Background
BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways (Calzetta et al. Vaccines 2023;11:282).
Aim
To assess if the BNT162b2 vaccine excipient polyethylene glycol (PEG) may elicit bronchospasm and the potential protective effect of beclometasone dipropionate (BDP)/formoterol fumarate (FF) fixed-dose combination (FDC).
Methods
Human isolated airways were passively sensitized overnight and then challenged 45 min with the platelet-activating factor (100 nM) to reproduce ex vivo the condition of airways of subjects suffering from severe eosinophilic asthma. Airways were mounted in an isolated organ bath system. Different concentrations of PEG were tested on airways partially pre-contracted by histamine at EC20. Further experiments were performed in the presence of BDP/FF FDC 50/3 ng/ml, a concentration detectable in the airways after inhalation of  BDP/FF FDC 200/12 ug according to FVC values (Stanojevic et al., Am J Respir Crit Care Med 2008;177:253-60).
Results
PEG 1.5-1500 ng/ml significantly increased the contractility to histamine EC20 (Emax +38.5±6.44 vs. control, P<0.05). Pre-treating isolated airways 30 min with BDP/FF FDC FDC 50/3 ng/ml significantly prevented the bronchospasm elicited by PEG (Emax: -32.8±5.75 vs. hyperresponsive airways, P<0.05).
Conclusions
The BNT162b2 vaccine excipient PEG elicits bronchospasm in hyperresponsive airways, a detrimental effect prevented by BDP/FF FDC. This research was granted by University of Parma through the action Bando di Ateneo 2021 per la ricerca co-funded by MUR-Italian Ministry of Universities and Research - D.M. 737/2021 - PNR - PNRR ? NextGenerationEU.