Oxidative Stress and Smoke-Related Lung Diseases: A Tentative Approach Through the Blood, Lungs, and Gut

  • Francesco Marotta
  • Jaganath Arunachalam
  • Antara Banerjee
  • Roberto Catanzaro
  • Sudhir Adalti
  • Aparimita Das
  • Alexander Kolyada
  • Surajit Pathak


Respiration renders the lungs vulnerable to infectious agents, smoke, and hazardous material that are inhaled in the process. During respiration, oxidants deposit in the lung which can cause oxidative stress and impair the defense mechanism. Due to the subsequent tissue damage, the antioxidant system is not always able to tackle the reactive oxygen species (ROS). When oxidative stress results in tissue damage, progenitor cells try to replace the tissue damaged by the ROS, where the regenerative capacity of the lungs plays a crucial role in preventing further lung damage or disease. Studying molecular pathways of lung cell regeneration is essential in the study of regenerative biology, although regeneration might fail to entirely replace the resulting tissue damage and lead to pathophysiological conditions. The lungs are prone to tissue damage due to continuous exposure to both endogenous and exogenous oxidative mediators and other oxidants, making the process of lung repair extremely important. Some of the damaged tissue can’t be repaired as the repair process cannot match up to the high levels of oxidant exposure resulting in disturbed oxidant and antioxidant balance, thus impacting the normal physiology. Concurrently, ROS and RNS cause oxidative damage and tissue dysfunction in pathological conditions of the lungs. They are responsible for the declining cellular function and compromised mitochondrial system. Prolonged exposure to tobacco and cigarettes is one of the main causative substances in the progression of oxidative stress, a detrimental process that can even lead to lung carcinogenesis. The knowledge in mechanisms of oxidative stress in the lung could lead to improved pharmacological manipulation of antioxidants in lung inflammation as well as injury. Tobacco carcinogens are involved in the upregulation of the redox-sensitive transcription factors and proinflammatory gene expression. Antioxidant defense mechanism consisting of antioxidant enzymes, proteins, and small molecules are impaired in most lung pathologies. Recent clinical investigations aim to develop precise treatment modalities targeting the functioning mechanism of antioxidants against oxidants. This will help in therapeutic management and improved treatment of respiratory diseases.


COPD Oxidative stress Antioxidants Cigarette smoking Oxidation GSH 



Secretion of Clara cell secretory protein


Vascular endothelial growth factor


Epithelial mesenchymal transition


Reactive oxygen species


Reactive nitrogen species



The authors are thankful to the Chettinad Academy of Research and Education (CARE), Chennai, India, for the support.

Author’s Contributions

JA and AD, SP, SA, AB and FM wrote the MS and conceived the idea of the book chapter, implemented by RC and corrected by SP, AB, SA, RC, AK, and FM.

Conflict of Interests

We declare no conflict of interest. All co-authors have agreed to transfer copyright to the publisher after accepted for publication.


