Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Respiratory Medicine Reviews
  4. Fast Track Articles
  5. Fast Track Article
image of Asthma: An Overview of Pathophysiology, Molecular Mechanisms and Combination Therapy

Abstract

Asthma is a chronic inflammatory disorder of the respiratory airways that is characterized by narrowing of airways, wheezing, difficulty in respiration, shortness of breath, stiffness in the chest region, and sometimes cough. In some cases, mucus secretion is enhanced. Several factors precipitate asthma. These factors may contribute individually or collectively to the pathophysiology of asthma. The objective of this review is to compile a detailed description of pathways involved in asthma. This compilation helps provide a better understanding of the disease. The information provided in this review may be used for planning a personalized therapy. Besides pathways, this review includes the current therapy used for asthma management. New combinations of drugs targeting multiple pathways can be developed to better manage the disease.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/crmr/10.2174/011573398X322807241009103428
2024-10-15
2025-04-06

  • From This Site

    /content/journals/crmr/10.2174/011573398X322807241009103428
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Kaplan A.G. Balter M.S. Bell A.D. Kim H. McIvor R.A. Diagnosis of asthma in adults. CMAJ 2009 181 10 E210 E220 10.1503/cmaj.080006 19770241
    [Google Scholar]
  2. Joseph T. Pharmacotherapy: A pathophysiological approach McGraw Hill Medical 2014
    [Google Scholar]
  3. Kharaba Z. Feghali E. El Husseini F. Sacre H. Abou Selwan C. Saadeh S. Hallit S. Jirjees F. AlObaidi H. Salameh P. Malaeb D. An Assessment of Quality of Life in Patients With Asthma Through Physical, Emotional, Social, and Occupational Aspects. A Cross-Sectional Study. Front. Public Health 2022 10 883784 10.3389/fpubh.2022.883784 36117601
    [Google Scholar]
  4. Gambadauro A. Galletta F. Li Pomi A. Manti S. Piedimonte G. Immune Response to Respiratory Viral Infections. Int. J. Mol. Sci. 2024 25 11 6178 10.3390/ijms25116178 38892370
    [Google Scholar]
  5. Steinke J.W. Borish L. Th2 cytokines and asthma — Interleukin-4: Its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir. Res. 2001 2 2 66 70 10.1186/rr40 11686867
    [Google Scholar]
  6. Manti S. Piedimonte G. An overview on the RSV-mediated mechanisms in the onset of non-allergic asthma. Front Pediatr. 2022 10 998296 10.3389/fped.2022.998296 36204661
    [Google Scholar]
  7. Sinyor B. Perez L. Pathophysiology Of Asthma. StatPearls Treasure Island (FL): StatPearls Publishing 2023
    [Google Scholar]
  8. Pelaia C. Heffler E. Crimi C. Maglio A. Vatrella A. Pelaia G. Canonica G.W. Interleukins 4 and 13 in asthma: Key pathophysiologic cytokines and druggable molecular targets. Front. Pharmacol. 2022 13 851940 10.3389/fphar.2022.851940 35350765
    [Google Scholar]
  9. Athari S.S. Athari S.M. Beyzay F. Movassaghi M. Mortaz E. Taghavi M. Critical role of Toll-like receptors in pathophysiology of allergic asthma. Eur. J. Pharmacol. 2017 808 21 27 10.1016/j.ejphar.2016.11.047 27894811
    [Google Scholar]
  10. Zakeri A. Russo M. Dual Role of Toll-like Receptors in Human and Experimental Asthma Models. Front. Immunol. 2018 9 1027 1027 10.3389/fimmu.2018.01027 29867994
    [Google Scholar]
  11. Koschinski A. Zaccolo M. Activation of PKA in cell requires higher concentration of cAMP than in vitro: implications for compartmentalization of cAMP signalling. Sci. Rep. 2017 7 1 14090 10.1038/s41598‑017‑13021‑y 29074866
    [Google Scholar]
