The triple-hit hypothesis: exploring pulmonary e-cigarette, PM_2.5 and viral polyexposure

Area of Science:

• Environmental Health
• Pulmonology
• Toxicology

Background:

• Real-world exposures to e-cigarette aerosols, fine particulate matter (PM$_{2.5}$), and respiratory viruses rarely occur in isolation.
• These exposures independently impair lung defenses, increasing susceptibility to viral infections.

Purpose of the Study:

• To explore the cellular and molecular impacts of combined exposure to vaping aerosols, PM$_{2.5}$, and respiratory viruses.
• To investigate the 'triple-hit hypothesis' regarding additive or synergistic effects on chronic airway inflammation.

Main Methods:

• The study reviews existing cellular and molecular data on individual and combined exposures.
• It proposes a polyexposure model to reflect real-world scenarios.

Main Results:

• Vaping induces lipid-laden macrophages and impairs epithelial function.
• PM$_{2.5}$ promotes pro-inflammatory and tissue-remodeling macrophage phenotypes.
• Combined exposures may amplify inflammation, impair cellular clearance (efferocytosis, autophagy), and exacerbate respiratory disease.

Conclusions:

• Concurrent exposure to vaping aerosols, PM$_{2.5}$, and viruses poses a significant risk to respiratory health.
• This polyexposure can accelerate chronic respiratory disease development and progression.
• Accurate polyexposure models are crucial for risk assessment and preventive strategies.