TABLE 1

Study characteristics of papers selected for full data extraction

First author, date [ref], origin	Description	Study population and attrition	CPET method and CPET parameters	Exclusion	Disease outcomes	Statistical methods to investigate CPET and outcome	Summary of key reported outcomes	Comments
Triantafillidou 2013 [28], Greece	Prospective study evaluating prognostic role of 6MWT and CPET in IPF. Follow-up 9–64 months.	25 pts with IPF	Cycle ergometer, pulse oximetry. VE/VCO₂ slope, VO₂ peak/kg, VE/VCO₂ ratio at AT.	Significant PH (PASP >45 mmHg on ECHO), pts taking beta blockers. Pulmonary fibrosis due to environmental and occupational exposure, drug toxicity or autoimmune rheumatological disease.	Survival	Parameters of study were evaluated by Wald test, likelihood ratio test and the score (log-rank) tests with Bonferroni correction. Parameters achieving statistical significance were then evaluated in a multiple regression Cox proportional hazard model with a stepwise model selection.	8 D by end of the observation period. 21 patients reached the AT. VE/VCO₂ slope, VO₂ peak·kg⁻¹ and VE/VCO₂ at AT were significant survival predictors. Optimal model for mortality risk estimation combined VO₂ peak·kg⁻¹ with DLCO (p<0.0001). Per 1 unit increase in VO₂ peak·kg⁻¹ (1 mL·kg⁻¹·min⁻¹) and DLCO% (1%), mortality rate was reduced by 32% and 13%, respectively. VO₂ peak threshold of 14.2 mL·min⁻¹·kg⁻¹ was associated with an increased mortality risk.	Prospective study with low mortality rate in small numbers of pts. Data generated from sub-analysis of RCT.
Vainshelboim 2016 [29], Israel	Prospective observational study evaluating role of 12 week exercise training programme on survival at 40 months follow-up. Evaluation of the role of CPET variables in the prognostication of IPF.	34 pts with IPF	Cycle ergometer, pulse oximetry. Peak VO₂·kg⁻¹, peak work rate, VE/VO₂ nadir, VE/VCO₂ ratio at AT, tidal volume reserve.	Non-IPF ILD. Clinically unstable in preceding 3–6 months, severe comorbid illness, unstable cardiac disease and any orthopaedic or neurological contraindications to CPET.	Mortality or transplantation	ROC curve analysis was used to determine cut-off points of CPET variables for mortality. Cox regression analysis for survival analysis and comparison between significant cut-off points (log-rank test). HR for death or LTx (Wald test).	9 deaths and 2 LTx (considered fatalities in statistical analysis). Poorer survival and increased mortality associated with cut-off points for: peak work rate <62 watts (AUC 0.854, 0.73–0.98 CI, p=0.005), peak VO₂ <13.8 mL·kg⁻¹·min⁻¹ (AUC 0.731, 0.56–0.90 CI, p=0.031), tidal volume reserve <0.48 L·breath⁻¹ (AUC 0.810, 0.66–0.96 CI, p=0.01), VE/VCO₂ at AT >34 (AUC 0.783, 0.6–0.96 CI, p=0.02) and VE/VO₂ nadir >34 (AUC 0.736, 0.56–0.90, p=0.002). Bivariate analysis of these cut-offs (above and below the threshold) revealed HRs as follows: peak work rate 9.2 (1.9–42.6), peak VO₂ 4.4 (0.94–20.3), tidal volume reserve 7.6 (1.6–35.2), VE/VO₂ nadir 8.3 (2.2–31.6), VE/VO₂ at AT 4.6 (1.2–17.3). Non-survivors were characterised by higher dyspnoea levels, the presence of PH (assessed by ECHO sPAP>35 mmHg), and CPET markers of reduced ventilatory efficiency (VE/VO₂ nadir p=0.039, VE/VCO₂ at AT p=0.008) and reduced exercise capacity (peak work rate p=0.01, peak VO₂ p=0.02).	Prospective observational study analysis as part of a wider single-centre RCT. Underpowered to detect survival differences between groups. Small sample size. Higher prevalence of PH in non-survivors.