  12. Athari S.S. Targeting cell signaling in allergic asthma. Signal Transduct. Target. Ther. 2019 4 1 45 10.1038/s41392‑019‑0079‑0 31637021
    [Google Scholar]
  13. Liu J. Xiao Q. Xiao J. Niu C. Li Y. Zhang X. Zhou Z. Shu G. Yin G. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct. Target. Ther. 2022 7 1 3 10.1038/s41392‑021‑00762‑6 34980884
    [Google Scholar]
  14. Lee H. Bae S. Choi B.W. Yoon Y. WNT/β-catenin pathway is modulated in asthma patients and LPS-stimulated RAW264.7 macrophage cell line. Immunopharmacol. Immunotoxicol. 2012 34 1 56 65 10.3109/08923973.2011.574704 21699440
    [Google Scholar]
  15. Kumar A. Singh U.K. Kini S.G. Garg V. Agrawal S. Tomar P.K. Pathak P. Chaudhary A. Gupta P. Malik A. JNK pathway signaling: a novel and smarter therapeutic targets for various biological diseases. Future Med. Chem. 2015 7 15 2065 2086 10.4155/fmc.15.132 26505831
    [Google Scholar]
  16. Audousset C. McGovern T. Martin J.G. Role of Nrf2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches – Pulmonary Disease/Asthma. Front. Physiol. 2021 12 727806 10.3389/fphys.2021.727806 34658913
    [Google Scholar]
  17. Li N. Nel A.E. Role of the Nrf2-mediated signaling pathway as a negative regulator of inflammation: implications for the impact of particulate pollutants on asthma. Antioxid. Redox Signal. 2006 8 1-2 88 98 10.1089/ars.2006.8.88 16487041
    [Google Scholar]
  18. Liu Q. Gao Y. Ci X. Role of Nrf2 and its activators in respiratory diseases. Oxid. Med. Cell. Longev. 2019 2019 1 17 10.1155/2019/7090534 30728889
    [Google Scholar]
  19. Clapham DE Calcium signaling. Cell 2007 131 6 1047 58 10.1016/j.cell.2007.11.028
    [Google Scholar]
  20. Druilhe A. Wallaert B. Tsicopoulos A. e Silva J-R.L. Tillie-Leblond I. Tonnel A.B. Pretolani M. Apoptosis, proliferation, and expression of Bcl-2, Fas, and Fas ligand in bronchial biopsies from asthmatics. Am. J. Respir. Cell Mol. Biol. 1998 19 5 747 757 10.1165/ajrcmb.19.5.3166 9806739
    [Google Scholar]
  21. Pirzad G. Jafari M. Tavana S. Sadrayee H. Ghavami S. Shajiei A. Ghanei M. The Role of Fas-FasL Signaling Pathway in Induction of Apoptosis in Patients with Sulfur Mustard-Induced Chronic Bronchiolitis. J. Toxicol. 2010 2010 1 7 10.1155/2010/373612 21317984
    [Google Scholar]
  22. Zhu L. Chen X. Chong L. Kong L. Wen S. Zhang H. Zhang W. Li C. Adiponectin alleviates exacerbation of airway inflammation and oxidative stress in obesity-related asthma mice partly through AMPK signaling pathway. Int. Immunopharmacol. 2019 67 396 407 10.1016/j.intimp.2018.12.030 30584969
    [Google Scholar]
  23. Rehan V.K. Dargan-Batra S.K. Wang Y. Cerny L. Sakurai R. Santos J. Beloosesky R. Gayle D. Torday J.S. A paradoxical temporal response of the PTHrP/PPARγ signaling pathway to lipopolysaccharide in an in vitro model of the developing rat lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007 293 1 L182 L190 10.1152/ajplung.00319.2006 17435078
    [Google Scholar]
  24. Domingo C. Palomares O. Sandham D.A. Erpenbeck V.J. Altman P. The prostaglandin D2 receptor 2 pathway in asthma: a key player in airway inflammation. Respir. Res. 2018 19 1 189 10.1186/s12931‑018‑0893‑x 30268119
    [Google Scholar]
  25. Soler X. Ramsdell J. Anticholinergics/antimuscarinic drugs in asthma. Curr. Allergy Asthma Rep. 2014 14 12 484 10.1007/s11882‑014‑0484‑y 25283149
    [Google Scholar]
  26. Trinh H.K.T. Suh D.H. Nguyen T.V.T. Choi Y. Park H.S. Shin Y.S. Characterization of cysteinyl leukotriene-related receptors and their interactions in a mouse model of asthma. Prostaglandins Leukot. Essent. Fatty Acids 2019 141 17 23 10.1016/j.plefa.2018.12.002 30661601
