Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

Vijayvel Jayaprakash, Gregory M. Loewen, Martin C. Mahoney, Samjot Dhillon, Sai Yendamuri, D. Kyle Hogarth, Enrique Machare-Delgado, Ravi J. Menezes, Sandra M. Jacob, Mary E. Reid

Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, USA.
Department of Medical Imaging, University Health Network, Toronto, Canada.
Department of Medicine, Roswell Park Cancer Institute, Buffalo, USA.
Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, USA.
Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, USA.
Pulmonary Oncology, Sacred Heart Medical Center, Spokane, USA.
School of Medicine, State University of New York at Buffalo, Buffalo, USA.
Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, USA.

DOI: 10.4236/jct.2012.324048                

Abstract

Background: Chronic obstructive pulmonary disease (COPD) and presence of endobronchial premalignant lesions (EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on the natural history of EPL has not been explored. Patients and Methods: This study included 217 high-risk participants from a hospital-based LC surveillance cohort who underwent pulmonary function testing followed by bronchoscopy with endobronchial biopsies. Baseline histopathology diagnoses included 91 cases (41.9%) with squamous metaplasia (SM), 25 (11.5%) with squamous dysplasia (SD), 1 (0.5%) with in-situ carcinoma and 5 (2.3%) with invasive LC. Follow-up biopsies were obtained for 69 patients, and 16 (23.2%) patients demonstrated progression to a higher grade lesion. Regression models were used to evaluate the relationship between ILF and EPL. All the models were adjusted for age, gender and tobacco smoking. Results: Patients with FEV1% of <50% had 4.5 times greater risk of being diagnosed with an EPL [95% confidence interval: 1.93-10.80] and 8-fold greater risk of SD, compared to patients with FEV1% ≥80. COPD was associated with 2.7 and 4.8 times greater risk of SM and SD, respectively. The mean time to progression to a higher-grade lesion was shorter in COPD patients compared to patients without COPD (27 versus 50 months, p = 0.02). Conclusion: Our results indicate that ILF may be a predictor of prevalence and progression of EPLs among patients at high risk of LC. Therefore, spirometry can be a complementary pre-screening tool for identifying patients with EPL who need more intense LC surveillance.

Keywords

COPD; Lung Cancer; Premalignant Lesions; Dysplasia; Pulmonary Function Test; Spirometry