King 2001 [23], USA	Retrospective analysis of clinical, radiological and physiological parameters predicting survival in IPF. Median follow-up 20 months (maximum 14.8 years).	238 IPF pts with histological UIP. 80 pts excluded from the final model derivation.	Cycle ergometer, blood gas analysis. P(A-a)O₂ corrected for FiO₂, VD/VT, VO₂, maximal workload.	CTD, left ventricular failure, occupational and environmental exposure, or history of drug exposure known to cause pulmonary fibrosis. Incomplete case records.	Survival (defined as death or time of censoring: censored if still alive at last contact n=79, received single LTx n=11, double LTx n=1, or heart and LTx n=1 or e) died from other cause than IPF (n=12).	Kaplan–Meier survival curves developed for group, stratified by sex, age and smoking status. Univariate Cox proportional hazards regression analysis (adjusted for age and smoking) for each variable. Variables with p<0.25 included in multivariate analysis. Pearson's correlation to avoid multicollinearity. Forward elimination process used to develop preliminary model. Multivariable influential points removed. Composite scoring system developed, weighting categories according to p values and HR, and using Akaike's information criteria.	155 D (125 IPF, 19 other causes, 11 unknown and attributed to IPF). 105 patients censored (n=79 alive at time of analysis, n=13 LTx, n=12 non-IPF deaths, n=1 lost to follow-up). Composite scoring model developed to predict survival in IPF (included age, smoking history, clubbing, extent of profusion of interstitial opacities, presence/absence of PH on CXR, % predicted TLC and PaO₂ at the end of maximal exercise). Exercise PaO₂ only exercise variable included in the model, accounting for 10.5% of score (PaO₂ maximal exercise HR 0.74, CI 0.67–0.82, p<0.0001).	CPET performed in study as part of wider analysis of predictive factors in IPF. Histological UIP increased potential selection bias of a less severe IPF population. The radiological component used CXR rather than HRCT in early years of the study. Only 158/238 (66%) of the original cohort were used to derive the complete model and thus possibility for selection bias.
Miki 2003 [21], Japan	Retrospective study: evaluation of the predictive value of CPET for IPF respiratory deaths. Mean follow-up 2.7 years (7.2 months–9.0 years).	41 IPF pts.	Exercise treadmill (Sheffield protocol). PaO₂, PaCO₂, HR, respiratory frequency (f), Vt, VE, peak VO₂, VE/VO₂, VE/VCO₂, VO₂/HR, AaDO₂ and PaO₂ slope.	CTD, sarcoid, OP, EP, HP, cardiac disease, anaemia, primary cardiac disease, PVD, cancer, pleural/chest wall disorders including respiratory muscle weakness. Steroid or immunosuppressive treatment prior to study entry. Death from a non-respiratory cause during follow-up.	Respiratory death	Exercise parameters (between groups split by PaO₂ slope) compared using Mann–Whitney. Univariate Cox proportional hazards model to compare initial parameters then entered into multiple regression analysis using stepwise evaluation. Relationship between PaO₂ slope and other variables were analysed by linear regression with stepwise technique. Survival times compared using Kaplan–Meier curves and statistical significance determined by log-rank test.	23 respiratory deaths. Median survival 2.9 years. In univariate analysis, VO₂ max (HR 0.997, 0.995–0.999 CI, p=0.012), VO₂/HRR max) (HR 0.69, 0.51–0.93 CI, p=0.014), PaO₂ slope (HR 0.68, 0.51–0.89 CI, p=0.006), VE/VCO₂ (HR 1.04, 1.006–1.07 CI, p=0.020) and age (HR 1.1, 1.02–1.18 CI, p=0.014) associated with survival in IPF. On multiple regression, PaO₂ slope (HR 0.84, 0.73–0.97 CI, p=0.015) and age (HR 1.096, 1.01–1.19 CI, p=0.025) independently related to survival. When PaO₂ slope was divided into steep (≤−60 mmHg·L⁻¹·min⁻¹) and gentle (>−60 mmHg·L⁻¹·min⁻¹), median survival time after CPET significantly shorter in steep group (1.6 versus 4.5 years).	Retrospective, single-centre cohort. Large number of exclusion criteria. Outcomes limited to respiratory deaths.