  1. Akram KM, Patel N, Spiteri MA, Forsyth NR (2016) Lung regeneration: endogenous and exogenous stem cell mediated therapeutic approaches. Int J Mol Sci 17(1):128PubMedCentralCrossRefGoogle Scholar
  2. Al Alam D, Green M, Irani RT, Parsa S, Danopoulos S, Sala FG, Branch J, El Agha E, Tiozzo C, Voswinckel R, Jesudason EC (2011) Contrasting expression of canonical Wnt signaling reporters TOPGAL, BATGAL and Axin2LacZ during murine lung development and repair. PLoS One 6(8):e23139PubMedPubMedCentralCrossRefGoogle Scholar
  3. Al-Awaida W, Akash M, Aburubaiha Z, Talib WH, Shehadeh H (2014) Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats. Iranian J Basic Med Sci 17(10):740Google Scholar
  4. Allais L, Kerckhof FM, Verschuere S, Bracke KR, De Smet R, Laukens D, Van den Abbeele P, De Vos M, Boon N, Brusselle GG (2016) Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut. Environ Microbiol 18:1352–1363PubMedCrossRefPubMedCentralGoogle Scholar
  5. Allais L, De Smet R, Verschuere S, Talavera K, Cuvelier CA, Maes T (2017) Transient receptor potential channels in intestinal inflammation: what is the impact of cigarette smoking? Pathobiology 84(1):1–15PubMedCrossRefPubMedCentralGoogle Scholar
  6. Anderson GP, Bozinovski S (2003) Acquired somatic mutations in the molecular pathogenesis of COPD. Trends Pharmacol Sci 24(2):71–76PubMedCrossRefPubMedCentralGoogle Scholar
  7. Aumiller V, Balsara N, Wilhelm J, Günther A, Königshoff M (2013) WNT/β-catenin signaling induces IL-1β expression by alveolar epithelial cells in pulmonary fibrosis. Am J Respir Cell Mol Biol 49(1):96–104PubMedCrossRefPubMedCentralGoogle Scholar
  8. Barnes PJ, Chung KF, Page CP (1998) Inflammatory mediators of asthma: an update. Pharmacol Rev 50(4):515–596PubMedCrossRefPubMedCentralGoogle Scholar
  9. Barrera G (2012) Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol 2012:1CrossRefGoogle Scholar
  10. Beers MF, Morrisey EE (2011) The three R’s of lung health and disease: repair, remodeling, and regeneration. J Clin Invest 121(6):2065–2073PubMedPubMedCentralCrossRefGoogle Scholar
  11. Benedikter BJ, Volgers C, van Eijck PH, Wouters EF, Savelkoul PH, Reynaert NL, Haenen GR, Rohde GG, Weseler AR, Stassen FR (2017) Cigarette smoke extract induced exosome release is mediated by depletion of exofacial thiols and can be inhibited by thiol-antioxidants. Free Radic Biol Med 108:334–344PubMedCrossRefPubMedCentralGoogle Scholar
  12. Biswas SW, Hwang J, A Kirkham P, Rahman I (2013) Pharmacological and dietary antioxidant therapies for chronic obstructive pulmonary disease. Curr Med Chem 20(12):1496–1530PubMedCrossRefPubMedCentralGoogle Scholar
  13. Blanpain C, Fuchs E (2014) Plasticity of epithelial stem cells in tissue regeneration. Science 344(6189):1242281PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bocci V, Paulesu L (1990) Studies on the biological effects of ozone 1. Induction of interferon gamma on human leucocytes. Haematologica 75(6):510–515PubMedPubMedCentralGoogle Scholar
  15. Bocci V, Borrelli E, Travagli V, Zanardi I (2009) The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev 29(4):646–682PubMedCrossRefPubMedCentralGoogle Scholar
  16. Borrelli E, Bocci V (2014) Oxygen ozone therapy in the treatment of chronic obstructive pulmonary disease: an integrative approach. Am J Clin Exp Med 2:9–13CrossRefGoogle Scholar
  17. Boutten A, Goven D, Boczkowski J, Bonay M (2010) Oxidative stress targets in pulmonary emphysema: focus on the Nrf2 pathway. Expert Opin Ther Targets 14(3):329–346PubMedCrossRefPubMedCentralGoogle Scholar
  18. Briggs DC, Vaughan RW, Welsh KI, Myers A, Black CM (1991) Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis. Lancet 338(8768):661–662PubMedCrossRefPubMedCentralGoogle Scholar
  19. Chen TS, Liou SY, Chang YL (2008) Antioxidant evaluation of three adaptogen extracts. Am J Chin Med 36(06):1209–1217PubMedCrossRefPubMedCentralGoogle Scholar
