reviewing serial imaging to assess evolution. Multidisciplinary review, common in Australian tertiary centres, brings together the expertise needed to weigh competing diagnoses.

  The differential diagnosis includes community-acquired pneumonia, pulmonary oedema, disease progression in known interstitial lung disease, and carcinomatous lymphangitis. Distinguishing these entities often requires bronchoscopy with bronchoalveolar lavage. Documenting suspected drug toxicity and notifying the Therapeutic Goods Administration are key elements of safe practice. Australian clinicians can access guidance from the Thoracic Society of Australia and New Zealand, which regularly updates consensus statements on interstitial lung disease.

  Clinical Management and Follow-up

  Management centres on early recognition and prompt withdrawal of the offending agent where possible. Corticosteroids are commonly used for immune-mediated patterns, although the evidence base is largely observational. Supportive care, including oxygen therapy and pulmonary rehabilitation, plays an important role in recovery, particularly for Australian patients in rural settings who benefit from telehealth-supported rehabilitation programs.

  Follow-up imaging is critical to document resolution and detect progression toward fibrosis. HRCT at three to six months after drug withdrawal provides a useful baseline, with further imaging guided by symptoms. Patients with established fibrotic change may require long-term surveillance.

  The next practical step for clinicians is to convene a multidisciplinary discussion within two weeks, document the suspected agent with the Therapeutic Goods Administration, and arrange HRCT review to guide ongoing management.

  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)