Drug-Induced Pulmonary Disease-2012

Drug-InducedPulmonary Disease

Drug-Induced Pulmonary DiseaseProposed Mechanisms

Immune-mediated

Usually have favorable outcome

Cytotoxic effect

Usually leads to fibrosis

Drug-Induced Pulmonary DiseaseTypes of Reactions

Bronchospasm

Lupus-like syndrome

Loeffler's syndrome

Interstitial or airspace pneumonitis

Interstitial fibrosis

Increased permeability pulmonary edema

IV abuse of oral medications

Drug-Induced Pulmonary DiseaseClinical

Insidious onset of cough and dyspneain patient receiving implicated drug

Frequently accompanied by fever

Restrictive pulmonary function tests

Drug-Induced Pulmonary DiseaseDrugs Which Produce Disease

Chemotherapeutic agents

Antimetabolites

Antimicrobials

Antiarrhythmics

Anticonvulsants

Analgesics

Drug-Induced Pulmonary DiseaseDrugs Which Produce Disease

Narcotics and sedatives

Sympathomimetics

Contrast media

Miscellaneous

Drug-InducedPulmonary DiseaseDiseases by Drugs

Chemotherapeutic Agents

Bleomycin

Busulfan

Cyclophosphamide

Mitomycin

Nitrosoureas

Chlorambucil

BleomycinGeneral

Used to rx lymphoma, squamous cell andtesticular ca

Dose-related, age-related

Up to 35% develop findings

Mortality of 1–2 %

Minority of patients: immune-mediatedeosinophilic pneumonia

Majority: cytotoxic interstitial pneumonia

Synergistic with XRT and high O2

BleomycinX-ray Findings

Reticular interstitial disease progressesto massive airspace consolidation

Mostly at bases

May produce nodules which simulatemets

Busulfan (Myleran)General

Used to treat CML

Not dose-related but need >500 mg

About 5% develop reaction

Frequently fatal

Takes 3-4 years to develop

Synergistic with XRT and other chemo

BusulfanPathology

Classical pathology: large, atypicaltype II pneumocytes

Hyperpigmentation of skin

2° increased melanin production

Resembles Addison’s disease

BusulfanX-ray Findings

Diffuse reticulonodular disease

Sometimes basilar predominance

Consolidation seen more often thanother chemotherapeutic drugs

CyclophosphamideGeneral

Alkylating cytotoxic drug

Used for

Auto-immune dzs

Malignancies

Dose-related

<1% pulmonary toxicity

60% recover

Synergistic with XRT and O2

CyclophosphamideX-ray Findings

Diffuse reticulonodular disease

Usually basal predominance

MitomycinGeneral

Alkylating antibiotic agent

Used for GI, breast and cervical ca

Usually combined with vincristine and5FU

Not dose-related

Occurs in 5%

50% mortality

MitomycinX-Ray

Coarse reticular and airspace disease

Basilar predominance

Pleural effusion more common thanwith other cytotoxic drugs

May look like BOOP

NitrosoureasGeneral

Intracranial neoplasms, melanoma, GIcarcinomas and lymphoma

BCNU frequently given withcyclophosphamide

Dose-related

Occurs in 50% over 1.5 grams

40% fatal

NitrosoureasX-Ray

Reticulonodular disease

Basilar predominance

Associated with pneumothorax

ChlorambucilGeneral

Used for leukemias

Rare cause of pulmonary toxicity

50% mortality

Basilar reticulonodular disease

AntimetabolitesMethotrexate

Folic acid analog that inhibits cellularreproduction

Used in variety of malignancies

Also psoriasis, RA

AntimetabolitesMethotrexate

Not dose-related

About 5% develop disease

1% mortality

Seen in patients who receive drugintrathecally

Associated with blood eosinophilia

MethotrexateX-Ray

Initially, diffuse reticular interstitialdisease

Progresses to patchy alveolarconsolidation

Reverts to interstitial pattern andresolution

Pleural effusion, hilar adenopathy andnodules described

Antimicrobials

Nitrofurantoin

Sulfasalazine

NitrofurantoinGeneral

Disease may be acute or chronic

Acute is more common

