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2000
Volume 21, Issue 4
  • ISSN: 1573-398X
  • E-ISSN: 1875-6387

Abstract

Purpose

This review examines COPD pathogenesis, biomarkers, and treatment. COPD, a progressive respiratory illness that blocks airflow, causes high morbidity and death. The complicated pathophysiology of COPD involves genetic predisposition, environmental variables (particularly tobacco smoke), and inflammatory pathways. COPD diagnosis, prognosis, and monitoring depend on biomarkers in clinical and preclinical investigations. COPD care should include pharmaceutical and non-pharmacological therapies to improve symptoms, lung function, and outcomes.

Materials and Methods

This review examines COPD pathogenesis, cytokines, and risk factors. This review article discusses how immune system signalling molecules called cytokines contribute to COPD's persistent inflammation. Smoking and environmental contaminants are also examined as COPD risk factors. The analysis also covers biomarkers needed to diagnose and track the condition.

Results

The review paper on COPD highlights the critical role of cytokines in the disease's pathophysiology, emphasizing their contribution to chronic inflammation. Various cytokines, particularly interleukins, are implicated in driving the inflammatory processes within the airways and lungs, resulting in tissue damage and airflow limitation, which are hallmark features of COPD. The paper also identifies smoking and exposure to environmental pollutants as major risk factors for the development of COPD.

Conclusion

This review illuminates COPD's complex pathogenesis, highlighting cytokines' involvement in chronic inflammation. To create targeted therapeutics, cytokine-mediated pathways must be understood. The review emphasizes biomarkers' use in preclinical and clinical investigations to diagnose and monitor COPD and provide disease progression insights.

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References

  1. EapenM.S. MyersS. WaltersE.H. SohalS.S. Airway inflammation in chronic obstructive pulmonary disease (COPD): A true paradox.Expert Rev. Respir. Med.2017111082783910.1080/17476348.2017.1360769
     [Google Scholar]
  2. SafiriS. Carson-ChahhoudK. NooriM. NejadghaderiS.A. SullmanM.J.M. Ahmadian HerisJ. AnsarinK. MansourniaM.A. CollinsG.S. KolahiA-A. KaufmanJ.S. Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: Results from the Global burden of disease study 2019.BMJ2022e06967910.1136/bmj‑2021‑069679
     [Google Scholar]
  3. NingsihN.S. Effectiveness of pursed-lip breathing on increasing oxygen saturation in COPD patients with RBBB symptoms, (Undergraduate thesis). Malang (ID): Muhammadiyah University of Malang2023
     [Google Scholar]
  4. AlfahadA.J. AlzaydiM.M. AldossaryA.M. AlshehriA.A. AlmughemF.A. ZaidanN.M. TawfikE.A. Current views in chronic obstructive pulmonary disease pathogenesis and management.Saudi Pharm. J.202129121361137310.1016/j.jsps.2021.10.008
     [Google Scholar]
  5. VogelmeierC.F. Román-RodríguezM. SinghD. HanM.L.K. Rodríguez-RoisinR. FergusonG.T. Goals of COPD treatment: Focus on symptoms and exacerbations.Respir. Med.202016610593810.1016/j.rmed.2020.105938
     [Google Scholar]
  6. MiravitllesM. RiberaA. Understanding the impact of symptoms on the burden of COPD.Respir. Res.20171816710.1186/s12931‑017‑0548‑3
     [Google Scholar]
  7. DivoM CoteC de TorresJP CasanovaC MarinJM Pinto-Plata V, Zulueta J, Cabrera C, Zagaceta J, Hunninghake G, Celli B. BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med.20121862155-6110.1164/rccm.201201‑0034oc22561964
     [Google Scholar]
  8. PrasadB. Chronic obstructive pulmonary disease (COPD).Int. J. Pharm. Res.Technol2020101677110.31838/ijprt/10.01.12
     [Google Scholar]
  9. SorianoJ.B. VisickG.T. MuellerovaH. PayvandiN. HansellA.L. Patterns of comorbidities in newly diagnosed COPD and asthma in primary care.Chest200512842099210710.1378/chest.128.4.2099
     [Google Scholar]
  10. WagenaE. HuibersM. Van SchayckC. Antidepressants in the treatment of patients with COPD: possible associations between smoking cigarettes, COPD and depression.Thorax2001567587588
     [Google Scholar]
  11. AgustiA. CelliB. Avoiding confusion in COPD: From risk factors to phenotypes to measures of disease characterisation.Eur Respiratory Soc.2011749751
     [Google Scholar]
  12. VestboJ. LangeP. Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease?Am. J. Respir. Crit. Care Med.2002166332933210.1164/rccm.2112048
     [Google Scholar]
  13. SorianoJ.B. PolverinoF. CosioB.G. What is early COPD and why is it important?Eur. Respir. J.2018526180144810.1183/13993003.01448‑2018
     [Google Scholar]
  14. LahousseL. LothD.W. JoosG.F. HofmanA. LeufkensH.G.M. BrusselleG.G. StrickerB.H. Statins, systemic inflammation and risk of death in COPD: The Rotterdam study.Pulm. Pharmacol. Ther.201326221221710.1016/j.pupt.2012.10.008
     [Google Scholar]
  15. KaplanA. LevitzS. Use of spirometry in family practice in Canada; Results of a nationwide survey.Eur Respiratory Soc.20164659PA406410.1183/13993003.congress‑2016.PA3938
     [Google Scholar]
  16. KaplanA. ThomasM. Screening for COPD: The gap between logic and evidence.Eur. Respir. Rev.20172614316011310.1183/16000617.0113‑2016
     [Google Scholar]
  17. CelliB.R. Update on the management of COPD.Chest200813361451146210.1378/chest.07‑2061
     [Google Scholar]
  18. StockleyR.A. Neutrophils and the pathogenesis of COPD.Chest20021215151S155S10.1378/chest.121.5_suppl.151S
     [Google Scholar]
  19. TetleyT.D. Macrophages and the pathogenesis of COPD.Chest20021215156S159S10.1378/chest.121.5_suppl.156S
     [Google Scholar]
  20. BarnesP.J. CosioM.G. Characterization of T lymphocytes in chronic obstructive pulmonary disease.PLoS Med.200411e2010.1371/journal.pmed.0010020
     [Google Scholar]
  21. MacNeeW. Oxidants/antioxidants and COPD.Chest20001175303S317S10.1378/chest.117.5_suppl_1.303S‑a
     [Google Scholar]
  22. BrashierB.B. KodguleR. Risk factors and pathophysiology of chronic obstructive pulmonary disease (COPD).J. Assoc. Physicians India201260Suppl.1721