    [Google Scholar]
  27. Koch S. Finotto S. Role of Interferon-λ in Allergic Asthma. J. Innate Immun. 2015 7 3 224 230 10.1159/000369459 25592858
    [Google Scholar]
  28. Sanchez-Cuellar S. de la Fuente H. Cruz-Adalia A. Lamana A. Cibrian D. Giron R.M. Vara A. Sanchez-Madrid F. Ancochea J. Reduced expression of galectin-1 and galectin-9 by leucocytes in asthma patients. Clin. Exp. Immunol. 2012 170 3 365 374 10.1111/j.1365‑2249.2012.04665.x 23121677
    [Google Scholar]
  29. Edwards M.R. Bartlett N.W. Clarke D. Birrell M. Belvisi M. Johnston S.L. Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease. Pharmacol. Ther. 2009 121 1 1 13 10.1016/j.pharmthera.2008.09.003 18950657
    [Google Scholar]
  30. Liu Y. Miao Y. Gao X. Wang Y.Y. Wang H. Zheng Y.W. Zhao Z.Y. MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice. Cell. Physiol. Biochem. 2018 50 6 2365 2389 10.1159/000495097 30423573
    [Google Scholar]
  31. Zhu X. Chen Q. Liu Z. Luo D. Li L. Zhong Y. Low expression and hypermethylation of FOXP3 in regulatory T cells are associated with asthma in children. Exp. Ther. Med. 2020 19 3 2045 2052 10.3892/etm.2020.8443 32104264
    [Google Scholar]
  32. Nagata Y. Suzuki R. Fcε R.I. FcεRI: A Master Regulator of Mast Cell Functions. Cells 2022 11 4 622 10.3390/cells11040622 35203273
    [Google Scholar]
  33. Zhao S. Wang C. Regulatory T cells and asthma. J. Zhejiang Univ. Sci. B 2018 19 9 663 673 10.1631/jzus.B1700346 30178633
    [Google Scholar]
  34. Ma Z. Paek D. Oh C.K. Plasminogen activator inhibitor-1 and asthma: role in the pathogenesis and molecular regulation. Clin. Exp. Allergy 2009 39 8 1136 1144 10.1111/j.1365‑2222.2009.03272.x 19438580
    [Google Scholar]
  35. Tripathi K.D. Essentials of medical pharmacology 7th 2013
    [Google Scholar]
  36. Hsu E. Bajaj T. Beta 2 Agonists. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  37. Tripathi K.D. Drugs for cough and bronchial asthma. Essentials of medical pharmacology 8th Ed 2021
    [Google Scholar]
  38. Picciotto M.R. Higley M.J. Mineur Y.S. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron 2012 76 1 116 129 10.1016/j.neuron.2012.08.036 23040810
    [Google Scholar]
  39. Fujii T. Mashimo M. Moriwaki Y. Misawa H. Ono S. Horiguchi K. Kawashima K. Expression and function of the cholinergic system in immune cells. Front. Immunol. 2017 8 1085 10.3389/fimmu.2017.01085 28932225
    [Google Scholar]
  40. Gosens R. Gross N. The mode of action of anticholinergics in asthma. Eur. Respir. J. 2018 52 4 1701247 10.1183/13993003.01247‑2017 30115613
    [Google Scholar]
  41. Brightling C.E. Brusselle G. Altman P. The impact of the prostaglandin D 2 receptor 2 and its downstream effects on the pathophysiology of asthma. Allergy 2020 75 4 761 768 10.1111/all.14001 31355946
    [Google Scholar]
  42. Campbell A.P. Smrcka A.V. Targeting G protein-coupled receptor signalling by blocking G proteins. Nat. Rev. Drug Discov. 2018 17 11 789 803 10.1038/nrd.2018.135 30262890
    [Google Scholar]
  43. Heredia J.L. Tiotropium bromide: an update. Open Respir. Med. J. 2009 3 1 43 52 10.2174/1874306400903010043 19461900
    [Google Scholar]
  44. Ghossein N. Kang M. Lakhkar A.D. Anticholinergic Medications. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  45. Gerretsen P. Pollock B.G. Drugs with anticholinergic properties: a current perspective on use and safety. Expert Opin. Drug Saf. 2011 10 5 751 765 10.1517/14740338.2011.579899 21635190
    [Google Scholar]
  46. Saberi F. O’Donnell D.E. The role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in the management of COPD. Treat. Respir. Med. 2005 4 4 275 281 10.2165/00151829‑200504040‑00005 16086600
