Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors

Respiration. 2020;99(2):181-186. doi: 10.1159/000504968. Epub 2020 Jan 8.

Abstract

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

Keywords: Bronchiolitis; Bronchitis; Drug-related side effects and adverse reactions; Immunotherapy; Ipilimumab; Lung; Nivolumab.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / secondary
  • Adrenal Gland Neoplasms / secondary
  • Adrenal Gland Neoplasms / surgery
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Aged
  • Bronchial Diseases / chemically induced*
  • Bronchial Diseases / drug therapy
  • Bronchial Diseases / physiopathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoscopy
  • Dyspnea / chemically induced*
  • Dyspnea / drug therapy
  • Dyspnea / physiopathology
  • Female
  • Forced Expiratory Volume
  • Glucocorticoids / therapeutic use
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Mediastinum
  • Melanoma / drug therapy*
  • Middle Aged
  • Nivolumab / adverse effects
  • Pulmonary Diffusing Capacity
  • Respiratory Insufficiency / chemically induced*
  • Respiratory Insufficiency / drug therapy
  • Respiratory Insufficiency / physiopathology
  • Skin Neoplasms / drug therapy*
  • Tomography, X-Ray Computed

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Glucocorticoids
  • Immune Checkpoint Inhibitors
  • Nivolumab