Smoking exposure, loss of forced expiratory volume in one second and the risk of lung cancer among patients with malignant disease who present with cardiac or pulmonary symptoms: a cross-sectional study
More details
Hide details
Department of Cardiology, Pulmonology and Critical Care Medicine, Offenburg Hospital, Offenburg, Germany
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
Siegfried Wieshammer   

Department of Cardiology, Pulmonology and Critical Care Medicine, Offenburg Hospital, Weingartenstrasse 70, D-77654 Offenburg, Germany
Publish date: 2017-03-09
Tob. Induc. Dis. 2017;15(March):16
Smokers with airway obstruction are at a higher risk of lung cancer than smokers without airway obstruction. Inflammation plays a key role in lung carcinogenesis. This single-center study prospectively assessed (i) the relationship between smoking exposure and the loss of forced expiratory volume in 1 s (FEV1) in determining lung cancer risk and (ii) the effect of lung cancer on systemic inflammation.

The study group comprised 475 consecutively enrolled patients with cancer who presented with pulmonary or cardiac symptoms. The effects of smoking exposure and FEV1 loss on the predicted lung cancer risk were assessed using multiple logistic regression analysis. C-reactive protein (CRP) was used as a marker of inflammation.

The prevalence of lung cancer was 0.23. The lung cancer risk increased with the number of pack years and FEV1 loss (p < 0.01). Moving from the 5th (−22% of the predicted value) to the 95th percentile of FEV1 loss (56% of the predicted value) increased lung cancer risk from 0.07 to 0.23 (Δ = 0.16) at 0 pack years and from 0.39 to 0.73 (Δ = 0.34) at 70 pack years (95th percentile). The values for Δ peaked at 61 pack years (0.34) and then decreased with a further increase in smoking exposure, without reaching the zero mark. Patients with lung cancer were more likely to have a CRP level above the median (4.05 mg/L) than patients with other cancers (adjusted odds ratio = 2.67).

Systemic inflammation is more pronounced in patients with lung cancer than in patients with other cancers. The effect of FEV1 loss on the patients’ predicted risks of lung cancer increases with increasing smoking exposure. Measurements of FEV1 loss are useful to identify patients facing an increased risk of developing lung cancer.