  20. Chi L, Mahbub R, Gao B, Bian X, Tu P, Ru H, Lu K (2017) Nicotine alters the gut microbiome and metabolites of gut-brain interactions in a sex-specific manner. Chem Res Toxicol 30:2110–2119PubMedCrossRefPubMedCentralGoogle Scholar
  21. Clarkson PM, Thompson HS (2000) Antioxidants: what role do they play in physical activity and health? Am J Clin Nutr 72(2):637S–646SPubMedCrossRefPubMedCentralGoogle Scholar
  22. Cosio MG, Saetta M, Agusti A (2009) Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med 360(23):2445–2454PubMedCrossRefPubMedCentralGoogle Scholar
  23. Demoly P, Simony-Lafontaine J, Chanez P, Pujol JL, Lequeux N, Michel FB, Bousquet J (1994) Cell proliferation in the bronchial mucosa of asthmatics and chronic bronchitics. Am J Respir Crit Care Med 150(1):214–217PubMedCrossRefPubMedCentralGoogle Scholar
  24. Domej W, Oettl K, Renner W (2014) Oxidative stress and free radicals in COPD–implications and relevance for treatment. Int J Chron Obstruct Pulmon Dis 9:1207PubMedPubMedCentralCrossRefGoogle Scholar
  25. Duarte TL, Lunec J (2005) When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C. Free Radic Res 39(7):671–686PubMedCrossRefPubMedCentralGoogle Scholar
  26. Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, Sánchez-Pérez P, Cadenas S, Lamas S (2015) Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol 6:183–197PubMedPubMedCentralCrossRefGoogle Scholar
  27. Ezzati M, Lopez AD (2003) Estimates of global mortality attributable to smoking in 2000. Lancet 362(9387):847–852PubMedCrossRefPubMedCentralGoogle Scholar
  28. Fernald K, Kurokawa M (2013) Evading apoptosis in cancer. Trends Cell Biol 23(12):620–633PubMedPubMedCentralCrossRefGoogle Scholar
  29. Flozak AS, Lam AP, Russell S, Jain M, Peled ON, Sheppard KA, Beri R, Mutlu GM, Budinger GS, Gottardi CJ (2010) β-catenin/T-cell factor signaling is activated during lung injury and promotes the survival and migration of alveolar epithelial cells. J Biol Chem 285(5):3157–3167PubMedCrossRefPubMedCentralGoogle Scholar
  30. Fuhrmann S, Zou C, Levine EM (2014) Retinal pigment epithelium development, plasticity, and tissue homeostasis. Exp Eye Res 123:141–150PubMedCrossRefPubMedCentralGoogle Scholar
  31. Furuie H, Yamasaki H, Suga M, Ando M (1997) Altered accessory cell function of alveolar macrophages: a possible mechanism for induction of Th2 secretory profile in idiopathic pulmonary fibrosis. Eur Respir J 10(4):787–794PubMedPubMedCentralGoogle Scholar
  32. Guan WJ, Zheng XY, Chung KF, Zhong NS (2016) Impact of air pollution on the burden of chronic respiratory diseases in China: time for urgent action. Lancet 388(10054):1939–1951PubMedCrossRefPubMedCentralGoogle Scholar
  33. Gupta I, Ganguly S, Rozanas CR, Stuehr DJ, Panda K (2016) Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis. Proc Natl Acad Sci 113(29):E4208–E 4217PubMedCrossRefPubMedCentralGoogle Scholar
  34. Halliwell B (2006) Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol 141(2):312–322PubMedPubMedCentralCrossRefGoogle Scholar
  35. Hancock A, Armstrong L, Gama R, Millar A (1998) Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol 18(1):60–65PubMedCrossRefPubMedCentralGoogle Scholar
  36. Hashimoto S, Chen H, Que J, Brockway BL, Drake JA, Snyder JC, Randell SH, Stripp BR (2012) β-Catenin–SOX2 signaling regulates the fate of developing airway epithelium. J Cell Sci, pp jcs-092734Google Scholar
  37. Hecht SS (1999) Tobacco smoke carcinogens and lung cancer. JNCI: J Nat Cancer Inst 91(14):1194–1210PubMedCrossRefPubMedCentralGoogle Scholar
  38. Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, Niklason L, Calle E, Le A, Randell SH, Rock J (2014) Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell 15(2):123–138PubMedPubMedCentralCrossRefGoogle Scholar
  39. Holz O, Jorres RA, Timm P, Mucke M, Richter K, Koschyk S, Magnussen H (1999) Ozone-induced airway inflammatory changes differ between individuals and are reproducible. Am J Respir Crit Care Med 159(3):776–784PubMedCrossRefGoogle Scholar
