Effect of Inhaled Tiotropium as the Perioperative Management of Patients Undergoing Pulmonary Resection for Primary Lung Cancer

Takanori Ayabe, Masaki Tomita, Eiichi Chosa, Katsuya Kawagoe, Kunihide Nakamura

Department of Surgery II, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

DOI: 10.4236/jct.2014.59093                

Abstract

Background: The purpose of this study was to evaluate the effectiveness of perioperative tiotropium therapy for patients undergoing pulmonary resection for primary lung cancer. The short-term tiotropium effect was investigated by perioperative pulmonary function and “lung age”. Methods: The fifty-five patients who underwent a lobectomy and had tiotropium treatment available from October 2007 through May 2009 were the subjects. The patients were divided into 3 groups according to their airway limitation such as Chronic Obstructive Pulmonary Disease (COPD) or a history of smoking; those with COPD (%FEV₁ ≤70%, C-group, n = 22), smokers (%FEV₁ > 70%, S-group, n = 10) and non-smokers (%FEV₁ > 70%, N-group, n = 23). As the bronchodilator groups, the C- and S-groups received inhaled tiotropium bromide (18 μg once daily) for 1 week before surgery until at least 3 weeks after surgery without interruption, and as a control, the N-group had no treatment. The preoperative baselines, the predicted postoperative values, and the actual postoperative ones were measured by the pulmonary function test. The changed rates were calculated and denoted as ΔVC, ΔFEV₁, ΔVC%, and ΔFEV₁/FVC, from the baseline of the predicted postoperative values. The mean “real age” and “lung age” were calculated. Results: In the S-group, the parameters of ΔVC, ΔFEV₁, ΔVC%, and ΔFEV₁/FVC significantly increased compared to those of the N-group. In the C-group, the increased extents of ΔFEV₁ and ΔFEV₁/FVC were lower compared to those in the S-group (not significant). In the N-group, the parameters of ΔVC, ΔFEV₁, and ΔVC% decreased. The postoperative “lung age” and “real age” were increased to 29.5 ± 18.0 year-old in the C-group, 25.8 ± 18.0 in the S-group, and 24.7 ± 17.0 in the N-group. Lung resection affected the “lung age”; the aging was a 28.9 ± 12.7 year-old increase in the N-group. In the C- and S-group, the “lung age” was a 14-year-old increase. The effect of tiotropium treatment affected the “lung age” as a 15-year-old increase. Conclusion: Perioperative interventional tiotropium contributed to the lobectomy patients with COPD and for smokers with a non-obstructive airway and played a role of preserving the postoperative lung function.

Keywords

Tiotropium, Pulmonary Function, Lung Age, Lobectomy, Lung Cancer

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Rabe, K.F., Hurd, S., Anzueto, A., Barnes, P.J., Buist, S.A., Calverley, P., Fukuchi, Y., Jenkins, C., Rodriguez-Roisin, R., Van Weel, C. and Zielinski J. (2007) Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary. American Journal of Respiratory and Critical Care Medicine, 176, 532-555. http://dx.doi.org/10.1164/rccm.200703-456SO
[2]	Decramer, M., Celli, B., Tashkin, D.P., Pauwels, R.A., Burkhart, D., Cassino, C. and Kesten, S. (2004) Clinical Trial Design Considerations in Assessing Long-Term Functional Impacts of Tiotropium in COPD: The UPLIFT Trial. COPD, 1, 303-312. http://dx.doi.org/10.1081/COPD-200026934
[3]	Tashkin, D.P., Celli, B., Senn, S., Burkhart, D., Kesten, S., Menjoge, S. and Decramer, M. (2008) UPLIFT Study Investigators. A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease. New England Journal of Medicine, 359, 1543-1554. http://dx.doi.org/10.1056/NEJMoa0805800