     [Google Scholar]
  23. LiuY. LiA. FengX. SunX. ZhuX. ZhaoZ. Pharmacological investigation of the anti-inflammation and anti-oxidation activities of diallyl disulfide in a rat emphysema model induced by cigarette smoke extract.Nutrients20181017910.3390/nu10010079
     [Google Scholar]
  24. ChenH. WangD. BaiC. WangX. Proteomics-based biomarkers in chronic obstructive pulmonary disease.J. Proteome Res.2010962798280810.1021/pr100063r
     [Google Scholar]
  25. KongJ. FanR. ZhangY. JiaZ. ZhangJ. PanH. WangQ. Oxidative stress in the brain–lung crosstalk: cellular and molecular perspectives.Front. Aging Neurosci.202416138945410.3389/fnagi.2024.1389454
     [Google Scholar]
  26. KorkmazB. HorwitzM.S. JenneD.E. GauthierF. Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases.Pharmacol. Rev.201062472675910.1124/pr.110.002733
     [Google Scholar]
  27. AgustíA, Celli BR, Criner GJ Global initiative for chronic obstructive lung disease 2023 report: Gold executive summary.Respirology2023284316338
     [Google Scholar]
  28. BrinkmanJ.E. ToroF. SharmaS. Physiology, respiratory drive.StatPearlsTreasure Island2018
     [Google Scholar]
  29. O’DonnellD.E. LavenezianaP. Physiology and consequences of lung hyperinflation in COPD.Eur. Respir. Rev.200615100616710.1183/09059180.00010002
     [Google Scholar]
  30. PowersK.A. DhamoonA.S. Physiology, pulmonary ventilation and perfusion.StatPearlsTreasure Island2019
     [Google Scholar]
  31. ShapiroS. The pathophysiology of COPD: What go wrong and why proceedings?Adv. Stud. Med.200332BS91S98
     [Google Scholar]
  32. DotanY. SoJ.Y. KimV. Chronic bronchitis: Where are we now? Chronic obstructive pulmonary diseases.Chronic Obstr. Pulm. Dis. (Miami)20196217819210.15326/jcopdf.6.2.2018.0151
     [Google Scholar]
  33. FerrisB. Epidemiology standardization project. II. Recommended respiratory disease questionnaires for use with adults and children in epidemiological research.Am. Rev. Respir. Dis.19781186753
     [Google Scholar]
  34. DevineJ.F. Chronic obstructive pulmonary disease: An overview.Am. Health. Drug. Benefits20081734
     [Google Scholar]
  35. LarsenB.T. SmithM.L. ElickerB.M. FernandezJ.M. de MorvilG.A.A-O. PereiraC.A.C. LeslieK.O. Diagnostic approach to advanced fibrotic interstitial lung disease: Bringing together clinical, radiologic, and histologic clues.Arch. Pathol. Lab. Med.2017141790191510.5858/arpa.2016‑0299‑SA
     [Google Scholar]
  36. KimV. CrinerG.J. Chronic bronchitis and chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med.2013187322823710.1164/rccm.201210‑1843CI
     [Google Scholar]
  37. JelicT.M. Emphysema. In: Jelic TM, editor. Update in Respiratory Diseases. London: IntechOpen; 2019.10.5772/intechopen.80230
  38. VillaB. ErranzB. CrucesP. RetamalJ. HurtadoD.E. Mechanical and morphological characterization of the emphysematous lung tissue.Acta Biomater.202418128229610.1016/j.actbio.2024.04.039
     [Google Scholar]
  39. CliniE, Holland AE, Pitta F, Troosters T editors. Textbook of Pulmonary Rehabilitation. Cham (CH): Springer; 2018.10.1007/978‑3‑319‑65888‑9
  40. ShahP.L. HerthF.J. van GeffenW.H. DesleeG. SlebosD-J. Lung volume reduction for emphysema.Lancet Respir. Med.20175214715610.1016/S2213‑2600(16)30221‑1
     [Google Scholar]
  41. KempS.V. PolkeyM.I. ShahP.L. The epidemiology, etiology, clinical features, and natural history of emphysema.Thorac. Surg. Clin.200919214915810.1016/j.thorsurg.2009.03.003
     [Google Scholar]
  42. GoldklangM. StockleyR. Pathophysiology of emphysema and implications.Chronic Obstr. Pulm. Dis. (Miami)20163145445810.15326/jcopdf.3.1.2015.0175
     [Google Scholar]
  43. YangI.A. JenkinsC.R. SalviS.S. Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment.Lancet Respir. Med.202210549751110.1016/S2213‑2600(21)00506‑3
     [Google Scholar]
  44. GuenegouA. BoczkowskiJ. AubierM. NeukirchF. LeynaertB. Interaction between a heme oxygenase-1 gene promoter polymorphism and serum β-carotene levels on 8-year lung function decline in a general population: The European Community Respiratory Health Survey (France).Am. J. Epidemiol.2007167213914410.1093/aje/kwm282
     [Google Scholar]
  45. CaramoriG. KirkhamP. BarczykA. Di StefanoA. AdcockI. Molecular pathogenesis of cigarette smoking–induced stable COPD.Ann. N. Y. Acad. Sci.201513401556410.1111/nyas.12619
     [Google Scholar]
  46. BarnesP.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease.Clin. Chest Med.2014351718610.1016/j.ccm.2013.10.004
     [Google Scholar]
  47. CaramoriG. StefanoA. CasolariP. KirkhamP.A. PadovaniA. ChungK.F. PapiA. AdcockI.M. Chemokines and chemokine receptors blockers as new drugs for the treatment of chronic obstructive pulmonary disease.Curr. Med. Chem.201320354317434910.2174/09298673113206660261
     [Google Scholar]
  48. CaramoriG, Adcock IM, Di Stefano A, Chung KF. Cytokine inhibition in the treatment of COPD.Int. J. Chron. Obstruct. Pulmon. Dis.2014397412
     [Google Scholar]
  49. XueJ. SchmidtS.V. SanderJ. DraffehnA. KrebsW. QuesterI. De NardoD. GohelT.D. EmdeM. SchmidleithnerL. GanesanH. Nino-CastroA. MallmannM.R. LabzinL. TheisH. KrautM. BeyerM. LatzE. FreemanT.C. UlasT. SchultzeJ.L. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.Immunity201440227428810.1016/j.immuni.2014.01.006
     [Google Scholar]
  50. CaramoriG. CasolariP. AdcockI. Role of transcription factors in the pathogenesis of asthma and COPD.Cell Commun. Adhes.2013201-2214010.3109/15419061.2013.775257
     [Google Scholar]
  51. KornR.J. DockeryD.W. SpeizerF.E. WareJ.H. FerrisB.G.Jr Occupational exposures and chronic respiratory symptoms.Am. Rev. Respir. Dis.1987136229830410.1164/ajrccm/136.2.298
     [Google Scholar]
  52. HagstadS. BackmanH. BjergA. EkerljungL. YeX. HedmanL. LindbergA. TorénK. LötvallJ. RönmarkE. LundbäckB. Prevalence and risk factors of COPD among never-smokers in two areas of Sweden – Occupational exposure to gas, dust or fumes is an important risk factor.Respir. Med.2015109111439144510.1016/j.rmed.2015.09.012
     [Google Scholar]
  53. JohannessenA, Omenaas ER, Bakke PS, Gulsvik A. Implications of reversibility testing on prevalence and risk factors for chronic obstructive pulmonary disease: a community study.Thorax2005601084284710.1136/thx.2005.043943
