Recent manuscripts
Archive
Aims and Scope
Editorial Board
Open Access
Indexing
Contact us
Authorship & COI
Principles of Transparency Checklist
Publication Ethics
Crossmark
Data Policies
Supporting Diversity
Instructions to authors (PDF)
Manuscript Types
Manuscript Formatting
Professional Editing Service
How to submit
Special Publications & Reprints
Preprints
TID on Twitter
REVIEW PAPER
Are healthy smokers really healthy?
| 1 | Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China |
CORRESPONDING AUTHOR
Ping Chen
Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011, People’s Republic of China
Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011, People’s Republic of China
Submission date: 2015-07-29
Acceptance date: 2016-11-10
Publication date: 2016-11-15
Tobacco Induced Diseases 2016;14(November):35
KEYWORDS
ABSTRACT
Cigarette smoke contains more than 4500 chemicals which have toxic, mutagenic and carcinogenic effects. Strong evidences have shown that current smokers take a significantly higher risk of cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and lung cancer than nonsmokers. However, less attention has been paid to the smoking induced abnormalities in the individuals defined as healthy smokers who are normal with spirometry, radiographic images, routine physical exam and categorized as healthy control group in many researches. Actually, ‘healthy smokers’ are not healthy. This narrative review focuses on the smoking related pathophysiologic changes mainly in the respiratory system of healthy smokers, including inflammation and immune changes, genetic alterations, structural changes and pulmonary dysfunction.
REFERENCES (146)
1.
Lee J, Taneja V, Vassallo R. Cigarette smoking and inflammation: cellular and molecular mechanisms. J Dent Res. 2012;91:142–9.
2.
Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, Diaz R, Rashed W, Freeman R, Jiang L, Zhang X, Yusuf S. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case–control study. Lancet. 2006;368:647–58.
3.
Jindal SK, Aggarwal AN, Chaudhry K, Chhabra SK, D’Souza GA, Gupta D, Katiyar SK, Kumar R, Shah B, Vijayan VK. A multicentric study on epidemiology of chronic obstructive pulmonary disease and its relationship with tobacco smoking and environmental tobacco smoke exposure. Indian J Chest Dis Allied Sci. 2006;48:23–9.
4.
Lubin JH, Blot WJ, Berrino F, Flamant R, Gillis CR, Kunze M, Schmahl D, Visco G. Modifying risk of developing lung cancer by changing habits of cigarette smoking. Br Med J (Clin Res Ed). 1984;288:1953–6.
5.
Wang R, Wang G, Ricard MJ, Ferris B, Strulovici-Barel Y, Salit J, Hackett NR, Gudas LJ, Crystal RG. Smoking-induced upregulation of AKR1B10 expression in the airway epithelium of healthy individuals. Chest. 2010;138:1402–10.
6.
Swan GE, Hodgkin JE, Roby T, Mittman C, Jacobo N, Peters J. Reversibility of airways injury over a 12-month period following smoking cessation. Chest. 1992;101:607–12.
7.
Besaratinia A, Maas LM, Van Breda SG, Curfs DM, Kleinjans JC, Wouters EF, Van Schooten FJ. Applicability of induced sputum for molecular dosimetry of exposure to inhalatory carcinogens: 32P-postlabeling of lipophilic DNA adducts in smokers and nonsmokers. Cancer Epidemiol Biomarkers Prev. 2000;9:367–72.
8.
Mazur W, Toljamo T, Ohlmeier S, Vuopala K, Nieminen P, Kobayashi H, Kinnula VL. Elevation of surfactant protein A in plasma and sputum in cigarette smokers. Eur Respir J. 2011;38:277–84.
9.
Rufino R, Costa CH, Souza HS, Madi K, Silva JR. Induced sputum and peripheral blood cell profile in chronic obstructive pulmonary disease. J Bras Pneumol. 2007;33:510–8.
10.
Domagala-Kulawik J, Maskey-Warzechowska M, Hermanowicz-Salamon J, Chazan R. Expression of macrophage surface markers in induced sputum of patients with chronic obstructive pulmonary disease. J Physiol Pharmacol. 2006;57 Suppl 4:75–84.
11.
Skold CM, Lundahl J, Hallden G, Hallgren M, Eklund A. Chronic smoke exposure alters the phenotype pattern and the metabolic response in human alveolar macrophages. Clin Exp Immunol. 1996;106:108–13.
12.
Le-Barillec K, Si-Tahar M, Balloy V, Chignard M. Proteolysis of monocyte CD14 by human leukocyte elastase inhibits lipopolysaccharide-mediated cell activation. J Clin Invest. 1999;103:1039–46.
13.
Bouloukaki I, Tsoumakidou M, Vardavas CI, Mitrouska I, Koutala E, Siafakas NM, Schiza SE, Tzanakis N. Maintained smoking cessation for 6 months equilibrates the percentage of sputum CD8+ lymphocyte cells with that of nonsmokers. Mediators Inflamm. 2009;2009:812102.
14.
Takanashi S, Hasegawa Y, Kanehira Y, Yamamoto K, Fujimoto K, Satoh K, Okamura K. Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers. Eur Respir J. 1999;14:309–14.
15.
Costa C, Rufino R, Traves SL, Lapa ESJR, Barnes PJ, Donnelly LE. CXCR3 and CCR5 chemokines in induced sputum from patients with COPD. Chest. 2008;133:26–33.
16.
Wang F, He B. CCR1 and CCR5 expression on inflammatory cells is related to cigarette smoking and chronic obstructive pulmonary disease severity. Chin Med J (Engl). 2012;125:4277–82.
17.
Hacievliyagil SS, Mutlu LC, Temel I. Airway inflammatory markers in chronic obstructive pulmonary disease patients and healthy smokers. Niger J Clin Pract. 2013;16:76–81.