    [Google Scholar]
  47. Patel P. Saab H. Aboeed A. Ipratropium. StatPearls Treasure Island (FL): StatPearls Publishing 2023
    [Google Scholar]
  48. Humphrey P. Rang & Dale's Pharmacology E-Book Elsevier 2023
    [Google Scholar]
  49. Gray S.L. Anderson M.L. Dublin S. Hanlon J.T. Hubbard R. Walker R. Yu O. Crane P.K. Larson E.B. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern. Med. 2015 175 3 401 407 10.1001/jamainternmed.2014.7663 25621434
    [Google Scholar]
  50. Delgado B.J. Bajaj T. Tiotropium. StatPearls Treasure Island (FL): StatPearls Publishing 2023
    [Google Scholar]
  51. Monteiro J. Alves M. Oliveira P. Silva B. Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks. Molecules 2016 21 8 974 10.3390/molecules21080974 27472311
    [Google Scholar]
  52. Gottwalt B. Tadi P. Methylxanthines. StatPearls Treasure Island (FL): StatPearls Publishing 2023
    [Google Scholar]
  53. Jackson E.K. The 2′,3′-cAMP-adenosine pathway. Am. J. Physiol. Renal Physiol. 2011 301 6 F1160 F1167 10.1152/ajprenal.00450.2011 21937608
    [Google Scholar]
  54. Pelleg A. Polosa R. Adenosine Receptors in the Lungs. Receptors 2018 34 461 470 10.1007/978‑3‑319‑90808‑3_18
    [Google Scholar]
  55. Wilson C.N. Nadeem A. Spina D. Brown R. Page C.P. Mustafa S.J. Adenosine receptors and asthma. Handb. Exp. Pharmacol. 2009 193 193 329 362 10.1007/978‑3‑540‑89615‑9_11 19639287
    [Google Scholar]
  56. Sutton B.J. Davies A.M. Bax H.J. Karagiannis S.N. IgE Antibodies: From Structure to Function and Clinical Translation. Antibodies (Basel) 2019 8 1 19 10.3390/antib8010019 31544825
    [Google Scholar]
  57. Berghea E.C. Balgradean M. Pavelescu C. Cirstoveanu C.G. Toma C.L. Ionescu M.D. Bumbacea R.S. Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) in Pediatric Severe Allergic Asthma—A Romanian Perspective. Children (Basel) 2021 8 12 1141 10.3390/children8121141 34943337
    [Google Scholar]
  58. Humbert M. Taillé C. Mala L. Le Gros V. Just J. Molimard M. STELLAIR investigators Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur. Respir. J. 2018 51 5 1702523 10.1183/13993003.02523‑2017 29545284
    [Google Scholar]
  59. Kumar C. Zito P.M. Omalizumab. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  60. Omalizumab in the Therapy of Pediatric Asthma Recent Pat. Inflamm. Allergy Drug Discov. 2018 12 2 103 109 10.2174/1872213X12666180430161351 29714140
    [Google Scholar]
  61. Normansell R. Walker S. Milan S.J. Walters E.H. Nair P. Omalizumab for asthma in adults and children. Cochrane Libr. 2014 2014 1 CD003559 10.1002/14651858.CD003559.pub4 24414989
    [Google Scholar]
  62. Gon Y. Maruoka S. Mizumura K. Omalizumab and IgE in the Control of Severe Allergic Asthma. Front. Pharmacol. 2022 13 13 839011 10.3389/fphar.2022.839011 35359867
    [Google Scholar]
  63. Thomson NC Chaudhuri R Omalizumab: clinical use for the management of asthma. Clin Med Insights Circ Respir Pulm Med. 2012 6 27 40 10.4137/CCRPM.S7793
    [Google Scholar]
  64. Lippincott's Illustrated Reviews: Pharmacology. 4th Edition Medicine and Science in Sports and Exercise 2009 41 7
    [Google Scholar]
  65. Gilfillan A.M. Austin S.J. Metcalfe D.D. Mast cell biology: introduction and overview. Adv. Exp. Med. Biol. 2011 716 2 12 10.1007/978‑1‑4419‑9533‑9_1 21713648
    [Google Scholar]
  66. Finn D.F. Walsh J.J. Twenty-first century mast cell stabilizers. Br. J. Pharmacol. 2013 170 1 23 37 10.1111/bph.12138 23441583
    [Google Scholar]