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	R. Siegel, D. Naishadham and A. Jemal, “Cancer Statistics, 2012,” CA: A Cancer Journal for Clinicians, Vol. 62, No. 1, 2012, pp. 10-29. doi:10.3322/caac.20138
[2]	C. I. Henschke, D. F.Yankelevitz, D. M. Libby, M. W. Pasmantier, J. P. Smith and O. S. Miettinen, “Survival of Patients with Stage I Lung Cancer Detected on CT Screening,” New England Journal of Medicine, Vol. 355, No. 17, 2006, pp. 1763-1771. doi:10.1056/NEJMoa060476
[3]	P. S. Frame, “Routine Screening for Lung Cancer? Maybe Someday, but Not Yet,” Journal of American Medical Association, Vol. 284, No. 15, 2000, pp. 1980-1983. doi:10.1001/jama.284.15.1980
[4]	W. D. Travis, E. Brambilla and H. K. Muller-Hermelink, Eds., “Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart,”IARC Press, Lyon, 2004.
[5]	P. B. Bach, G. A. Silvestri, M. Hanger and J. R. Jett, “Screening for Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines,” Chest, Vol. 132, No. 3, 2007, pp. 69S-77S.
[6]	I. Wistuba, “Genetics of Preneoplasia: Lessons from Lung Cancer,” Current Molecular Medicine, Vol. 7, No. 1, 2007, pp. 3-14. doi:10.2174/156652407779940468
[7]	R. H. Breuer, A. Pasic, E. F. Smit, E. van Vliet, A. Vonk Noordegraaf, E. J. Risse, P. E. Postmus and T. G. Sutedja, “The Natural Course of Preneoplastic Lesions in Bronchial Epithelium,” Clinical Cancer Research, Vol. 11, No. 2, 2005, pp. 537-543.
[8]	K. M. Kerr, “Pulmonary Preinvasive Neoplasia,” Journal of Clinical Pathology, Vol. 54, No. 4, 2001, pp. 257-271. doi:10.1136/jcp.54.4.257
[9]	M. B. Beasley, E. Brambilla and W. D. Travis, “The 2004 World Health Organization Classification of Lung Tumors,” Seminars in Roentgenology, Vol. 40, No. 2, 2005, pp. 90-97. doi:10.1053/j.ro.2005.01.001
[10]	H. Yao and I. Rahman, “Current Concepts on the Role of Inflammation in COPD and Lung Cancer,” Current Opinion in Pharmacology, Vol. 9, No. 4, 2009, pp. 375-383. doi:10.1016/j.coph.2009.06.009
[11]	A. Punturieri, E. Szabo, T. L. Croxton, S. D. Shapiro, S. M. Dubinett, “Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research,” Journal of the National Cancer Institute, Vol. 101, No. 8, 2009, pp. 554-559. doi:10.1093/jnci/djp023
[12]	A. M. Houghton, M. Mouded and S. D. Shapiro, “Common Origins of Lung Cancer and COPD,” Nature Medicine, Vol. 14, No. 10, 2008, pp. 1023-1024. doi:10.1038/nm1008-1023
[13]	K. F. Rabe, S. Hurd, A. Anzueto, P. J. Barnes, S. A. Buist, P. Calverley, Y. Fukuchi, C. Jenkins, R. Rodriguez-Roisin and C. van Weel, “Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary,” American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 6, 2007, pp. 532-555. doi:10.1164/rccm.200703-456SO
[14]	D. M. Mannino, S. M. Aguayo, T. L. Petty and S. C. Redd, “Low Lung Function and Incident Lung Cancer in the United States: Data from the First National Health and Nutrition Examination Survey Follow-Up,” Archives of Internal Medicine, Vol. 163, No. 12, 2003, pp. 1475-1480. doi:10.1001/archinte.163.12.1475
[15]	M. S. Tockman, N. R. Anthonisen, E. C. Wright and M. G. Donithan, “Airways Obstruction and the Risk for Lung Cancer,” Annals of Internal Medicine, Vol. 106, No. 4, 1987, pp. 512-518.
[16]	D. M. Skillrud, K. P. Offord and R. D. Miller, “Higher Risk of Lung Cancer in Chronic Obstructive Pulmonary Disease. A Prospective, Matched, Controlled Study,” Annals of Internal Medicine, Vol. 105, No. 4, 1986, pp. 503-507.
[17]	A. Papi, G. Casoni, G. Caramori, I. Guzzinati, P. Boschetto, F. Ravenna, N. Calia, S. Petruzzelli, L. Corbetta and G. Cavallesco, “COPD Increases the Risk of Squamous Histological Subtype in Smokers Who Develop Non-Small Cell Lung Carcinoma,” Thorax, Vol. 59, No. 8, 2004, pp. 679-681. doi:10.1136/thx.2003.018291
[18]	A. Nomura, G. N. Stemmermann, P. H. Chyou, E. B. Marcus and A. S. Buist, “Prospective Study of Pulmonary Function and Lung Cancer,” The American Review of Respiratory Disease, Vol. 144, No. 2, 1991, pp. 307-311. doi:10.1164/ajrccm/144.2.307
