Background: It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. Objective: The aim of this study is to identify prognostic determinants in these patients. Methods: The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest high-resolution computed tomography (HRCT), and survival. Results: Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). Conclusion: The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery.

1.
Cottin V, Nunes H, Brillet PY, Delaval P, Devouassoux G, Tillie-Leblond I, Israel-Biet D, Court-Fortune I, Valeyre D, Cordier JF; Groupe d'Etude et de Recherche sur les Maladies Orphelines Pulmonaires (GERM O P): Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J 2005;26:586-593.
2.
Jankowich MD, Polsky M, Klein M, Rounds S: Heterogeneity in combined pulmonary fibrosis and emphysema. Respiration 2008;75:411-417.
3.
Kitaguchi Y, Fujimoto K, Hanaoka M, Kawakami S, Honda T, Kubo K: Clinical characteristics of combined pulmonary fibrosis and emphysema. Respirology 2010;15:265-271.
4.
Grubstein A, Bendayan D, Schactman I, Cohen M, Shitrit D, Kramer MR: Concomitant upper-lobe bullous emphysema, lower-lobe interstitial fibrosis and pulmonary hypertension in heavy smokers: report of eight cases and review of the literature. Respir Med 2005;99:948-954.
5.
Mura M, Zompatori M, Pacilli AM, Fasano L, Schiavina M, Fabbri M: The presence of emphysema further impairs physiologic function in patients with idiopathic pulmonary fibrosis. Respir Care 2006;51:257-265.
6.
Kwak N, Park CM, Lee J, Park YS, Lee SM, Yim JJ, Yoo CG, Kim YW, Han SK, Lee CH: Lung cancer risk among patients with combined pulmonary fibrosis and emphysema. Respir Med 2014;108:524-530.
7.
Sugino K, Ishida F, Kikuchi N, Hirota N, Sano G, Sato K, Isobe K, Sakamoto S, Takai Y, Homma S: Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone. Respirology 2014;19:239-245.
8.
Usui K, Tanai C, Tanaka Y, Noda H, Ishihara T: The prevalence of pulmonary fibrosis combined with emphysema in patients with lung cancer. Respirology 2011;16:326-331.
9.
Kumagai S, Marumo S, Yamanashi K, Tokuno J, Ueda Y, Shoji T, Nishimura T, Huang CL, Fukui M: Prognostic significance of combined pulmonary fibrosis and emphysema in patients with resected non-small-cell lung cancer: a retrospective cohort study. Eur J Cardiothorac Surg 2014;46:e113-e119.
10.
Mimae T, Suzuki K, Tsuboi M, Nagai K, Ikeda N, Mitsudomi T, Saji H, Okumura S, Okumura M, Yoshimura K, Okada M: Surgical outcomes of lung cancer in patients with combined pulmonary fibrosis and emphysema. Ann Surg Oncol 2015;22:S1371-S1379.
11.
Nakagawa T, Toyazaki T, Chiba N, Ueda Y, Gotoh M: Prognostic value of body mass index and change in body weight in postoperative outcomes of lung cancer surgery. Interact Cardiovasc Thorac Surg 2016;23:560-566.
12.
Kitaguchi Y, Fujimoto K, Hotta J, Horie S, Hirayama J, Hanaoka M: Clinical characteristics and predictors of mortality in patients with combined pulmonary fibrosis and emphysema syndrome and lung cancer. J Pulm Respir Med 2015;5:263.
13.
Wells AU, Desai SR, Rubens MB, Goh NS, Cramer D, Nicholson AG, Colby TV, du Bois RM, Hansell DM: Idiopathic pulmonary fibrosis: a composite physiologic index derived from disease extent observed by computed tomography. Am J Respir Crit Care Med 2003;167:962-969.
14.
Schmidt SL, Nambiar AM, Tayob N, Sundaram B, Han MK, Gross BH, Kazerooni EA, Chughtai AR, Lagstein A, Myers JL, Murray S, Toews GB, Martinez FJ, Flaherty KR: Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema. Eur Respir J 2011;38:176-183.
15.
Zhang L, Zhang C, Dong F, Song Q, Chi F, Liu L, Wang Y, Che C: Combined pulmonary fibrosis and emphysema: a retrospective analysis of clinical characteristics, treatment and prognosis. BMC Pulm Med 2016;16:137.
16.
Shoji F, Morodomi Y, Akamine T, Takamori S, Katsura M, Takada K, Suzuki Y, Fujishita T, Okamoto T, Maehara Y: Predictive impact for postoperative recurrence using the preoperative prognostic nutritional index in pathological stage I non-small cell lung cancer. Lung Cancer 2016;98:15-21.
17.
Shimizu K, Okita R, Saisho S, Yukawa T, Maeda A, Nojima Y, Nakata M: Prognostic nutritional index before adjuvant chemotherapy predicts chemotherapy compliance and survival among patients with non-small-cell lung cancer. Ther Clin Risk Manag 2015;11:1555-1561.
18.
Shimizu K, Okita R, Saisho S, Maeda A, Nojima Y, Nakata M: Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer. World J Surg Oncol 2015;13:291.
19.