  40. Hoshino T, Okamoto M, Takei S, Sakazaki Y, Iwanaga T, Aizawa H (2008) Redox-regulated mechanisms in asthma. Antioxid Redox Signal 10(4):769–784PubMedCrossRefGoogle Scholar
  41. Scholar
  42. Hu G, Cassano PA (2000) Antioxidant nutrients and pulmonary function: the third national health and nutrition examination survey (NHANES III). Am J Epidemiol 151(10):975–981PubMedCrossRefPubMedCentralGoogle Scholar
  43. Isbaniah F, Wiyono WH, Yunus F, Setiawati A, Totzke U, Verbruggen MA (2011) Echinacea purpurea along with zinc, selenium and vitamin C to alleviate exacerbations of chronic obstructive pulmonary disease: results from a randomized controlled trial. J Clin Pharm Ther 36(5):568–576PubMedCrossRefGoogle Scholar
  44. Ischiropoulos H, Zhu L, Beckman JS (1992) Peroxynitrite formation from macrophage-derived nitric oxide. Arch Biochem Biophys 298(2):446–451PubMedCrossRefPubMedCentralGoogle Scholar
  45. Janczewski A, Wojtkiewicz J, Malinowska E, Doboszyńska A (2017) Can youthful mesenchymal stem cells from Wharton’s jelly bring a breath of fresh air for COPD? Int J Mol Sci 18(11):2449PubMedCentralCrossRefGoogle Scholar
  46. Jarjour NN, Calhoun WJ (1994) Enhanced production of oxygen radicals in asthma. J Lab Clin Med 123(1):131–136PubMedPubMedCentralGoogle Scholar
  47. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59(4):225–249CrossRefGoogle Scholar
  48. Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116CrossRefGoogle Scholar
  49. Kim HJ, Choi MG, Park MK, Seo YR (2017) Predictive and prognostic biomarkers of respiratory diseases due to particulate matter exposure. J Cancer Prev 22(1):6PubMedPubMedCentralCrossRefGoogle Scholar
  50. Kinnula VL (2005) Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases. Thorax 60(8):693–700PubMedPubMedCentralCrossRefGoogle Scholar
  51. Koike K, Ishigami A, Sato Y, Hirai T, Yuan Y, Kobayashi E, Tobino K, Sato T, Sekiya M, Takahashi K, Fukuchi Y (2014) Vitamin C prevents cigarette smoke–induced pulmonary emphysema in mice and provides pulmonary restoration. Am J Respir Cell Mol Biol 50(2):347–357PubMedPubMedCentralGoogle Scholar
  52. Krishna MT, Chauhan AJ, Frew AJ, Holgate ST (1998) Toxicological mechanisms underlying oxidant pollutant-induced airway injury. Rev Environ Health 13(1–2):59–71PubMedGoogle Scholar
  53. Kunkel SL, Lukacs NW, Strieter RM, Chensue SW (1996) Th1 and Th2 responses regulate experimental lung granuloma development. Sarcoidosis Vasc Diffuse Lung Dis: Off J WASOG 13(2):120–128Google Scholar
  54. Kurutas EB (2015) The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J 15(1):71CrossRefGoogle Scholar
  55. Lau AN, Goodwin M, Kim CF, Weiss DJ (2012) Stem cells and regenerative medicine in lung biology and diseases. Mol Ther 20(6):1116–1130PubMedPubMedCentralCrossRefGoogle Scholar
  56. Lee J, Taneja V, Vassallo R (2012) Cigarette smoking and inflammation: cellular and molecular mechanisms. J Dent Res 91(2):142–149PubMedPubMedCentralCrossRefGoogle Scholar
  57. Lee S, Yun Y, Kim S, Lee EJ, Chang Y, Ryu S, Shin H, Kim HL, Kim HN, Lee J (2018) Association between cigarette smoking status and composition of gut microbiota: population-based cross-sectional study. J Clin Med 7(9):282PubMedCentralCrossRefGoogle Scholar
  58. Leibel S, Post M (2016) Endogenous and exogenous stem/progenitor cells in the lung and their role in the pathogenesis and treatment of pediatric lung disease. Front Pediatr 4:36PubMedPubMedCentralCrossRefGoogle Scholar
  59. Lin HH, Murray M, Cohen T, Colijn C, Ezzati M (2008) Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor, modelling study. Lancet 372(9648):1473–1483PubMedPubMedCentralCrossRefGoogle Scholar
  60. Liu X, Ma C, Wang X, Wang W, Li Z, Wang X, Wang P, Sun W, Xue B (2017) Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Int J Chron Obstruct Pulmon Dis 12:1309PubMedPubMedCentralCrossRefGoogle Scholar