18.
Chung KF. Cytokines in chronic obstructive pulmonary disease. Eur Respir J Suppl. 2001;34:50s–9.
19.
Kostikas K, Papatheodorou G, Ganas K, Psathakis K, Panagou P, Loukides S. pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med. 2002;165:1364–70.
20.
MacNee W, Rennard SI, Hunt JF, Edwards LD, Miller BE, Locantore NW, Tal-Singer R. Evaluation of exhaled breath condensate pH as a biomarker for COPD. Respir Med. 2011;105:1037–45.
21.
Koczulla AR, Noeske S, Herr C, Jorres RA, Rommelt H, Vogelmeier C, Bals R. Acute and chronic effects of smoking on inflammation markers in exhaled breath condensate in current smokers. Respiration. 2010;79:61–7.
22.
Nicola ML, Carvalho HB, Yoshida CT, Anjos FM, Nakao M, Santos Ude P, Cardozo KH, Carvalho VM, Pinto E, Farsky SH, Saldiva PH, Rubin BK, Nakagawa NK. Young “healthy” smokers have functional and inflammatory changes in the nasal and the lower airways. Chest. 2014;145:998–1005.
23.
Carpagnano GE, Kharitonov SA, Foschino-Barbaro MP, Resta O, Gramiccioni E, Barnes PJ. Increased inflammatory markers in the exhaled breath condensate of cigarette smokers. Eur Respir J. 2003;21:589–93.
24.
Garey KW, Neuhauser MM, Robbins RA, Danziger LH, Rubinstein I. Markers of inflammation in exhaled breath condensate of young healthy smokers. Chest. 2004;125:22–6.
25.
Corhay JL, Hemelaers L, Henket M, Sele J, Louis R. Granulocyte chemotactic activity in exhaled breath condensate of healthy subjects and patients with COPD. Chest. 2007;131:1672–7.
26.
Diez-Pina JM, Fernandez-Acenero MJ, Llorente-Alonso MJ, Diaz-Lobato S, Mayoralas S, Florez A. Tumor necrosis factor alpha as a marker of systemic and local inflammation in “healthy” smokers. Int J Gen Med. 2009;2:9–14.
27.
Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, Barnes PJ. Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175–7.
28.
Reynolds HY, Newball HH. Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage. J Lab Clin Med. 1974;84:559–73.
29.
Wallace JM, Oishi JS, Barbers RG, Simmons MS, Tashkin DP. Lymphocytic subpopulation profiles in bronchoalveolar lavage fluid and peripheral blood from tobacco and marijuana smokers. Chest. 1994;105:847–52.
30.
Rutgers SR, Timens W, Kaufmann HF, van der Mark TW, Koeter GH, Postma DS. Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD. Eur Respir J. 2000;15:109–15.
31.
Erjefalt JS, Uller L, Malm-Erjefalt M, Persson CG. Rapid and efficient clearance of airway tissue granulocytes through transepithelial migration. Thorax. 2004;59:136–43.
32.
Yu MQ, Liu XS, Wang JM, Xu YJ. CD8(+) Tc-lymphocytes immunodeviation in peripheral blood and airway from patients of chronic obstructive pulmonary disease and changes after short-term smoking cessation. Chin Med J (Engl). 2013;126:3608–15.
33.
Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE, Maestrelli P, Ciaccia A, Fabbri LM. CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157:822–6.
34.
Mosmann TR, Li L, Sad S. Functions of CD8 T-cell subsets secreting different cytokine patterns. Semin Immunol. 1997;9:87–92.
35.
Kuschner WG, D’Alessandro A, Wong H, Blanc PD. Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J. 1996;9:1989–94.
36.
Blomberg A, Mudway I, Svensson M, Hagenbjork-Gustafsson A, Thomasson L, Helleday R, Dumont X, Forsberg B, Nordberg G, Bernard A. Clara cell protein as a biomarker for ozone-induced lung injury in humans. Eur Respir J. 2003;22:883–8.
37.
Shijubo N, Itoh Y, Yamaguchi T, Shibuya Y, Morita Y, Hirasawa M, Okutani R, Kawai T, Abe S. Serum and BAL Clara cell 10 kDa protein (CC10) levels and CC10-positive bronchiolar cells are decreased in smokers. Eur Respir J. 1997;10:1108–14.
38.
Lim S, Roche N, Oliver BG, Mattos W, Barnes PJ, Chung KF. Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. Regulation by interleukin-10. Am J Respir Crit Care Med. 2000;162:1355–60.
39.
Babusyte A, Stravinskaite K, Jeroch J, Lotvall J, Sakalauskas R, Sitkauskiene B. Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD. Respir Res. 2007;8:81.
40.
McCormack FX, Whitsett JA. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest. 2002;109:707–12.
41.
Honda Y, Takahashi H, Kuroki Y, Akino T, Abe S. Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers. Chest. 1996;109:1006–9.
42.
Pacht ER, Kaseki H, Mohammed JR, Cornwell DG, Davis WB. Deficiency of vitamin E in the alveolar fluid of cigarette smokers. Influence on alveolar macrophage cytotoxicity. J Clin Invest. 1986;77:789–96.
43.
Pons AR, Sauleda J, Noguera A, Pons J, Barcelo B, Fuster A, Agusti AG. Decreased macrophage release of TGF-beta and TIMP-1 in chronic obstructive pulmonary disease. Eur Respir J. 2005;26:60–6.
44.
Harris JO, Swenson EW, Johnson 3rd JE. Human alveolar macrophages: comparison of phagocytic ability, glucose utilization, and ultrastructure in smokers and nonsmokers. J Clin Invest. 1970;49:2086–96.