Fell 2009 [24], USA	Retrospective study evaluating prognostic value of CPET in IPF. Mean follow-up not reported.	117 IPF pts. 10 pts excluded from survival analysis as VO₂ max changed between baseline and 6 months.	Cycle ergometer. Blood gas analysis. Peak VO₂·kg⁻¹	Patients with CTD, occupational or environmental exposure, histological pattern other than UIP.	Survival	Multivariate Cox proportional hazard models studied the predictive value of peak VO₂ adjusting for age, gender, smoking status, baseline FVC% and baseline DLCO%. Resulting HR were plotted against peak VO₂ to determine thresholds. Survival thresholds examined with Kaplan–Meier survival curves, log-rank tests and multivariate Cox proportional hazard models.	Peak VO₂·kg⁻¹ examined as a continuous variable did not predict survival HR 0.969 (p=0.55). Baseline threshold peak VO₂ <8.3 mL·kg⁻¹·min⁻¹ was associated with an increased risk of death (n=8; HR 3.24, 1.10–9.56 CI, p=0.03). No other CPET variables reported.	Retrospective, single-centre study. Number of deaths in each group not reported. Analysis was not by a priori plan. Small number of pts below VO₂ max threshold in analysis. Caution in interpreting generalisability to IPF population as 64% (75/117) required a surgical lung biopsy for diagnosis. No other CPET outcomes reported.
Wallaert 2011 [22], France	Retrospective multicentre study evaluating prognostic role of CPET in determining 3-year survival in IPF.	63 IPF patients	Cycle ergometer. Blood gas analysis. Peak VO₂·kg⁻¹, VE/VO₂ at ventilatory threshold, VE/CO₂, (VO₂/HRR), P(A-a)O₂, ventilatory reserve and lactate.	Non-IPF associated ILD. Pts in which blood gas analysis had not been performed.	3-year survival (absence of D or LTx).	Demographic data, resting pulmonary function and CPET parameters in the survivors were compared to those who died/received lung transplantation by univariate survival analysis. Multivariate logistic regression analysis explored prognosis at 3 years. Kaplan–Meier curve and log-rank test was performed, with model validation by ROC curve analysis.	19 patients: D (n=14) or LTx (n=5) at 3 years. Multivariate logistic regression analysis highlighted four parameters to be independently correlated with mortality: TLC (% pred), VE/VO₂ at ventilatory threshold, FVC (% pred) and P(A-a)O₂. The most appropriate logistic regression model incorporated two variables, with the lowest 3 year survival when TLC (<65%) and VE/VO₂ at ventilatory threshold (>45) (AUC 0.811, sensitivity was 98%, specificity 50%, positive predictive value 80% and the negative predictive value 64%).	Retrospective study. Presence of PH not studied. Inadequate description of exclusion criteria.
