TABLE 3

Definition of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) in clinical trials

First author [ref.]	Year	Intervention	AE-IPF	Symptom	Radiology	Oxygenation	DDx
Kubo [19]	2005	Warfarin	Part of the primary outcome	Deterioration of dyspnoea within a few weeks	New GGO/consolidation and honeycombing on HRCT or CXR	P_aO₂/F_IO₂ <300	Exclusion of identifiable cause
Azuma [52]	2005	Pirfenidone	Secondary outcome	Deterioration of dyspnoea within a month	New GGO/consolidation and honeycombing on HRCT	Deterioration of P_aO₂ ≥10 torr	Exclusion of identifiable cause
King [53]	2008	Bosentan 1	Part of the primary outcome	Deterioration of dyspnoea within a month		Supplemental oxygen ≥5 L
King [54]	2009	IFNγ1b	Tertiary outcome	Deterioration of dyspnoea	New GGO on HRCT	Deterioration of P_aO₂ ≥8 torr	Exclusion of identifiable cause
Taniguchi [55]	2010	Pirfenidone	Tertiary outcome	Deterioration of dyspnoea within a month	New GGO/consolidation and honeycombing on HRCT	Deterioration of P_aO₂ ≥10 torr	Exclusion of identifiable cause
Zisman [56]	2010	Sildenafil	Secondary outcome	Deterioration of dyspnoea or cough within a month	New GGO/consolidation on HRCT or new infiltrates on CXR	Deterioration of S_pO₂ ≥5% or P_aO₂ ≥8 torr	Exclusion of identifiable cause with no physical and microbiological findings suggesting infection
King [57]	2011	Bosentan	Part of the primary outcome	Deterioration of dyspnoea within 4 weeks		Needs supplemental oxygen ≥5 L
Richeldi [58]	2011	Nintedanib	Secondary outcome	Progression of dyspnoea within 4 weeks	New GGO on CXR or HRCT	Deterioration of P_aO₂ ≥10 torr	Exclusion of identifiable cause of acute lung injury
Noble [59]	2011	Pirfenidone	Secondary outcome	Deterioration of dyspnoea within 4 weeks	New GGO ≥ one lobe on HRCT	Deterioration of P_aO₂ ≥8 torr	Exclusion of identifiable cause, cardiac disorder, pulmonary embolism, aspiration and infection
Noth [60]	2012	Warfarin	Secondary outcome	Deteriooration of dyspnoea within 30 days	New GGO/consolidation on HRCT or new infiltrates on CXR	Deterioration of S_pO₂ ≥5% or deterioration of P_aO₂ ≥8 torr	Exclusion of infection by sputum culture or BAL culture, and identifiable cause of acute lung injury
Martinez [62]	2014	Pirfenidone+ azathioprin+ N-acetylcystein	Secondary outcome	Deterioration of dyspnoea within 30 days	New GGO/consolidation on HRCT or new infiltrates on CXR	Deterioration of S_pO₂ ≥5% or deterioration of P_aO₂ ≥8 torr	Exclusion of infection by sputum culture or BAL culture, and identifiable cause of acute lung injury
Richeldi [61]	2014	Nintedanib	Secondary outcome	Deterioration of dyspnoea within 30 days	New diffuse infiltrates on CXR or GGO on CT		Exclusion of infection by routine clinical practice and microbiological studies, left heart failure, pulmonary embolism, and identifiable cause of acute lung injury

DDx: differential diagnosis; GGO: ground-glass opacities; HRCT: high-resolution CT; CXR: chest X-ray; P_aO₂: arterial oxygen tension; F_IO₂: inhaled oxygen fraction; BAL: Bronchoalveolar lavage; S_pO₂: arterial oxygen saturation measured by pulse oximetry.