45.
Pratt SA, Smith MH, Ladman AJ, Finley TN. The ultrastructure of alveolar macrophages from human cigarette smokers and nonsmokers. Lab Invest. 1971;24:331–8.
46.
Harris JO, Olsen GN, Castle JR, Maloney AS. Comparison of proteolytic enzyme activity in pulmonary alveolar macrophages and blood leukocytes in smokers and nonsmokers. Am Rev Respir Dis. 1975;111:579–86.
47.
Hinman LM, Stevens CA, Matthay RA, Gee JB. Elastase and lysozyme activities in human alveolar macrophages. Effects of cigarette smoking. Am Rev Respir Dis. 1980;121:263–71.
48.
Fisher GL, McNeill KL, Finch GL, Wilson FD, Golde DW. Functional evaluation of lung macrophages from cigarette smokers and nonsmokers. J Reticuloendothel Soc. 1982;32:311–21.
49.
Nagai S, Takeuchi M, Watanabe K, Aung H, Izumi T. Smoking and interleukin-1 activity released from human alveolar macrophages in healthy subjects. Chest. 1988;94:694–700.
50.
Ohta T, Yamashita N, Maruyama M, Sugiyama E, Kobayashi M. Cigarette smoking decreases interleukin-8 secretion by human alveolar macrophages. Respir Med. 1998;92:922–7.
51.
Soliman DM, Twigg 3rd HL. Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages. Am J Physiol. 1992;263:L471–8.
52.
Yamaguchi E, Itoh A, Furuya K, Miyamoto H, Abe S, Kawakami Y. Release of tumor necrosis factor-alpha from human alveolar macrophages is decreased in smokers. Chest. 1993;103:479–83.
53.
Hoidal JR, Fox RB, LeMarbre PA, Takiff HE, Repine JE. Oxidative metabolism of alveolar macrophages from young asymptomatic cigarette smokers. Increased superoxide anion release and its potential consequences. Chest. 1980;77:270–1.
54.
Hubbard RC, Ogushi F, Fells GA, Cantin AM, Jallat S, Courtney M, Crystal RG. Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactivate the active site of alpha 1-antitrypsin, rendering it ineffective as an inhibitor of neutrophil elastase. J Clin Invest. 1987;80:1289–95.
55.
Schaberg T, Lauer C, Lode H, Fischer J, Haller H. Increased number of alveolar macrophages expressing adhesion molecules of the leukocyte adhesion molecule family in smoking subjects. Association with cell-binding ability and superoxide anion production. Am Rev Respir Dis. 1992;146:1287–93.
56.
Shaykhiev R, Krause A, Salit J, Strulovici-Barel Y, Harvey BG, O’Connor TP, Crystal RG. Smoking-dependent reprogramming of alveolar macrophage polarization: implication for pathogenesis of chronic obstructive pulmonary disease. J Immunol. 2009;183:2867–83.
57.
Roth MD, Arora A, Barsky SH, Kleerup EC, Simmons M, Tashkin DP. Airway inflammation in young marijuana and tobacco smokers. Am J Respir Crit Care Med. 1998;157:928–37.
58.
Lams BE, Sousa AR, Rees PJ, Lee TH. Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;158:1518–23.
59.
Ricciardolo FL, Caramori G, Ito K, Capelli A, Brun P, Abatangelo G, Papi A, Chung KF, Adcock I, Barnes PJ, Donner CF, Rossi A, Di Stefano A. Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2005;116:1028–35.
60.
Di Stefano A, Caramori G, Gnemmi I, Contoli M, Vicari C, Capelli A, Magno F, D’Anna SE, Zanini A, Brun P, Casolari P, Chung KF, Barnes PJ, Papi A, Adcock I, Balbi B. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin Exp Immunol. 2009;157:316–24.
61.
Isajevs S, Taivans I, Svirina D, Strazda G, Kopeika U. Patterns of inflammatory responses in large and small airways in smokers with and without chronic obstructive pulmonary disease. Respiration. 2011;81:362–71.
62.
Rahman I, Marwick J, Kirkham P. Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol. 2004;68:1255–67.
63.
Di Stefano A, Caramori G, Oates T, Capelli A, Lusuardi M, Gnemmi I, Ioli F, Chung KF, Donner CF, Barnes PJ, Adcock IM. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD. Eur Respir J. 2002;20:556–63.
64.
Raghuwanshi SK, Su Y, Singh V, Haynes K, Richmond A, Richardson RM. The chemokine receptors CXCR1 and CXCR2 couple to distinct G protein-coupled receptor kinases to mediate and regulate leukocyte functions. J Immunol. 2012;189:2824–32.
65.
Di Stefano A, Caramori G, Gnemmi I, Contoli M, Bristot L, Capelli A, Ricciardolo FL, Magno F, D’Anna SE, Zanini A, Carbone M, Sabatini F, Usai C, Brun P, Chung KF, Barnes PJ, Papi A, Adcock IM, Balbi B. Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD. Thorax. 2009;64:968–75.
66.
Wang R, Ahmed J, Wang G, Hassan I, Strulovici-Barel Y, Salit J, Mezey JG, Crystal RG. Airway epithelial expression of TLR5 is downregulated in healthy smokers and smokers with chronic obstructive pulmonary disease. J Immunol. 2012;189:2217–25.
67.
Letran SE, Lee SJ, Atif SM, Flores-Langarica A, Uematsu S, Akira S, Cunningham AF, McSorley SJ. TLR5-deficient mice lack basal inflammatory and metabolic defects but exhibit impaired CD4 T cell responses to a flagellated pathogen. J Immunol. 2011;186:5406–12.
68.
