The Drug-Induced Respiratory Disease Website and App

Chemotherapy, antineoplastic

Collectively, antineoplastic chemotherapy, myeloablative and conditioning regimens for HSCT, alkylating chemo agents, regimens containing bleomycin, busulfan, cyclophosphamide, gemcitabine, taxanes, G-CSF, FOLFOX/FOLFIRI produce lung injury including pulmonary edema, ARDS, diffuse alveolar hemorrhage and noninfectious lung injury. See under each specific drug or agent including radiation therapy and/or TBI. In a sizable fraction of patients, identification of the causal agent is difficult. A likelihood analysis is performed relating incidence, clinical, imaging and pathologic pattern of injury and the specific drug. Toxicity in lung cancer see PMID 21283982. The risk of developing pulmonary toxicity with chemotherapy may be increased in patients with preexisting ILD or IPF (PMID 19420811, 23171837, 25316105)

Frequency - Incidence

Incidence of respiratory adverse event(s) due to the specific drug as assessed by number of reported/published cases in the literature. Red digits in stars indicate: 0 = Very rare, questionable signal · 1 = < 10 cases · 2 = 10-50 cases · 3 = 50–100 cases · 4 = 100-200 cases · 5 = >200 cases

Evidence level/grade

Evidence level for respiratory adverse event(s) due to the specific drug as estimated using Hill’s (1965), Naranjo’s (1981), and Bégaud’s (1985) criteria applied to published cases. Blue digits in stars indicate: 0 = Questionable · 1 = Low · 2 = Moderate · 3 = Robust · 4 = Definite · 5 = Unquestionable, pathognomonic

I - Interstitial/parenchymal lung disease

I.a

Pneumonitis (ILD)

I.b

Pneumonitis (ILD), acute and/or severe (may cause ARDS)

I.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

I.e

Organizing pneumonia pattern (an area or areas of consolidation on imaging)

I.f

Acute fibrinous organizing pneumonia (AFOP)

I.g

Pulmonary fibrosis

I.i

Subclinical pulmonary infiltrates/ILD

I.l

Lung nodule or nodules

I.m

Diffuse alveolar damage (DAD) (see alsoo under IIb and XVf)

I.n

ILD with a granulomatous component

I.o

Pulmonary alveolar proteinosis (PAP)

I.w

Abnormal lung function/pulmonary physiology (PFTs) without necessarily imaging or clinical evidence

I.x

Rapidly progressive ILD/pulmonary fibrosis (Hamman-Rich syndrome)

I.y

Pleuroparenchymal fibroelastosis (PPFE)

I.z

Progression, acceleration or exacerbation of preexisting ILD/fibrosis

I.ab

Delayed ILD, -pneumonitis, -fibrosis

I.ae

Radiation recall pneumonitis

I.av

The chemotherapy lung

II - Pulmonary edema - Acute lung injury - ARDS

II.a

Pulmonary edema, noncardiogenic (NCPE)

II.b

Pulmonary edema, cardiogenic

II.e

ARDS - Acute lung injury

II.f

ARDS and the hemolytic-uremic syndrome (HUS)

III - Pulmonary/alveolar./airway hemorrhage/bleeding

III.a

Alveolar hemorrhage (AH), diffuse AH (DAH)

IV - Airway involvement

IV.a

Bronchospasm - Wheezing - Asthma

IV.j

Bronchiectasis

V - Central-large-upper airway (incl. pharyngeal-nasal) involvement

V.a

Angioedema (may cause UAO, asphyxia and death)

V.g

Vocal cord paresis/paralysis

VI - Pleural and/or pericardial involvement

VI.a

Pleural effusion (uni- or bilateral) (can accompany DI-LDs)

VI.f

Pneumothorax

VI.ac

Pneumothorax, bilateral

VII - Pulmonary vasculopathy

VII.b

Pulmonary arterial hypertension

VII.c

Pulmonary veno-occlusive disease

VII.f

Hemolytic and uremic syndrome (HUS). See also under Xaf

VIII - Mediastinal involvement

VIII.a

Lymphadenopathy (intrathoracic)

