Honesty about unknowns is essential for evidence-based decision-making. Here are the key gaps in our understanding:

• Long-term cancer risk: Vaping has existed for ~20 years. Cancer latency periods are 20-30 years. We don't yet have epidemiological data on whether decades of low-level carcinogen exposure from vape aerosol increases cancer risk.
• Chronic PG/VG inhalation: Propylene glycol is generally recognized as safe (GRAS) for ingestion. But inhalation is a different exposure route. Decades of inhaling PG/VG aerosol — the long-term effects are genuinely unknown.
• Flavoring compound accumulation: Some flavoring compounds (diacetyl, cinnamaldehyde, sucralose) have known respiratory toxicity at high concentrations. Whether chronic low-level exposure causes cumulative damage is unclear.
• Immune function over time: Vaping's effect on lung macrophages and immune response is an active research area. Short-term studies show mild impairment, but long-term data is lacking.
• Dual use health outcomes: Most studies compare exclusive vapers to exclusive smokers. Real-world data on long-term dual users is limited but suggests outcomes closer to smoking than to exclusive vaping.