Drug-induced interstitial lung disease: a narrative review of a clinical conundrum

ABSTRACT

Introduction

Drug-induced interstitial lung disease (DI-ILD) is increasing in incidence, due to the use of many new drugs across a broad range of cancers and chronic inflammatory diseases. The presentation and onset of DI-ILD are variable even for the same drug across different individuals. Clinical suspicion is essential for identifying these conditions, with timely drug cessation an important determinant of outcomes.

Areas covered

This review provides a comprehensive and up-to-date summary of epidemiology, risk factors, pathogenesis, diagnosis, treatment, and prognosis of DI-ILD. Relevant research articles from PubMed and Medline searches up to September 2023 were screened and summarized. Specific drugs including immune checkpoint inhibitors, CAR-T cell therapy, methotrexate, and amiodarone are discussed in detail. The potential role of pharmacogenomic profiling for lung toxicity risk is considered.

Expert opinion

DI-ILD is likely to be an increasingly important contributor to respiratory disability in the community. These conditions can negatively impact quality of life and patient longevity, due to associated respiratory compromise as well as cessation of evidence-based therapy for the underlying disease. This clinical conundrum is relevant to all areas of medicine, necessitating increased understanding and greater vigilance for drug-related lung toxicity.

KEYWORDS:

• Drug-induced interstitial lung disease
• pneumonitis
• pulmonary fibrosis
• pulmonary toxicity
• immune checkpoint inhibitors
• methotrexate
• amiodarone
• CAR-T cell therapy

Article highlights

• Drug-induced interstitial lung disease (DI-ILD) is increasing in incidence but remains under-recognized. The spectrum of presentations includes asymptomatic transient lung infiltrates to fulminant respiratory failure from diffuse alveolar damage, with fatal outcomes.

• Diagnostic evaluation includes having a suspicion of the culprit drug and exclusion of other potential etiologies. Tissue diagnosis is seldom indicated; however, bronchoalveolar lavage can provide useful diagnostic information and may help to exclude alternative causes.

• Immune checkpoint inhibitors (ICIs) are important causes for DI-ILD, along with many other cancer and rheumatologic therapies.

• Careful screening and surveillance for pulmonary toxicity is essential, particularly in those with risk factors such preexisting lung disease (particularly ILD), older age, smoking, and concomitant therapies including chemotherapy and ionizing radiation.

• Drug withdrawal may lead to resolution of lung pathology, with corticosteroids and supportive care required for more severe cases.

• Future priorities include evaluation of biomarkers to allow for more precise risk evaluation and harm minimization; utilization of population level data-linkage for pharmacovigilance; and identification of potential therapies to mitigate the risk of lung toxicity when co-administered with the lung-toxic agent.

Declaration of interest

L Troy reports research grants from Erbe Elektromedizin GmbH, Medtronic, and Rymed, and personal fees from Erbe, Boehringer Ingelheim and Roche. T Corte has received research grants and personal fees from Boehringer Ingelheim, Roche, and Bristol Myers Squibb; personal fees from Promedior, Vicore, and DevPro Therapeutics; and research grants from Actelion, Galapagos, and Biogen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.