Indoor VOC Filtration Mitigates Pulmonary Inflammation in Murine Models of Allergic Asthma and LPS-Induced Acute Lung Injury

Abstract

Indoor volatile organic compounds (VOCs) are ubiquitous and often within guideline ranges, yet their impact on allergic lung disease and pharmacologic responses remains unclear. We tested whether lowering VOCs attenuates lung inflammation and modifies antihistamine efficacy in murine asthma and acute lung injury (ALI) models, and related these findings to VOC levels in operating veterinary hospitals. BALB/c mice with Dermatophagoides farinae–induced asthma or lipopolysaccharide-induced ALI were housed in ambient, specific pathogen–free air or in the same air circulated through an activated carbon/HEPA filter that reduced supply-air VOCs to near their detection limits. Mice with asthma received fexofenadine (20 mg/kg/day, oral) or vehicle (0.5% methylcellulose in water) during allergen challenge. Lung function, histopathology, bronchoalveolar cells, Th2 cytokines, type 2 innate lymphoid cells, and dorsal root ganglion Ca²⁺ responses were measured, and total VOCs were quantified by thermal desorption–gas chromatography–mass spectrometry at five veterinary hospitals. VOC filtration significantly reduced lung injury in both models and improved oxygen saturation in animals with ALI. In those with asthma, filtration reduced eosinophilia, Th2 cytokines, type 2 innate lymphoid cells, and lymphocyte activation, and filtration combined with fexofenadine produced the greatest reductions in airway inflammation and the lowest histamine-evoked Ca²⁺ responses in dorsal root ganglion neurons isolated from these animals. VOCs amplified lipopolysaccharide-induced inflammatory responses in BEAS-2B cells. Hospital VOC levels ranged from < 50 to > 600 μg·m⁻³, overlapping with or exceeding the low-level VOC burdens observed in the animal housing experiments. Under the tested experimental conditions, reducing low-level indoor VOCs was associated with attenuated inflammatory phenotypes in both allergic asthma and ALI models, and with greater reductions in airway inflammation when combined with fexofenadine in the asthma model. These findings warrant further investigation of indoor VOC control as an adjunctive environmental strategy in clinical and veterinary settings, particularly for susceptible hosts.