RT Journal Article SR Electronic T1 Asthma, classical conditioning, and the autonomic nervous system – a hypothesis for why children wheeze JF Archives of Disease in Childhood JO Arch Dis Child FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health SP archdischild-2023-325441 DO 10.1136/archdischild-2023-325441 A1 Gary James Connett YR 2023 UL http://adc.bmj.com/content/early/2023/08/30/archdischild-2023-325441.abstract AB 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.Data sharing is not applicable as no data sets were generated and/or analysed for this study.