[4]	Celli, B., Decramer, M., Kesten, S., Liu, D., Mehra, S. and Tashkin, D.P. (2009) UPLIFT Study Investigators. Mortality in the 4-Year Trial of Tiotropium (UPLIFT) in Patients with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine, 180, 948-955. http://dx.doi.org/10.1164/rccm.200906-0876OC
[5]	Loganathan, R.S., Stover, D.E., Shi, W. and Venkatraman, E. (2006) Prevalence of COPD in Women Compared to Men around the Time of Diagnosis of Primary Lung Cancer. Chest, 129, 1305-1312. http://dx.doi.org/10.1378/chest.129.5.1305
[6]	Young, R.P., Hopkins, R.J., Christmas, T., Black, P.N., Metcalf, P. and Gamble, G.D. (2009) COPD Prevalence Is Increased in Lung Cancer, Independent of Age, Sex and Smoking History. European Respiratory Journal, 34, 380-386. http://dx.doi.org/10.1378/chest.129.5.1305
[7]	Bednarek, M., Maciejewski, J., Wozniak, M., Kuca, P. and Zielinski, J. (2008) Prevalence, Severity and Underdiagnosis of COPD in the Primary Care Setting. Thorax, 63, 402-407. http://dx.doi.org/10.1136/thx.2007.085456
[8]	Sekine, Y., Kesler, K.A., Behnia, M., Brooks-Brunn, J., Sekine, E. and Brown, J.W. (2001) COPD May Increase the Incidence of Refractory Supraventricular Arrhythmias Following Pulmonary Resection for Non-Small Cell Lung Cancer. Chest, 120, 1783-1790. http://dx.doi.org/10.1378/chest.120.6.1783
[9]	Win, T., Jackson, A., Sharples, L., Groves, A.M., Wells, F.C., Ritchie, A.J. and Laroche, C.M. (2005) Relationship between Pulmonary Function and Lung Cancer Surgical Outcome. European Respiratory Journal, 25, 594-599. http://dx.doi.org/10.1183/09031936.05.00077504
[10]	Nakamura, H., Haruki, T., Adachi, Y., Fujioka, S., Miwa, K. and Taniguchi, Y. (2008) Smoking Affects Prognosis after Lung Cancer Surgery. Surgery Today, 38, 227-231. http://dx.doi.org/10.1007/s00595-007-3599-0
[11]	Celli, B.R., MacNee, W., Agusti, A., Anzueto, A., Berg, B., Buist, A.S., et al. and ATS/ERS Task Force (2004) Standards for the Diagnosis and Treatment of Patients with COPD: A Summary of the ATS/ERS Position Paper. European Respiratory Journal, 23, 932-946. http://dx.doi.org/10.1183/09031936.04.00014304
[12]	Suzuki, H., Sekine, Y., Yoshida, S., Suzuki, M., Shibuya, K., Takiguchi, Y., Tatsumi, K. and Yoshino, I. (2010) Efficacy of Perioperative Administration of Long-Acting Bronchodilator on Postoperative Pulmonary Function and Quality of Life in Lung Cancer Patients with Chronic Obstructive Pulmonary Disease. Preliminary Results of a Randomized Control Study. Surgery Today, 40, 923-930. http://dx.doi.org/10.1007/s00595-009-4196-1
[13]	Global Initiative for Chronic Obstructive Lung Disease (GOLD) Criteria (2014). http://www.goldcopd.org/
[14]	Juhl, B. and Frost, N. (1975) A Comparison between Measured and Calculated Changes in the Lung Function after Operation for Pulmonary Cancer. Acta Anaesthesiologica Scandinavica, 19, 39-45. http://dx.doi.org/10.1111/j.1399-6576.1975.tb05411.x
[15]	Fukuchi, Y., Nishimura, M., Ichinose, M., Adachi, M., Nagai, A., Kuriyama, T., Takahashi, K., Nishimura, K., Ishioka, S., Aizawa, H. and Zaher, C. (2004) COPD in Japan: The Nippon COPD Epidemiology Study. Respirology, 9, 458-465. http://dx.doi.org/10.1111/j.1440-1843.2004.00637.x
[16]	Sekine, Y., Iwata, T., Chiyo, M., Yasufuku, K., Motohashi, S., Yoshida, S., Suzuki, M., Iizasa, T., Saitoh, Y. and Fujisawa, T. (2003) Minimal Alteration of Pulmonary Function after Lobectomy in Lung Cancer Patients with Chronic Obstructive Pulmonary Disease. Annals of Thoracic Surgery, 76, 356-361; Discussion 362. http://dx.doi.org/10.1016/S0003-4975(03)00489-2
[17]	Congleton, J. and Muers, M.F. (1995) The Incidence of Airflow Obstruction in Bronchial Carcinoma, Its Relation to Breathlessness, and Response to Bronchodilator Therapy. Respiratory Medicine, 89, 291-296. http://dx.doi.org/10.1016/0954-6111(95)90090-X
