Lung Injury Caused By Pharmacologic Agents

Question 1

Most frequent offenders

Answer 1

Chemotherapeutic drugs

Question 2

Most frequent clinical syndrome

Answer 2

Diffuse interstitial pneumonitis and fibrosis

Question 3

Risk factors associated with cytotoxic drug therapy

Answer 3

Cumulative dose
Age of patient
Radiation
O2 therapy
Use of other toxic drugs

Question 4

Criteria for diagnosing drug-induced lung disease

Answer 4

1. History of ingestion of drug known to cause lung injury
2. Clinical manifestations have been reported to be induced by the drug
3. Other causes have been ruled out
4. Improvement on discontinuation of drug
5. Exacerbation after resuming drug

Question 5

2 patterns of bleomycin toxicity

Answer 5

1. Progressive fibrosis
2. Acute hypersensitivity reaction

Question 6

Severe pneumonitis in adults develops after administration of this amount of bleomycin

Answer 6

283 mg/m2
*less severe if slow IV administration

Question 7

___ and ___ receiving bleomycin have increased risk for radiation pneumonitis

Answer 7

Pediatric sarcoma
Hodgkin

Question 8

Pulmonary injury due to bleomycin occurs by:

Answer 8

Direct injury
1. Oxidant injury through production of reactive O2 metabolites and inactivation of antioxidants
2. Induces apoptosis of AEC type II

Immunologic reaction
1. Generates inflammatory mediators
2. Increased collagen synthesis by fibroblasts through TGFb

Question 9

PFT of bleomycin lung injury

Answer 9

Restrictive (low VC, TLC)

Question 10

Gas properties of bleomycin lung injury

Answer 10

Reduced DLCO
Reduced arterial O2 saturation

Question 11

Signs of bleomycin lung injury

Answer 11

DRY HACKING COUGH
Dyspnea

Question 12

CXR findings of bleomycin lung injury

Answer 12

Diffuse linear densities

Question 13

Biopsy findings in bleomycin lung injury

Answer 13

Interstitial pneumonitis
Fibrosis
Extensive alveolar damage with hyperplasia of type II cells, mostly subpleural and basilar

Question 14

Monitoring of bleomycin lung injury

Answer 14

Serial DLCO

Question 15

Management of bleomycin lung injury

Answer 15

Withdrawal
Supportive
CS in severe toxicity, hypersensitivity reactions, and eosinophilic pneumonitis

Question 16

Mechanism of cyclophosphamide lung toxicity

Answer 16

1. Oxidant and inflammatory
2. Immune

Question 17

Pulmonary reactions in total doses of cyclophosphamide between __ and __

Answer 17

0.15 and 50 g

Question 18

Chest wall deformity secondary to failure of lung growth during adolescent growth spurt is a striking feature of:

Answer 18

Cyclophosphamide lung toxicity

Question 19

Herald onset of cyclophosphamide lung toxicity

Answer 19

SUBACUTE DRY COUGH
Dyspnea

Question 20

PE of cyclophosphamide lung toxicity

Answer 20

Tahcypnea
Diffusely diminished breath sounds

Question 21

PFT of cyclophosphamide lung toxicity

Answer 21

Restrictive
Hypoxemia

Question 22

Biopsy findings of cyclophosphamide lung toxicity

Answer 22

Interstitial fibrosis
Alveolar exudates
Atypical alveolar epithelial cells

Question 23

Treatment of cyclophosphamide lung toxicity

Answer 23

Withdrawal
Supportive
CS

Question 24

Etoposide lung toxicity

Answer 24

Alveolar hemorrhage

Question 25

Mechanism of methotrexate lung toxicity

Answer 25

MAP kinase pathway activation causing cytokines activation

Question 26

Features of methotrexate toxicity

Answer 26

Hypersensitivity pneumonitis Decreased DLCO

Question 27

CXR abnormalities in methotrexate toxicity

Answer 27

Bilateral interstitial infiltrates Mixed interstitial and alveolar infiltrates

Question 28

Treatment of methotrexate toxicity

Answer 28

Withdrawal CS Avoid resuming

Question 29

Cytosine arabinoside (Ara-C) toxicity

Answer 29

Pulmonary edema Rare: ARDS BOOP

Question 30

Gemticabine toxicity

Answer 30

ARDS

Question 31

Procarbazine, VM-26, vinca alkaloids toxicity

Answer 31

Hypersensitivity pneumonitis

Question 32

Imatinib toxicity

Answer 32

Pleural effusion, pulmonary edema

Question 33

IL-2 toxicity

Answer 33

Vascular leak syndrome (pleural effusion, pulmonary edema) Increased AaDO2 gradient Decreased FVC, FEV1, DLCO

Question 34

ATRA toxicity

Answer 34

Interstitial infiltrates Pleural and pericardial effusion Hyperleukocytosis

Question 35

Treatment of ATRA toxicity

Answer 35

CS (dexamethasone 10mg/day)

Question 36

Nitrofurantoin PFTs

Answer 36

Restrictive Reduced DLCO

Question 37

2 clinical patterns of nitrofurantoin toxicity

Answer 37

1. Acute - fever, cough, dyspnea; bilateral interstitial or alveolar infiltrates with or without pleural effusion 2. Chronic - cough, dyspnea, chest pain months to years after intake; lupus-like syndrome: pleural effusion is less common

Question 38

Treatment and prognosis of nitrofurantoin toxicity

Answer 38

Withdrawal CS May not resolve completely

Question 39

Sulfasalazine toxicity

Answer 39

Obstructive > restrictive Hypoxemia Eosinophilia

Question 40

Carbamazepine, levetiracetam toxicity

Answer 40

DRESS Restrictive pattern Reduced DLCO

Question 41

Minocycline toxicity

Answer 41

DRESS Eosinophilic pneumonia

Question 42

Penicillamine toxicity

Answer 42

Short: hypersensitivity Intermediate: diffuse alveolitis, bronchiolitis obliterans Prolonged: alveolar hemorrhage

Question 43

PFT in penicillamine toxicity

Answer 43

BO: obstructive Alveolitis, hypersensitivity: restrictive

Question 44

Other immunomodulatory agents with lung toxicity

Answer 44

Rituximab (RALI) Alemtuzumab Cetuximab Trastuzumab Tacrolimus Sirolimus Pegylated interferon

Question 45

Amiodarone toxicity

Answer 45

Rapidly progressive alveolar hemorrhage ARDS

Question 46

Risk for ARDS in amiodarone

Answer 46

High FiO2 Cardiothoracic surgery Contrast

Question 47

BAL fluid in amiodarone toxicity

Answer 47

“Amiodarone effect” Accumulation of drug in the macrophage lysosomes Foamy macrophages

Question 48

HMG-CoA reductase inhibitors (statins) toxicity

Answer 48

Restrictive pattern Reduced DLCO Foamy macrophages Phospholipidosis

Question 49

LTRA toxicity

Answer 49

EGPA

Question 50

Aspirin and NSAIDs toxicity

Answer 50

Bronchoconstriction in aspirin-exacerbated respiratory disease (chronic sinusitis, polyposis, severe asthma)

Question 51

Heroin overdose

Answer 51

Pulmonary edema

Question 52

Crack cocaine

Answer 52

Air leak Pulmonary edema Interstitial pneumonitis BOOP

Question 53

Cannabis

Answer 53

Chronic bronchitis Emphysematous changes

Question 54

OCPs

Answer 54

Venous thrombosis Pulmonary embolism