[19]	M. P. Purdue, L. Gold, B. Jarvholm, M. C. Alavanja, M. H. Ward and R. Vermeulen, “Impaired Lung Function and Lung Cancer Incidence in a Cohort of Swedish Construction Workers,” Thorax, Vol. 62, No. 1, 2007, pp. 51-56. doi:10.1136/thx.2006.064196
[20]	B. R. Celli and W. MacNee, “Standards for the Diagnosis and Treatment of Patients with COPD: A Summary of the ATS/ERS Position Paper,” European Respiriratory Journal, Vol. 23, No. 6, 2004, pp. 932-946. doi:10.1183/09031936.04.00014304
[21]	R. O. Crapo, A. H. Morris and R. M. Gardner, “Reference Spirometric Values Using Techniques and Equipment That Meet ATS Recommendations,” The American Review of Respiratory Disease, Vol. 123, No. 6, 1981, pp. 659-664.
[22]	L. H. Kuller, J. Ockene, E. Meilahn and K. H. Svendsen, “Relation of Forced Expiratory Volume in One Second (FEV1) to Lung Cancer Mortality in the Multiple Risk Factor Intervention Trial (MRFIT),” American Journal of Epidemiology, Vol. 132, No. 2, 1990, pp. 265-274.
[23]	L. E. Eberly, J. Ockene, R. Sherwin, L. Yang and L. Kuller, “Pulmonary Function as a Predictor of Lung Cancer Mortality in Continuing Cigarette Smokers and in Quitters,” International Journal of Epidemiology, Vol. 32, No. 4, 2003, pp. 592-599. doi:10.1093/ije/dyg177
[24]	J. C. Hogg, F. Chu, S. Utokaparch, R. Woods, W. M. Elliott, L. Buzatu, R. M. Cherniack, R. M. Rogers, F. C. Sciurba and H. O. Coxson, “The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease,” The New England Journal of Medicine, Vol. 350, No. 26, 2004, pp. 2645-2653. doi:10.1056/NEJMoa032158
[25]	S. Wasswa-Kintu, W. Q. Gan, S. F. Man, P. D. Pare and D. D. Sin, “Relationship between Reduced Forced Expiratory Volume in One Second and the Risk of Lung Cancer: A Systematic Review and Meta-Analysis,” Thorax, Vol. 60, No. 7, 2005, pp. 570-575. doi:10.1136/thx.2004.037135
[26]	J. S. Brody and A. Spira, “State of the Art. Chronic Obstructive Pulmonary Disease, Inflammation, and Lung Cancer,” Proceedings of the American Thoracic Society, Vol. 3, No. 6, 2006, pp. 535-537. doi:10.1513/pats.200603-089MS
[27]	S. A. Prindiville, T. Byers, F. R. Hirsch, W. A. Franklin, Y. E. Miller, K. O. Vu, H. J. Wolf , A. E. Baron, K. R. Shroyer and C. Zeng, “Sputum Cytological Atypia as a Predictor of Incident Lung Cancer in a Cohort of Heavy Smokers with Airflow Obstruction,” Cancer Epidemiology Biomarkers and Prevention, Vol. 12, No. 10, 2003, pp. 987-993.
[28]	T. C. Kennedy, S. P. Proudfoot, W. . Franklin, T. A. Merrick, G. Saccomanno, M. E. Corkill, D. L. Mumma, K. E. Sirgi, Y. E. Miller and P. G. Archer, “Cytopathological Analysis of Sputum in Patients with Airflow Obstruction and Significant Smoking Histories,” Cancer Research, Vol. 56, No. 20, 1996, pp. 4673-4678.
[29]	S. Lam, J. C. leRiche, Y. Zheng, A. Coldman, C. Mac-Aulay, E. Hawk, G. Kelloff and A. F. Gazdar, “Sex-Related Differences in Bronchial Epithelial Changes Associated with Tobacco Smoking,” Journal of the National Cancer Institute, Vol. 91, No. 8, 1999, pp. 691-696. doi:10.1093/jnci/91.8.691
[30]	S. Malhotra, S. Lam, S. F. Man, W. Q. Gan and D. D. Sin, “The Relationship between Stage 1 and 2 Non-Small Cell Lung Cancer and Lung Function in Men and Women,” BMC Pulmonary Medicine, Vol. 6, No. 2, 2006.
[31]	R. A. Segal, T. B. Martonen, C. S. Kim and M. Shearer, “Computer Simulations of Particle Deposition in the Lungs of Chronic Obstructive Pulmonary Disease Patients,” Inhalation Toxicology, Vol. 14, No. 7, 2002, pp. 705-720. doi:10.1080/08958370290084593
[32]	C. S. Kim and T. C. Kang, “Comparative Measurement of Lung Deposition of Inhaled Fine Particles in Normal Subjects and Patients with Obstructive Airway Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 155, No. 3, 1997, pp. 899-905.