The Drug-Induced Respiratory Disease Website and App

Pembrolizumab

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.n

ILD with a granulomatous component

I.p

Focal/localized area of pneumonitis/fibrosis

I.z

Progression, acceleration or exacerbation of preexisting ILD/fibrosis

I.ae

Radiation recall pneumonitis

II - Pulmonary edema - Acute lung injury - ARDS

II.e

ARDS - Acute lung injury

III - Pulmonary/alveolar./airway hemorrhage/bleeding

III.h

Major/massive hemoptysis

III.l

Alveolar hemorrhage, localized (e.g. lobar)

IV - Airway involvement

IV.a

Bronchospasm - Wheezing - Asthma

IV.c

Exacerbation or deterioration of preexisting asthma

IV.d

Exacerbation or deterioration of preexisting COPD

IV.j

Bronchiectasis

IV.l

Large airway inflammation - Tracheitis (w/wo tissue eosinophilia)

IV.t

Eosinophilic airway disease (asthma, bronchitis, bronchiolitis)

IV.u

Sptutum production - Bronchorrhea - 'Bronchitis'

IV.w

Bronchiolitis (a clinical-imaging pattern suggestive of)

IV.x

Obliterative bronchiolitis (a pattern consistent with) (see also IVn, XVx)

IV.ab

Cough (lone)

IV.af

Sputum production - Bonchorrhea - ‘Bronchitis’

IV.ag

Obstructive airway dysfunction (see also IVc, XVx)

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

V.g

Vocal cord paresis/paralysis

V.r

Tongue involvement (edema, glossitis, hematoma)

VI - Pleural and/or pericardial involvement

VI.m

Pleuropericarditis - Pleuropericardial effusion (ANA unknown or negative)

VII - Pulmonary vasculopathy

VII.a

Pulmonary embolism - Venous thrombosis/thromboembolism

VII.b

Pulmonary arterial hypertension

VIII - Mediastinal involvement

VIII.a

Lymphadenopathy (intrathoracic)

VIII.e

Granulomatous mediastinal lymphadenopathy

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

IX.r

Myasthenia gravis - Myasthenic-like syndrome

X - Systemic/Distant conditions, syndromes and reactions

X.b

Antiphospholipid antibodies w/wo the APL syndrome

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.l

Myopathy-Myositis-Polymyositis (see also under Xba)

X.m

Sarcoid-like granulomatosis (endo-/extrathoracic)

X.o

Vascultis (pulmonary, extrathoracic or systemic)-ANCA status unknown or negative)

X.u

Vasculitis, pulmonary (w/wo AH), extrapulmonary, systemic: ANCA-positive

X.aj

Granulomatosis with polyangiitis (typically ANCA pos.) - GPA flare

X.ap

Cytokine release syndrome - Cytokine storm

X.ax

Connective tissue disease

X.ay

Scleroderma

X.az

Polymyalgia rheumatica

X.bj

Temporal arteritis (Horton’s)

XI - Miscellaneous

XI.e

Metabolic acidosis (incl. lactic acidosis/-gap). May cause hyperpnea/dyspnea

XI.l

Neutropenia, agranulocytosis (w/wo infection/sepsis)

XII - Cardiovascular involvement / toxicity

XII.a

Left or biventricular dysfunction/failure

XII.c

Pericardial effusion (w/wo tamponade)

XII.d

Myocarditis (can be fulminant)

XII.s

Heart failure (biventricular, congestive)

XII.t

Heart block (bundle branch- or AV-)

XVI - Imaging

XVI.b

Imaging: Ground-glass opacities (GGO) / shadowing

XVI.e

Imaging: Pulmonary opacities with a subpleural distribution

XVI.k

Imaging: An area or areas of consolidation

XVI.v

Imaging: Centrilobular micronodules (can be diffuse)

XVI.aa

Imaging: A large nodule or a mass

XVI.ak

Imaging: A 'tree-in-bud' pattern

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

XVIII.a

BAL: An excess proportion of lymphocytes

XVIII.b

BAL: An excess proportion of neutrophils

XIX - Pathology

XIX.a

Path: NSIP-cellular pattern (see also Ia, Ib)

XIX.b

Path: Eosinophilic pneumonia (subacute or acute) (see also Ic)

XIX.d

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

XIX.e

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

XIX.f

Path: ILD with a granulomatous component (see also Im)

XIX.o

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

XIX.al

Path: Acute/subacute bronchiolitis (see also IVc, IVi)

XIX.au

Path: Airway inflammation

XIX.co

Path: Myocarditis

XIX.cr

Path: Myocardial vasculitis

XX - Infections & related conditions

XX.c

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

XX.g

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

XX.o

Nocardia pulmonary/systemic infection