[18]	Hill, K., Goldstein, R.S., Guyatt, G.H., Blouin, M., Tan, W.C., Davis, L.L., Heels-Ansdell, D.M., Erak, M., Bragaglia, P.J., Tamari, I.E., Hodder, R. and Stanbrook, M.B. (2010) Prevalence and Underdiagnosis of Chronic Obstructive Pulmonary Disease among Patients at Risk in Primary Care. Canadian Medical Association Journal, 182, 673-678. http://dx.doi.org/10.1503/cmaj.091784
[19]	Smetana, G.W., Lawrence, V.A., Cornell, J.E. and American College of Physicians (2006) Preoperative Pulmonary risk Stratification for Noncardiothoracic Surgery: Systematic Review for the American College of Physicians. Annals of Internal Medicine, 144, 581-595. http://dx.doi.org/10.7326/0003-4819-144-8-200604180-00009
[20]	Markos, J., Mullan, B.P., Hillman, D.R., Musk, A.W., Antico, V.F., Lovegrove, F.T., Carter, M.J. and Finucane, K.E. (1989) Preoperative Assessment as a Predictor of Mortality and Morbidity after Lung Resection. American Review of Respiratory Disease, 139, 902-910. http://dx.doi.org/10.1164/ajrccm/139.4.902
[21]	Leo, F., Venissac, N., Pop, D., Solli, P., Filosso, P., Minniti, A., Radice, D. and Mouroux, J. (2008) Postoperative Exacerbation of Chronic Obstructive Pulmonary Disease. Does It Exist? European Journal Cardio-Thoracic Surgery, 33, 424-429. http://dx.doi.org/10.1016/j.ejcts.2007.11.024
[22]	Lawrence, V.A., Cornell, J.E., Smetana, G.W. and American College of Physicians (2006) Strategies to Reduce Postoperative Pulmonary Complications after Noncardiothoracic Surgery: Systematic Review for the American College of Physicians. Annals of Internal Medicine, 144, 596-608. http://dx.doi.org/10.7326/0003-4819-144-8-200604180-00011
[23]	Kobayashi, S., Suzuki, S., Niikawa, H., Sugawara, T. and Yanai, M. (2009) Preoperative Use of Inhaled Tiotropium in Lung Cancer Patients with Untreated COPD. Respirology, 14, 675-679. http://dx.doi.org/10.1111/j.1440-1843.2009.01543.x
[24]	Calverley, P.M., Anderson, J.A., Celli, B., Ferguson, G.T., Jenkins, C., Jones, P.W., Yates, J.C., Vestbo, J. and TORCH Investigators (2007) Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease. New England Journal of Medicine, 356, 775-789. http://dx.doi.org/10.1056/NEJMoa063070
[25]	Bolükbas, S., Eberlein, M., Eckhoff, J. and Schirren, J. (2011) Short-Term Effects of Inhalative Tiotropium/Formoterol/Budenoside versus Tiotropium/Formoterol in Patients with Newly Diagnosed Chronic Obstructive Pulmonary Disease Requiring Surgery for Lung Cancer: A Prospective Randomized Trial. European Journal Cardio-Thoracic Surgery, 39, 995-1000. http://dx.doi.org/10.1016/j.ejcts.2010.09.025
[26]	Anthonisen, N.R. and Wright, E.C. (1986) Bronchodilator Response in Chronic Obstructive Pulmonary Disease. American Review of Respiratory Disease, 133, 814-819.
[27]	Anthonisen, N.R., Lindgren, P.G., Tashkin, D.P., Kanner, R.E., Scanlon, P.D., Connett, J.E. and Lung Health Study Research Group (2005) Bronchodilator Response in the Lung Health Study over 11 Yrs. European Respiratory Journal, 26, 45-51. http://dx.doi.org/10.1183/09031936.05.00102604
[28]	Tashkin, D. and Kesten, S. (2003) Long-Term Treatment Benefits with Tiotropium in COPD Patients with and without Short-Term Bronchodilator Responses. Chest, 123, 1441-1449. http://dx.doi.org/10.1378/chest.123.5.1441
[29]	American Thoracic Society (1995) Standardization of Spirometory, 1994 Update. American Journal of Respiratory and Critical Care Medicine, 152, 1107-1136. http://dx.doi.org/10.1164/ajrccm.152.3.7663792
[30]	(1974) Criteria for the Assessment of Reversibility in Airways Obstruction. Report of the Committee on Emphysema American College of Chest Physicians. Chest, 65, 552-553.
