Drug-induced lung disease

Drug-induced lung disease can result from a number of agents and may have a myriad of presentations, ranging from an adult respiratory distress syndrome type picture to established pulmonary fibrosis.

Due to this, it can be extremely difficult to pinpoint the offending agent on imaging appearances alone and correlation with the medical history is mandatory. 

Pathology

Etiology

Chemotherapy agents

These can give several patterns of disease which include ^1,5:

• interstitial fibrosis: typically NSIP ⁵ pattern

• hypersensitivity pneumonitis pattern

• adult respiratory distress syndrome / diffuse alveolar damage pattern 

• bronchiolitis obliterans organizing pneumonia type pattern

• pulmonary hemorrhage

Example agents include:

• bleomycin lung toxicity

• busulfan lung toxicity

• carmustine lung toxicity

• chlorambucil lung toxicity

• cyclophosphamide toxicity

• docetaxel induced interstitial pneumonitis ^11,12

• gemcitabine lung toxicity ¹⁴

• melphalan associated pulmonary toxicity

• methotrexate lung disease

• paclitaxel lung toxicity

• pemtrexed: pemtrexed induced pneumonitis 

• thalidomide-induced interstitial pneumonitis

• ALK inhibitors

  • crizotinib: crizotinib associated intersitial pneumonitis

• tyrosine kinase inhibitors: alectinib ¹⁸

• epidermal growth factor receptor inhibitors tyrosine kinae inhibitors:

  osimertinib ¹⁹

Immunosuppressive agents

• sirolimus: sirolimus-associated pulmonary toxicity ⁹

• leflunomide (arava): leflunomide-induced acute interstitial pneumonia ¹⁰

• sulfasalazine lung toxicity

Immunotherapy agents

Immune checkpoint inhibitor therapy-related pneumonitis / immune-mediated pneumonitis usually happens between 8 to 14 weeks after the start of treatment ¹³. Examples of agents include:

• nivolumab

• pembrolizumab 

  • pembrolizumab-induced sarcoid-like reaction

  • pembrolizumab-induced pneumonitis

• ipilimumab

Monoclonal antibody

• rituximab-induced interstitial lung disease

Disease-modifying antirheumatic drugs (DMARDs)

• TNF-alpha blockers: adalimumab-induced interstitial lung disease ¹⁶

Cardiovascular agents

• amiodarone lung toxicity

Antibiotic agents

Can also give similar patterns to that of chemotherapeutic agents:

• nitrofurantoin lung toxicity

• amphotericin B lung toxicity

• sulfonamide lung toxicity

Anti-inflammatory agents

• gold-induced lung toxicity

Non-medical drug use

• IV methylphenidate: Ritalin lung, panacinar emphysema

• IV heroin: pulmonary edema, pulmonary hemorrhage, eosinophilic pneumonia ⁶

• IV cocaine: pulmonary edema

• vaping-associated lung disease

Anticonvulsants

• phenytoin: eosinophilic pneumonia ⁴

Others

• herbicides

  • paraquat (N,N′-dimethyl-4,4′-bipyridinium dichloride): paraquat-induced lung disease