  61. Løkke A, Lange P, Scharling H, Fabricius P, Vestbo J (2006) Developing COPD: a 25 year follow up study of the general population. Thorax 61(11):935–939PubMedPubMedCentralCrossRefGoogle Scholar
  62. MacNee W (2001) Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 429(1–3):195–207PubMedCrossRefPubMedCentralGoogle Scholar
  63. MacNee W (2006) Pathology, pathogenesis, and pathophysiology. BMJ 332(7551):1202–1204PubMedCentralCrossRefGoogle Scholar
  64. Malhotra D, Thimmulappa R, Navas-Acien A, Sandford A, Elliott M, Singh A, Chen L, Zhuang X, Hogg J, Pare P, Tuder RM (2008) Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am J Respir Crit Care Med 178(6):592–604PubMedPubMedCentralCrossRefGoogle Scholar
  65. Markele M, Ozoliòa A, Sabeïòikovs O, Ðíesters A, Silova A, Jaunalksne I, Strîíe E, Krûmiòa A, Vanags I (2014) The role of oxidative stress markers in developing of acute respiratory distress Syndrome/Oksidatîvâ Stresa Marķieru Loma AkûtaRespiratoraDistresaSindromaAttîstîbâ. In Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences. (Vol. 68, No. 5–6, pp. 200–206). De Gruyter OpenGoogle Scholar
  66. Marrack P, Kappler J, Kotzin BL (2001) Autoimmune disease: why and where it occurs. Nat Med 7(8):899PubMedCrossRefPubMedCentralGoogle Scholar
  67. Matalon S, Egan EA (1981) Effects of 100% O2 breathing on permeability of alveolar epithelium to solute. J Appl Physiol 50(4):859–863PubMedCrossRefPubMedCentralGoogle Scholar
  68. Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030, vol 3, p e442. CrossRefGoogle Scholar
  69. McGuinness AJA, Sapey E (2017) Oxidative stress in COPD: sources, markers, and potential mechanisms. J Clin Med 6(2):21PubMedCentralCrossRefGoogle Scholar
  70. Mortaz E, Adcock IM, Folkerts G, Barnes PJ, Paul Vos A, Garssen J (2013) Probiotics in the management of lung diseases. Mediat Inflamm 2013:751068CrossRefGoogle Scholar
  71. Ochs-Balcom HM, Grant BJB, Muti P, Sempos CT, Freudenheim JL, Browne RW, McCann SE, Trevisan M, Cassano PA, Iacoviello L, Schünemann HJ (2006) Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD. Eur J Clin Nutr 60(8):991PubMedCrossRefPubMedCentralGoogle Scholar
  72. Park HS, Kim SR, Lee YC (2009a) Impact of oxidative stress on lung diseases. Respirology 14(1):27–38CrossRefGoogle Scholar
  73. Park HS, Kim SR, Lee YC (2009b Jan) Impact of oxidative stress on lung diseases. Respirology 14(1):27–38CrossRefGoogle Scholar
  74. Park HJ, Byun MK, Kim HJ, Kim JY, Kim YI, Yoo KH, Chun EM, Jung JY, Lee SH, Ahn CM (2016) Dietary vitamin C intake protects against COPD: the Korea national health and nutrition examination survey in 2012. Int J Chron Obstruct Pulmon Dis 11:2721PubMedPubMedCentralCrossRefGoogle Scholar
  75. Paul MK, Bisht B, Darmawan DO, Chiou R, Ha VL, Wallace WD, Chon AT, Hegab AE, Grogan T, Elashoff DA, Alva-Ornelas JA (2014) Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling. Cell Stem Cell 15(2):199–214PubMedPubMedCentralCrossRefGoogle Scholar
  76. Peden DB, Setzer RW Jr, Devlin RB (1995) Ozone exposure has both a priming effect on allergen-induced responses and an intrinsic inflammatory action in the nasal airways of perennially allergic asthmatics. Am J Respir Crit Care Med 151(5):1336–1345PubMedCrossRefPubMedCentralGoogle Scholar
  77. Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30(1):11–26PubMedCrossRefPubMedCentralGoogle Scholar
  78. Pignatelli B, Li CQ, Boffetta P, Chen Q, Ahrens W, Nyberg F, Mukeria A, Bruske-Hohlfeld I, Fortes C, Constantinescu V, Ischiropoulos H (2001) Nitrated and oxidized plasma proteins in smokers and lung cancer patients. Cancer Res 61(2):778–784PubMedPubMedCentralGoogle Scholar
  79. Pirabbasi E, Shahar S, Manaf ZA, Rajab NF, Manap RA (2016) Efficacy of ascorbic acid (vitamin C) and/N-acetylcysteine (NAC) supplementation on nutritional and antioxidant status of male chronic obstructive pulmonary disease (COPD) patients. J Nutr Sci Vitaminol 62(1):54–61PubMedCrossRefPubMedCentralGoogle Scholar