Woodruff PG, Koth LL, Yang YH, Rodriguez MW, Favoreto S, Dolganov GM, Paquet AC, Erle DJ. A distinctive alveolar macrophage activation state induced by cigarette smoking. Am J Respir Crit Care Med. 2005;172:1383–92.
69.
Graff JW, Powers LS, Dickson AM, Kim J, Reisetter AC, Hassan IH, Kremens K, Gross TJ, Wilson ME, Monick MM. Cigarette smoking decreases global microRNA expression in human alveolar macrophages. PLoS One. 2012;7:e44066.
70.
Philibert RA, Sears RA, Powers LS, Nash E, Bair T, Gerke AK, Hassan I, Thomas CP, Gross TJ, Monick MM. Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression. J Leukoc Biol. 2012;92:621–31.
71.
Heguy A, O’Connor TP, Luettich K, Worgall S, Cieciuch A, Harvey BG, Hackett NR, Crystal RG. Gene expression profiling of human alveolar macrophages of phenotypically normal smokers and nonsmokers reveals a previously unrecognized subset of genes modulated by cigarette smoking. J Mol Med (Berl). 2006;84:318–28.
72.
Rose RM, Kobzik L, Filderman AE, Vermeulen MW, Dushay K, Donahue RE. Characterization of colony stimulating factor activity in the human respiratory tract. Comparison of healthy smokers and nonsmokers. Am Rev Respir Dis. 1992;145:394–9.
73.
Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997;277:2002–4.
74.
Qu P, Du H, Wang X, Yan C. Matrix metalloproteinase 12 overexpression in lung epithelial cells plays a key role in emphysema to lung bronchioalveolar adenocarcinoma transition. Cancer Res. 2009;69:7252–61.
75.
Spivack SD, Hurteau GJ, Reilly AA, Aldous KM, Ding X, Kaminsky LS. CYP1B1 expression in human lung. Drug Metab Dispos. 2001;29:916–22.
76.
Lao X, Qin X, Peng Q, Chen Z, Lu Y, Liu Y, Li S. Association of CYP1B1 Leu432Val Polymorphism and Lung Cancer Risk: An Updated Meta-Analysis. Lung. 2014.
77.
Tam A, Wadsworth S, Dorscheid D, Man SF, Sin DD. The airway epithelium: more than just a structural barrier. Ther Adv Respir Dis. 2011;5:255–73.
78.
Carolan BJ, Harvey BG, Hackett NR, O’Connor TP, Cassano PA, Crystal RG. Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers. Respir Res. 2009;10:111.
79.
Hackett NR, Heguy A, Harvey BG, O’Connor TP, Luettich K, Flieder DB, Kaplan R, Crystal RG. Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol. 2003;29:331–43.
80.
Harvey BG, Heguy A, Leopold PL, Carolan BJ, Ferris B, Crystal RG. Modification of gene expression of the small airway epithelium in response to cigarette smoking. J Mol Med (Berl). 2007;85:39–53.
81.
Turetz ML, O’Connor TP, Tilley AE, Strulovici-Barel Y, Salit J, Dang D, Teater M, Mezey J, Clark AG, Crystal RG. Trachea epithelium as a “canary” for cigarette smoking-induced biologic phenotype of the small airway epithelium. Clin Transl Sci. 2009;2:260–72.
82.
Spira A, Beane J, Shah V, Liu G, Schembri F, Yang X, Palma J, Brody JS. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A. 2004;101:10143–8.
83.
Zhang L, Lee JJ, Tang H, Fan YH, Xiao L, Ren H, Kurie J, Morice RC, Hong WK, Mao L. Impact of smoking cessation on global gene expression in the bronchial epithelium of chronic smokers. Cancer Prev Res (Phila). 2008;1:112–8.
84.
Leopold PL, O’Mahony MJ, Lian XJ, Tilley AE, Harvey BG, Crystal RG. Smoking is associated with shortened airway cilia. PLoS One. 2009;4:e8157.
85.
Hessel J, Heldrich J, Fuller J, Staudt MR, Radisch S, Hollmann C, Harvey BG, Kaner RJ, Salit J, Yee-Levin J, Sridhar S, Pillai S, Hilton H, Wolff G, Bitter H, Visvanathan S, Fine J, Stevenson CS, Crystal RG, Tilley AE. Intraflagellar transport gene expression associated with short cilia in smoking and COPD. PLoS One. 2014;9, e85453.
86.
Wang G, Xu Z, Wang R, Al-Hijji M, Salit J, Strulovici-Barel Y, Tilley AE, Mezey JG, Crystal RG. Genes associated with MUC5AC expression in small airway epithelium of human smokers and non-smokers. BMC Med Genomics. 2012;5:21.
87.
Shaykhiev R, Otaki F, Bonsu P, Dang DT, Teater M, Strulovici-Barel Y, Salit J, Harvey BG, Crystal RG. Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo. Cell Mol Life Sci. 2011;68:877–92.
88.
Carolan BJ, Heguy A, Harvey BG, Leopold PL, Ferris B, Crystal RG. Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers. Cancer Res. 2006;66:10729–40.
89.
Tilley AE, Harvey BG, Heguy A, Hackett NR, Wang R, O’Connor TP, Crystal RG. Down-regulation of the notch pathway in human airway epithelium in association with smoking and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;179:457–66.
90.
Buro-Auriemma LJ, Salit J, Hackett NR, Walters MS, Strulovici-Barel Y, Staudt MR, Fuller J, Mahmoud M, Stevenson CS, Hilton H, Ho MW, Crystal RG. Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression. Hum Mol Genet. 2013;22:4726–38.
91.
Monick MM, Beach SR, Plume J, Sears R, Gerrard M, Brody GH, Philibert RA. Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers. Am J Med Genet B Neuropsychiatr Genet. 2012;159b:141–51.
