TABLE 2.

Reported associations between CPET parameters and outcomes in studies of ILD

CPET measurement	Studies	Threshold	Outcome
Maximal oxygen consumption (peak VO2)	Fell 2009	No association as continuous variable (HR 0.969, p=0.55). Peak VO2 <8.3 mL·kg−1·min−1 associated with worse outcome (n=8; HR 3.24, 1.10–9.56 CI, p=0.03).	Survival in IPF.
	Gläser 2013	Peak VO2% pred <56.3% Peak VO2% pred (multivariate analysis) – no threshold determined.	Presence of PH. Survival in IPF.
	Kawut 2005	Peak VO2·kg−1 (no threshold determined), associated with worse outcome.	Mortality at 1 year of mixed ILD patients referred for transplantation.
	King 2001	Methodology suggested peak VO2 was recorded but result not reported in results section.	Survival in IPF.
	Kollert 2011	Not measured.	Prolonged immunosuppressive therapy (>1 year) in sarcoidosis.
	Layton 2017	Peak VO2·kg−1 and peak VO2% pred (association with univariate analysis but not multivariate). A 1 mL·kg−1·min−1 greater VO2 reduced the risk of mortality/transplantation by 9%.	1-year mortality or transplantation in mixed population of ILD.
	Lopes 2012	Peak VO2 <50% pred (association on univariate but not multivariate analysis).	Decline of >10% FVC% pred and DLCO% pred at 5 years follow-up from baseline, in thoracic sarcoidosis.
	Miki 2003	Peak VO2 (associated with worse outcome using univariate analysis, but not on multivariate).	Respiratory deaths in IPF.
	Swigris 2009	Although measured, not part of planned statistical analysis.	Mortality in SSc-ILD.
	Triantafillidou 2013	Peak VO2 <14.2 mL·kg−1·min−1 associated with worse outcome and further enforced when the model combines DLCO.	Survival in IPF.
	Vainshelboim 2016	Peak VO2 <13.8 mL·kg−1·min−1 associated with worse outcome (AUC 0.731, 0.56–0.9, p=0.031).	Mortality or transplantation in IPF.
	van der Plas 2014	Peak VO2·kg−1 – no association.	Survival in IPF.
	Wallaert 2011	Peak VO2 and peak VO2·kg−1 – no association as continuous variable.	3-year survival in IPF.
Ventilatory efficiency (VE/VO2, VE/VCO2)	Fell 2009	Not measured	Survival in IPF.
	Gläser 2013	VE/VCO2 slopepred ≥152.4 predicted outcome (sensitivity 87.2%, specificity 88.4%).	Development of interceding PH in IPF.
	Kawut 2005	VE/VCO2 >46 associated with worse outcome. The risk was non-proportional so could not be estimated with a single hazard ratio.	All-cause mortality at 1 year of mixed ILD patients referred for transplantation.
	King 2005	VE/VO2 associated with worse outcome when results adjusted for age and smoking status (HR 1.06). Not included in multivariable model.	Survival in IPF.
	Kollert 2011	Not measured	Prolonged immunosuppressive therapy (>1 year) in sarcoidosis.
	Layton 2017	VE/VCO2 slope (association with univariate analysis but not multivariate)	1-year mortality or transplantation in mixed population of ILD.
	Lopes 2012	Not measured	Decline in FVC and DLCO at 5 years in sarcoidosis.
	Miki 2003	VE/VO2 at max VE/VCO2 at max (associated with worse outcome using univariate analysis, but not on multivariate).	Respiratory deaths in IPF.
	Swigris 2009	Not measured	Survival in SSc-ILD.
	Triantafillidou 2013	VE/VCO2 slope and higher VE/VCO2 at AT predicted worse outcome.	Survival in IPF.
	Vainshelboim 2016	VE/VCO2 at AT >34 and nadir VE/VO2 >34 predicted worse outcome in univariate and bivariate analysis	Mortality in IPF.
	van der Plas 2014	VE/VCO2 at AT >45 associated with poorer survival (HR 4.58, p=0.001), even after correcting for lung function severity.	Survival in IPF.
	Wallaert 2011	VE/VO2 at AT >45 associated with worse outcome (multivariate analysis).	3-year survival in IPF.
Diffusion limitation or exercise-induced hypoxaemia	Fell 2009	Resting PaO2 was associated with worse outcome (HR 0.934) when adjusted for age, sex, baseline physiology and smoking status. No threshold could be determined.	Survival in IPF.
	Gläser	Although SpO2 monitored during CPET, not included in analysis.	Survival in IPF or development of interceding PH.
	Kawut 2013	SaO2 <95% during unloaded exercise (one of several variables) predicting worse outcome (p=0.0025). SaO2 <95% during unloaded exercise (one of several variables) predicting worse outcome (sens. of 86%, spec. 89%).	All-cause mortality at 1 year of mixed ILD patients referred for transplantation. Death on waiting list for lung transplantation.
	King 2001	PaO2 at maximal exercise associated with worse outcome and included in multivariable model (accounted for as much as 10.5% of the maximum score in the model).	Survival in IPF.
	Kollert 2011	P(A-a)O2 associated with worse outcome (multivariate analysis, OR 1.098, p<0.001).	Prolonged immunosuppressive therapy (>1 year) in sarcoidosis.
	Layton 2017	Nadir CPET SpO2 <86% independently associated with worse outcome (HR 2.27, p=0.001). Risk of death/lung transplantation increased two-fold when SpO2 <86%.	1-year mortality or transplantation in mixed population of ILD.
	Lopes 2012	P(A-a)O2 >22 mmHg associated with worse outcome (multivariate analysis, RR 70.0, p<0.001).	Decline of >10% FVC% pred and DLCO% pred at 5 years follow-up from baseline, in thoracic sarcoidosis.
	Miki 2003	PaO2 slope (ΔPaO2/ΔVO2) predicted worse outcome (multivariate analysis, HR 0.841, p=0.015). Those stratified ≤−60 mmHg·L−1·min−1 associated with worse survival (1.6 years versus 4.5 years).	Respiratory deaths in IPF.
	Swigris 2009	SpO2 at maximum exercise <89% (HR 2.4) or SpO2 at maximum exercise fall >4 points from baseline (HR 2.4) associated with worse outcome.	Survival in SSc-ILD.
	Triantafillidou 2013	SpO2 at peak exercise – no association	Survival in IPF.
	Vainshelboim 2016	Although SpO2 monitored during CPET, not included in analysis.	Mortality in IPF.
	van der Plas 2014	Not specifically reported on.	Survival in IPF.
	Wallaert 2011	Higher P(A-a)O2 associated with worse outcome using multivariate analysis, but was not included in the final logistic regression model.	3-year survival in IPF.

Abbreviations: AT: anaerobic threshold; DLCO: diffusion capacity of lungs for carbon dioxide; FVC: forced vital capacity; HR: hazard ratio; ILD: interstitial lung disease; IPF: idiopathic pulmonary fibrosis; max: maximum; OR: odds ratio; P(A-a)O₂: alveolar–arterial oxygen pressure gradient at peak exercise; pred: predicted; RR: relative risk; SaO₂: oxygen saturation of arterial blood; sens.: sensitivity; spec.: specificity; SpO₂: oxygen saturation measured by pulse oximetry; SSc: systemic sclerosis; VE/VCO₂: ventilatory equivalent for carbon dioxide; VE/VO₂: ventilatory equivalent for oxygen; VO₂: oxygen uptake.