Gläser 2013 [18], Germany	Retrospective study evaluating predictive value of CPET measures for the presence of PH in IPF. Follow-up 2 years.	135 pts (73 with PH) IPF. No follow-up data for 2 pts, reducing cohort to 133.	Cycle ergometer, pulse oximetry. Peak VO₂, VO₂ at AT (mL·min⁻¹), VE/MVV, VE versus VCO₂ slope, VE max, Vt max, Vt max/IC, VE/MVV.	Pts with left heart disease (ECHO ± PWP>14 mmHg by RHC), non-IPF pulmonary fibrosis and/or PH resulting in a life expectancy <24 months, inability to perform CPET due to orthopaedic or neurological impairment.	Interceding pulmonary hypertension. Survival (death and lung transplantation combined endpoint)	Mann–Whitney or chi-squared test used for comparison of IPF pts with/without PH. Cox proportional hazards analysis used for pulmonary variables and endpoint. Kaplan–Meier survival plots constructed with differences in survival analysed by log-rank test. Cut-off values for best discrimination determined using ROC curve analysis.	37 D and 6 LTx during follow-up. Presence of PH best predicted by gas exchange efficiency during exercise and peak oxygen uptake (VE versus VO₂ slope pred (≥152.4, AUC 0.938, 0.892–0.984 CI) and VO₂ peak (≤56.3, AUC 0.832, 0.753–0.911 CI)). By univariate analysis, the presence of PH (by RHC) was the most powerful prognosticator in IPF (whole group) (mPAP HR 1.07, 1.04–1.11 CI), with CPET outcomes of peak VO₂ pred (HR 0.96, p=0.001) and VO₂ at AT pred (HR 0.97, p=0.017) also being statistically significant. In multivariate analysis, invasively measured pH and peak VO₂ pred were independent predictors for survival.	Retrospective multicentre study. Potential recruitment bias due to selected cohort (specialist centres, excluded left heart disease).
van der Plas 2014 [20], Netherlands	Retrospective study exploring predictive value of CPET and ECHO parameters for survival in IPF. Mean follow-up 42.3 ± 42.2 months.	38 pts with IPF. Follow-up for 3 pts who received transplantation was censored at date of transplantation.	Cycle ergometer. Peak workload (% predicted), VO₂ peak (% pred), VE peak (% pred), breathing reserve (%), HRR peak (% pred), VE/VCO₂ ratio at AT, VO₂/HRR (% pred), ETCO₂ at max (kPa).	Non-IPF ILD. Pts where CPET and ECHO were performed more than 2 weeks apart.	Survival	Pearson's correlation coefficients were calculated for sPAP and CPET parameters. Patients were grouped into those with/without sPAP ≥40 mmHg and differences in exercise parameters analysed with unpaired t-test or chi-squared test. ROC curve analysis was used to determine variables that predict sPAP ≥40 mmHg. Kaplan–Meier survival curves then evaluated the prognostic value of these parameters on survival. HRs were calculated using multivariate Cox proportional hazard models (with FVC and CPI included in the model to correct for functional severity of IPF) to determine predictive value of parameters on survival.	24 D and 3 LTx during follow-up. 29/38 (76%) had a reduced VO₂ peak (i.e. <84% predicted). VE/VCO₂ at AT was significantly higher in patients with sPAP ≥40 mmHg (n=11) compared to those with sPAP ≤40 mmHg (n=27), (54.0 ± 21.9 versus 37.9 ± 7.5, p=0.021). VE/VCO₂ at AT was shown to be a good predictor of sPAP ≥40 mmHg by ROC curve analysis but only VE/VCO₂ at AT and not sPAP ≥40 mmHg was shown to predict survival. Pts with VE/VCO₂ at AT ≤45 (n=24) had a significantly better prognosis that those with VE/VCO₂ ≥45 (n=14), 81.3 ± 14.1 versus 21.0 ± 4.9 months, respectively; HR 4.58, p=0.001. Parameters reflecting functional severity of IPF did not add to the predictive value of VE/VCO₂ at AT for survival.	Retrospective analysis of prospective database. Single centre.