92.
Chang SC. Microscopic properties of whole mounts and sections of human bronchial epithelium of smokers and nonsmokers. Cancer. 1957;10:1246–62.
93.
Ide G, Suntzeff V, Cowdry EV. A comparison of the histopathology of tracheal and bronchial epithelium of smokers and nonsmokers. Cancer. 1959;12:473–84.
94.
Auerbach O, Hammond EC, Garfinkel L. Changes in bronchial epithelium in relation to cigarette smoking, 1955–1960 vs. 1970–1977. N Engl J Med. 1979;300:381–5.
95.
Peters EJ, Morice R, Benner SE, Lippman S, Lukeman J, Lee JS, Ro JY, Hong WK. Squamous metaplasia of the bronchial mucosa and its relationship to smoking. Chest. 1993;103:1429–32.
96.
Hoffmann RF, Zarrintan S, Brandenburg SM, Kol A, de Bruin HG, Jafari S, Dijk F, Kalicharan D, Kelders M, Gosker HR, Ten Hacken NH, van der Want JJ, van Oosterhout AJ, Heijink IH. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells. Respir Res. 2013;14:97.
97.
Bertram JF, Rogers AW. Recovery of bronchial epithelium on stopping smoking. Br Med J (Clin Res Ed). 1981;283:1567–9.
98.
Soltani A, Reid DW, Sohal SS, Wood-Baker R, Weston S, Muller HK, Walters EH. Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study. Respir Res. 2010;11:105.
99.
Corbin RP, Loveland M, Martin RR, Macklem PT. A four-year follow-up study of lung mechanics in smokers. Am Rev Respir Dis. 1979;120:293–304.
100.
Seaton D, Ogilvie CM. Regional lung function in asymptomatic cigarette smokers. Am Rev Respir Dis. 1978;118:265–70.
101.
Seppanen A. Comparison of different kinds of tests in the evaluation of lung function among healthy smokers and nonsmokers. Ann Clin Res. 1977;9:275–80.
102.
Walter S, Nancy NR, Collier CR. Changes in the forced expiratory spirogram in young male smokers. Am Rev Respir Dis. 1979;119:717–24.
103.
Barter SJ, Cunningham DA, Lavender JP, Gibellino F, Connellan SJ, Pride NB. Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function. Am Rev Respir Dis. 1985;132:148–51.
104.
Bosse R, Sparrow D, Garvey AJ, Costa Jr PT, Weiss ST, Rowe JW. Cigarette smoking, aging, and decline in pulmonary function: A longitudinal study. Arch Environ Health. 1980;35:247–52.
105.
Xu X, Li B, Wang L. Gender difference in smoking effects on adult pulmonary function. Eur Respir J. 1994;7:477–83.
106.
Lee SK, Park JW, Kim KH, Jung JH. An Analysis of the Thickness of Abdominal Muscles during Forceful Expiration and Pulmonary Function in Teenage Smokers and Nonsmokers. J Phys Ther Sci. 2013;25:789–91.
107.
Nemery B, Moavero NE, Brasseur L, Stanescu DC. Changes in lung function after smoking cessation: an assessment from a cross-sectional survey. Am Rev Respir Dis. 1982;125:122–4.
108.
Frette C, Barrett-Connor E, Clausen JL. Effect of active and passive smoking on ventilatory function in elderly men and women. Am J Epidemiol. 1996;143:757–65.
109.
Costabel U, Bross KJ, Reuter C, Ruhle KH, Matthys H. Alterations in immunoregulatory T-cell subsets in cigarette smokers. A phenotypic analysis of bronchoalveolar and blood lymphocytes. Chest. 1986;90:39–44.
110.
Ortlepp JR, Metrikat J, Vesper K, Mevissen V, Schmitz F, Albrecht M, Maya-Pelzer P, Hanrath P, Weber C, Zerres K, Hoffmann R. The interleukin-6 promoter polymorphism is associated with elevated leukocyte, lymphocyte, and monocyte counts and reduced physical fitness in young healthy smokers. J Mol Med (Berl). 2003;81:578–84.
111.
Fernandez JA, Prats JM, Artero JV, Mora AC, Farinas AV, Espinal A, Mendez JA. Systemic inflammation in 222.841 healthy employed smokers and nonsmokers: white blood cell count and relationship to spirometry. Tob Induc Dis. 2012;10:7.
112.
Petrescu F, Voican SC, Silosi I. Tumor necrosis factor-alpha serum levels in healthy smokers and nonsmokers. Int J Chron Obstruct Pulmon Dis. 2010;5:217–22.
113.
Alyan O, Kacmaz F, Ozdemir O, Karahan Z, Taskesen T, Iyem H, Alan S, Karadede A, Ilkay E. High levels of high-sensitivity C-reactive protein and impaired autonomic activity in smokers. Turk Kardiyol Dern Ars. 2008;36:368–75.
114.
Dogan MV, Shields B, Cutrona C, Gao L, Gibbons FX, Simons R, Monick M, Brody GH, Tan K, Beach SR, Philibert RA. The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genomics. 2014;15:151.
115.
Mathai RT, Bhat S. Peripheral blood T-cell populations in COPD, asymptomatic smokers and healthy Non-smokers in Indian subpopulation- a pilot study. J Clin Diagn Res. 2013;7:1109–13.
116.
Miller LG, Goldstein G, Murphy M, Ginns LC. Reversible alterations in immunoregulatory T cells in smoking. Analysis by monoclonal antibodies and flow cytometry. Chest. 1982;82:526–9.
