The Drug-Induced Respiratory Disease Website and App

Immune checkpoint inhibitors (ICI) - ICI combinatorial Rx

The manifold possible adverse effects from ICI in varied organs must be checked in every patient receiving these medications. AEs tend to occur with higher frequency with combo theray than when these agent are taken in isolation. Anti CTLA-4, anti-CD52, anti-PD1, anti-PDL-1 antibodies (PMID 23714523, 24904570, 25776466). For review of pulmonary and nonpulmonary AEs, and management guidelines see under PMID 26371282, 29442540. Can be fatal (PMID: 29735504). For review see PMID 32158597.

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 (interstitial lung disease/ILD)

I.b

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

I.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

I.d

Acute eosinophilic pneumonia (AEP)

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.v

Relapsing or migrating pneumonitis/pneumonia (see also Id)

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.z

Progression, acceleration or exacerbation of preexisting ILD/fibrosis

I.ab

Delayed ILD, -pneumonitis, -fibrosis

I.ae

Radiation recall pneumonitis

I.ak

Shrinking lung syndrome

I.ay

Chronic pneumonitis

XLI - Pulmonary edema - Acute lung injury - ARDS

XLI.b

Pulmonary edema, cardiogenic

XLI.e

ARDS - Acute lung injury

XLII - Pulmonary/alveolar./airway hemorrhage/bleeding

XLII.m

Coagulopathy

XLIII - Airway involvement

XLIII.a

Bronchospasm - Wheezing - Asthma

XLIII.d

Exacerbation or deterioration of preexisting COPD

XLIII.t

Eosinophilic airway disease (asthma, bronchitis, bronchiolitis)

XLIII.x

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

XLIII.af

Sputum production - Bonchorrhea - ‘Bronchitis’

XLIII.ag

Obstructive airway dysfunction (see also IVc, XVx)

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

XLIV.g

Vocal cord paresis/paralysis

XLV - Pleural and/or pericardial involvement

XLV.a

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

XLV.i

Pleuritis (can cause chest pain)

XLV.t

Serositis - Polyserositis

XLVI - Pulmonary vasculopathy

XLVI.a

Pulmonary embolism - Venous thrombosis/thromboembolism

XLVI.b

Pulmonary arterial hypertension

XLVII - Mediastinal involvement

XLVII.a

Lymphadenopathy (intrathoracic)

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

XLVIII.a

Diaphragm/inspiratory muscle weakness/paralysis (w/wo ARF)

XLVIII.d

Respiratory failure from ventilatory depression (due to neuromuscular blockade/paralysis)

XLVIII.r

Myasthenia gravis - Myasthenic-like syndrome

XLVIII.ab

Guillain-Barré (or GB-like) syndrome (w/wo ARF)

XLVIII.ac

Myositis of the respiratory muscles (May lead to respiratory muscle paralysis)

XLIX - Systemic/Distant conditions, syndromes and reactions

XLIX.a

DRES syndrome - DRESS-like reaction

XLIX.c

Capillary leak syndrome (CLS)

XLIX.d

Lupus - Lupus syndrome (see also Vd)

XLIX.e

Autoimmunity-Autoimmune conditions (+ANA, +anti-ds-DNA, +ANCAs, other auto-Abs)

XLIX.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)

XLIX.i

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

XLIX.j

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

XLIX.l

Myopathy-Myositis-Polymyositis (see also under Xba)

XLIX.m

Sarcoid-like granulomatosis (endo-/extrathoracic)

XLIX.o

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

XLIX.p

Tumor lysis syndrome (TLS)

XLIX.u

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

XLIX.w

Multiple organ dysfunction/failure (MODS/MOF)

XLIX.ao

Immune-related adverse effect/toxicity

XLIX.ap

Cytokine release syndrome - Cytokine storm

XLIX.ax

Connective tissue disease

XLIX.az

Polymyalgia rheumatica

XLIX.bj

Temporal arteritis (Horton’s)

L - Miscellaneous

L.l

Neutropenia, agranulocytosis (w/wo infection/sepsis)

L.v

Adrenal suppression

L.ad

Vertebral compression fracture

L.ar

Graft vs. host disease in transplant recipients

L.as

Deterioration of graft function in SOT recipients

L.av

Nonrespiratory AE of interest

LI - Cardiovascular involvement / toxicity

LI.a

Left or biventricular dysfunction/failure

LI.c

Pericardial effusion (w/wo tamponade)

LI.d

Myocarditis (can be fulminant)

LI.f

Takotsubo (stress) cardiomyopathy

LI.h

Coronary artery disease (acute) - Myocardial ischemia/infarction

LI.n

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

LI.o

Cardiovascular collapse - Cardiogenic shock - Hypotension

LI.s

Heart failure (biventricular, congestive)

LI.t

Heart block (bundle branch- or AV-)

LI.ak

Cardiotoxicity

LI.az

Necrotizing myocarditis (w/o evidence for CAD)

LI.bd

Sudden cardiac death

LV - Imaging

LV.k

Imaging: An area or areas of consolidation

LV.v

Imaging: Centrilobular micronodules (can be diffuse)

LV.w

Imaging: Lung nodule or nodules

LV.bj

Imaging: Avid pleural uptake on PET-scan

LV.bk

Imaging: F18-PET scan positive lympadenopathy

LV.bv

Imaging: A subsolid lung nodule or nodules

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

LVII.a

BAL: An excess proportion of lymphocytes

LVII.b

BAL: An excess proportion of neutrophils

LVII.c

BAL: An excess proportion of eosinophils

LVIII - Pathology

LVIII.a

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

LVIII.b

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

LVIII.d

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

LVIII.e

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

LVIII.f

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

LVIII.j

Path: Micronodular organizing pneumonia/BOOP

LVIII.o

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

LVIII.x

Path: Pulmonary fibrosis (not otherwise specified or unclassifiable)

LVIII.ae

Path: Foamy inclusions in alveolar macrophages and/or in other lung cells

LVIII.al

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

LVIII.bx

Path: Granulomatous lymphadenopathy

LVIII.co

Path: Myocarditis

LVIII.cr

Path: Myocardial vasculitis

LVIII.cv

Path: Pneumocyte vacuolization

LIX - Infections & related conditions

LIX.b

Opportunistic pulmonary/systemic infections

LIX.c

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

LIX.e

Pneumocystis jiroveci pneumonia

LIX.g

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

LIX.q

Viral pneumonia

LIX.r

Fungal infection (pulmonary/extrapulmonary)