  67. Pundir P. Kulka M. The role of G protein-coupled receptors in mast cell activation by antimicrobial peptides: is there a connection? Immunol. Cell Biol. 2010 88 6 632 640 10.1038/icb.2010.27 20309008
    [Google Scholar]
  68. Banafea G.H. Bakhashab S. Alshaibi H.F. Natesan Pushparaj P. Rasool M. The role of human mast cells in allergy and asthma. Bioengineered 2022 13 3 7049 7064 10.1080/21655979.2022.2044278 35266441
    [Google Scholar]
  69. Zhang T. Finn D.F. Barlow J.W. Walsh J.J. Mast cell stabilisers. Eur. J. Pharmacol. 2016 778 158 168 10.1016/j.ejphar.2015.05.071 26130122
    [Google Scholar]
  70. Agier J. Pastwińska J. Brzezińska-Błaszczyk E. An overview of mast cell pattern recognition receptors. Inflamm. Res. 2018 67 9 737 746 10.1007/s00011‑018‑1164‑5 29909493
    [Google Scholar]
  71. Monticelli S. Leoni C. Epigenetic and transcriptional control of mast cell responses. F1000Res. 2017 6 2064 10.12688/f1000research.12384.1
    [Google Scholar]
  72. Brooks C.R. van Dalen C.J. Hermans I.F. Gibson P.G. Simpson J.L. Douwes J. Sputum basophils are increased in eosinophilic asthma compared with non-eosinophilic asthma phenotypes. Allergy 2017 72 10 1583 1586 10.1111/all.13185 28426171
    [Google Scholar]
  73. Poddighe D. Mathias C.B. Brambilla I. Marseglia G.L. Oettgen H.C. Importance of basophils in eosinophilic asthma: the murine counterpart. J. Biol. Regul. Homeost. Agents 2018 32 2 335 339 29685015
    [Google Scholar]
  74. Choi J. Azmat C.E. Leukotriene Receptor Antagonists. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  75. Trinh H.K.T. Lee S.H. Cao T.B.T. Park H.S. Asthma pharmacotherapy: an update on leukotriene treatments. Expert Rev. Respir. Med. 2019 13 12 1169 1178 10.1080/17476348.2019.1670640 31544544
    [Google Scholar]
  76. Berger A. Science commentary: What are leukotrienes and how do they work in asthma? BMJ 1999 319 7202 90 10.1136/bmj.319.7202.90 10398630
    [Google Scholar]
  77. Pyasi K. Tufvesson E. Moitra S. Evaluating the role of leukotriene-modifying drugs in asthma management: Are their benefits ‘losing in translation’? Pulm. Pharmacol. Ther. 2016 41 52 59 10.1016/j.pupt.2016.09.006 27651322
    [Google Scholar]
  78. Cuzzo B. Lappin S.L. Physiology, Leukotrienes. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  79. Peters-Golden M. Canetti C. Mancuso P. Coffey M.J. Leukotrienes: underappreciated mediators of innate immune responses. J. Immunol. 2005 174 2 589 594 10.4049/jimmunol.174.2.589 15634873
    [Google Scholar]
  80. Peters-Golden M. Henderson W.R. Jr Leukotrienes. N. Engl. J. Med. 2007 357 18 1841 1854 10.1056/NEJMra071371
    [Google Scholar]
  81. Ramamoorthy S. Cidlowski J.A. Corticosteroids. Rheum. Dis. Clin. North Am. 2016 42 1 15 31, vii 10.1016/j.rdc.2015.08.002 26611548
    [Google Scholar]
  82. Barnes P.J. Corticosteroid effects on cell signalling. Eur. Respir. J. 2006 27 2 413 426 10.1183/09031936.06.00125404 16452600
    [Google Scholar]
  83. Hodgens A. Sharman T. Corticosteroids. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  84. Barnes PJ Inhaled Corticosteroids. Pharmaceuticals 2010 3 3 514 540 10.3390/ph3030514
    [Google Scholar]
  85. Tranchant C. Braun S. Warter J.M. Mechanisms of action of glucocorticoids: role of lipocortins. Neurological Review 1989 145 813 818
    [Google Scholar]
  86. Kragballe K. Topical corticosteroids: mechanisms of action. Acta Derm. Venereol. Suppl. (Stockh.) 1989 151 7 10 https:// pubmed.ncbi.nlm.nih.gov/2533778/ 2533778
    [Google Scholar]
  87. Herrera-Luis E. Hernandez-Pacheco N. Vijverberg S.J. Flores C. Pino-Yanes M. Role of genomics in asthma exacerbations. Curr. Opin. Pulm. Med. 2019 25 1 101 112 10.1097/MCP.0000000000000533 30334825