117.
van Antwerpen VL, Theron AJ, Richards GA, Steenkamp KJ, van der Merwe CA, van der Walt R, Anderson R. Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers. Free Radic Biol Med. 1995;18:935–41.
118.
Ben Moussa S, Sfaxi I, Tabka Z, Ben Saad H, Rouatbi S. Oxidative stress and lung function profiles of male smokers free from COPD compared to those with COPD: a case–control study. Libyan J Med. 2014;9:23873.
119.
Erguder IB, Erguder T, Ozkan C, Bozkurt N, Soylu K, Devrim E, Durak I. Short-term effects of smoking cessation on blood antioxidant parameters and paraoxonase activity in healthy asymptomatic long-term cigarette smokers. Inhal Toxicol. 2006;18:575–9.
120.
Kim SH, Kim JS, Shin HS, Keen CL. Influence of smoking on markers of oxidative stress and serum mineral concentrations in teenage girls in Korea. Nutrition. 2003;19:240–3.
121.
Hulea SA, Olinescu R, Nita S, Crocnan D, Kummerow FA. Cigarette smoking causes biochemical changes in blood that are suggestive of oxidative stress: a case–control study. J Environ Pathol Toxicol Oncol. 1995;14:173–80.
122.
Abou-Seif MA. Blood antioxidant status and urine sulfate and thiocyanate levels in smokers. J Biochem Toxicol. 1996;11:133–8.
123.
Kim SH, Ensunsa JL, Zhu QY, Kim JS, Shin HS, Keen CL. An 18-month follow-up study on the influence of smoking on blood antioxidant status of teenage girls in comparison with adult male smokers in Korea. Nutrition. 2004;20:437–44.
124.
Guthikonda S, Sinkey C, Barenz T, Haynes WG. Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers. Circulation. 2003;107:416–21.
125.
Hirai N, Kawano H, Hirashima O, Motoyama T, Moriyama Y, Sakamoto T, Kugiyama K, Ogawa H, Nakao K, Yasue H. Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C. Am J Physiol Heart Circ Physiol. 2000;279:H1172–8.
126.
Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, Deanfield JE. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 1993;88:2149–55.
127.
Yufu K, Takahashi N, Okada N, Shinohara T, Hara M, Saikawa T, Yoshimatsu H. Influence of systolic blood pressure and cigarette smoking on endothelial function in young healthy people. Circ J. 2009;73:174–8.
128.
Mendes ES, Cancado JE, Rebolledo P, Arana J, Parker M, Gonzalez A, Hurwitz BE, Wanner A. Airway vascular endothelial function in healthy smokers without systemic endothelial dysfunction. Chest. 2013;143:1733–9.
129.
Heiss C, Amabile N, Lee AC, Real WM, Schick SF, Lao D, Wong ML, Jahn S, Angeli FS, Minasi P, Springer ML, Hammond SK, Glantz SA, Grossman W, Balmes JR, Yeghiazarians Y. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: sustained vascular injury and blunted nitric oxide production. J Am Coll Cardiol. 2008;51:1760–71.
130.
Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600.
131.
Michaud SE, Dussault S, Haddad P, Groleau J, Rivard A. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis. 2006;187:423–32.
132.
Paschalaki KE, Starke RD, Hu Y, Mercado N, Margariti A, Gorgoulis VG, Randi AM, Barnes PJ. Dysfunction of endothelial progenitor cells from smokers and chronic obstructive pulmonary disease patients due to increased DNA damage and senescence. Stem Cells. 2013;31:2813–26.
133.
Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, Iino S, Inden Y, Murohara T. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol. 2004;24:1442–7.
134.
Adan A, Sanchez-Turet M. Smoking effects on diurnal variations of cardiovascular parameters. Int J Psychophysiol. 1995;20:189–98.
135.
Zevin S, Saunders S, Gourlay SG, Jacob P, Benowitz NL. Cardiovascular effects of carbon monoxide and cigarette smoking. J Am Coll Cardiol. 2001;38:1633–8.
136.
Craig WY, Palomaki GE, Haddow JE. Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. BMJ. 1989;298:784–8.
137.
Michael PR. Cigarette smoking, endothelial injury and cardiovascular disease. Int J Exp Pathol. 2000;81:219–30.
138.
Jee SH, Park JY, Kim HS, Lee TY, Samet JM. White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of Koreans. Am J Epidemiol. 2005;162:1062–9.
139.
Tang J, Liao Y, Deng Q, Liu T, Chen X, Wang X, Xiang X, Chen H, Hao W. Altered spontaneous activity in young chronic cigarette smokers revealed by regional homogeneity. Behav Brain Funct. 2012;8:44.
140.
Durazzo TC, Insel PS, Weiner MW. Greater regional brain atrophy rate in healthy elderly subjects with a history of cigarette smoking. Alzheimers Dement. 2012;8:513–9.
141.
Liu JT, Lee IH, Wang CH, Chen KC, Lee CI, Yang YK. Cigarette smoking might impair memory and sleep quality. J Formos Med Assoc. 2013;112:287–90.
142.
Jimenez-Ruiz CA, Masa F, Miravitlles M, Gabriel R, Viejo JL, Villasante C, Sobradillo V. Smoking characteristics: differences in attitudes and dependence between healthy smokers and smokers with COPD. Chest. 2001;119:1365–70.
143.
2008 PHS Guideline Update Panel, Liaisons, and Staff. Treating tobacco use and dependence: 2008 update U.S. Public Health Service Clinical Practice Guideline executive summary. Respir Care. 2008;53:1217–22.
144.
Attvall S, Fowelin J, Lager I, Von Schenck H, Smith U. Smoking induces insulin resistance--a potential link with the insulin resistance syndrome. J Intern Med. 1993;233:327–32.
145.