Kollert 2011 [25], Germany	Retrospective study evaluating whether gas exchange during CPET reflects disease activity and clinical course in sarcoidosis. 2 year follow-up.	149 histologically confirmed sarcoidosis. Analysis of 102 patients (47 incomplete notes).	Cycle ergometer, capillary blood gas analysis. P(A-a)O₂	Patients who could not complete CPET >6 min, in the absence of extra-cardiopulmonary limitations. Patients with clinical signs of acute infection. For the longitudinal subgroup analysis: patients with incomplete records.	Longitudinal component: duration of immunosuppressive therapy (no treatment, treatment ≤1 year, treatment >1 year)	Associations between sarcoidosis clinical parameters (including the need for prolonged immunosuppressive therapy >1 year) and P(A-a)O₂ during exercise were assessed by analysis of variance statistical methodology. Univariate then multivariate backward binary logistic regression analysis used to assess clinical variables independently associated with need for prolonged immunosuppression.	Multivariate regression analysis suggested FVC (OR 0.954, 0.917–0.992 CI, p=0.009) and P(A-a)O₂ (OR 1.098, 1.039–1.160 CI, p<0.0001) during exercise were independently associated with a need for prolonged immunosuppressive treatment. No other CPET variables reported.	No other CPET variables described in analysis and thus potential for reporting bias. Unable to determine exact clinical characteristics of this longitudinal cohort from the data presented.
Lopes 2012 [26], Brazil	Retrospective study to identify CPET measures that predict FVC and DLCO progression over 5 years in patients with thoracic sarcoidosis.	42 pts with histologically confirmed sarcoidosis.	Cycle ergometer, blood gas analysis. Peak VO₂ (% pred), % peak VO₂ at lactate threshold, VCO₂/VO₂, VO₂/HRR, maximum respiratory rate, breathing reserve, HRR, P(A-a)O₂, ΔSpO₂, Δlactate.	History of smoking. Mycobacterial infection, exposure to aero-contaminants or medications known to cause granulomatous disorders. Those with known medical history or laboratory diagnosis of concomitant respiratory, cardiac or neuromuscular disease.	Decline FVC% and DLCO%	FVC/DLCO variation over study period evaluated by Wilcoxon signed rank test. Correlations between CPET measures and FVC/DLCO variation over 5 years used Spearman's rank correlation (except breathing reserve and relative variations of FVC). ROC curve analysis used to determine cut-offs for CPET measurements are predictors for lung function decline. MLR used to identify factors independently related to decreased lung function.	Significant reductions in FVC (relative variation −5.1% (−23.1 to 0%)) and DLCO (relative variation −2.5% (−44.4 to 0.93%)) at 5 years follow-up. Peak VO₂ (% pred), breathing reserve, maximum RR, P(A-a)O₂ and ΔSpO₂ correlated with FVC and DLCO values that had declined >10% from baseline (p<0.0001 for all parameters). P(A-a)O₂ >22 mmHg (RR 70.0, p=0.001) and breathing reserve <40% (RR 20.8, p=0.014) independently predicted lung function decline (FVC% pred and DLCO% pred).	Retrospective, single-centre study. Potential for selection bias (tertiary centre for sarcoid - more likely to have severe patients). Small number of patients resulting in high RR values. Cardiac circulatory status not determined.