    [Google Scholar]
  88. Ntontsi P. Photiades A. Zervas E. Xanthou G. Samitas K. Genetics and Epigenetics in Asthma. Int. J. Mol. Sci. 2021 22 5 2412 10.3390/ijms22052412 33673725
    [Google Scholar]
  89. Akhabir L. Sandford A.J. Genome-wide association studies for discovery of genes involved in asthma. Respirology 2011 16 3 396 406 10.1111/j.1440‑1843.2011.01939.x 21276132
    [Google Scholar]
  90. Tripathi P. Awasthi S. Gao P. ADAM metallopeptidase domain 33 (ADAM33): a promising target for asthma. Mediators Inflamm. 2014 2014 1 8 10.1155/2014/572025 24817794
    [Google Scholar]
  91. Holgate S.T. Davies D.E. Rorke S. Cakebread J. Murphy G. Powell R.M. Holloway J.W. ADAM 33 and its association with airway remodeling and hyperresponsiveness in asthma. Clin. Rev. Allergy Immunol. 2004 27 1 023 034 10.1385/CRIAI:27:1:023 15347848
    [Google Scholar]
  92. Babu KS Davies DE Holgate ST Role of tumor necrosis factor alpha in asthma. Immunol Allergy Clin North Am. 2004 24 4 583 97 10.1016/j.iac.2004.06.010
    [Google Scholar]
  93. Kim S-H. Cho B-Y. Park C-S. Shin E-S. Cho E-Y. Yang E-M. Kim C-W. Hong C-S. Lee J-E. Park H-S. Alpha-T-catenin ( CTNNA3 ) gene was identified as a risk variant for toluene diisocyanate-induced asthma by genome-wide association analysis. Clin. Exp. Allergy 2009 39 2 203 212 10.1111/j.1365‑2222.2008.03117.x 19187332
    [Google Scholar]
  94. McGeachie M.J. Wu A.C. Tse S.M. Clemmer G.L. Sordillo J. Himes B.E. Lasky-Su J. Chase R.P. Martinez F.D. Weeke P. Shaffer C.M. Xu H. Denny J.C. Roden D.M. Panettieri R.A. Jr Raby B.A. Weiss S.T. Tantisira K.G. CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies. J. Allergy Clin. Immunol. 2015 136 6 1503 1510 10.1016/j.jaci.2015.04.039 26073756
    [Google Scholar]
  95. Labuda M. Laberge S. Brière J. Bérubé D. Beaulieu P. Pastinen T. Krajinovic M. Phosphodiesterase type 4D gene polymorphism: association with the response to short-acting bronchodilators in paediatric asthma patients. Mediators Inflamm. 2011 2011 1 6 10.1155/2011/301695 21876611
    [Google Scholar]
  96. Himes B.E. Hunninghake G.M. Baurley J.W. Rafaels N.M. Sleiman P. Strachan D.P. Wilk J.B. Willis-Owen S.A.G. Klanderman B. Lasky-Su J. Lazarus R. Murphy A.J. Soto-Quiros M.E. Avila L. Beaty T. Mathias R.A. Ruczinski I. Barnes K.C. Celedón J.C. Cookson W.O.C. Gauderman W.J. Gilliland F.D. Hakonarson H. Lange C. Moffatt M.F. O’Connor G.T. Raby B.A. Silverman E.K. Weiss S.T. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am. J. Hum. Genet. 2009 84 5 581 593 10.1016/j.ajhg.2009.04.006 19426955
    [Google Scholar]
  97. Kim S.H. Choi H. Yoon M.G. Ye Y.M. Park H.S. Dipeptidyl-peptidase 10 as a genetic biomarker for the aspirin-exacerbated respiratory disease phenotype. Ann. Allergy Asthma Immunol. 2015 114 3 208 213 10.1016/j.anai.2014.12.003 25592153
    [Google Scholar]
  98. Zhang Y. Poobalasingam T. Yates L.L. Walker S.A. Taylor M.S. Chessum L. Harrison J. Tsaprouni L. Adcock I.M. Lloyd C.M. Cookson W.O. Moffatt M.F. Dean C.H. Manipulation of dipeptidylpeptidase 10 in mouse and human in vivo and in vitro models indicates a protective role in asthma. Dis. Model. Mech. 2018 11 1 dmm031369 10.1242/dmm.031369 29361513
    [Google Scholar]
  99. Murk W. Walsh K. Hsu L.I. Zhao L. Bracken M.B. DeWan A.T. Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma. Hum. Hered. 2011 71 2 97 105 10.1159/000319536 21734400
    [Google Scholar]
  100. Li X. Howard T.D. Zheng S.L. Haselkorn T. Peters S.P. Meyers D.A. Bleecker E.R. Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. J. Allergy Clin. Immunol. 2010 125 2 328 335.e11 10.1016/j.jaci.2009.11.018 20159242