Eliasson B, Attvall S, Taskinen MR, Smith U. Smoking cessation improves insulin sensitivity in healthy middle-aged men. Eur J Clin Invest. 1997;27:450–6.
146.
Taha EA, Ez-Aldin AM, Sayed SK, Ghandour NM, Mostafa T. Effect of smoking on sperm vitality, DNA integrity, seminal oxidative stress, zinc in fertile men. Urology. 2012;80:822–5.
CITATIONS (31):
1.
The Patient Who Continues to Smoke On-Treatment: An Ethical Dilemma
Ankita Patro, Christi J. Guerrini, Andrew T. Huang, Andrew G. Sikora
Otolaryngology–Head and Neck Surgery
Ankita Patro, Christi J. Guerrini, Andrew T. Huang, Andrew G. Sikora
Otolaryngology–Head and Neck Surgery
2.
Biochemical strategies for the detection and detoxification of toxic chemicals in the environment
Ferdinando Febbraio
World Journal of Biological Chemistry
Ferdinando Febbraio
World Journal of Biological Chemistry
3.
Augmenting autophagy for prognosis based intervention of COPD-pathophysiology
Manish Bodas, Neeraj Vij
Respiratory Research
Manish Bodas, Neeraj Vij
Respiratory Research
4.
The Potential Health Benefits of Noni Juice: A Review of Human Intervention Studies
Brett West, Shixin Deng, Fumiyuki Isami, Akemi Uwaya, Claude Jensen
Foods
Brett West, Shixin Deng, Fumiyuki Isami, Akemi Uwaya, Claude Jensen
Foods
5.
Long-term cigarette smoking suppresses NLRP3 inflammasome activation in oral mucosal epithelium and attenuates host defense against Candida albicans in a rat model
Pei Ye, Xiang Wang, Sheng Ge, Wei Chen, Wenmei Wang, Xiaodong Han
Biomedicine & Pharmacotherapy
Pei Ye, Xiang Wang, Sheng Ge, Wei Chen, Wenmei Wang, Xiaodong Han
Biomedicine & Pharmacotherapy
6.
Cigarette smoke alters the transcriptome of non-involved lung tissue in lung adenocarcinoma patients
Giulia Pintarelli, Sara Noci, Davide Maspero, Angela Pettinicchio, Matteo Dugo, Cecco De, Matteo Incarbone, Davide Tosi, Luigi Santambrogio, Tommaso Dragani, Francesca Colombo
Scientific Reports
Giulia Pintarelli, Sara Noci, Davide Maspero, Angela Pettinicchio, Matteo Dugo, Cecco De, Matteo Incarbone, Davide Tosi, Luigi Santambrogio, Tommaso Dragani, Francesca Colombo
Scientific Reports
7.
The role of cigarette smoke-induced epigenetic alterations in inflammation
Dandan Zong, Xiangming Liu, Jinhua Li, Ruoyun Ouyang, Ping Chen
Epigenetics & Chromatin
Dandan Zong, Xiangming Liu, Jinhua Li, Ruoyun Ouyang, Ping Chen
Epigenetics & Chromatin
8.
COVID-19 and smoking: A systematic review of the evidence
Constantine Vardavas, Katerina Nikitara
Tobacco Induced Diseases
Constantine Vardavas, Katerina Nikitara
Tobacco Induced Diseases
9.
Wandering along the epigenetic timeline
Clémence Topart, Emilie Werner, Paola Arimondo
Clinical Epigenetics
Clémence Topart, Emilie Werner, Paola Arimondo
Clinical Epigenetics
10.
Psychosocial Vulnerabilities to Upper Respiratory Infectious Illness: Implications for Susceptibility to Coronavirus Disease 2019 (COVID-19)
Sheldon Cohen
Perspectives on Psychological Science
Sheldon Cohen
Perspectives on Psychological Science
11.
Electronic nicotine delivery systems (ECs) and COVID-19: the perfect storm for young consumers
L. Pino, I. Triana, C. Pérez, A. Piotrostanalzki, A. Ruiz-Patiño, G. Lopes, A. Cardona
Clinical and Translational Oncology
L. Pino, I. Triana, C. Pérez, A. Piotrostanalzki, A. Ruiz-Patiño, G. Lopes, A. Cardona
Clinical and Translational Oncology
12.
Substance Use Disorder in the COVID-19 Pandemic: A Systematic Review of Vulnerabilities and Complications
Yufeng Wei, Rameen Shah
Pharmaceuticals
Yufeng Wei, Rameen Shah
Pharmaceuticals
13.
Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement
Hamideh Amirfakhryan, Fatemeh safari
Hellenic Journal of Cardiology
Hamideh Amirfakhryan, Fatemeh safari
Hellenic Journal of Cardiology
14.
SARS-CoV-2 Tackles the Tobacco Industry: Comment on “Tobacco Industry Interference Index: Implementation of the World Health Organization’s Framework Convention on Tobacco Control Article 5.3 in India”
Frédéric Dutheil, Hijrah Nasir, Valentin Navel
Asia Pacific Journal of Public Health
Frédéric Dutheil, Hijrah Nasir, Valentin Navel
Asia Pacific Journal of Public Health
15.
How has the COVID-19 pandemic affected tobacco users in India: Lessons from an ongoing tobacco cessation program
Himanshu Gupte, Gauri Mandal, Dinesh Jagiasi
Tobacco Prevention & Cessation
Himanshu Gupte, Gauri Mandal, Dinesh Jagiasi
Tobacco Prevention & Cessation
16.
COVID-19 (Coronavirus Disease 2019): A New Coronavirus Disease
Dousari Sadeghi, Moghadam Taati, Naghmeh Satarzadeh
Infection and Drug Resistance
17.