     [Google Scholar]
  54. TagiyevaN. SadhraS. MohammedN. FieldingS. DevereuxG. TeoE. AyresJ. Graham DouglasJ. Occupational airborne exposure in relation to Chronic Obstructive Pulmonary Disease (COPD) and lung function in individuals without childhood wheezing illness: A 50-year cohort study.Environ. Res.201715312613410.1016/j.envres.2016.11.018
     [Google Scholar]
  55. LiangG.B. HeZ.H. Animal models of emphysema.Chin. Med. J. (Engl.)2019132202465247510.1097/CM9.0000000000000469
     [Google Scholar]
  56. MinovJ. Occupational chronic obstructive pulmonary disorder: prevalence and prevention.Expert Rev. Respir. Med.2022164429436
     [Google Scholar]
  57. RodríguezE. FerrerJ. MartíS. ZockJ-P. PlanaE. MorellF. Impact of occupational exposure on severity of COPD.Chest200813461237124310.1378/chest.08‑0622
     [Google Scholar]
  58. SilverS.R. AlarconW.A. LiJ. Incident chronic obstructive pulmonary disease associated with occupation, industry, and workplace exposures in the Health and Retirement Study.Am. J. Ind. Med.2021641263810.1002/ajim.23196
     [Google Scholar]
  59. MurgiaN. GambelungheA. Occupational COPD —The most under-recognized occupational lung disease?Respirology202227639941010.1111/resp.14272
     [Google Scholar]
  60. FrankE.F. FerrerJ. CharlesP. RichardT. CecilyS. The Natural history of chronic bronchitis and emphysema: An eight-year study of early chronic obstructive lung disease in working men in London.Oxford University Press1976
     [Google Scholar]
  61. ManninoD.M. BuistA.S. Global burden of COPD: Risk factors, prevalence, and future trends.Lancet2007370958976577310.1016/S0140‑6736(07)61380‑4
     [Google Scholar]
  62. ManninoD.M. DavisK.J. Lung function decline and outcomes in an elderly population.Thorax200661647247710.1136/thx.2005.052449
     [Google Scholar]
  63. JemalA, Ward E, Hao Y, Thun M. Trends in the leading causes of death in the United States, 1970-2002.JAMA2005294101255125910.1001/jama.294.10.1255
     [Google Scholar]
  64. WedzichaJ.A. SeemungalT.A.R. COPD exacerbations: Defining their cause and prevention.Lancet2007370958978679610.1016/S0140‑6736(07)61382‑8
     [Google Scholar]
  65. SinghD. AgustiA. AnzuetoA. BarnesP.J. BourbeauJ. CelliB.R. CrinerG.J. FrithP. HalpinD.M.G. HanM. López VarelaM.V. MartinezF. Montes de OcaM. PapiA. PavordI.D. RocheN. SinD.D. StockleyR. VestboJ. WedzichaJ.A. VogelmeierC. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: The GOLD science committee report 2019.Eur. Respir. J.2019535190016410.1183/13993003.00164‑2019
     [Google Scholar]
  66. SorianoJ.B. AbajobirA.A. AbateK.H. AberaS.F. AgrawalA. AhmedM.B. AichourA.N. AichourI. AichourM.T.E. AlamK. AlamN. AlkaabiJ.M. Al-MaskariF. Alvis-GuzmanN. AmberbirA. AmoakoY.A. AnshaM.G. AntóJ.M. AsayeshH. AteyT.M. AvokpahoE.F.G.A. BaracA. BasuS. BediN. BensenorI.M. BerhaneA. BeyeneA.S. BhuttaZ.A. BiryukovS. BoneyaD.J. BrauerM. CarpenterD.O. CaseyD. ChristopherD.J. DandonaL. DandonaR. DharmaratneS.D. DoH.P. FischerF. GebrehiwotT.T. GeletoA. GhoshalA.G. GillumR.F. GinawiI.A.M. GuptaV. HayS.I. HedayatiM.T. HoritaN. HosgoodH.D. JakovljevicM.M.B. JamesS.L. JonasJ.B. KasaeianA. KhaderY.S. KhalilI.A. KhanE.A. KhangY-H. KhubchandaniJ. KnibbsL.D. KosenS. KoulP.A. KumarG.A. LeshargieC.T. LiangX. El RazekH.M.A. MajeedA. MaltaD.C. ManhertzT. MarquezN. MehariA. MensahG.A. MillerT.R. MohammadK.A. MohammedK.E. MohammedS. MokdadA.H. NaghaviM. NguyenC.T. NguyenG. Le NguyenQ. NguyenT.H. NingrumD.N.A. NongV.M. ObiJ.I. OdeyemiY.E. OgboF.A. OrenE. PaM. ParkE-K. PattonG.C. PaulsonK. QorbaniM. QuansahR. RafayA. RahmanM.H.U. RaiR.K. RawafS. ReinigN. SafiriS. Sarmiento-SuarezR. SartoriusB. SavicM. SawhneyM. ShigematsuM. SmithM. TadeseF. ThurstonG.D. Topor-MadryR. TranB.X. UkwajaK.N. van BovenJ.F.M. VlassovV.V. VollsetS.E. WanX. WerdeckerA. HansonS.W. YanoY. YimamH.H. YonemotoN. YuC. ZaidiZ. El Sayed ZakiM. LopezA.D. MurrayC.J.L. VosT. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015.Lancet Respir. Med.20175969170610.1016/S2213‑2600(17)30293‑X
     [Google Scholar]
  67. RycroftCE, Heyes A, Lanza L, Becker K. Epidemiology of chronic obstructive pulmonary disease: A literature review.Int. J. Chron. Obstruct. Pulmon. Dis.201245749410.2147/COPD.S32330
     [Google Scholar]
  68. RuvunaL. SoodA. Epidemiology of chronic obstructive pulmonary disease.Clin. Chest Med.202041331532710.1016/j.ccm.2020.05.002
     [Google Scholar]
  69. MitraS. AnandU. GhoraiM. VellingiriB. JhaN.K. BehlT. KumarM. Radha ShekhawatM.S. ProćkówJ. DeyA. Unravelling the therapeutic potential of botanicals against chronic obstructive pulmonary disease (COPD): Molecular insights and future perspectives.Front. Pharmacol.20221382413210.3389/fphar.2022.824132
     [Google Scholar]
  70. AdeloyeD. ChuaS. LeeC. BasquillC. PapanaA. TheodoratouE. NairH. GasevicD. SridharD. CampbellH. ChanK.Y. SheikhA. RudanI. Global and regional estimates of COPD prevalence: Systematic review and meta–analysis.J. Glob. Health20155202041510.7189/jogh.05.020415
     [Google Scholar]
  71. BiomarkersDefinitions Working Group, Atkinson Jr AJ, Colburn WA Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework.Clin. Pharmacol. Ther.2001693899510.1067/mcp.2001.113989
     [Google Scholar]
  72. PantazopoulosI. MagounakiK. KotsiouO. RoukaE. PerlikosF. KakavasS. GourgoulianisK. Incorporating biomarkers in COPD management: The research keeps going.J. Pers. Med.202212337910.3390/jpm12030379
     [Google Scholar]
  73. TakahashiT. KobayashiS. FujinoN. SuzukiT. OtaC. TandoY. YamadaM. YanaiM. YamayaM. KurosawaS. YamauchiM. KuboH. Annual FEV 1 changes and numbers of circulating endothelial microparticles in patients with COPD: a prospective study.BMJ Open201443e00457110.1136/bmjopen‑2013‑004571
     [Google Scholar]
  74. HoT. DasguptaA. HargreaveF.E. NairP. The use of cellular and molecular biomarkers to manage COPD exacerbations.Expert Rev. Respir. Med.20171151910.1080/17476348.2017.1307738
     [Google Scholar]