    [Google Scholar]
  101. Thomsen S.F. Genetics of asthma: an introduction for the clinician. Eur. Clin. Respir. J. 2015 2 1 24643 10.3402/ecrj.v2.24643 26557257
    [Google Scholar]
  102. Bønnelykke K. Pipper C.B. Tavendale R. Palmer C.N.A. Bisgaard H. Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth. Pediatr. Allergy Immunol. 2010 21 6 954 961 10.1111/j.1399‑3038.2010.01073.x 20573035
    [Google Scholar]
  103. Osawa R. Akiyama M. Shimizu H. Filaggrin gene defects and the risk of developing allergic disorders. Allergol. Int. 2011 60 1 1 9 10.2332/allergolint.10‑RAI‑0270 21173567
    [Google Scholar]
  104. Liu Q Xia Y Zhang W A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population. BMC Med Genet. 2009 10 59 10.1186/1471‑2350‑10‑59
    [Google Scholar]
  105. Birben E. Sackesen C. Turgutoğlu N. Kalayci Ö. The role of SPINK5 in asthma related physiological events in the airway epithelium. Respir. Med. 2012 106 3 349 355 10.1016/j.rmed.2011.11.007 22133475
    [Google Scholar]
  106. Li J. Hao Y. Li W. Lv X. Gao P. HLA-G in asthma and its potential as an effective therapeutic agent. Allergol. Immunopathol. (Madr.) 2023 51 1 22 29 10.15586/aei.v51i1.650 36617818
    [Google Scholar]
  107. Naidoo D. Wu A.C. Brilliant M.H. Denny J. Ingram C. Kitchner T.E. Linneman J.G. McGeachie M.J. Roden D.M. Shaffer C.M. Shah A. Weeke P. Weiss S.T. Xu H. Medina M.W. A polymorphism in HLA-G modifies statin benefit in asthma. Pharmacogenomics J. 2015 15 3 272 277 10.1038/tpj.2014.55 25266681
    [Google Scholar]
  108. Gu W. Lei J. Zhu H. Xiao Y. Zhang Z. Zhao L. Effect of the BMPR-II-SMAD3/MRTF pathway on proliferation and migration of ASMCs and the mechanism in asthma. Mol. Biol. Rep. 2022 49 10 9283 9296 10.1007/s11033‑022‑07764‑9 36008606
    [Google Scholar]
  109. Anthoni M. Wang G. Leino M.S. Lauerma A.I. Alenius H.T. Wolff H.J. Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model of asthma. Int. J. Biol. Sci. 2007 3 7 477 485 10.7150/ijbs.3.477 18071588
    [Google Scholar]
  110. Gao J. Lin Y. Qiu C. Liu Y. Ma Y. Liu Y. Association between HLA-DQA1, -DQB1 gene polymorphisms and susceptibility to asthma in northern Chinese subjects. Chin. Med. J. (Engl.) 2003 116 7 1078 1082 https://pubmed.ncbi.nlm.nih.gov/12890388/ 12890388
    [Google Scholar]
  111. Guo X. Ni P. Li L. [Association between asthma and the polymorphism of HLA-DQ genes]. Zhonghua Jie He He Hu Xi Za Zhi. 2001 24 3 139 41
    [Google Scholar]
  112. Godava M. Vrtel R. Vodicka R. STAT6 - polymorphisms, haplotypes and epistasis in relation to atopy and asthma. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2013 157 2 172 180 10.5507/bp.2013.043 23752766
    [Google Scholar]
  113. Walford H.H. Doherty T.A. STAT6 and lung inflammation. JAK-STAT 2013 2 4 e25301 10.4161/jkst.25301 24416647
    [Google Scholar]
  114. Rael EL Lockey RF Interleukin-13 signaling and its role in asthma. World Allergy Organ J. 2011 4 3 54 64 10.1097/WOX.0b013e31821188e0
    [Google Scholar]
  115. Corren J. Role of interleukin-13 in asthma. Curr. Allergy Asthma Rep. 2013 13 5 415 420 10.1007/s11882‑013‑0373‑9 24026573
    [Google Scholar]
  116. Eder W. Klimecki W. Yu L. von Mutius E. Riedler J. Braun-Fahrländer C. Nowak D. Martinez F.D. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J. Allergy Clin. Immunol. 2004 113 3 482 488 10.1016/j.jaci.2003.12.374 15007351
    [Google Scholar]
  117. Zuo L. Lucas K. Fortuna C.A. Chuang C.C. Best T.M. Molecular Regulation of Toll-like Receptors in Asthma and COPD. Front. Physiol. 2015 6 312 10.3389/fphys.2015.00312 26617525