Bar-Ad V, Palmer J, Li L, Lai Y, Lu B, Myers RE, Ye Z, Axelrod R, Johnson JM, Werner-Wasik M, Cowan SW, Evans NR, Hehn BT, Solomides CC, Wang C: Neutrophil to lymphocyte ratio associated with prognosis of lung cancer. Clin Transl Oncol 2017;19:711-717.
20.
Ding N, Pang Z, Shen H, Ni Y, Du J, Liu Q: The prognostic value of PLR in lung cancer, a meta-analysis based on results from a large consecutive cohort. Sci Rep 2016;6:34823.
21.
Kitaguchi Y, Fujimoto K, Hayashi R, Hanaoka M, Honda T, Kubo K: Annual changes in pulmonary function in combined pulmonary fibrosis and emphysema: over a 5-year follow-up. Respir Med 2013;107:1986-1992.
22.
Kitaguchi Y, Fujimoto K, Hanaoka M, Honda T, Hotta J, Hirayama J: Pulmonary function impairment in patients with combined pulmonary fibrosis and emphysema with and without airflow obstruction. Int J Chron Obstruct Pulmon Dis 2014;9:805-811.
23.
Goddard PR, Nicholson EM, Laszlo G, Watt I: Computed tomography in pulmonary emphysema. Clin Radiol 1982;33:379-387.
24.
Kitaguchi Y, Fujimoto K, Kubo K, Honda T: Characteristics of COPD phenotypes classified according to the findings of HRCT. Respir Med 2006;100:1742-1752.
25.
Fujimoto K, Kitaguchi Y, Kubo K, Honda T: Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using high-resolution computed tomography. Respirology 2006;11:731-740.
26.
Kurashima K, Takayanagi N, Tsuchiya N, Kanauchi T, Ueda M, Hoshi T, Miyahara Y, Sugita Y: The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis. Respirology 2010;15:843-848.
27.
Japanese Society of Chest Disease: Standards of pulmonary function tests for Japanese. Jpn J Respir Dis 1993;31:421-427.
28.
Nishida S, Kambe M, Sewake N, Takano M, Kawane H: Pulmonary function in healthy subjects and its prediction. 5. Pulmonary diffusing capacity in adults. Jpn J Clin Pathol 1976;24:941-947.
29.
Boren HG, Kory RC, Syner JC: The Veterans Administration-Army cooperative study of pulmonary function. 2. The lung volume and its subdivisions in normal men. Am J Med 1966;41:96-101.
30.
Mura M, Porretta MA, Bargagli E, Sergiacomi G, Zompatori M, Sverzellati N, Taglieri A, Mezzasalma F, Rottoli P, Saltini C, Rogliani P: Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study. Eur Respir J 2012;40:101-109.
31.
Altman DG, Royston P: The cost of dichotomising continuous variables. BMJ 2006;332:1080.
32.
Grunnet M, Sorensen JB: Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer 2012;76:138-143.
33.
Sawabata N, Ohta M, Takeda S, Hirano H, Okumura Y, Asada H, Maeda H: Serum carcinoembryonic antigen level in surgically resected clinical stage I patients with non-small cell lung cancer. Ann Thorac Surg 2002;74:174-179.
34.
Okada M, Nishio W, Sakamoto T, Uchino K, Yuki T, Nakagawa A, Tsubota N: Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease. Ann Thorac Surg 2004;78:216-221.
35.
Tomita M, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Onitsuka T: Prognostic significance of preoperative serum carcinoembryonic antigen level in lung adenocarcinoma but not squamous cell carcinoma. Ann Thorac Cardiovasc Surg 2004;10:76-80.
36.
Fahim A, Crooks MG, Wilmot R, Campbell AP, Morice AH, Hart SP: Serum carcinoembryonic antigen correlates with severity of idiopathic pulmonary fibrosis. Respirology 2012;17:1247-1252.
37.
Kohno N, Inoue Y, Hamada H, Fujioka S, Fujino S, Yokoyama A, Hiwada K, Ueda N, Akiyama M: Difference in sero-diagnostic values among KL-6-associated mucins classified as cluster 9. Int J Cancer Suppl 1994;8:81-83.
38.
Stahel RA, Gilks WR, Lehmann HP, Schenker T: Third International Workshop on Lung Tumor and Differentiation Antigens: overview of the results of the central data analysis. Int J Cancer Suppl 1994;8:6-26.
39.
Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M: New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. Chest 1989;96:68-73.
40.
Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, Yokoyama A, Hamada H, Fujioka S, Hiwada K: KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis 1993;148:637-642.
41.
Kishaba T, Shimaoka Y, Fukuyama H, Yoshida K, Tanaka M, Yamashiro S, Tamaki H: A cohort study of mortality predictors and characteristics of patients with combined pulmonary fibrosis and emphysema. BMJ Open 2012;2:e000988.
42.
Sakamoto S, Homma S, Mun M, Fujii T, Kurosaki A, Yoshimura K: Acute exacerbation of idiopathic interstitial pneumonia following lung surgery in 3 of 68 consecutive patients: a retrospective study. Intern Med 2011;50: 77-85.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.