  75. AgustíA. EdwardsL.D. RennardS.I. MacNeeW. Tal-SingerR. MillerB.E. VestboJ. LomasD.A. CalverleyP.M.A. WoutersE. CrimC. YatesJ.C. SilvermanE.K. CoxsonH.O. BakkeP. MayerR.J. CelliB. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: A novel phenotype.PLoS One201275e3748310.1371/journal.pone.0037483
     [Google Scholar]
  76. ThomsenM. DahlM. LangeP. VestboJ. NordestgaardB.G. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med.20121861098298810.1164/rccm.201206‑1113OC
     [Google Scholar]
  77. HurstJ.R. AnzuetoA. VestboJ. Susceptibility to exacerbation in COPD.Lancet Respir. Med.201759e2910.1016/S2213‑2600(17)30307‑7
     [Google Scholar]
  78. MüllerovaH. MaselliD.J. LocantoreN. VestboJ. HurstJ.R. WedzichaJ.A. BakkeP. AgustiA. AnzuetoA. Hospitalized exacerbations of COPD.Chest20151474999100710.1378/chest.14‑0655
     [Google Scholar]
  79. PavordI.D. LettisS. LocantoreN. PascoeS. JonesP.W. WedzichaJ.A. BarnesN.C. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD.Thorax201671211812510.1136/thoraxjnl‑2015‑207021
     [Google Scholar]
  80. PascoeS. LocantoreN. DransfieldM.T. BarnesN.C. PavordI.D. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: A secondary analysis of data from two parallel randomised controlled trials.Lancet Respir. Med.20153643544210.1016/S2213‑2600(15)00106‑X
     [Google Scholar]
  81. SiddiquiS.H. GuasconiA. VestboJ. JonesP. AgustiA. PaggiaroP. WedzichaJ.A. SinghD. Blood eosinophils: A biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med.2015192452352510.1164/rccm.201502‑0235LE
     [Google Scholar]
  82. MagnussenH. DisseB. Rodriguez-RoisinR. KirstenA. WatzH. TetzlaffK. TowseL. FinniganH. DahlR. DecramerM. ChanezP. WoutersE.F.M. CalverleyP.M.A. Withdrawal of inhaled glucocorticoids and exacerbations of COPD.N. Engl. J. Med.2014371141285129410.1056/NEJMoa1407154
     [Google Scholar]
  83. BrightlingC.E. PavordI.D. BafadhelM. Inhaled glucocorticoids and COPD exacerbations.N Engl J Med.2015372193
     [Google Scholar]
  84. WatzH. TetzlaffK. WoutersE.F.M. KirstenA. MagnussenH. Rodriguez-RoisinR. VogelmeierC. FabbriL.M. ChanezP. DahlR. DisseB. FinniganH. CalverleyP.M.A. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: A post-hoc analysis of the WISDOM trial.Lancet Respir. Med.20164539039810.1016/S2213‑2600(16)00100‑4
     [Google Scholar]
  85. ZinelluE. ZinelluA. FoisA.G. PauM.C. ScanoV. PirasB. CarruC. PirinaP. Oxidative stress biomarkers in chronic obstructive pulmonary disease exacerbations: A systematic review.Antioxidants202110571010.3390/antiox10050710
     [Google Scholar]
  86. ChamitavaL. CazzolettiL. FerrariM. Garcia-LarsenV. JalilA. DeganP. FoisA.G. ZinelluE. FoisS.S. Fratta PasiniA.M. NicolisM. OlivieriM. CorsicoA. BonoR. PirinaP. ZanolinM.E. Biomarkers of oxidative stress and inflammation in chronic airway diseases.Int. J. Mol. Sci.20202112433910.3390/ijms21124339
     [Google Scholar]
  87. ZinelluE. ZinelluA. FoisA.G. CarruC. PirinaP. Circulating biomarkers of oxidative stress in chronic obstructive pulmonary disease: A systematic review.Respir. Res.201617115010.1186/s12931‑016‑0471‑z
     [Google Scholar]
  88. AlbrechtE. SillanpaaE. KarraschS. AlvesA.C. CoddV. HovattaI. BuxtonJ.L. NelsonC.P. BroerL. HaggS. ManginoM. WillemsenG. SurakkaI. FerreiraM.A.R. AminN. OostraB.A. BackmandH.M. PeltonenM. SarnaS. RantanenT. SipilaS. KorhonenT. MaddenP.A.F. GiegerC. JorresR.A. HeinrichJ. BehrJ. HuberR.M. PetersA. StrauchK. WichmannH.E. WaldenbergerM. BlakemoreA.I.F. de GeusE.J.C. NyholtD.R. HendersA.K. PiirilaP.L. RissanenA. MagnussonP.K.E. VinuelaA. PietilainenK.H. MartinN.G. PedersenN.L. BoomsmaD.I. SpectorT.D. van DuijnC.M. KaprioJ. SamaniN.J. JarvelinM-R. SchulzH. Telomere length in circulating leukocytes is associated with lung function and disease.Eur. Respir. J.201443498399210.1183/09031936.00046213
     [Google Scholar]
  89. BirchJ. AndersonR.K. Correia-MeloC. JurkD. HewittG. MarquesF.M. GreenN.J. MoiseyE. BirrellM.A. BelvisiM.G. BlackF. TaylorJ.J. FisherA.J. De SoyzaA. PassosJ.F. DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease.Am. J. Physiol. Lung Cell. Mol. Physiol.201530910L1124L113710.1152/ajplung.00293.2015
     [Google Scholar]
  90. EasterM. BollenbeckerS. BarnesJ.W. KrickS. Targeting aging pathways in chronic obstructive pulmonary disease.Int. J. Mol. Sci.20202118692410.3390/ijms21186924
     [Google Scholar]
  91. AngelisN, Porpodis K, Zarogoulidis P Airway inflammation in chronic obstructive pulmonary disease.J. Thorac. Dis.20146Suppl. 1S167
     [Google Scholar]
  92. BarnesP.J. ChowdhuryB. KharitonovS.A. MagnussenH. PageC.P. PostmaD. SaettaM. Pulmonary biomarkers in chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med.2006174161410.1164/rccm.200510‑1659PP
     [Google Scholar]
  93. KoutsokeraA, Kostikas K, Nicod LD, Fitting JW. Pulmonary biomarkers in COPD exacerbations: A systematic review.Respir. Res.201314112
     [Google Scholar]
  94. RadicioniG. CeppeA. FordA.A. AlexisN.E. BarrR.G. BleeckerE.R. ChristensonS.A. CooperC.B. HanM.L.K. HanselN.N. HastieA.T. HoffmanE.A. KannerR.E. MartinezF.J. OzkanE. PaineR.III WoodruffP.G. O’NealW.K. BoucherR.C. KesimerM. Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: An analysis of the SPIROMICS cohort.Lancet Respir. Med.20219111241125410.1016/S2213‑2600(21)00079‑5
     [Google Scholar]
  95. KesimerM. SmithB.M. CeppeA. FordA.A. AndersonW.H. BarrR.G. O’NealW.K. BoucherR.C. WoodruffP.G. HanM.L.K. HoffmanE.A. MartinezF. CurtisJ.L. PaineR.III CooperC.B. BleeckerE.R. Mucin concentrations and peripheral airway obstruction in chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med.2018198111453145610.1164/rccm.201806‑1016LE
     [Google Scholar]
  96. FujisawaT. VelichkoS. ThaiP. HungL-Y. HuangF. WuR. Regulation of airway MUC5AC expression by IL-1β and IL-17A; the NF-κB paradigm.J. Immunol.2009183106236624310.4049/jimmunol.0900614
     [Google Scholar]
  97. ReidL.V. SpallutoC.M. WatsonA. StaplesK.J. WilkinsonT.M.A. The role of extracellular vesicles as a shared disease mechanism contributing to multimorbidity in patients with COPD.Front. Immunol.20211275400410.3389/fimmu.2021.754004
     [Google Scholar]