Layton 2017 [7], USA	Retrospective study evaluating predictive value of CPET for 1-year transplant-free survival in a population of ILD patients undergoing lung transplant evaluation.	192 pts had CPET performed on oxygen. Four tests terminated due to oxygen desaturation (nadir SpO₂ <80% despite 30% FiO₂). Three tests terminated early due to low ETCO₂ (<18 mmHg) or elevated ETCO₂ (>60 mmHg), reducing cohort to 185 pts.	Cycle ergometer, pulse oximetry. Peak VO₂ (mL·kg⁻¹·min⁻¹, % predicted), workload (watts, % predicted), VE/VCO₂ slope (% predicted), ETCO₂ mmHg and O₂ pulse.	Pts not being evaluated for lung transplant, those that did not require oxygen with exercise, no follow-up data available at 1 year post-CPET.	Survival without the need for transplantation (at 1 year).	Comparison of variables between those who died / transplanted (D/LTx) and those who survived transplant-free were compared using two-sample independent t-test. Survival was calculated by Kaplan–Meier method, with univariable Cox regression analysis to identify predictors of 1 year transplant-free survival. Multivariable Cox model with forward stepwise elimination method to identify prediction of transplant-free survival (and to predict survival excluding those transplanted). ROC used to test thresholds of these predictors.	79 D/LTx during follow-up period. Mixed cohort of ILD patients analysed: IPF n=135 (70%), sarcoidosis n=15 (8%), HP n=6 (3%), NSIP n=12 (6%), ILD with mixed connective tissue disorder n=24 (13%). 113/192 (59%) survived transplant-free. More patients with sarcoidosis in the survival transplant-free group than the D/LTx group and more patients with NSIP in the D/LTx group (p=0.028). Multivariable Cox regression identified CPET variables of: peak workload <35% predicted (HR 4.71, 2.64–8.38 CI, AUC=0.740) nadir CPET SpO₂ <86% despite 30% FiO₂ (HR 2.27, 1.41–3.68 CI, AUC=0.645) FVC% predicted <45% (HR 1.82, 1.15–2.87 CI, AUC 0.624) as discriminatory parameters predicting 1-year mortality or need for transplant. Notably the presence of PH (present in 50% pts determined by combination of RHC or ECHO) was not an independent predictor of prognosis in this study.	Retrospective, single-centre cohort. Potential for selection bias, unidentified confounding and missing covariate data. Generalisability to general ILD patients questionable as highly selected cohort of advanced ILD patients. Source population, patterns of referral transplant, waiting times and cohort characteristics may differ from other transplant programmes.
Kawut 2005 [19], USA	Retrospective study of CPET and 6MWTD variables associated with survival in pts referred for lung transplant. Median follow-up 271 days (23–983).	51 pts with IIP or DPLD of known cause (e.g. drugs, occupational or environmental exposures, CTD) referred for lung transplant.	Cycle ergometer. Pulse oximetry. SaO₂ (unloaded, peak, recovery), peak VO₂·kg⁻¹, VO₂/HR peak, VCO₂ unloaded, VE unloaded.	Pts evaluated at another lung transplantation centre. Other forms of DPLD, e.g. LAM, pulmonary Langerhans cell histiocytosis/histiocytosis X, EP and granulomatous DPLD, e.g. sarcoidosis.	All-cause mortality. Death on the lung transplantation waiting list.	Cox proportional hazards regression to identify predictors of time-to-death. Individual models were constructed using LTx as a time-dependent covariate to “control” for receiving a LTx. ROC curve analysis was used to define cut-off for variables associated with dying on the transplantation list.	7 lung transplantations and 17 deaths (1 post-transplantation). 28/51 (55%) UIP/IPF, CTD-UIP (n=4), NSIP (n=6), HP (n=2), DIP (n=1), COP (n=1), LIP (n=1) and unclassifiable ILD (n=7). A 6MWTD <350 m (HR 4.6, 1.5–14.2 CI, p=0.009), peak VO₂·kg⁻¹ (HR 0.88, 0.79–0.99 CI, p=0.039) (no threshold determined) and VE/VCO₂ >46 (p=0.05) (were each associated with increased risk of death). SpO₂ <95% during unloaded exercise had 75% chance of dying on transplantation list (sensitivity 86%, specificity 89%). 67% chance of death if 6MWTD <350 m.	Retrospective single-centre cohort. Only half pts reached AT which limited analysis (low number of endpoints). Additional oxygen use during CPET was variable. Generalisability questionable as highly selected cohort of severe ILD. Source population, patterns of referral to transplant centre, waiting times and cohort characteristics may differ from other transplant programmes.
