Asthma, classical conditioning, and the autonomic nervous system - a hypothesis for why children wheeze.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Author(s): Connett GJ;Connett GJ
  • Source:
    Archives of disease in childhood [Arch Dis Child] 2024 May 17; Vol. 109 (6), pp. 462-467. Date of Electronic Publication: 2024 May 17.
  • Publication Type:
    Journal Article; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BMJ Pub. Group [etc.] Country of Publication: England NLM ID: 0372434 Publication Model: Electronic Cited Medium: Internet ISSN: 1468-2044 (Electronic) Linking ISSN: 00039888 NLM ISO Abbreviation: Arch Dis Child Subsets: MEDLINE
    • Publication Information:
      Publication: London :, BMJ Pub. Group [etc.]
      Original Publication: London : British Medical Association
    • Subject Terms:
    • Abstract:
      Paediatric asthma is an increasing global healthcare problem for which current treatments are not always effective. This review explores how abnormal triggering of the autonomic diving reflex might be important in explaining research findings and the real-world experience of asthma. It hypothesises that the way in which stress during pregnancy is associated with childhood asthma could be through effects on the developing nervous system. This results in increased parasympathetic responsiveness and specifically, excessive triggering of the diving reflex in response to wetting and cooling of the face and nose as occurs with upper airway infections and allergic rhinitis. In aquatic mammals the reflex importantly includes the contraction of airway smooth muscle to minimise lung volume and prevent nitrogen narcosis from diving at depth. Misfiring of this reflex in humans could result in the pathological airway narrowing that occurs in asthma. The diving reflex, and possibly also smooth muscle, is a vestigial remnant of our aquatic past. The hypothesis further suggests that classically conditioned reflex responses to neutral cues and contexts that were present at the same time as the stimuli that initially caused symptoms, become of themselves ongoing triggers of recurrent wheeze. Symptoms occurring in this way, irrespective of the presence of allergens and ongoing airway sensitisation, explain why allergen avoidance is poorly effective in alleviating wheeze and why asthma is made worse by stress. Interventions to suppress the diving reflex and to prevent reflex conditioned wheezing could result in more effective asthma management.
      Competing Interests: Competing interests: None declared.
      (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
    • References:
      Front Pediatr. 2019 Jun 18;7:246. (PMID: 31275909)
      Eur J Appl Physiol Occup Physiol. 1984;53(2):155-8. (PMID: 6239775)
      Curr Opin Allergy Clin Immunol. 2017 Jun;17(3):188-193. (PMID: 28333691)
      Br J Pharmacol. 2011 May;163(1):44-52. (PMID: 21198547)
      Am J Respir Crit Care Med. 2015 Aug 15;192(4):520-3. (PMID: 26278798)
      Clin Transl Immunology. 2017 Dec 15;6(12):e165. (PMID: 29333270)
      Neurosci Biobehav Rev. 2017 Sep;80:99-114. (PMID: 28506927)
      J Allergy Clin Immunol. 2015 Sep;136(3):588-94. (PMID: 25819982)
      Int J Environ Res Public Health. 2018 May 23;15(6):. (PMID: 29882850)
      Med Hypotheses. 2011 Aug;77(2):188-91. (PMID: 21550175)
      Thorax. 1999 Mar;54(3):268-72. (PMID: 10325905)
      Eur Respir J. 2015 Aug;46(2):364-74. (PMID: 25537562)
      PLoS One. 2016 Sep 29;11(9):e0163853. (PMID: 27685802)
      Clin Epigenetics. 2021 Mar 29;13(1):65. (PMID: 33781317)