  98. TakahashiT. KobayashiS. FujinoN. SuzukiT. OtaC. HeM. YamadaM. SuzukiS. YanaiM. KurosawaS. YamayaM. KuboH. Increased circulating endothelial microparticles in COPD patients: A potential biomarker for COPD exacerbation susceptibility.Thorax201267121067107410.1136/thoraxjnl‑2011‑201395
     [Google Scholar]
  99. ThomashowM.A. ShimboD. ParikhM.A. HoffmanE.A. Vogel-ClaussenJ. HueperK. FuJ. LiuC-Y. BluemkeD.A. VentetuoloC.E. DoyleM.F. BarrR.G. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease Study Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. The multi-ethnic study of atherosclerosis chronic obstructive pulmonary disease study.Am. J. Respir. Crit. Care Med.20131881606810.1164/rccm.201209‑1697OC
     [Google Scholar]
  100. ChapmanK.R. BurdonJ.G.W. PiitulainenE. SandhausR.A. SeersholmN. StocksJ.M. StoelB.C. HuangL. YaoZ. EdelmanJ.M. McElvaneyN.G. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): A randomised, double-blind, placebo-controlled trial.Lancet2015386999136036810.1016/S0140‑6736(15)60860‑1
     [Google Scholar]
  101. SilvermanE.K. SandhausR.A. Alpha1-antitrypsin deficiency.N. Engl. J. Med.2009360262749275710.1056/NEJMcp0900449
     [Google Scholar]
  102. GuenegouA, Leynaert B, Benessiano J Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample. Results from the European Community Respiratory Health Survey (ECRHS).J. Med. Genet.2006438e43e4310.1136/jmg.2005.039743
     [Google Scholar]
  103. YamadaN. YamayaM. OkinagaS. NakayamaK. SekizawaK. ShibaharaS. SasakiH. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema.Am. J. Hum. Genet.200066118719510.1086/302729
     [Google Scholar]
  104. KongX. ChoM.H. AndersonW. CoxsonH.O. MullerN. WashkoG. HoffmanE.A. BakkeP. GulsvikA. LomasD.A. SilvermanE.K. PillaiS.G. Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema.Am. J. Respir. Crit. Care Med.20111831434910.1164/rccm.201004‑0541OC
     [Google Scholar]
  105. WurstK.E. RheaultT.R. EdwardsL. Tal-SingerR. AgustiA. VestboJ. A comparison of COPD patients with and without ACOS in the ECLIPSE study.Eur. Respir. J.20164751559156210.1183/13993003.02045‑2015
     [Google Scholar]
  106. LiD. WuY. GuoS. QinJ. FengM. AnY. ZhangJ. LiY. XiongS. ZhouH. ZengQ. ChenL. WenF. Circulating syndecan-1 as a novel biomarker relates to lung function, systemic inflammation, and exacerbation in COPD.Int. J. Chron. Obstruct. Pulmon. Dis.2019141933194110.2147/COPD.S207855
     [Google Scholar]
  107. MathioudakisA.G. JanssensW. SivapalanP. SinganayagamA. DransfieldM.T. JensenJ-U.S. VestboJ. Acute exacerbations of chronic obstructive pulmonary disease: in search of diagnostic biomarkers and treatable traits.Thorax202075652052710.1136/thoraxjnl‑2019‑214484
     [Google Scholar]
  108. NoellG. CosíoB.G. FanerR. MonsóE. Peces-BarbaG. de DiegoA. EstebanC. GeaJ. Rodriguez-RoisinR. Garcia-NuñezM. Pozo-RodriguezF. KalkoS.G. AgustíA. Multi-level differential network analysis of COPD exacerbations.Eur. Respir. J.2017503170007510.1183/13993003.00075‑2017
     [Google Scholar]
  109. ZemansR.L. JacobsonS. KeeneJ. KechrisK. MillerB.E. Tal-SingerR. BowlerR.P. Multiple biomarkers predict disease severity, progression and mortality in COPD.Respir. Res.201718111710.1186/s12931‑017‑0597‑7
     [Google Scholar]
  110. CelliB.R. AndersonJ.A. BrookR. CalverleyP. CowansN.J. CrimC. DixonI. KimV. MartinezF.J. MorrisA. NewbyD.E. YatesJ. VestboJ. Serum biomarkers and outcomes in patients with moderate COPD: A substudy of the randomised SUMMIT trial.BMJ Open Respir. Res.201961e00043110.1136/bmjresp‑2019‑000431
     [Google Scholar]
  111. RidkerP.M. C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: Moving an inflammatory hypothesis toward consensus.J. Am. Coll. Cardiol.200749212129213810.1016/j.jacc.2007.02.052
     [Google Scholar]
  112. ManSF, Connett JE, Anthonisen NR. C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease.Thorax2006611084985310.1136/thx.2006.059808
     [Google Scholar]
  113. EllingsenJ. JansonC. BrömsK. HårdstedtM. HögmanM. LisspersK. PalmA. StällbergB. MalinovschiA. CRP, Fibrinogen, white blood cells, and blood cell indices as prognostic biomarkers of future COPD exacerbation frequency: The TIE cohort study.J. Clin. Med.20241313385510.3390/jcm13133855
     [Google Scholar]
  114. BarnesP.J. CelliB.R. Systemic manifestations and comorbidities of COPD.Eur. Respir. J.20093351165118510.1183/09031936.00128008
     [Google Scholar]
  115. PerngD.W. ChenP.K. The relationship between airway inflammation and exacerbation in chronic obstructive pulmonary disease.Tuberc. Respir. Dis. (Seoul)201780432510.4046/trd.2017.0085
     [Google Scholar]
  116. AgustíA.G.N. NogueraA. SauledaJ. SalaE. PonsJ. BusquetsX. Systemic effects of chronic obstructive pulmonary disease.Eur. Respir. J.200321234736010.1183/09031936.03.00405703
     [Google Scholar]
  117. SapeyE. StockleyR.A. COPD exacerbations middle dot 2: Aetiology.Thorax200661325025810.1136/thx.2005.041822
     [Google Scholar]
  118. SinghD. BafadhelM. BrightlingC.E. SciurbaF.C. CurtisJ.L. MartinezF.J. PasqualeC.B. MerrillD.D. MetzdorfN. PetruzzelliS. Tal-SingerR. ComptonC. RennardS. MartinU.J. Blood eosinophil counts in clinical trials for chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med.2020202566067110.1164/rccm.201912‑2384PP
     [Google Scholar]
  119. LenferinkA. CitgezE. van der ValkP.D.L.P.M. van der PalenJ. EffingT.W. Brusse-KeizerM.G.J. Potential for personalised and biomarker-guided COPD self-treatment approaches.Lancet Respir. Med.2024128e48e4910.1016/S2213‑2600(24)00180‑2
     [Google Scholar]
  120. ProfitaM, Chiappara G, Mirabella F. Effect of cilomilast (Ariflo) on TNF-, IL-8, and GM-CSF release by airway cells of patients with COPD.Thorax200358757357910.1136/thorax.58.7.573
     [Google Scholar]
  121. HuangY. NiuY. WangX. LiX. HeY. LiuX. Identification of novel biomarkers related to neutrophilic inflammation in COPD.Front. Immunol.202415141015810.3389/fimmu.2024.1410158
     [Google Scholar]
  122. TakahashiK, Tanabe K, Ohnuki M. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell2007131586187210.1016/j.cell.2007.11.019
     [Google Scholar]
