Immunomodulatory treatment of interstitial lung disease

Ther Adv Respir Dis. 2022 Jan-Dec:16:17534666221117002. doi: 10.1177/17534666221117002.


Interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) have an array of immunomodulatory treatment options compared with IPF, due to their inflammatory component. However, there is a relative paucity of guidance on the management of this heterogeneous group of diseases. In ILDs other than IPF, immunosuppression is the cornerstone of therapy, with varying levels of evidence for different immunomodulatory agents and for each specific ILD. Classification of ILDs is important for guiding treatment decisions. Immunomodulatory agents mainly include corticosteroids, mycophenolate mofetil (MMF), azathioprine, methotrexate, cyclophosphamide and rituximab. In this review, the available evidence for single agents in the most common ILDs is first discussed. We then reviewed practical therapeutic approaches in connective tissue disease-related ILD and interstitial pneumonia with autoimmune features, scleroderma-related ILD, vasculitis and dermatomyositis with hypoxemic respiratory failure, idiopathic non-specific interstitial pneumonia, hypersensitivity pneumonitis sarcoidosis, fibrosing organizing pneumonia and eosinophilic pneumonia. The treatment of acute exacerbations of ILD is also discussed. Therapy augmentation in ILD is dictated by the recognition of progression of disease. Criteria for the evaluation of progression of disease are then discussed. Finally, specific protocol and measures to increase patients' safety are reviewed as well, including general monitoring and serologic surveillance, Pneumocystis jirovecii prophylaxis, patients' education, genetic testing for azathioprine, MMF serum levels and cyclophosphamide administration protocols. Immunomodulatory therapies are largely successful in the management of ILDs and can be safely managed with the application of specific protocols, precautions and monitoring.

Keywords: immunomodulatory; immunosuppressive; interstitial lung disease; therapy; treatment.

Publication types

  • Review

MeSH terms

  • Azathioprine / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Humans
  • Idiopathic Pulmonary Fibrosis* / drug therapy
  • Immunomodulation
  • Lung Diseases, Interstitial* / diagnosis
  • Lung Diseases, Interstitial* / drug therapy


  • Cyclophosphamide
  • Azathioprine