Beclomethasone dipropionate and sodium cromoglycate protect against airway hyperresponsiveness in a human ex vivo model of cow's milk aspiration

Background: Recurrent cow's milk (CM) aspiration is often associated with gastroesophageal reflux in infants and toddlers and it seems to be implicated in the etiology of different inflammatory lung disorders. This study aimed to investigate ex vivo the impact of CM aspiration on human airways and whether treatment with beclomethasone dipropionate (BDP) or sodium cromoglycate (SCG) may prevent the potential CM-induced airway hyperresponsiveness (AHR). Methods: Human isolated bronchi were contracted by electrical field stimulation (EFS10Hz) to mimic the contractile tone induced by the parasympathetic activity and challenged with CM, fat/lactose-free CM, or human breast milk (HM). The effect of pre-treatment with beclomethasone dipropionate (BDP) and sodium cromoglycate (SCG) was also investigated on the AHR induced by CM. Results: After a 60 min-challenge with CM 1:10 v/v and fat/lactose-free CM 1:10 v/v, ASM significantly (P ​< ​0.05) increased compared to control (+67.04 ​± ​17.08% and +77.91 ​± ​1.34%, respectively), a condition that remained stable for 150 ​min post-treatment, whereas HM did not alter ASM contractility. BDP 1 ​μM and 10 ​μM significantly (P ​< ​0.05) reduced the AHR elicited by CM (-52.49 ​± ​10.97% and -66.98 ​± ​7.90%, respectively vs. control). At the same manner, SCG 1 ​μM and 10 ​μM significantly (P ​< ​0.05) inhibited the CM-induced AHR (-59.03 ​± ​9.24% and -73.52 ​± ​7.41%, respectively vs. control). Conclusion: CM induces AHR in human ASM by eliciting an increased parasympathetic contractile response. Preventive treatment with nebulized SCG may be indicated in infants or toddlers fed with CM, rather than with BDP due to a superior safety profile.