[31]	Brand, P.L., Quanjer, P.H., Postma, D.S., Kerstjens, H.A., Ko?ter, G.H., Dekhuijzen, P.N. and Sluiter, H.J. (1992) Interpretation of Bronchodilator Response in Patients with Obstructive Airways Disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group. Thorax, 47, 429-436. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC463807/ http://dx.doi.org/10.1136/thx.47.6.429
[32]	Eliasson, O. and Degraff Jr., A.C. (1985) The Use of Criteria for Reversibility and Obstruction to Define Patient Groups for Bronchodilator Trials. Influence of Clinical Diagnosis, Spirometric, and Anthropometric Variables. American Review of Respiratory Disease, 132, 858-864.
[33]	Ueda, K., Hayashi, M., Tanaka, N., Tanaka, T. and Hamano, K. (2014) Long-Term Pulmonary Function after Major Lung Resection. General Thoracic and Cardiovascular Surgery, 62, 24-30. http://dx.doi.org/10.1007/s11748-013-0346-x
[34]	Colice, G.L., Shafazand, S., Griffin, J.P., Keenan, R., Bolliger, C.T. and American College of Chest Physicians (2007) Physiologic Evaluation of the Patient with Lung Cancer Being Considered for Resectional Surgery: ACCP Evidenced-Based Clinical Practice Guidelines (2nd Edition). Chest, 132, 161S-177S.
[35]	Bremer, J.L. (1936) The Fate of the Remaining Lung Tissue after Lobectomy or Pneumonectomy. The Journal of Thoracic Surgery, 6, 336-343.
[36]	Endoh, H., Tanaka, S., Yajima, T., Ito, T., Tajima, K., Mogi, A., Shitara, Y. and Kuwano, H. (2010) Pulmonary Function after Pulmonary Resection by Posterior Thoracotomy, Anterior Thoracotomy or Video-Assisted Surgery. European Journal Cardio-Thoracic Surgery, 37, 1209-1214. http://dx.doi.org/10.1016/j.ejcts.2009.11.016
[37]	Nakata, M., Saeki, H., Yokoyama, N., Kurita, A., Takiyama, W. and Takashima, S. (2000) Pulmonary Function after Lobectomy: Video-Assisted Thoracic Surgery versus Thoracotomy. Annals of Thoracic Surgery, 70, 938-941. http://dx.doi.org/10.1016/S0003-4975(00)01513-7
[38]	Sciurba, F.C., Rogers, R.M., Keenan, R.J., Slivka, W.A., Gorcsan III, J., Ferson, P.F., Holbert, J.M., Brown, M.L. and Landreneau, R.J. (1996) Improvement in Pulmonary Function and Elastic Recoil after Lung-Reduction Surgery for Diffuse Emphysema. New England Journal of Medicine, 334, 1095-1099. http://dx.doi.org/10.1056/NEJM199604253341704
[39]	Jubran, A., Laghi, F., Mazur, M., Parthasarathy, S., Garrity Jr., E.R., Fahey, P.J. and Tobin, M.J. (1998) Partitioning of Lung and Chest-Wall Mechanics before and after Lung-Volume-Reduction Surgery. American Journal of Respiratory and Critical Care Medicine, 158, 306-310. http://dx.doi.org/10.1164/ajrccm.158.1.9706082
[40]	Laghi, F., Jubran, A., Topeli, A., Fahey, P.J., Garrity Jr., E.R., De Pinto, D.J., Tobin, M.J. and Loyola/Hines Lung Volume Reduction Surgery Research Group (2004) Effect of Lung Volume Reduction Surgery on Diaphragmatic Neuromechanical Coupling at 2 Years. Chest, 125, 2188-2195. http://dx.doi.org/10.1378/chest.125.6.2188
[41]	Rapicetta, C., Tenconi, S., Voltolini, L., Luzzi, L., Scala, V. and Gotti, G. (2011) Impact of Lobectomy for Non-Small-Cell Lung Cancer on Respiratory Function in Octogenarian Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease. European Journal Cardio-Thoracic Surgery, 39, 555-559. http://dx.doi.org/10.1016/j.ejcts.2010.07.043
[42]	Korst, R.J., Ginsberg, R.J., Ailawadi, M., Bains, M.S., Downey Jr., R.J., Rusch, V.W. and Stover, D. (1998) Lobectomy Improves Ventilatory Function in Selected Patients with Severe COPD. Annals of Thoracic Surgery, 66, 898-902. http://dx.doi.org/10.1016/S0003-4975(98)00697-3