Durham AL, Adcock IM. The relationship between COPD and lung cancer. Lung Cancer. 2015;90:121–7. doi:10.1016/j.lungcan.2015.08.017.
El-Zein RA, Young RP, Hopkins RJ, Etzel CJ. Genetic predisposition to chronic obstructive pulmonary disease and/or lung cancer: important considerations when evaluating risk. Cancer Prev Res. 2012;5:522–7. doi:10.1158/1940-6207.CAPR-12-0042.
Wasswa-Kintu S, Gan WQ, Man SF, Pare PD, Sin DD. Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Thorax. 2005;60:570–5. Erratum in: Thorax. 2005;60:975. doi:10.1136/thx.2004.037135.
Calabro E, Randi G, La Vecchia C, Sverzellati N, Marchiano A, Villani M, Zompatori M, Cassandro R, Harari S, Pastorino U. Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes. Eur Respir J. 2010;35:146–51. doi:10.1183/09031936.00049909.
Wieshammer S, Dreyhaupt J, Müller D, Momm F, Jakob A. Limitations of Nterminal pro-B-type natriuretic peptide in the diagnosis of heart disease among cancer patients who present with cardiac or pulmonary symptoms. Oncology. 2016;90:143–50. doi:10.1159/000443505.
Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. 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 Suppl. 1993;16:5–40. doi:10.1183/09041950.005s1693.
Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, van Lente F, for Chronic Kidney Disease Epidemiology Collaboration. Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766–72. doi:10.1373/clinchem.2006.077180.
Dietrich M, Jialal I. The effect of weight loss on a stable biomarker of inflammation, C-reactive protein. Nutr Rev. 2005;63:22–8. doi:10.1111/j.1753 4887.2005.tb00107.x.
Rumley A, Emberson JR, Wannamethee SG, Lennon L, Whincup PH, Lowe GD. Effects of older age on fibrin D-dimer, C-reactive protein, and other hemostatic and inflammatory variables in men aged 60-79 years. J Thromb Haemost. 2006;4:982–7. doi:10.1111/j.1538-7836.2006.01889.x.
Stuveling EM, Hillege HL, Bakker SJ, Gans RO, De Jong PE, De Zeeuw D. C-reactive protein is associated with renal function abnormalities in a non-diabetic population. Kidney Int. 2003;63:654–61. doi:10.1046/j.1523-1755.2003.00762.x.
Gan WQ, Man SF, Sin DD. The interactions between cigarette smoking and reduced lung function on systemic inflammation. Chest. 2005;127:558–64. doi:10.1378/chest.127.2.558.
Khera A, Vega GL, Das SR, Ayers C, McGuire DK, Grundy SM, de Lemos JA. Sex differences in the relationship between C-reactive protein and body fat. J Clin Endocrinol Metab. 2009;94:3251–8. doi:10.1210/jc.2008-2406.
Wieshammer S, Dreyhaupt J, Basler B. A link between impaired lung function and increased cardiac stress. Respiration. 2010;79:355–62. doi:10.1159/000265751
National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Lung cancer screening. Version 1. 2017.
Young RP, Hopkins RJ. How the genetics of lung cancer may overlap with COPD. Respirology. 2011;16:1047–55. doi:10.1111/j.1440-1843.2011.02019.x.
Lundbäck B, Lindberg A, Lindström M, Rönmark E, Jonsson AC, Jönsson E, Larsson LG, Andersson S, Sandström T, Larsson K. Obstructive Lung Disease in Northern Sweden Studies. Not 15 but 50% of smokers develop COPD?– Report from the Obstructive Lung Disease in Northern Sweden Studies. Respir Med. 2003;97:115–22. doi:10.1053/rmed.2003.1446.
Ramanakumar AV, Parent ME, Menzies D, Siemiatycki J. Risk of lung cancer following nonmalignant respiratory conditions: evidence from two case control studies in Montreal. Lung Cancer. 2006;53:5–12. doi:10.1016/j.lungcan.2006.04.007.
Gardner ZS, Ruppel GL, Kaminsky DA. Grading the severity of obstruction in mixed obstructive-restrictive lung disease. Chest. 2011;140:598–603. doi:10.1378/chest.10-2860.
Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, Calverley PM, Celli B, Coxson HO, Crim C, Lomas DA, MacNee W, Miller BE, Silverman EK, Tal-Singer R, Wouters E, Rennard SI, Investigators ECLIPSE. Changes in forced expiratory volume in 1 s over time in COPD. N Engl J Med. 2011;365:1184–92. doi:10.1056/NEJMoa1105482.
de Torres JP, Cordoba-Lanus E, López-Aguilar C, Muros de Fuentes M, Montejo de Garcini A, Aguirre-Jaime A, Celli BR, Casanova C. C-reactive protein levels and clinically important predictive outcomes in stable COPD patients. Eur Respir J. 2006;27:902–7. doi:10.1183/09031936.06.00109605.
Aksu F, Capan N, Aksu K, Ofluoğlu R, Canbakan S, Yavuz B, Akin KO. C-reactive protein levels are raised in stable chronic obstructive pulmonary disease patients independent of smoking behavior and biomass exposure. J Thorac Dis. 2013;5:414–21. doi:10.3978/j.issn.2072-1439.2013.06.27.
Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation. 2003;107: 1514–9. doi:10.1161/01.CIR.0000056767.69054.B3.
Man SFP, Connett JE, Anthonisen NR, Wise RA, Tashkin DP, Sin DD. C‐reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease. Thorax. 2006;61:849–53. doi:10.1136/thx.2006.059808.
De Matteis S, Consonni D, Pesatori AC, Bergen AW, Bertazzi PA, Caporaso NE, Lubin JH, Wacholder S, Landi MT. Are women who smoke at higher risk for lung cancer than men who smoke? Am J Epidemiol. 2013;177:601–12. doi:10.1093/aje/kws445.
Ryu JS, Jeon SH, Kim JS, Lee JH, Kim SH, Hong JT, Jeong JH, Jeong JJ, Lee MD, Min SJ, Nam HS, Cho JH, Kwak SM, Lee HL, Kim HJ. Gender differences in susceptibility to smoking among patients with lung cancer. Korean J Intern Med. 2011;26:427–31. doi:10.3904/kjim.2011.26.4.427.
Papi A, Casoni G, Caramori G, Guzzinati I, Boschetto P, Ravenna F, Calia N, Petruzzelli S, Corbetta L, Cavallesco G, Forini E, Saetta M, Ciaccia A, Fabbri LM. COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax. 2004;59:679–81. doi:10.1136/thx.2003.018291.
Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer
Spiros Vlahopoulos, Maria Adamaki, Nikolas Khoury, Vassilis Zoumpourlis, Istvan Boldogh
Pharmacology & Therapeutics