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)

• Immunotherapy-related pneumonitis in lung cancer care

  Immune checkpoint inhibitors have changed treatment for many people with non-small cell lung cancer and small cell lung cancer. By releasing the immune system’s brakes, medicines such as pembrolizumab, nivolumab, atezolizumab and durvalumab can produce durable tumour control. The same immune activation can, however, inflame healthy lung tissue and cause pneumonitis.

  This complication ranges from mild radiographic changes to rapidly progressive respiratory failure. Early recognition is especially important in Australia, where patients may travel long distances between regional areas and specialist centres in Sydney, Melbourne, Brisbane or Perth. A new cough or breathlessness should be assessed promptly rather than attributed to seasonal infection, smoking history or reduced fitness.

  Recognising the clinical pattern

  Symptoms commonly include dry cough, exertional dyspnoea, fever, chest tightness and falling oxygen saturation. Some patients have no symptoms and are diagnosed when a surveillance CT shows new ground-glass opacities or organising pneumonia. Symptoms may develop after a few treatment cycles, although late presentations can occur months after immunotherapy has stopped.

  The differential diagnosis is broad. Infection, pulmonary embolism, tumour progression, lymphangitic spread, heart failure, aspiration and radiation pneumonitis can appear similar. In Australia, clinicians should also consider influenza, COVID-19, bacterial pneumonia and environmental exposures associated with bushfire smoke or dust. A careful medication history, recent radiotherapy review and comparison with prior imaging are essential.

  Respiratory symptoms need a severity assessment based on functional change, oxygenation and radiological extent. A patient who is comfortable at rest but becomes breathless walking from the bedroom to the kitchen is clinically different from someone who needs oxygen or cannot complete a sentence. Pulse oximetry, full blood count, inflammatory markers, renal and liver tests, and chest imaging help establish an initial baseline.

  Investigating suspected immune-mediated lung injury

  High-resolution CT is generally more informative than a plain chest X-ray. Common patterns include organising pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis and diffuse alveolar damage. The imaging pattern can support the diagnosis, but it cannot prove that checkpoint blockade is responsible.

  Microbiological testing should be guided by the presentation and immune status. Depending on severity, this may include respiratory viral PCR, sputum culture, blood cultures, urinary antigens and testing for Pneumocystis jirovecii. Bronchoscopy with bronchoalveolar lavage can help exclude infection or malignant cells, particularly when the diagnosis is uncertain or the patient is deteriorating. It should not delay treatment in severe hypoxaemia.

  Multidisciplinary discussion is valuable. A medical oncologist, respiratory physician, radiologist, infectious diseases specialist and, when required, an intensive care team can balance diagnostic certainty against treatment urgency. Education from major respiratory meetings, including the respiratory congress context, can support consistent approaches to complex immune-related adverse events.

  Treatment according to severity

  For asymptomatic grade 1 changes, the oncology team may continue or temporarily pause immunotherapy, repeat imaging and monitor symptoms closely. Any deterioration should trigger reassessment. Patients should receive clear advice about reporting increasing cough, fever, chest pain or breathlessness, rather than waiting for their next infusion appointment.

  For symptomatic grade 2 disease, checkpoint therapy is usually withheld and corticosteroids are commenced, commonly oral prednisone at approximately 1 mg/kg/day after infection has been considered. Improvement is often followed by a slow taper over at least four to six weeks, because rapid reduction can lead to relapse. Grade 3 or 4 pneumonitis requires hospital admission, oxygen support and intravenous methylprednisolone, often at 1–2 mg/kg/day or according to local protocol.

  If severe disease fails to improve after 48–72 hours, specialist teams may consider additional immunosuppression such as mycophenolate mofetil, intravenous immunoglobulin or infliximab. Treatment choices depend on infection risk, liver function, cardiac status and the possibility of an alternative diagnosis. Prolonged corticosteroid exposure also raises the risk of hyperglycaemia, mood change, osteoporosis and opportunistic infection, so monitoring and prevention matter.

  Balancing cancer control and treatment safety

  The decision to restart immunotherapy is individual. Permanent discontinuation is generally favoured after life-threatening pneumonitis or recurrent clinically significant toxicity. Rechallenge may be discussed after complete resolution of a mild episode, particularly when the cancer has limited alternatives and the initial event had a clear, reversible trigger.

  Before restarting, clinicians should review symptoms, oxygen requirements, CT findings and lung function. A patient with pre-existing chronic obstructive pulmonary disease, pulmonary fibrosis, previous thoracic radiotherapy or extensive smoking exposure may have less respiratory reserve. The risk can be higher when immune checkpoint inhibitors are combined with chemotherapy or other systemic treatments.

  Australian access and governance also influence care. Medicines used for lung cancer may be supplied through the Pharmaceutical Benefits Scheme under specific eligibility criteria, while the Therapeutic Goods Administration regulates approval and safety reporting. Treatment discussions should explain both the clinical evidence and practical realities, including travel to infusion services, private versus public hospital pathways and the cost of repeated investigations.

  Distinguishing common causes of breathlessness

  Feature	Immune-mediated pneumonitis	Infection	Tumour progression	Radiation pneumonitis
  Typical timing	Weeks to months after checkpoint therapy, sometimes later	Any time, often with exposure or immune suppression	Gradual or progressive	Usually 1–6 months after thoracic radiotherapy
  Symptoms	Dry cough, exertional breathlessness, fever possible	Fever, productive cough, rigors or systemic illness	Worsening cough, pain, weight loss or declining exercise tolerance	Cough and breathlessness within the irradiated field
  CT pattern	Ground glass, organising pneumonia or diffuse bilateral change	Lobar, bronchopneumonia or diffuse infectious pattern	New masses, nodules, lymphangitic spread or effusion	Geographic change matching the radiation field
  Key tests	High-resolution CT, cultures and sometimes bronchoscopy	Viral PCR, cultures, antigens and bronchoscopy when needed	CT comparison, PET-CT or tissue sampling	Imaging distribution and radiotherapy plan
  Initial direction	Hold therapy and use corticosteroids when appropriate	Prompt antimicrobial treatment	Reassess cancer treatment and obtain tissue when needed	Corticosteroids after infection is excluded

  Building a safer follow-up plan

  Every patient starting immune checkpoint blockade should know which respiratory symptoms require urgent contact. Written instructions are useful because mild cough can become significant between appointments. A baseline assessment of smoking, previous lung disease, oxygen saturation, CT findings and exercise tolerance makes later changes easier to identify.

  Follow-up should combine symptom review with examination, pulse oximetry and imaging when clinically indicated. Telehealth can help people in rural and regional Australia report early changes, but it cannot replace an examination when oxygen levels are falling. Smoke haze, long drives to metropolitan hospitals and delays in obtaining pathology should be considered when arranging monitoring.

  Patients receiving high-dose steroids may need glucose monitoring, bone protection and prophylaxis against Pneumocystis jirovecii, depending on dose and duration. Vaccination, infection precautions and medication reconciliation should be discussed in line with local policy. A practical safety rule is to treat new breathlessness during or after immunotherapy as a clinical warning: check oxygenation, exclude infection and other urgent causes, pause the suspected treatment when indicated, and involve respiratory and oncology specialists early.

  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)