  123. GlassbergM.K. CseteI. SimonetE. ElliotS.J. Stem cell therapy for COPD: Hope and exploitation.Chest202116041271128110.1016/j.chest.2021.04.020
     [Google Scholar]
  124. NicolaT. WengerN. XuX. EvansM. QiaoL. RezonzewG. YangY. JillingT. MargaroliC. GenschmerK. WillisK. AmbalavananN. BlalockJ.E. GaggarA. LalC.V. A lactobacilli-based inhaled live biotherapeutic product attenuates pulmonary neutrophilic inflammation.Nat. Commun.2024151711310.1038/s41467‑024‑51169‑0
     [Google Scholar]
  125. TannerL. SingleA.B. Animal models reflecting chronic obstructive pulmonary disease and related respiratory disorders: Translating pre-clinical data into clinical relevance.J. Innate Immun.202012320322510.1159/000502489
     [Google Scholar]
  126. GhoraniV. BoskabadyM.H. KhazdairM.R. KianmeherM. Experimental animal models for COPD: A methodological review.Tob. Induc. Dis.20171512510.1186/s12971‑017‑0130‑2
     [Google Scholar]
  127. FrickerM. DeaneA. HansbroP.M. Animal models of chronic obstructive pulmonary disease.Expert Opin. Drug Discov.20149662964510.1517/17460441.2014.909805
     [Google Scholar]
  128. LeberlM. KratzerA. Taraseviciene-StewartL. Tobacco smoke induced COPD/emphysema in the animal model—are we all on the same page?Front. Physiol.201349110.3389/fphys.2013.00091
     [Google Scholar]
  129. StevensonC.S. BirrellM.A. Moving towards a new generation of animal models for asthma and COPD with improved clinical relevance.Pharmacol. Ther.201113029310510.1016/j.pharmthera.2010.10.008
     [Google Scholar]
  130. CanningB.J. WrightJ.L. Animal models of asthma and chronic obstructive pulmonary disease.Pulm. Pharmacol. Ther.200821569569510.1016/j.pupt.2008.04.007
     [Google Scholar]
  131. GronebergD.A. ChungK.F. Models of chronic obstructive pulmonary disease.Respir. Res.2004511810.1186/1465‑9921‑5‑18
     [Google Scholar]
  132. WilliamsK. RomanJ. Studying human respiratory disease in animals – role of induced and naturally occurring models.J. Pathol.2016238222023210.1002/path.4658
     [Google Scholar]
  133. BailaB. OhnoY. NagamotoH. KotosaiK. YabuuchiY. FunaguchiN. ItoF. EndoJ. MoriH. TakemuraG. FujiwaraT. FujiwaraH. MinatoguchiS. Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of oxidative stress in rabbits.Biol. Pharm. Bull.201235449450210.1248/bpb.35.494
     [Google Scholar]
  134. LucasS.D. GonçalvesL.M. CardoteT.A.F. CorreiaH.F. MoreiraR. GuedesR.C. Structure based virtual screening for discovery of novel human neutrophil elastase inhibitors.MedChemComm20123101299130410.1039/c2md20090b
     [Google Scholar]
  135. AntunesM.A. RoccoP.R.M. Elastase-induced pulmonary emphysema: insights from experimental models.An. Acad. Bras. Cienc.20118341385139610.1590/S0001‑37652011005000039
     [Google Scholar]
  136. de OliveiraM.V. SilvaP.L. RoccoP.R.M. Animal models of chronic obstructive pulmonary disease exacerbations: A review of the current status.J. Biomed. Sci.20165188
     [Google Scholar]
  137. BrusselleG.G. BrackeK.R. MaesT. D’hulstA.I. MoerlooseK.B. JoosG.F. PauwelsR.A. Murine models of COPD.Pulm. Pharmacol. Ther.200619315516510.1016/j.pupt.2005.06.001
     [Google Scholar]
  138. ForonjyR.F. OkadaY. ColeR. D’ArmientoJ. Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung.Am. J. Physiol. Lung Cell. Mol. Physiol.20032845L727L73710.1152/ajplung.00349.2002
     [Google Scholar]
  139. ShiomiT. OkadaY. ForonjyR. SchiltzJ. JaenishR. KraneS. D’ArmientoJ. Emphysematous changes are caused by degradation of type III collagen in transgenic mice expressing MMP-1.Exp. Lung Res.200329111510.1080/01902140303761
     [Google Scholar]
  140. D’ArmientoJ. DalalS.S. OkadaY. BergR.A. ChadaK. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema.Cell199271695596110.1016/0092‑8674(92)90391‑O
     [Google Scholar]
  141. WangZ. ZhengT. ZhuZ. HomerR.J. RieseR.J. ChapmanH.A.Jr ShapiroS.D. EliasJ.A. Interferon γ induction of pulmonary emphysema in the adult murine lung.J. Exp. Med.2000192111587160010.1084/jem.192.11.1587
     [Google Scholar]
  142. TazakiG. KondoT. TajiriS. Functional residual capacity and airway resistance in rats of COPD model induced by systemic hyaluronidase.Tokai J. Exp. Clin. Med.2006313125127
     [Google Scholar]
  143. MisakaS. SatoH. YamauchiY. OnoueS. YamadaS. Novel dry powder formulation of ovalbumin for development of COPD-like animal model: Physicochemical characterization and biomarker profiling in rats.Eur. J. Pharm. Sci.2009373-446947610.1016/j.ejps.2009.04.002
     [Google Scholar]
  144. GuptaV. BanyardA. MullanA. SriskantharajahS. SouthworthT. SinghD. Characterization of the inflammatory response to inhaled lipopolysaccharide in mild to moderate chronic obstructive pulmonary disease.Br. J. Clin. Pharmacol.201579576777610.1111/bcp.12546
     [Google Scholar]
  145. GaschlerG.J. BauerC.M.T. ZavitzC.C.J. StämpfliM.R. Animal models of chronic obstructive pulmonary disease exacerbations.Contrib. Microbiol.20071412614110.1159/000107059
     [Google Scholar]
  146. NieY.C. WuH. LiP-B. LuoY-L. ZhangC-C. ShenJ-G. SuW-W. Characteristic comparison of three rat models induced by cigarette smoke or combined with LPS: To establish a suitable model for study of airway mucus hypersecretion in chronic obstructive pulmonary disease.Pulm. Pharmacol. Ther.201225534935610.1016/j.pupt.2012.06.004
     [Google Scholar]
  147. DonovanC. SeowH.J. BourkeJ.E. VlahosR. Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.Clin. Sci. (Lond.)20161301082983710.1042/CS20160093
     [Google Scholar]
  148. TanC.L. ChanY. CandasamyM. ChellianJ. MadheswaranT. SakthivelL.P. PatelV.K. ChakrabortyA. MacLoughlinR. KumarD. VermaN. MalylaV. GuptaP.K. JhaN.K. ThangaveluL. DevkotaH.P. BhattS. PrasherP. GuptaG. GulatiM. SinghS.K. PaudelK.R. HansbroP.M. OliverB.G. DuaK. ChellappanD.K. Unravelling the molecular mechanisms underlying chronic respiratory diseases for the development of novel therapeutics via in vitro experimental models.Eur. J. Pharmacol.202291917482110.1016/j.ejphar.2022.174821
     [Google Scholar]
  149. BucherH. Pre-clinical modeling of viral- and bacterial-induced exacerbations of chronic obstructive pulmonary disease [dissertation].Würzburg (DE): University of Würzburg; 2018.
