INTRODUCTION: In recent years, ventilatory efficiency (minute ventilation (V'E)/carbon dioxide production (V'CO2 ) slope) and partial pressure of end-tidal carbon dioxide (P ETCO2 ) have emerged as independent predictors of postoperative pulmonary complications (PPC). Single parameters may give only partial information regarding periprocedural hazards. Accordingly, our aim was to create prediction models with improved ability to stratify PPC risk in patients scheduled for elective lung resection surgery. METHODS: This post hoc analysis was comprised of consecutive lung resection candidates from two prior prospective trials. All individuals completed pulmonary function tests and cardiopulmonary exercise testing (CPET). Logistic regression analyses were used for identification of risk factors for PPC that were entered into the final risk prediction models. Two risk models were developed; the first used rest P ETCO2 (for patients with no available CPET data), the second used V'E/ V'CO2 slope (for patients with available CPET data). Receiver operating characteristic analysis with the De-Long test and area under the curve (AUC) were used for comparison of models. RESULTS: The dataset from 423 patients was randomly split into the derivation (n=310) and validation (n=113) cohorts. Two final models were developed, both including sex, thoracotomy, "atypical" resection and forced expiratory volume in 1 s/forced vital capacity ratio as risk factors. In addition, the first model also included rest P ETCO2 , while the second model used V'E/V'CO2 slope from CPET. AUCs of risk scores were 0.795 (95% CI: 0.739-0.851) and 0.793 (95% CI: 0.737-0.849); both p<0.001. No differences in AUCs were found between the derivation and validation cohorts. CONCLUSIONS: We created two multicomponental models for PPC risk prediction, both having excellent predictive properties.

1st Department of Surgery St Anne's University Hospital Brno Czech Republic

Department of Anesthesiology and Intensive Care St Anne's University Hospital Brno Czech Republic

Department of Cardiovascular Diseases Mayo Clinic Rochester MN USA

Department of Respiratory Diseases University Hospital Brno Brno Czech Republic

Department of Sports Medicine and Rehabilitation St Anne's University Hospital Brno Czech Republic

Department of Surgery University Hospital Brno Brno Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Biostatistics and Analyses Ltd Brno Czech Republic

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

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Detillon DDEMA, Aarts MJ, De Jaeger K, et al. Video-assisted thoracic lobectomy versus stereotactic body radiotherapy for stage I nonsmall cell lung cancer in elderly patients: a propensity matched comparative analysis. Eur Respir J 2019; 53: 1801561. doi: 10.1183/13993003.01561-2018 PubMed DOI

Agostini PJ, Lugg ST, Adams K, et al. Risk factors and short-term outcomes of postoperative pulmonary complications after VATS lobectomy. J Cardiothorac Surg 2018; 13: 28. doi: 10.1186/s13019-018-0717-6 PubMed DOI PMC

Agostini P, Cieslik H, Rathinam S, et al. Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors? Thorax 2010; 65: 815–818. doi: 10.1136/thx.2009.123083 PubMed DOI

Stéphan F, Boucheseiche S, Hollande J, et al. Pulmonary complications following lung resection: a comprehensive analysis of incidence and possible risk factors. Chest 2000; 118: 1263–1270. doi: 10.1378/chest.118.5.1263 PubMed DOI

Boffa DJ, Allen MS, Grab JD, et al. Data from The Society of Thoracic Surgeons General Thoracic Surgery database: the surgical management of primary lung tumors. J Thorac Cardiovasc Surg 2008; 135: 247–254. doi: 10.1016/j.jtcvs.2007.07.060 PubMed DOI

Powell HA, Tata LJ, Baldwin DR, et al. Early mortality after surgical resection for lung cancer: an analysis of the English National Lung cancer audit. Thorax 2013; 68: 826–834. doi: 10.1136/thoraxjnl-2012-203123 PubMed DOI