Probably due to hypersensitivity reaction

Blood and lung eosinophilia

NitrofurantoinGeneral

Chronic probably 2° direct tissuetoxicity from oxidants

Interstitial pneumonitis and fibrosis

Acute prognosis is excellent; chronichas 10% mortality

NitrofurantoinX-Ray

Diffuse reticular disease

In both acute and chronic

Basilar predominance

Resembles pulmonary interstitialedema

Pleural effusion may be present

AntiarrhythmicsAmiodarone

Pathologically, phospholipid storageincreased (phospholipidosis)

Dose-related

Incidence about 6%

Prognosis is excellent

Drug is deposited mainly in lungs

Damage usually takes months to occur

AmiodaronePathology

Macrophages have distinctive foamyappearance

Contain many lysosomal inclusions

Their presence indicates amiodarone inlung

Doesn’t necessarily mean cell damage

AmiodaroneX-Ray

Diffuse reticular or patchy airspacedisease

Primarily upper lung field and peripheral

Resembles eosinophilic pneumonia

Pleural thickening and effusions

CT: High attenuation lesions fromiodinated nature of compound

AnticonvulsantsDiphenylhydantoin (Dilantin)

Pathologically interstitial pneumonitisand necrotizing vasculitis

Blood eosinophilia

Good prognosis

DiphenylhydantoinX-Ray

Diffuse reticulonodular disease

Mediastinal adenopathy

True lymphoma, pseudolymphoma

Lupus-like syndrome

Drug-induced LupusDrugs which account for 90% of cases

Dilantin

Hydralazine

Pronestyl (procainamide)

INH

Drug-induced LupusDiffers from SLE

Pleuroparenchymal changes morecommon than SLE

Does not involve kidney

Disappears if drug is stopped

LupusThoracic Changes

Pleural effusions

Discoid atelectasis at both bases

Pericardial effusions

Lupus pneumonitis

AnalgesicsAcetylsalicylic acid

Usually occurs in adults who ingestlarge quantities to alleviate pain

Increased capillary permeabilitypulmonary edema

Bronchospasm and asthma

Good prognosis

Narcotics and sedatives

50% of heroin overdosers developpulmonary edema

Increased capillary permeability

Hypoxemia

Acidosis

Neurologic disorder

May take 6 hours to appear

May also occur with benzodiazepines

Contrast Media

Pulmonary edema with water solublemedia probably related to highosmolarity

Lymphangiography with ethiodol mayproduce ARDS

Resembles fat embolism

MiscellaneousL-Tryptophan

Cause of a myalgia-eosinophiliasyndrome

Associated with diffuse interstitialpulmonary disease

Not dose-related

Pulmonary Mainline Granulomatosis

Pulmonary embolism in drug addictsfrom IV injection of oral meds

Drugs

Amphetamines

Methadone

Dilaudid

Meperidine

Pulmonary Mainline Granulomatosis

Added talc (magnesium silicate)produces foreign body rxs—perivascular fibrosis

Fine nodularity at bases

Pulmonary hypertension

Take Home Points

Take Home Points

Almost all have cough, dyspnea andsometimes fever

Almost all produce reticulonodularinterstitial disease at the bases

Bleomycin may produce nodules whichsimulate mets

Busulfan produces large, atypical typeII pneumocytes, hyperpigmentation andconsolidation

Take Home Points

Mitomycin reactions not dose-related, morecommonly have pleural effusions

Nitrosoureas associated with pneumothorax

Methotrexate not dose-related, can occurwith intrathecal route, may produceadenopathy

Acute hypersensitivity rxs are common withNitrofurantoin, produces P.I.E.

Take Home Points

Macrophages in Amiodarone rx are foamy,contain lysosomal inclusions, rx is mostlyat apex, associated with pleural disease

Dilantin rxs include adenopathy and lupus

Salicylates produce asthma, pulmonaryedema

Tryptophan produces myalgia-eosinophiliasyndrome, diffuse interstitial dz and is notdose related

The End