What is pneumonitis?

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From the Guidelines

Pneumonitis is a potentially serious toxicity characterized by inflammation of the lung tissue, which can be triggered by various factors including immune checkpoint inhibitors, with an overall incidence of 2.7% reported in patients treated with PD-1 inhibition 1.

Definition and Causes

Pneumonitis occurs when the tiny air sacs in the lungs (alveoli) become irritated and inflamed, making it difficult to breathe and potentially causing permanent scarring. It can be triggered by exposure to allergens, chemicals, radiation therapy, certain medications, or autoimmune conditions.

Symptoms and Diagnosis

Common symptoms include shortness of breath, dry cough, fatigue, loss of appetite, and unintentional weight loss. The diagnosis of pneumonitis is based on clinical presentation, radiologic findings, and laboratory tests. Ground-glass opacities or patchy nodular infiltrates, predominantly in the lower lobes, are common findings on chest imaging 1.

Treatment and Management

The primary treatment approach involves removing the triggering substance if possible and using corticosteroids like prednisone to reduce inflammation. In severe cases, oxygen therapy or immunosuppressant medications may be necessary. The treatment of patients with symptomatic ICPi pneumonitis with corticosteroids is recommended as an initial treatment, based on several studies that report clinical improvement in > 80% of cases 1.

Key Considerations

Pneumonitis can progress to pulmonary fibrosis, causing permanent lung damage if left untreated. The condition differs from pneumonia because pneumonitis is non-infectious inflammation, while pneumonia is typically caused by infection. Anyone experiencing persistent breathing difficulties should seek medical attention promptly for proper diagnosis and treatment. Some key points to consider in the management of pneumonitis include:

  • The role of transbronchial biopsy is currently debated but generally not required 1
  • The decision to proceed with biopsy should be taken after careful risk-benefit analysis 1
  • The treatment of patients with steroid-refractory pneumonitis is not standardized, but options include infliximab, mycophenolate mofetil, intravenous immune globulin (IVIG), or cyclophosphamide 1

From the Research

Definition of Pneumonitis

  • Pneumonitis is defined as a focal or diffuse inflammation of the lung parenchyma 2
  • It is a known, potentially fatal toxicity of anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors 2

Types of Pneumonitis

  • Hypersensitivity pneumonitis: an immunologically mediated lung disease caused by repeated inhalations of organic antigens 3
  • Immune-related pneumonitis: an uncommon but potentially life-threatening adverse event associated with anti-programmed cell death protein-1 therapy 4

Clinical Presentations

  • Acute form: flu-like symptomatology, followed by dyspnea and dry cough 5
  • Subacute form: progressive dyspnea and dry cough, with constitutional symptoms such as fatigue, anorexia, and weight loss 5
  • Chronic form: insidious onset of dyspnea, coughing, and weight loss, with possible superimposed acute episodes 6

Diagnosis

  • Diagnosis usually rests on a variable combination of findings from history, serology, radiography, lung biopsy, and bronchoalveolar lavage 6
  • Characteristic findings include diffuse ground-glass opacification, centrilobular ground-glass opacities, air trapping, fibrosis, lung cysts, and emphysema on radiologic examination 6
  • Bronchoalveolar lavage reveals a significant increase in lymphocytes, mostly over 40% 5

Treatment

  • Avoidance of the offending antigen(s) is the best therapy 3
  • Corticosteroids are recommended in subacute and chronic forms, and may be necessary to suppress inflammation 2, 3
  • Low-dose glucocorticoids may be maintained in some patients to prevent immune-related pneumonitis 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pneumonitis From Anti-PD-1/ PD-L1 Therapy.

Oncology (Williston Park, N.Y.), 2017

Research

Hypersensitivity pneumonitis: a noninfectious granulomatosis.

Seminars in respiratory infections, 1995

Research

Immune-related pneumonitis requiring low-dose prednisone maintenance in one patient with durable complete response.

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2023

Research

Hypersensitivity pneumonitis : a broader perspective.

Treatments in respiratory medicine, 2006

Research

Hypersensitivity pneumonitis: a historical, clinical, and radiologic review.

Radiographics : a review publication of the Radiological Society of North America, Inc, 2009

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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