Brat K, Tothova Z, Merta Z, et al. Resting end-tidal carbon dioxide predicts respiratory complications in patients undergoing thoracic surgical procedures. Ann Thorac Surg 2016; 102: 1725–1730. doi: 10.1016/j.athoracsur.2016.05.070 PubMed DOI

Brunelli A, Charloux A, Bolliger CT, et al. ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemoradiotherapy). Eur Respir J 2009; 34: 17–41. doi: 10.1183/09031936.00184308 PubMed DOI

Brunelli A, Kim AW, Berger KI, et al. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143: e166S–e190S. doi: 10.1378/chest.12-2395 PubMed DOI

Sandblom G, Videhult P, Crona Guterstam Y, et al. Mortality after a cholecystectomy: a population-based study. HPB (Oxford) 2015; 17: 239–243. doi: 10.1111/hpb.12356 PubMed DOI PMC

Humes DJ, Simpson J. Acute appendicitis. BMJ 2006; 333: 530–534. doi: 10.1136/bmj.38940.664363.AE PubMed DOI PMC

Brat K, Homolka P, Merta Z, et al. Prediction of postoperative complications: ventilatory efficiency and rest end-tidal carbon dioxide. Ann Thorac Surg 2023; 115: 1305–1311. doi: 10.1016/j.athoracsur.2021.11.073 PubMed DOI

Torchio R, Mazzucco A, Guglielmo M, et al. Minute ventilation to carbon dioxide output (V'E/V' PubMed DOI

Shafiek H, Valera JL, Togores B, et al. Risk of postoperative complications in chronic obstructive lung diseases patients considered fit for lung cancer surgery: beyond oxygen consumption. Eur J Cardiothorac Surg 2016; 50: 772–779. doi: 10.1093/ejcts/ezw104 PubMed DOI

Brunelli A, Belardinelli R, Pompili C, et al. Minute ventilation-to-carbon dioxide output (VE/VCO PubMed DOI

Miyazaki T, Callister MEJ, Franks K, et al. Minute ventilation-to-carbon dioxide slope is associated with postoperative survival after anatomical lung resection. Lung Cancer 2018; 125: 218–222. doi: 10.1016/j.lungcan.2018.10.003 PubMed DOI

Rushwan A, Stefanou D, Tariq J, et al. Increased minute ventilation to carbon dioxide slope during cardiopulmonary exercise test is associated with poor postoperative outcome following lung cancer resection. Eur J Cardiothorac Surg 2023; 65: ezad337. doi: 10.1093/ejcts/ezad337 PubMed DOI

Graham BL, Steenbruggen I, Miller MR, et al. Standardization of spirometry 2019 update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med 2019; 200: e70–e88. doi: 10.1164/rccm.201908-1590ST PubMed DOI PMC

Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J 2017; 49: 1600016. doi: 10.1183/13993003.00016-2016 PubMed DOI

Quanjer PH, Tammeling GJ, Cotes JE, et al. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J 1993; 6: Suppl. 16, 5–40. doi: 10.1183/09041950.005s1693 PubMed DOI

Quanjer PH, Stanojevic S, Cole TJ, et al. Multiethnic reference values for spirometry for the 395yr age range: the global lung function 2012 equations. Eur Respir J 2012; 40: 1324–1343. doi: 10.1183/09031936.00080312 PubMed DOI PMC

Crapo RO, Morris AH. Standardized single breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis 1981; 123: 185–189. PubMed

Stanojevic S, Graham BL, Cooper BG, et al. Official ERS technical standards: global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians. Eur Respir J 2017; 50: 1700010. doi: 10.1183/13993003.00010-2017 PubMed DOI

Global Lung Function Initiative (GLI). Global Lung Function Initiative calculators for Spirometry, TLCO and Lung volume. Date last accessed: 31 March 2024. https://gli-calculator.ersnet.org/index.html

Licker MJ, Widikker I, Robert J, et al. Operative mortality and respiratory complications after lung resection for cancer: impact of chronic obstructive pulmonary disease and time trends. Ann Thorac Surg 2006; 81: 1830–1837. doi: 10.1016/j.athoracsur.2005.11.048 PubMed DOI