Tobacco and COVID-19: A position from Sociedade Portuguesa de Pneumologia
Cláudia Matos, José Boléo-Tomé, Paula Rosa, António Morais
Pulmonology
Cláudia Matos, José Boléo-Tomé, Paula Rosa, António Morais
Pulmonology
18.
Who are we missing with EHR-based smoking cessation treatments? A descriptive study of patients who smoke and do not regularly visit primary care clinics
Margaret Nolan, Deejay Zwaga, Danielle McCarthy, Christian Kastman, Timothy Baker, Mark Zehner, Stevens Smith, Michael Fiore
Journal of Smoking Cessation
Margaret Nolan, Deejay Zwaga, Danielle McCarthy, Christian Kastman, Timothy Baker, Mark Zehner, Stevens Smith, Michael Fiore
Journal of Smoking Cessation
19.
Insights From the SmokeFree.gov Initiative Regarding the Use of Smoking Cessation Digital Platforms During the COVID-19 Pandemic: Cross-sectional Trends Analysis Study
Sherine El-Toukhy
Journal of Medical Internet Research
Sherine El-Toukhy
Journal of Medical Internet Research
20.
COVID-19 and smoking: More severity and death – An experience from Iran
Gholamreza Heydari, Hossein Arfaeinia
Lung India
Gholamreza Heydari, Hossein Arfaeinia
Lung India
21.
COVID-19 and Smoking: What Evidence Needs Our Attention?
Jianghua Xie, Rui Zhong, Wei Wang, Ouying Chen, Yanhui Zou
Frontiers in Physiology
Jianghua Xie, Rui Zhong, Wei Wang, Ouying Chen, Yanhui Zou
Frontiers in Physiology
22.
Changes in Tobacco Use Patterns during COVID-19 and Their Correlates among Older Adults in Bangladesh
Sabuj Mistry, Armm Ali, Md. Rahman, Uday Yadav, Bhawna Gupta, Muhammad Rahman, Rumana Huque
International Journal of Environmental Research and Public Health
Sabuj Mistry, Armm Ali, Md. Rahman, Uday Yadav, Bhawna Gupta, Muhammad Rahman, Rumana Huque
International Journal of Environmental Research and Public Health
23.
Insights From the SmokeFree.gov Initiative Regarding the Use of Smoking Cessation Digital Platforms During the COVID-19 Pandemic: Cross-sectional Trends Analysis Study (Preprint)
Sherine El-Toukhy
Sherine El-Toukhy
24.
Interrelations between COVID-19 and other disorders
Amin Gasmi, Massimiliano Peana, Lyudmila Pivina, Shvetha Srinath, Benahmed Gasmi, Yuliya Semenova, Alain Menzel, Maryam Dadar, Geir Bjørklund
Clinical Immunology
Amin Gasmi, Massimiliano Peana, Lyudmila Pivina, Shvetha Srinath, Benahmed Gasmi, Yuliya Semenova, Alain Menzel, Maryam Dadar, Geir Bjørklund
Clinical Immunology
25.
A Review of Pulmonary Toxicity of Electronic Cigarettes in the Context of Smoking: A Focus on Inflammation
Peter Shields, Micah Berman, Theodore Brasky, Jo Freudenheim, Ewy Mathe, Joseph McElroy, Min-Ae Song, Mark Wewers
Cancer Epidemiology Biomarkers & Prevention
Peter Shields, Micah Berman, Theodore Brasky, Jo Freudenheim, Ewy Mathe, Joseph McElroy, Min-Ae Song, Mark Wewers
Cancer Epidemiology Biomarkers & Prevention
26.
Executive Functions in Tobacco Use Disorder: New Challenges and Opportunities
Ríos Martín, Francisca López-Torrecillas, Tamayo Martín
Frontiers in Psychiatry
Ríos Martín, Francisca López-Torrecillas, Tamayo Martín
Frontiers in Psychiatry
27.
The influence of comorbidity on the severity of COVID-19 disease: A systematic review and analysis
Nazar Zaki, Elfadil Mohamed, Sahar Ibrahim, Gulfaraz Khan
Nazar Zaki, Elfadil Mohamed, Sahar Ibrahim, Gulfaraz Khan
28.
An overview of Covid-19 pandemic: immunology and pharmacology
Amin Arif, Sana Ansari, Haseeb Ahsan, Riaz Mahmood, Fahim Khan
Journal of Immunoassay and Immunochemistry
Amin Arif, Sana Ansari, Haseeb Ahsan, Riaz Mahmood, Fahim Khan
Journal of Immunoassay and Immunochemistry
29.
IP
3
R attenuates oxidative stress and inflammation damage in smoking‐induced COPD by promoting autophagy
Qiang Zhang, Wei Li, Nahemuguli Ayidaerhan, Wuxin Han, Yingying Chen, Wei Song, Yuanyi Yue
Journal of Cellular and Molecular Medicine
Qiang Zhang, Wei Li, Nahemuguli Ayidaerhan, Wuxin Han, Yingying Chen, Wei Song, Yuanyi Yue
Journal of Cellular and Molecular Medicine
30.
What could be the potential reasons for relatively low coronavirus disease 2019 (COVID-19) fatality rates in Africa? The case for Ethiopia
Taddese Zerfu, Amare Tareke
Journal of Global Health
Taddese Zerfu, Amare Tareke
Journal of Global Health
31.
Susceptibility of lung cancer patients to
COVID
‐19: A review of the pandemic data from multiple nationalities
Ana Lemos, Gabriela Silva, Etel Gimba, Aline Matos
Thoracic Cancer
Ana Lemos, Gabriela Silva, Etel Gimba, Aline Matos
Thoracic Cancer
RELATED ARTICLE
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.