Cold atmospheric plasma (CAP) devices generate reactive oxygen and nitrogen species,
have antimicrobial and antiviral properties, but also affect the molecular and cellular mechanisms of
eukaryotic cells. The aim of this study is to investigate CAP treatment in the upper respiratory tract
(URT) to reduce the incidence of ventilator-associated bacterial pneumonia (especially superinfections
with multi-resistant pathogens) or viral infections (e.g., COVID-19). For this purpose, the surfacemicrodischarge-
based plasma intensive care (PIC) device was developed by terraplasma medical
GmbH. This study analyzes the safety aspects using in vitro assays and molecular characterization
of human oral keratinocytes (hOK), human bronchial–tracheal epithelial cells (hBTE), and human
lung fibroblasts (hLF). A 5 min CAP treatment with the PIC device at the “throat” and “subglottis”
positions in the URT model did not show any significant differences from the untreated control (ctrl.)
and the corresponding pressurized air (PA) treatment in terms of cell morphology, viability, apoptosis,
DNA damage, and migration. However, pro-inflammatory cytokines (MCP-1, IL-6, and TNFα) were
induced in hBTE and hOK cells and profibrotic molecules (collagen-I, FKBP10, and αSMA) in hLF
at the mRNA level. The use of CAP in the oropharynx may make an important contribution to the
recovery of intensive care patients. The results indicate that a 5 min CAP treatment in the URT with
the PIC device does not cause any cell damage. The extent to which immune cell activation is induced
and whether it has long-term effects on the organism need to be carefully examined in follow-up
studies in vivo.