     [Google Scholar]
  150. MehtaM. DhanjalD.S. PaudelK.R. SinghB. GuptaG. RajeshkumarS. ThangaveluL. TambuwalaM.M. BakshiH.A. ChellappanD.K. PandeyP. DurejaH. CharbeN.B. SinghS.K. ShuklaS.D. NammiS. AljabaliA.A. WichP.R. HansbroP.M. SatijaS. DuaK. Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: An update.Inflammopharmacology202028479581710.1007/s10787‑020‑00698‑3
     [Google Scholar]
  151. PaulT. Salazar-DegraciaA. PeinadoV.I. Tura-CeideO. BlancoI. BarreiroE. BarberàJ.A. Soluble guanylate cyclase stimulation reduces oxidative stress in experimental chronic obstructive Pulmonary disease.PLoS One2018131e019062810.1371/journal.pone.0190628
     [Google Scholar]
  152. BölükbasD.A. IranA.S. KristinaR.T. Preclinical evidence for the role of stem/stromal cells in COPD. In:Stem Cell-Based Therapy for Lung DiseaseSpringer 2019; pp. 73-96.
     [Google Scholar]
  153. EnrightK. DesaiT. SutradharR. GonzalezA. PowisM. TabackN. BoothC.M. TrudeauM.E. KrzyzanowskaM.K. Factors associated with imaging in patients with early breast cancer after initial treatment.Curr. Oncol.201825212613210.3747/co.25.3838
     [Google Scholar]
  154. JungS. Implications of publicly available genomic data resources in searching for therapeutic targets of obesity and type 2 diabetes.Exp. Mol. Med.201850411310.1038/s12276‑018‑0066‑5
     [Google Scholar]
  155. HusereauD. GoodfieldJ. LeighR. BorrelliR. CloutierM. GendronA. Severe, eosinophilic asthma in primary care in Canada: a longitudinal study of the clinical burden and economic impact based on linked electronic medical record data.Allergy Asthma Clin. Immunol.20181411510.1186/s13223‑018‑0241‑1
     [Google Scholar]
  156. AmdahlJ. DiazJ. SharmaA. ParkJ. ChandiwanaD. DeleaT.E. Cost-effectiveness of pazopanib versus sunitinib for metastatic renal cell carcinoma in the United Kingdom.PLoS One2017126e017592010.1371/journal.pone.0175920
     [Google Scholar]
  157. ObeidatM. Dvorkin-GhevaA. LiX. BosséY. BrandsmaC-A. NickleD.C. HansbroP.M. FanerR. AgustiA. ParéP.D. StampfliM.R. SinD.D. The overlap of lung tissue transcriptome of smoke exposed mice with human smoking and COPD.Sci. Rep.2018811188110.1038/s41598‑018‑30313‑z
     [Google Scholar]
  158. WangS. JiangB. LiY. ShangY. LiuZ. ZhangY. A case report of disseminated nocardiosis with ocular involvement in a myasthenia gravis patient and literature review.BMC Neurol.201919124310.1186/s12883‑019‑1482‑4
     [Google Scholar]
  159. CollenJ.F. WilliamsS.G. LettieriC.J. Doomed to repeat history: The burden of trauma-related nightmares in military personnel.J. Clin. Sleep Med.201814330330510.5664/jcsm.6964
     [Google Scholar]
  160. LacomaA. PratC. AndreoF. DominguezJ. Biomarkers in the management of COPD.Eur. Respir. Rev.2009181129610410.1183/09059180.00000609
     [Google Scholar]
  161. EjioforS. TurnerA.M. Pharmacotherapies for COPD.Clin Med Insights Circ Respir Pulm Med201371734
     [Google Scholar]
  162. TanimuraK. SatoS. FujitaY. YamamotoY. HajiroT. HoritaN. KawayamaT. MuroS. The efficacy and safety of additional treatment with short-acting muscarinic antagonist combined with long-acting beta-2 agonist in stable patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.Chron. Respir. Dis.2023201479973123116600810.1177/14799731231166008
     [Google Scholar]
  163. BallD.I. BrittainR.T. ColemanR.A. DenyerL.H. JackD. JohnsonM. LuntsL.H.C. NialsA.T. SheldrickK.E. SkidmoreI.F. Salmeterol, a novel, long-acting β 2 -adrenoceptor agonist: Characterization of pharmacological activity in vitro and in vivo .Br. J. Pharmacol.1991104366567110.1111/j.1476‑5381.1991.tb12486.x
     [Google Scholar]
  164. ChongJ. KarnerC. PooleP. Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease.Cochrane Database Syst Rev.201220199CD00915710.1002/14651858.CD009157.pub2
     [Google Scholar]
  165. MelaniA.S. Long-acting muscarinic antagonists.Expert Rev. Clin. Pharmacol.20158447950110.1586/17512433.2015.1058154
     [Google Scholar]
  166. NetworkB.T.S.S.I.G. British guideline on the management of asthma.Thorax200863Suppl. 4iv1iv12110.1136/thx.2008.097741
     [Google Scholar]
  167. van NoordJ.A. BuhlR. LaForceC. MartinC. JonesF. DolkerM. OverendT. QVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease.Thorax201065121086109110.1136/thx.2010.139113
     [Google Scholar]
  168. CooperC.B. Airflow obstruction and exercise.Respir. Med.2009103332533410.1016/j.rmed.2008.10.026
     [Google Scholar]
  169. BeehK.M. WagnerF. KhindriS. DrollmannA.F. Effect of indacaterol on dynamic lung hyperinflation and breathlessness in hyperinflated patients with COPD.COPD20118534034510.3109/15412555.2011.594464
     [Google Scholar]
  170. DonaldsonGC, Seemungal TA, Bhowmik A, Wedzicha J. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.Thorax2002571084785210.1136/thorax.57.10.847
     [Google Scholar]
  171. RoveiV. ChanoineF. BenedettiS.M. Pharmacokinetics of theophylline: a dose-range study.Br. J. Clin. Pharmacol.198214676977810.1111/j.1365‑2125.1982.tb02035.x
     [Google Scholar]
  172. HananiaN.A. SharafkhanehA. BarberR. DickeyB.F. β-agonist intrinsic efficacy: Measurement and clinical significance.Am. J. Respir. Crit. Care Med.2002165101353135810.1164/rccm.2109060
     [Google Scholar]
  173. FazioF. LafortunaC. Effect of inhaled salbutamol on mucociliary clearance in patients with chronic bronchitis.Chest198180682783010.1378/chest.80.6.827
     [Google Scholar]
  174. MarisN.A. van der SluijsK.F. FlorquinS. de VosA.F. PaterJ.M. JansenH.M. van der PollT. Salmeterol, a β 2 -receptor agonist, attenuates lipopolysaccharide-induced lung inflammation in mice.Am. J. Physiol. Lung Cell. Mol. Physiol.20042866L1122L112810.1152/ajplung.00125.2003