  80. Pirie K, Peto R, Reeves GK, Green J, Beral V, Million Women Study Collaborators (2013) The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UKGoogle Scholar
  81. Qiu F, Liang CL, Liu H, Zeng YQ, Hou S, Huang S, Lai X, Dai Z (2017) Mpacts of cigarette smoking on immune responsiveness: up and down or upside down? Oncotarget 3;8(1):268–284Google Scholar
  82. Rahman I, Kinnula VL (2012) Strategies to decrease ongoing oxidant burden in chronic obstructive pulmonary disease. Expert Rev Clin Pharmacol 5(3):293–309PubMedPubMedCentralCrossRefGoogle Scholar
  83. Reale M, Boscolo P, Bellante V, Tarantelli C, Di Nicola M, Forcella L, Li Q, Morimoto K, Muraro R (2012) Daily intake of Lactobacillus casei Shirota increases natural killer cell activity in smokers. Br J Nutr 108(2):308–314PubMedCrossRefPubMedCentralGoogle Scholar
  84. Rock JR, Barkauskas CE, Cronce MJ, Xue Y, Harris JR, Liang J, Noble PW, Hogan BL (2011) Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci 108(52):E1475–E1483PubMedCrossRefPubMedCentralGoogle Scholar
  85. Ryoo HD, Bergmann A (2012) The role of apoptosis-induced proliferation for regeneration and cancer. Cold Spring Harb Perspect Biol 4(8):a008797PubMedPubMedCentralCrossRefGoogle Scholar
  86. Sato T, Seyama K, Sato Y, Mori H, Souma S, Akiyoshi T, Kodama Y, Mori T, Goto S, Takahashi K, Fukuchi Y (2006) Senescence marker protein-30 protects mice lungs from oxidative stress, aging, and smoking. Am J Respir Crit Care Med 174(5):530–537PubMedCrossRefPubMedCentralGoogle Scholar
  87. Savin Z, Kivity S, Yonath H, Yehuda S (2018) Smoking and the intestinal microbiome. Arch Microbiol 200(5):677–684PubMedCrossRefPubMedCentralGoogle Scholar
  88. Schünemann HJ, Grant BJ, Freudenheim JL, Muti P, Browne RW, Drake JA, Klocke RA, Trevisan M (2001) The relation of serum levels of antioxidant vitamins C and E, retinol and carotenoids with pulmonary function in the general population. Am J Respir Crit Care Med 163(5):1246–1255PubMedCrossRefPubMedCentralGoogle Scholar
  89. Schwartz DA, Merchant RK, Helmers RA, Gilbert SR, Dayton CS, Hunninghake GW (1991a) The influence of cigarette smoking on lung function in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 144(3):504–506Google Scholar
  90. Schwartz DA, Helmers RA, Dayton CS, Merchant RK, Hunninghake GW (1991b) Determinants of bronchoalveolar lavage cellularity in idiopathic pulmonary fibrosis. J Appl Physiol 71(5):1688–1693PubMedCrossRefPubMedCentralGoogle Scholar
  91. Seidel C, Boehm V, Vogelsang H, Wagner A, Persin C, Glei M, Pool-Zobel BL, Jahreis G (2007) Influence of prebiotics and antioxidants in bread on the immune system, antioxidative status and antioxidative capacity in male smokers and non-smokers. Br J Nutr 97(2):349–356PubMedCrossRefPubMedCentralGoogle Scholar
  92. Strieter RM, Gomperts BN, Keane MP (2007) The role of CXC chemokines in pulmonary fibrosis. J Clin Invest 117(3):549–556PubMedPubMedCentralCrossRefGoogle Scholar
  93. Sundar IK, Yao H, Rahman I (2013 May 20) Oxidative stress and chromatin remodeling in chronic obstructive pulmonary disease and smoking-related diseases. Antioxid Redox Signal 18(15):1956–1971PubMedPubMedCentralCrossRefGoogle Scholar
  94. Taito S, Hamada H, Sekikawa K, Kamikawa N, Takahashi M (2017) Oxidative stress in cigarette smokers and patients with chronic obstructive pulmonary disease. Oxid Antioxidants Med Sci 6(2):19CrossRefGoogle Scholar
  95. Takahashi A, Ohtani N, Yamakoshi K, Iida SI, Tahara H, Nakayama K, Nakayama KI, Ide T, Saya H, Hara E (2006) Mitogenic signalling and the p16 INK4a–Rb pathway cooperate to enforce irreversible cellular senescence. Nat Cell Biol 8(11):1291PubMedCrossRefPubMedCentralGoogle Scholar