Torchio R, Guglielmo M, Giardino R, et al. Exercise ventilatory inefficiency and mortality in patients with chronic obstructive pulmonary disease undergoing surgery for non-small-cell lung cancer. Eur J Cardiothorac Surg 2010; 38: 14–19. doi: 10.1016/j.ejcts.2010.01.032 PubMed DOI

Fanelli V, Vlachou A, Ghannadian S, et al. Acute respiratory distress syndrome: new definition, current and future therapeutic options. J Thorac Dis 2013; 5: 326–334. PubMed PMC

Brunelli A, Cassivi SD, Halgren L. Risk factors for prolonged air leak after pulmonary resection. Thorac Surg Clin 2010; 20: 359–364. doi: 10.1016/j.thorsurg.2010.03.002 PubMed DOI

Cundrle I Jr, Merta Z, Bratova M, et al. The risk of post-operative pulmonary complications in lung resection candidates with normal forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide: a prospective multicentre study. ERJ Open Res 2023; 9: 00421-2022. doi: 10.1183/23120541.00421-2022 PubMed DOI PMC

Holden DA, Rice TW, Stelmach K, et al. Exercise testing, 6-min walk, and stair climb in the evaluation of patients at high risk for pulmonary resection. Chest 1992; 102: 1774–1779. doi: 10.1378/chest.102.6.1774 PubMed DOI

Wahi R, McMurtrey MJ, DeCaro LF, et al. Determinants of perioperative morbidity and mortality after pneumonectomy. Ann Thorac Surg 1989; 48: 33–37. doi: 10.1016/0003-4975(89)90172-0 PubMed DOI

Nakahara K, Ohno K, Hashimoto J, et al. Prediction of postoperative respiratory failure in patients undergoing lung resection for lung cancer. Ann Thorac Surg 1988; 46: 549–552. doi: 10.1016/S0003-4975(10)64694-2 PubMed DOI

Santini M, Fiorello A, Vicidomini G, et al. Role of diffusing capacity in predicting complications after lung resection for cancer. Thorac Cardiovasc Surg 2007; 55: 391–394. doi: 10.1055/s-2007-965326 PubMed DOI

Brunelli A, Refai MA, Salati M, et al. Carbon monoxide lung diffusion capacity improves risk stratification in patients without airflow limitation: evidence for systematic measurement before lung resection. Eur J Cardiothorac Surg 2006; 29: 567–570. doi: 10.1016/j.ejcts.2006.01.014 PubMed DOI

Pipanmekaporn T, Bunchungmongkol N, Punjasawadwong Y, et al. A risk score for predicting respiratory complications after thoracic surgery. Asian Cardiovasc Thorac Ann 2019; 27: 278–287. doi: 10.1177/0218492319835994 PubMed DOI

Sanchez-Lorente D, Navarro-Ripoll R, Guzman R, et al. Prehabilitation in thoracic surgery. J Thorac Dis 2018; 10: S2593–S2600. doi: 10.21037/jtd.2018.08.18 PubMed DOI PMC

Cundrle I Jr, Somers VK, Johnson BD, et al. Exercise end-tidal CO PubMed DOI PMC

Charloux A, Quoix E. Lung segmentectomy: does it offer a real functional benefit over lobectomy? Eur Respir Rev 2017; 26: 170079. doi: 10.1183/16000617.0079-2017 PubMed DOI PMC

Draeger TB, Gibson VR, Fernandes G, et al. Enhanced recovery after thoracic surgery (ERATS). Heart Lung Circ 2021; 30: 1251–1255. doi: 10.1016/j.hlc.2021.01.014 PubMed DOI

Subramanian MP, Liu J, Chapman WC Jr, et al. Utilization trends, outcomes, and cost in minimally invasive lobectomy. Ann Thorac Surg 2019; 108: 1648–1655. doi: 10.1016/j.athoracsur.2019.06.049 PubMed DOI PMC