    [Google Scholar]
  118. Moreira A.P. Cavassani K.A. Ismailoglu U.B. Hullinger R. Dunleavy M.P. Knight D.A. Kunkel S.L. Uematsu S. Akira S. Hogaboam C.M. The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A. J. Clin. Invest. 2011 121 11 4420 4432 10.1172/JCI44999 22005301
    [Google Scholar]
  119. Murakami Y. Ishii T. Nunokawa H. Kurata K. Narita T. Yamashita N. TLR9–IL-2 axis exacerbates allergic asthma by preventing IL-17A hyperproduction. Sci. Rep. 2020 10 1 18110 10.1038/s41598‑020‑75153‑y 33093516
    [Google Scholar]
  120. Lazarus R. Raby B.A. Lange C. Silverman E.K. Kwiatkowski D.J. Vercelli D. Klimecki W.J. Martinez F.D. Weiss S.T. TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples. Am. J. Respir. Crit. Care Med. 2004 170 6 594 600 10.1164/rccm.200404‑491OC 15201134
    [Google Scholar]
  121. Dijk F.N. Vijverberg S.J. Hernandez-Pacheco N. Repnik K. Karimi L. Mitratza M. Farzan N. Nawijn M.C. Burchard e.g. Engelkes M. Verhamme K.M. Potočnik U. Pino-Yanes M. Postma D.S. Maitland-van der Zee A.H. Koppelman G.H. IL1RL1 gene variations are associated with asthma exacerbations in children and adolescents using inhaled corticosteroids. Allergy 2020 75 4 984 989 10.1111/all.14125 31755552
    [Google Scholar]
  122. Gordon E.D. Palandra J. Wesolowska-Andersen A. Ringel L. Rios C.L. Lachowicz-Scroggins M.E. Sharp L.Z. Everman J.L. MacLeod H.J. Lee J.W. Mason R.J. Matthay M.A. Sheldon R.T. Peters M.C. Nocka K.H. Fahy J.V. Seibold M.A. IL1RL1 asthma risk variants regulate airway type 2 inflammation. JCI Insight 2016 1 14 e87871 10.1172/jci.insight.87871 27699235
    [Google Scholar]
  123. Kilic M. Ecin S. Taskin E. Sen A. Kara M. The Vitamin D Receptor Gene Polymorphisms in Asthmatic Children: A Case-Control Study. Pediatr. Allergy Immunol. Pulmonol. 2019 32 2 63 69 10.1089/ped.2018.0948 31508258
    [Google Scholar]
  124. Zhou Y. Li S. Meta-Analysis of Vitamin D Receptor Gene Polymorphisms in Childhood Asthma. Front Pediatr. 2022 10 843691 10.3389/fped.2022.843691 35433530
    [Google Scholar]
  125. Zhou L. Ding Y. Effect of Montelukast Combined with Terbutaline on Tiffeneau-Pinelli Index and Clinical Efficacy in Patients with Chronic Obstructive Pulmonary Disease. Lat. Am. J. Pharm. 2021 40 3 620 625 http://www.latamjpharm.org/resumenes/40/3/LAJOP_40_3_1_27
    [Google Scholar]
  126. Jin W. Zhao Z. Zhou D. Effect of Montelukast sodium combined with Budesonide aerosol on airway function and T lymphocytes in asthmatic children. Pak. J. Med. Sci. 2022 38 5 1265 1270 10.12669/pjms.38.5.5749 35799724
    [Google Scholar]
  127. Hambleton G Weinberger M Taylor J Comparison of cromoglycate (cromolyn) and theophylline in controlling symptoms of chronic asthma. A collaborative study. Lancet 1977 1 8008 381 5 10.1016/S0140‑6736(77)92601‑0
    [Google Scholar]
  128. Karpel J.P. Kotch A. Zinny M. Pesin J. Alleyne W. A comparison of inhaled ipratropium, oral theophylline plus inhaled β-agonist, and the combination of all three in patients with COPD. Chest 1994 105 4 1089 1094 10.1378/chest.105.4.1089 8162730
    [Google Scholar]
/content/journals/crmr/10.2174/011573398X322807241009103428
Loading
Asthma: An Overview of Pathophysiology, Molecular Mechanisms and Combination Therapy
Bentham Science Publishers ; https://doi.org/10.2174/011573398X322807241009103428
/content/journals/crmr/10.2174/011573398X322807241009103428
/content/journals/crmr/10.2174/011573398X322807241009103428
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Asthma ; airway obstruction ; bronchodilator therapy ; bronchoconstriction ; lungs

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test