VIII.h

Pneumomediastinum

IX - Neuromuscular / CNS involvement - Disordered breathing (during sleep)

IX.f

Hiccup

IX.j

Phrenic nerve injury - Hemi- or bilateral diaphragmatic paralysis

IX.o

Pneumorachis

X - Systemic/Distant conditions, syndromes and reactions

X.c

Capillary leak syndrome (CLS)

X.d

Lupus - Lupus syndrome (see also Vd)

X.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)

X.i

Hypersensitivity reaction (may manifest with fever and/or skin, throat or airway involvement)

X.m

Sarcoid-like granulomatosis (endo-/extrathoracic)

X.p

Tumor lysis syndrome (TLS)

XI - Miscellaneous

XI.b

Chest pain (acute or subacute), lone or prominent

XI.l

Neutropenia, agranulocytosis (w/wo infection/sepsis)

XI.t

Cavitation/necrosis of lung tumor or metastases

XII - Cardiovascular involvement / toxicity

XII.a

Left or biventricular dysfunction/failure

XII.b

Valvular heart disease and/or dysfunction

XII.c

Pericardial effusion (w/wo tamponade)

XII.f

Takotsubo (stress) cardiomyopathy

XII.g

Cardiomyopathy (acute, subacute, chronic)

XII.h

Coronary artery disease (acute) - Myocardial ischemia/infarction

XII.m

Atrial fibrillation

XII.n

Cardiac arrhythmias or dysrhythmias (AF, VT, VF, TdP)

XII.t

Heart block (bundle branch- or AV-)

XII.ak

Cardiotoxicity

XVI - Imaging

XVI.ac

Imaging: Cavitating/cavitary lung nodule, mass or nodules (see also Iq, XIs, XIIi, XVIaa and XVIIp)

XVI.ad

Imaging: Lung cysts or bullae (see also XVI ah/bf)

XVI.bh

Imaging: Tumoral cavitation

XVI.bp

Imaging: An area or areas of avid tracer uptake in the lung/chest on 18F-PET scan

XVI.by

Imaging: Air or an air crescent around lung tumor or metastase(s)

XVIII - Cytological, biochemical features of/in BAL, pleural fluid or FNA

XVIII.g

BAL: Atypical epithelial cells (at times poetically named

XIX - Pathology

XIX.d

Path: Organizing pneumonia (OP/BOOP) pattern (see also Id)

XIX.e

Path: Acute fibrinous organizing pneumonia (AFOP-pattern) (see also If)

XIX.o

Path: Diffuse alveolar damage (DAD-pattern) (see also IL)

XIX.q

Path: Pneumocyte atypia (reactive epithelial cells) (a.k.a. the "Napoleon Hat" sign)

XIX.x

Path: Pulmonary fibrosis (not otherwise specified or unclassifiable)

XIX.ba

Path: Thrombosis in pulmonary arterioles/venules

XIX.bd

Path: Pulmonary veno-occlusive disease (PVOD)

XIX.bx

Path: Granulomatous lymphadenopathy

XX - Infections & related conditions

XX.b

Opportunistic pulmonary/systemic infections

XX.c

Aspergillosis, pulmonary (invasive, allergic [ABPA], or mycetoma)

XX.e

Pneumocystis jiroveci pneumonia

XX.g

Tuberculosis (pulmonary, pulmonary, extrapulmonary or disseminated). Reactivation or de novo

XX.j

Mucormycosis (pulmonary, tracheobronchial or systemic)

XX.r

Fungal infection (pulmonary/extrapulmonary)

XX.ae

Reactivation of a prior pulmonary infection (TB, melioidosis)

XXI - Neoplastic conditions

XXI.a

Lung cancer

XXI.b

Lymphoproliferative disease (pulmonary, endobronchial, endothoracic)

XXI.d

Malignant mesothelioma (pleural, pericardial)