Swigris 2009 [27], USA	Retrospective study exploring prognostic role of SpO₂ and SaO₂ at rest and during maximal exercise in SSc-ILD exercise. Median follow-up 7.1 years.	83 patients with SSc-ILD	Cycle ergometer. Blood gas analysis and pulse oximetry. SpO₂ and SaO₂ at rest and during maximal exercise (SpO₂ max). VO₂ max measured but not reported.	Pulmonary hypertension, overlap syndromes.	Mortality	Cox proportional hazard models were used to examine the prognostic capabilities of SpO₂, dichotomised by <89% or ≥89% and also as continuous variables. Kaplan–Meier survival curves were generated.	39 deaths (number of transplantations not recorded). In Cox proportional hazards models, SpO₂ predicted mortality; SpO₂max <89% (HR 2.4, 95% CI 1.2 to 4.9, p=0.02), SpO₂max fall >4% from baseline (HR 2.4, 95% CI 1.1 to 5.0, p=0.02), alongside ΔSpO₂ (HR 1.08, 95% CI 1.03 to 1.14, p=0.002). Controlling for FVC%, the ΔSpO₂ remained a significant predictor of mortality (HR 1.07, 95% CI 1.01 to 1.14, p=0.02). No other CPET variables reported.	No other CPET variables described in analysis and thus potential for reporting bias.

Abbreviations: ΔSpO₂: difference between peak and resting oxygen saturation; 6MWTD: 6-minute walk test distance; AaDO₂: alveolar–arterial oxygen pressure difference; AT: anaerobic threshold; AUC: area under the curve; BR: breathing reserve [1 – (VE during exercise/MVV)] × 100; CI: confidence interval; COP: cryptogenic organising pneumonia; CPET: cardiopulmonary exercise testing; CPI: composite physiologic index; CTD: connective tissue disease; CXR: chest X-ray; D: died/deaths; DLCO: diffusion capacity of lungs for carbon dioxide; DPLD: diffuse parenchymal lung disease; ECHO: echocardiogram; EP: eosinophilic pneumonia; ETCO₂: end tidal carbon dioxide; FiO₂: fraction of inspired oxygen; FVC: forced vital capacity; HP: hypersensitivity pneumonitis; HR: hazard ratio; HRCT: high-resolution computed tomography; HRR: heart rate; IC: inspiratory capacity; ILD: interstitial lung disease; IPF: idiopathic pulmonary fibrosis; LAM: lymphangioleiomyomatosis; LTx: lung transplantation; max: maximal; MLR: multiple logistic regression; MVV: maximum voluntary ventilation (can be measured or estimated as FEV1 × 41); OR: odds ratio; PaCO₂: partial pressure of carbon dioxide; PaO₂: partial pressure of oxygen; pts: patients; NSIP: non-specific interstitial pneumonia; P(A-a)O₂: alveolar–arterial oxygen pressure gradient at peak exercise; PH: pulmonary hypertension; pred: predicted; PVD: peripheral vascular disease; PWP: pulmonary capillary wedge pressure; RCT: randomised controlled trial; RHC; right heart catheter; ROC: receiver operating characteristic curve; RR: respiratory rate; SaO₂: oxygen saturation of arterial blood; sPAP: systolic pulmonary artery pressure; SpO₂: oxygen saturation measured by pulse oximetry; SSc: systemic sclerosis; TLC: total lung capacity; UIP: usual interstitial pneumonia; VCO₂: carbon dioxide production; VD/VT: physiological dead space/tidal volume ratio; VE: minute ventilation; VE/VCO₂: ventilatory equivalent for carbon dioxide; VE/VO₂: ventilatory equivalent for oxygen; VO₂: oxygen uptake; VO₂ slope: PaO₂ plotted against VO₂; VO₂/HRR max or oxygen pulse: oxygen delivery per heartbeat; VT: ventilatory threshold (highest VO₂ sustained without lactic acidosis); Vt: tidal volume; tidal volume reserve: Vt max-Vt resting.