     [Google Scholar]
  175. TomlinsonP.R. WilsonJ.W. StewartA.G. Inhibition by salbutamol of the proliferation of human airway smooth muscle cells grown in culture.Br. J. Pharmacol.1994111264164710.1111/j.1476‑5381.1994.tb14784.x
     [Google Scholar]
  176. LipsonD.A. Tiotropium bromide.Int. J. Chron. Obstruct. Pulmon. Dis.20061210711410.2147/copd.2006.1.2.107
     [Google Scholar]
  177. OrlovaE.A. PetrovV.I. DorfmanI.P. ShatalovaO.V. OrlovM.A. Analysis of the availability of bronchodilators and anti-inflammatory drugs for patients with chronic obstructive pulmonary disease.Modern. Pharmacoeconomic. and Pharmacoepidemiol.2024171627510.17749/2070‑4909/farmakoekonomika.2024.232
     [Google Scholar]
  178. LiX. ZhengJ. LuoD. LiuR. The optimal dose of indacaterol for treatment of chronic obstructive pulmonary disease: A systematic review and Bayesian network meta-analysis.J. Thorac. Dis.202416134435510.21037/jtd‑23‑1044
     [Google Scholar]
  179. FernandesF.L.A. CukierA. CamelierA.A. FritscherC.C. CostaC.H. PereiraE.D.B. GodoyI. CançadoJ.E.D. RomaldiniJ.G. ChatkinJ.M. JardimJ.R. RabahiM.F. NucciM.C.N.M. SalesM.P.U. CastellanoM.V.C.O. AidéM.A. TeixeiraP.J.Z. MacielR. CorrêaR.A. StirbulovR. AthanazioR.A. RussoR. MinamotoS.T. LundgrenF.L.C. Recommendations for the pharmacological treatment of COPD: Questions and answers.J. Bras. Pneumol.201743429030110.1590/s1806‑37562017000000153
     [Google Scholar]
  180. ChenC. WuL.B. WangL.J. TangX.H. Probiotics combined with Budesonide and Ipratropium bromide for chronic obstructive pulmonary disease: A retrospective analysis.Medicine (Baltimore)202410310e3730910.1097/MD.0000000000037309
     [Google Scholar]
  181. FosterK. WongC.Y.J. Advances in inhaler therapy for asthma and chronic obstructive pulmonary disease: A comprehensive review of Fostair™ and Trimbow™.J. Pharm. Pharmacol.202476101301130910.1093/jpp/rgae090
     [Google Scholar]
  182. GarbeE, Hoti F, Schink T. Long-term safety of roflumilast in patients with chronic obstructive pulmonary disease, a multinational observational database cohort study.J Chron Obstruct Pulmon Dis.20241918791892
     [Google Scholar]
  183. GyselinckI. JanssensW. Macrolide use in chronic obstructive pulmonary diseaseMacrolides as immunomodulatory agentsSpringer202411514810.1007/978‑3‑031‑42859‑3_6
     [Google Scholar]
  184. PapiA. AlfanoF. BigoniT. ManciniL. MawassA. BaraldiF. AljamaC. ContoliM. MiravitllesM. N-acetylcysteine treatment in chronic obstructive pulmonary disease (COPD) and chronic bronchitis/Pre-COPD: Distinct meta-analyses.Arch. Bronconeumol.202460526927810.1016/j.arbres.2024.03.010
     [Google Scholar]
  185. VarsakiyaJ. GoyalM. Chronic obstructive pulmonary disease (COPD): Critical review from Ayurveda perspective.J. Ayurveda. Herb. Med201732929410.31254/jahm.2017.3208
     [Google Scholar]
  186. ÇifciA. Ginger (Zingiber officinale) prevents severe damage to the lungs due to hyperoxia andinflammation.Turk. J. Med. Sci.2018484892900
     [Google Scholar]
  187. McKayD.L. BlumbergJ.B. A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.).Phytother. Res.200620861963310.1002/ptr.1936
     [Google Scholar]
  188. ScaglioneF. WeiserK. AlessandriaM. Effects of the standardised ginseng extract G115® in patients with chronic bronchitis: A nonblinded, randomised, comparative pilot study.Clin. Drug Investig.2001211414510.2165/00044011‑200121010‑00006
     [Google Scholar]
  189. BhartiV.K. MalikJ.K. GuptaR.C. Ashwagandha: Multiple health benefitsNutraceuticalsElsevier2016717733
     [Google Scholar]
  190. SinghN. BhallaM. De JagerP. GilcaM. An overview on ashwagandha: A Rasayana (rejuvenator) of Ayurveda.Afr. J. Tradit. Complement. Altern. Med.201185S10.4314/ajtcam.v8i5S.9
     [Google Scholar]
  191. MandalA. ReddyJ.M. A review on potential therapeutic uses of Withania somnifera.World J. Pharm. Res.2017684686010.20959/wjpr20177‑8882
     [Google Scholar]
  192. SinghN.A. JyotiK.P. KumarN. Spices and herbs: Potential antiviral preventives and immunity boosters during COVID -19.Phytother. Res.20213552745275710.1002/ptr.7019
     [Google Scholar]
  193. MikailiP, Maadirad S, Moloudizargari M. Therapeutic uses and pharmacological properties of garlic, shallot, and their biologically active compounds.Iran. J. Basic Med. Sci.201316101031
     [Google Scholar]
  194. HallerC.A. AndersonI.B. KimS.Y. BlancP.D. An evaluation of selected herbal reference texts and comparison to published reports of adverse herbal events.Adverse Drug React. Toxicol. Rev.200221314315010.1007/BF03256189
     [Google Scholar]
  195. KayodeO.T. RotimiD. EmmanuelF. IyobhebheM. KayodeA.A.A. AdelekeO.O. Contraceptive and biochemical effect of juice extract of Allium cepa, Allium sativum, and their combination in Canton S fruit flies.J. Food Biochem.2021458e1382110.1111/jfbc.13821
     [Google Scholar]
  196. IslamM.N. YadavR.L. YadavP.K. Modulation of lung function by increased nitric oxide production.J. Clin. Diagn. Res.2017116CC0910.7860/JCDR/2017/24650.9981
     [Google Scholar]
/content/journals/crmr/10.2174/011573398X334447241104114932
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Investigating Biomarkers and Molecular Mechanisms in COPD: Perspectives from In-vivo Models
Curr. Respir. Med. Rev. 21, 324 (2025); https://doi.org/10.2174/011573398X334447241104114932
/content/journals/crmr/10.2174/011573398X334447241104114932
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  • Article Type:     Review Article
Keyword(s): airway inflammation, cytokine-mediated pathways; chronic bronchitis; COPD; respiratory disease; smoking

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