Drug-Induced Pulmonary Toxicity Treatment & Management

Updated: Apr 09, 2019
  • Author: Klaus-Dieter Lessnau, MD, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Treatment

Approach Considerations

The treatment of drug-induced lung disease consists of immediately discontinuing the offending drug and appropriately managing the pulmonary symptoms. Acute episodes of drug-induced pulmonary disease usually disappear 24-48 hours after the drug has been discontinued, but chronic syndromes may take longer to resolve.

General supportive measures include the following:

  • Smoking cessation

  • Control of the underlying lung disease

  • Prompt treatment of concomitant respiratory infections

Anecdotal reports indicate that glucocorticoid therapy has been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. If cytotoxic drug-induced disease is severe or appears to progress despite elimination of further drug exposure, an empirical course of glucocorticoids is advisable. Conditions that have favorable corticosteroid responses are cryptogenic organizing pneumonia (COP) (bronchiolitis obliterans-organizing pneumonia [BOOP]) and drug-induced eosinophilic pneumonia.

In cases of severe lung toxicity and irreversible fibrosis, patients may be considered for lung transplantation. According to the 2018 registry of the International Society of Heart and Lung Transplantation (ISHLT), 1-, 3-, and 5-year actuarial survival rates after adult lung transplantation are >80%, >60%, and >45%, respectively. [77, 78]

Complications of drug-induced lung toxicity, such as hypoxia, pulmonary thromboembolic disease, and pneumothorax, may require hospital admission. Consultation with a pulmonologist may be helpful.

Most patients with drug-induced lung toxicity can be treated in community settings. Transfer to a tertiary care center is indicated when the diagnosis is in doubt or when treatment is ineffective. Patients with drug-mediated interstitial lung disease are generally treated in an outpatient setting.

For long-term follow-up, patients are seen monthly at first. Subsequently, patients are seen every 3-6 months. Pulmonary function tests (especially diffusing capacity of the lungs for carbon monoxide [DLCO]), the 6-minute walk test, and chest radiographs are usually needed to monitor the course of the disease.

Precautions

Drug reactions are a common cause for litigation. Therefore, before starting therapy with any potentially toxic drug, clinicians should explain its risks, benefits, and alternatives to the patient. When drug reactions occur, proper documentation of the type of drug reaction in the medical chart is crucial.

Management of immunotherapy-related toxicities 

With regard to checkpoint inhibitor pneumonitis (CIP), there have been no prospective trials performed to evaluate the optimal treatment plan for patients with CIP. The National Comprehensive Cancer Network (NCCN) recommends that immunotherapy should be held for CIP; for moderate-severe pneumonitis (grade 2-4), an infectious workup should be performed (nasal swab, bronchoalveolar lavage, and cultures [sputum, blood, urine]). [79]  Once the diagnosed of CIP is made, the mainstay of management is corticosteroid therapy—typically 1 mg/kg/day for lower grade CIP (grade 2) and 2-4 mg/kg/day for higher grade CIP (grade 3-4). [80]  It is recommended the patient's response to therapy be reassessed after 48-72 hours. [79]

If there is little to no response to corticosteroid therapy after 48-72 hours, the NCCN recommends that any of the following treatment modalities may be considered [79] :

  • Infliximab 5 mg/kg intravenous (IV) (Clinicians may consider a second dose 14 days after the first dose),
  • Mycophenolate mofetil 1-1.5g twice daily, and then taper with consultation of the pulmonary service, or
  • IV immunoglobulin (IVIG) 0.4g/kg/day for 5 days

Note that the use of infliximab for steroid-refractory CIP is extrapolated from clinical trials investigating the use of tumor necrosis factor alpha (TNF-a) inhibitors for immune checkpoint inhibitor-related colitis. [80]  IVIG may be a more viable option, particularly when clinical suspicion for a comorbid infection is high—as sepsis is often the cause of death for most patients with refractory CIP. [80]