Drugs and Lung Injury

Question 1

Cytotoxic drugs that can cause Interstitial pneumonitis/pulmonary fibrosis

Answer 1

Bleomycin 
Cyclophosphamide 
Chlorambucil 
Busulfan 
Melphalan 
Carmustine
MTX
6-MPC
Cytosine arabinoside
Gemcitabine Fludarabin
All-trans retinoic acid

Question 2

Drugs that can cause Hypersenstivity lung reaction

Answer 2

Nitrofurantoin 
Sulfasalazine 
Diphenylhydantoin 
Carbamazepine 
Penicillamine 
Amiodarone
Hydroxyurea
Bleomycin 
MTX

Question 3

Drugs that can cause Pleural effusion

Answer 3

Bleomycin 
Busulfan 
MTX 
Imitanib 
IL-2 
ATRA
Nitrofurantoin 
Amiodarone

Question 4

Drugs that can cause Eosinophilic pneumonitis/pneumonia

Answer 4

Bleomycin

Minocycline

Question 5

Key points re: pulmonary toxicity from drugs

Answer 5

Some pulmonary damage is reversible, some not.
-Toxicity may result from direct injury to lung cells or be immune mediated.
- Noncytotoxic toxicity is often idiosyncratic.
- Features = fever, malaise, dyspnea, nonproductive cough.
- Diffuse alveolar or interstitial involvement on imaging.
o If segmental/lobar/unilateral disease —- look for another cause
-Path does not distinguish cytotoxic agents.
-Interstitial pneumonitis can be part of DIHS/DRESS (drug-induced hypersensitivity syndrome/drug rash
with eosinophilia and systemic symptoms)

Question 6

Risk factors for drug-induced pulmonary toxicity

Answer 6

Dose
Age
Radiation
Oxygen
Other drugs

Question 7

Criteria for diagnosis of drug-induced pulmonary toxicity

Answer 7

1. No other likely cause
2. Symptoms consistent with suspected drug
3. Time course compatible with drug-induced lung disease
4. Compatible tissue or BAL findings
5. Improvement after drug is discontinued

Question 8

2 patterns of lung toxicity for Bleomycin

Answer 8

1. Progressive fibrosis (common)

2. Acute hypersensitivity (rare)

Question 9

Mechanism of lung toxicity secondary to Bleomycin

Answer 9

1. Direct toxicity, mediated by reactive oxygen metabolites or inactivation of antioxidants.
2. Induces senescence or apoptosis of type 2 epithelial cells.
3. Generates inflammatory mediators.
4. Increases collagen synthesis by fibroblasts.

Question 10

Presentation of lung toxicity secondary to Bleomycin

Answer 10

Asymptomatic with decrease in DLCO, SpO2, VC, TLC. Dry cough and dyspnea.
Fever suggests hypersensitivity reaction.
Tachypnea, fine crackles.
CXR – diffuse linear densities, widespread reticulonodular or alveolar pattern.

Question 11

Pathology of lung toxicity secondary to Bleomycin

Answer 11

Interstitial pneumonitis, fibrosis
Extensive alveolar damage with hyperplasia of type II cells
Worse in subpleural/basilar regions.

Question 12

Lung toxicity related to Cyclophosphamide

Answer 12

Lung toxicity is not common – but can be severe

• Interstitial pneumonitis
• Acute alveolitis
• DAH
• ARDS
• BO

Question 13

Management of lung toxicity secondary to Bleomycin

Answer 13

Monitor DLCO, O2 therapy.

High-dose steroids has been described to reverse toxicity (especially if hypersensitivity or eosinophilic pneumonitis).

Question 14

Mechanism of lung toxicity secondary to Cyclophosphamide

Answer 14

Oxidant and inflammatory/immune mechanisms
Acute IgE-mediated systemic reactions with angioedema and bronchospasm.
Atopy is associated with lung complications.

Question 15

2 patterns of lung toxicity associated with Nitrofurantoin

Answer 15

1. Acute fever, cough, dyspnea within hours
   Within 2 weeks of initial therapy.
   Rash, flulike symptoms.
   Diffuse fine crackles.
   Bilateral interstitial or alveolar infiltrates +/- pleural effusion. Hypoxemia, RLD, reduced DLCO.
   Eosinophilia, leukocytosis, raised ESR. Symptoms resolve on discontinuing drug.
2. Less common – insidious onset cough, dyspnea, chest pain after months to years of therapy. +/- fever
   Crackles
   Diffuse interstitial infiltrates.
   Path: interstitial pneumonitis with variable fibrosis. DIP, BOOP, giant cell interstitial pneumonia also reported.
   Discontinue and steroids.