      Biologicals. 2009 Oct;37(5):338-44. (PMID: 19525124)
      Am J Respir Crit Care Med. 2019 Jun 15;199(12):1471-1477. (PMID: 30645143)
      Pediatrics. 2012 Apr;129(4):735-44. (PMID: 22430451)
      Children (Basel). 2023 Feb 03;10(2):. (PMID: 36832429)
      J Thorac Dis. 2017 Sep;9(9):3412-3414. (PMID: 29221327)
      Int J Epidemiol. 2015 Feb;44(1):199-208. (PMID: 25626439)
      Pediatrics. 2014 Aug;134(2):e535-46. (PMID: 25049351)
      Lancet. 1986 May 10;1(8489):1077-81. (PMID: 2871345)
      JAMA. 2015 Oct 27;314(16):1720-30. (PMID: 26505596)
      Proc Natl Acad Sci U S A. 2020 May 19;117(20):10983-10988. (PMID: 32366650)
      PLoS One. 2010 Apr 12;5(4):e10134. (PMID: 20405032)
      Br Med J (Clin Res Ed). 1985 Jan 26;290(6464):267-9. (PMID: 3917781)
      Respir Med. 2000 May;94(5):409-15. (PMID: 10868701)
      Am Psychol. 1999 Oct;54(10):817-20. (PMID: 10540594)
      Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 3):S154-60. (PMID: 9817739)
      PLoS One. 2017 Sep 18;12(9):e0184920. (PMID: 28922410)
      Eur Respir J. 2016 Feb;47(2):406-9. (PMID: 26828054)
      Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003534. (PMID: 16034902)
      BMC Pregnancy Childbirth. 2017 Jun 19;17(1):195. (PMID: 28629393)
      Psychosom Med. 1958 Sep-Oct;20(5):395-400. (PMID: 13591465)
      Eur Respir J. 2016 Jan;47(1):133-46. (PMID: 26541526)
      Int Arch Allergy Immunol. 2020;181(1):1-10. (PMID: 31593946)
      Respiration. 1985;48(4):321-8. (PMID: 3909278)
      J Allergy Clin Immunol. 1986 Jun;77(6):791-5. (PMID: 2872246)
      Front Cell Dev Biol. 2020 Feb 05;8:38. (PMID: 32117969)
      Microbiome. 2022 Jun 10;10(1):88. (PMID: 35689294)
      Respir Physiol Neurobiol. 2012 Sep 30;183(3):206-10. (PMID: 22789502)
      Front Neuroanat. 2018 Nov 13;12:85. (PMID: 30483070)
      Science. 1970 Nov 20;170(3960):864-6. (PMID: 5482579)
      Eur Clin Respir J. 2014 Sep 01;1(Suppl 1):. (PMID: 26557247)
      Cochrane Database Syst Rev. 2013 Aug 21;(8):CD000060. (PMID: 23966133)
      Annu Rev Physiol. 1998;60:19-32. (PMID: 9558452)
      Lancet. 2018 Jan 27;391(10118):350-400. (PMID: 28911920)
      Curr Obes Rep. 2012 Mar;1(1):16-25. (PMID: 22943039)
      Psychosom Med. 1968 Nov-Dec;30(6):819-25. (PMID: 5726052)
      Allergy Asthma Clin Immunol. 2019 Oct 29;15:62. (PMID: 31687033)
      J Leukoc Biol. 2018 Jul;104(1):61-67. (PMID: 29633324)
      PLoS One. 2018 Jul 17;13(7):e0200799. (PMID: 30016343)
      J Pharmacol Exp Ther. 2014 Feb;348(2):303-10. (PMID: 24307202)
      Cochrane Database Syst Rev. 2001;(4):CD003271. (PMID: 11687182)
      Am J Respir Crit Care Med. 2008 Oct 1;178(7):667-72. (PMID: 18565953)
      J Allergy Clin Immunol. 2018 May;141(5):1880-1886. (PMID: 28801196)
      J Clin Invest. 1998 Jul 1;102(1):242-8. (PMID: 9649578)
      Am J Respir Crit Care Med. 2016 Aug 1;194(3):379-81. (PMID: 27479062)
      Eur Respir J. 2021 Nov 4;58(5):. (PMID: 33863747)
      J Allergy Clin Immunol. 2014 May;133(5):1317-29. (PMID: 24529685)
      Clin Transl Allergy. 2020 Jan 06;10:2. (PMID: 31921410)
      Cochrane Database Syst Rev. 2001;(1):CD002879. (PMID: 11279769)
      Front Med (Lausanne). 2023 May 05;10:1169639. (PMID: 37215731)
    • Contributed Indexing:
      Keywords: Child Health; Respiratory Medicine
    • Publication Date:
      Date Created: 20230830 Date Completed: 20240517 Latest Revision: 20240522
    • Publication Date:
      20240522
    • Accession Number:
      PMC11103287
    • Accession Number:
      10.1136/archdischild-2023-325441
    • Accession Number:
      37648401