The Relationship Between e-Cigarette Exposure, Sex Steroids, and COVID-19

How Vaping and Nicotine Affect Airway Inflammation and Respiratory Function

Research during the COVID-19 pandemic highlighted important sex differences in respiratory disease outcomes. A study by Sharma and Zeki investigated whether e-cigarette vapor exposure, nicotine, and biological sex influence pulmonary ACE2 expression and lung function—factors relevant to respiratory infection and inflammation.

The Link Between Vaping, ACE2, and Respiratory Health

The renin-angiotensin system (RAS) plays an important role in cardiopulmonary function and inflammation. Within this system, angiotensin-converting enzyme 2 (ACE2) is particularly relevant to respiratory research because it acts as a cellular receptor for SARS-CoV-2.

ACE2 expression can be increased in the airways and lungs of smokers and individuals with COPD. This led researchers to investigate whether e-cigarette vapor exposure could similarly alter pulmonary ACE2 expression.

How Does Vaping Affect ACE2 Expression?

In the study, 7–8-week-old mice were exposed to e-cigarette vapor, with or without nicotine, for 30 minutes twice daily over 21 days. Researchers then assessed airway inflammation, ACE2 expression, and pulmonary function.

Using the flexiVent system, the team measured basal inspiratory capacity and airway responsiveness following increasing concentrations of methacholine.

Key Findings

The study found that e-cigarette vapor exposure:

• Increased airway inflammation
• Increased ACE2 expression in the lungs
• Impaired lung function
• Increased airway resistance
• Reduced basal inspiratory capacity

Importantly, several effects differed between male and female mice.

ACE2 expression was higher in male mice and was particularly associated with nicotine exposure. Airway resistance also increased following e-cigarette vapor exposure, although the relationship with nicotine differed between sexes.

In males, increased airway resistance appeared to be nicotine-independent, whereas in females, the increase was more closely associated with nicotine exposure.

Reduced basal inspiratory capacity was observed following vapor exposure regardless of sex or nicotine concentration.

Measuring Vaping-Related Lung Dysfunction with flexiVent

The flexiVent respiratory mechanics system provided quantitative measurements of lung function following e-cigarette vapor exposure.

Measurements of airway resistance, inspiratory capacity, and methacholine responsiveness helped identify functional changes associated with vaping and provided insight into potential sex-dependent effects.

What Do These Findings Mean for Vaping Research?

The study demonstrates that e-cigarette vapor can alter pulmonary ACE2 expression, promote airway inflammation, and impair lung function in mice. Nicotine further increased ACE2 expression, while some effects on airway resistance differed between male and female animals.

The mechanisms underlying these sex-dependent responses remain unclear. The researchers suggest that nicotinic acetylcholine receptors (nAChRs) may contribute to the effects of nicotine on ACE2 expression.

These findings highlight the importance of considering sex, nicotine exposure, and vaping history when investigating the respiratory effects of e-cigarettes and their potential implications for lung health.

Read the full publication here.