  96. To N, Gracie DJ, Ford AC (2016) Systematic review with meta-analysis: the adverse effects of tobacco smoking on the natural history of Crohn’s disease. Aliment Pharmacol Ther 43(5):549–561CrossRefGoogle Scholar
  97. US Department of Health and Human Services (2004) The health consequences of smoking: a report of the Surgeon GeneralGoogle Scholar
  98. Valdivieso ÁG, Dugour AV, Sotomayor V, Clauzure M, Figueroa JM, Santa-Coloma TA (2018) N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke extract in lung Calu-3 cells. Redox Biol 16:294–302PubMedPubMedCentralCrossRefGoogle Scholar
  99. Voltan R, Secchiero P, Casciano F, Milani D, Zauli G, Tisato V (2016) Redox signaling and oxidative stress: cross talk with TNF-related apoptosis inducing ligand activity. Int J Biochem Cell Biol 81:364–374PubMedCrossRefPubMedCentralGoogle Scholar
  100. Wang X, Tomso DJ, Chorley BN, Cho HY, Cheung VG, Kleeberger SR, Bell DA (2007) Identification of polymorphic antioxidant response elements in the human genome. Hum Mol Genet 16(10):1188–1200PubMedPubMedCentralCrossRefGoogle Scholar
  101. Waris G, Ahsan H (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. J carcinogenesis 5:14CrossRefGoogle Scholar
  102. Wells AU, King AD, Rubens MB, Cramer D, Du Bois RM, Hansell DM (1997) Lone cryptogenic fibrosing alveolitis: a functional-morphologic correlation based on extent of disease on thin-section computed tomography. Am J Respir Crit Care Med 155(4):1367–1375PubMedCrossRefPubMedCentralGoogle Scholar
  103. Whyte M, Hubbard R, Meliconi R, Whidborne M, Eaton V, Bingle C, Timms J, Duff G, Facchini A, Pacilli A, Fabbri M (2000) Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-α gene polymorphisms. Am J Respir Crit Care Med 162(2):755–758PubMedCrossRefPubMedCentralGoogle Scholar
  104. World Health Organization. Chronic respiratory disease, Asthma.
  105. Xing Y, Li A, Borok Z, Li C, Minoo P (2012) NOTCH1 is required for regeneration of Clara cells during repair of airway injury. Stem Cells 30(5):946–955PubMedPubMedCentralCrossRefGoogle Scholar
  106. Youlden DR, Cramb SM, Baade PD (2008) The international epidemiology of lung Cancer: geographical distribution and secular trends. J Thorac Oncol 3(8):819–831PubMedCrossRefPubMedCentralGoogle Scholar
  107. Zhang Y, Goss AM, Cohen ED, Kadzik R, Lepore JJ, Muthukumaraswamy K, Yang J, DeMayo FJ, Whitsett JA, Parmacek MS, Morrisey EE (2008) A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration. Nat Genet 40(7):862PubMedPubMedCentralCrossRefGoogle Scholar
  108. Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ, Chapman HA, Shapiro SD, Elias JA (2000) Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase–and cathepsin-dependent emphysema. J Clin Invest 106(9):1081–1093PubMedPubMedCentralCrossRefGoogle Scholar
  109. Zhu S, Manuel M, Tanaka S, Choe N, Kagan E, Matalon S (1998) Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury. Environ Health Perspect 106(Suppl 5):1157PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Francesco Marotta
    • 1
    • 2
  • Jaganath Arunachalam
    • 3
  • Antara Banerjee
    • 3
  • Roberto Catanzaro
    • 4
  • Sudhir Adalti
    • 5
  • Aparimita Das
    • 6
  • Alexander Kolyada
    • 7
  • Surajit Pathak
    • 3
  1. 1.ReGenera R&D International for Aging InterventionMilanItaly
  2. 2.VCC Preventive Medical Promotion FoundationBeijingChina
  3. 3.Faculty of Allied Health Sciences, Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), KelambakkamChennaiIndia
  4. 4.Department of Clinical & Experimental Medicine, Gastroenterology SectionUniversity of CataniaCataniaItaly
  5. 5.Department of CVTS, U N Mehta institute of cardiology and research centreAhmedabadIndia
  6. 6.Faculty of Medicine, Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE)ChennaiIndia
  7. 7.National Academy of Medical Sciences of Ukraine, Chebotareva Institute of GerontologyKievUkraine

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