[43]	Zeiher, B.G., Gross, T.J., Kern, J.A., Lanza, L.A. and Peterson, M.W. (1995) Predicting Postoperative Pulmonary Function in Patients Undergoing Lung Resection. Chest, 108, 68-72. http://dx.doi.org/10.1378/chest.108.1.68
[44]	Ginsberg, R.J. and Rubinstein, L.V. (1995) Randomized Trial of Lobectomy versus Limited Resection for T1 No Non-Small Cell Lung Cancer. Lung Cancer Study Group. Annals of Thoracic Surgery, 60, 615-622; Discussion 622-623. http://dx.doi.org/10.1016/0003-4975(95)00537-U
[45]	Bolliger, C.T., Jordan, P., Solèr, M., Stulz, P., Tamm, M., Wyser, C., Gonon, M. and Perruchoud, A.P. (1996) Pulmonary Function and Exercise Capacity after Lung Resection. European Respiratory Journal, 9, 415-421. http://erj.ersjournals.com/content/9/3/415.long
[46]	Funakoshi, Y., Takeda, S., Sawabata, N., Okumura, Y. and Maeda, H. (2005) Long-Term Pulmonary Function after Lobectomy for Primary Lung Cancer. Asian Cardiovascular and Thoracic Annals, 13, 311-315. http://dx.doi.org/10.1177/021849230501300404
[47]	Wang, J.S., Abboud, R.T. and Wang, L.M. (2006) Effect of Lung Resection on Exercise Capacity and on Carbon Monoxide Diffusing Capacity during Exercise. Chest, 129, 863-872. http://dx.doi.org/10.1378/chest.129.4.863
[48]	Brunelli, A., Xiumé, F., Refai, M., Salati, M., Marasco, R., Sciarra, V. and Sabbatini, A. (2007) Evaluation of Expiratory Volume, Diffusion Capacity, and Exercise Tolerance Following Major Lung Resection: A Prospective Follow-Up Analysis. Chest, 131, 141-147. http://dx.doi.org/10.1378/chest.06-1345
[49]	Win, T., Groves, A.M., Ritchie, A.J., Wells, F.C., Cafferty, F. and Laroche, C.M. (2007) The Effect of Lung Resection on Pulmonary Function and Exercise Capacity in Lung Cancer Patients. Respiratory Care, 52, 720-726. http://rc.rcjournal.com/content/52/6/720.full.pdf+html
[50]	Kearney, D.J., Lee, T.H., Reilly, J.J., DeCamp, M.M. and Sugarbaker, D.J. (1994) Assessment of Operative Risk in Patients Undergoing Lung Resection—Importance of Predicted Pulmonary Function. Chest, 105, 753-759. http://dx.doi.org/10.1378/chest.105.3.753
[51]	Imaeda, T., Kanematsu, M., Asada, S., Seki, M., Matsui, E., Doi, H., Sakai, S., Kokubo, M. and Hirose, H. (1995) Prediction of Pulmonary Function after Resection of Primary Lung Cancer. Utility of Inhalation-Perfusion SPECT Imaging. Clinical Nuclear Medicine, 20, 792. http://dx.doi.org/10.1097/00003072-199509000-00007
[52]	Giordano, A., Calcagni, M.L., Meduri, G., Valente, S. and Galli, G. (1997) Perfusion Lung Scintigraphy for the Prediction of Postlobectomy Residual Pulmonary Function. Chest, 111, 1542-1547. http://dx.doi.org/10.1378/chest.111.6.1542
[53]	Wu, M.T., Chang, J.M., Chiang, A.A., Lu, J.Y., Hsu, H.K., Hsu, W.H. and Yang, C.F. (1994) Use of Quantitative CT to Predict Postoperative Lung Function in Patients with Lung Cancer. Radiology, 191, 257-262. http://pubs.rsna.org/doi/abs/10.1148/radiology.191.1.8134584?url_ver=Z39.88-2003& rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed http://dx.doi.org/10.1148/radiology.191.1.8134584
[54]	Sangalli, M., Spiliopoulos, A. and Mrgevand, R. (1992) Predictability of FEV1 after Pulmonary Resection for Bronchogenic Carcinoma. European Journal Cardio-Thoracic Surgery, 6, 242-245. http://dx.doi.org/10.1016/1010-7940(92)90105-7
[55]	Haruki, T., Nakamura, H., Taniguchi, Y., Miwa, K., Adachi, Y. and Fujioka, S. (2010) “Lung Age” Predicts Post-Opeartive Complications and Survival in Lung Cancer Patients. Respirology, 15, 495-500. http://dx.doi.org/10.1111/j.1440-1843.2010.01708.x