Vaping-associated Chronic Lung Disease: Q&A With Lida Hariri, MD, PhD

Electronic cigarettes (e-cigarettes) and vaping have become increasingly popular, particularly among young individuals. However, there is a lack of knowledge surrounding the potential long-term health risks of vaping.

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Lida P. Hariri, MD, PhD, pulmonary pathologist in the Department of Pathology and Division of Pulmonary and Critical Care Medicine at Massachusetts General Hospital, and colleagues recently investigated four patients diagnosed with chronic lung disease. The study, published in the New England Journal of Medicine Evidence, determined that vaping was the most likely cause of chronic lung disease in all patients, revealing a histological pattern of small airway–centered fibrosis.

In this Q&A, Dr. Hariri discusses how this study paves the way to further understanding the health risks of vaping.

Q: Why are the health risks of e-cigarettes and vaping being increasingly investigated?

Hariri: E-cigarettes were initially developed as a safe, alternative method to help people to quit traditional combustible cigarette smoking. However, it's clear that many vaping products are now being used by younger age groups, including at the middle and high school level.

Just before the COVID-19 pandemic, the CDC reported over 2,800 hospitalized e-cigarette or vaping product use-associated lung injury (EVALI) cases or deaths in the U.S., illustrating that vaping use was not "safe" or without risks. The EVALI epidemic encouraged many individuals to investigate the long- and short-term risks of vaping. From a scientific and epidemiologic perspective, there is a heavy focus on this topic because there is no data to support that vaping is a safe alternative compared to combustible cigarette smoking, or to better understand what the risks are for those who vape.

Q: Why are adverse reactions to toxic agents, such as e-cigarettes, difficult to diagnose?

Hariri: Any time you look at an association between a toxic agent and chronic abnormality, it's challenging because you must establish a temporal relationship and thoroughly evaluate all other potential causes of the abnormality. As we saw with the EVALI epidemic, it took a while to find an association between vitamin E acetate, which was being used to cut vaping fluid products, and EVALI. With chronic disease, it can be even more challenging to establish a relationship between an injurious agent and disease due to the longer time lag.

Q: Can you describe your recent study published in the New England Journal of Medicine?

Hariri: This study describes four patients with chronic lung disease that was ultimately associated with e-cigarette use. All patients had a thorough clinical evaluation, with lung function tests, chest computed tomography (CT), and histology assessment on surgical lung biopsy. Each patient presented with shortness of breath in association with 3- to 8-years of e-cigarette use. There was mild progressive airway obstruction on lung function testing. Chest CT findings showed evidence of mild air trapping and bronchial wall thickening, which are suggestive of a small airway abnormality. Endobronchial optical coherence tomography (EB-OCT) imaging was performed in two patients, which is a bronchoscopic imaging modality with microscopic resolution, and showed small airway–centered fibrosis with narrowing and lumen irregularities. Small airway fibrosis was also seen as the main feature on surgical lung biopsy. A thorough evaluation was performed to evaluate for all known causes of small airway fibrosis. After ruling out all other possibilities, it was determined that vaping was considered to be the most likely common causal etiology. Patients who stopped vaping had partial reversal of disease over 1 to 4 years.

Q: What were the adverse reactions noted in these patients, and how did your findings attribute this to vaping?

Hariri: All the patients had a temporal association between their e-cigarette use and the onset of their symptoms. They all had evidence of fibrosis involving the small airway, including constructive bronchiolitis, which is fibrosis that surrounds the small airways between the epithelium and smooth muscle layer and narrows the diameter of the airway. These findings were identified on histology from surgical lung biopsies and on EB-OCT imaging performed in the small airways during bronchoscopy. Each patient underwent a systematic evaluation for all known causes of fibrosis in the small airways. After thorough evaluation and exclusion of other possible causes, it was determined that each patient had vaping-associated chronic lung disease.

Interestingly, the histopathologic features of these patients were very similar, even though they were vaping for different time periods (3-8 years) and used different vape devices and vaping fluids. In the 3 of 4 patients who stopped vaping, they had symptom improvement and improvement of findings on chest CT and/or lung function testing, which further increased confidence in the diagnosis of vaping-associated chronic lung disease. However, the improvement was not back to each patient's respective baseline, which is not surprising since fibrosis of this nature is not typically reversible.

Q: What are the implications of these findings?

Hariri: There have been a number of epidemiological studies comparing e-cigarette users to never-smokers and have reported a higher odds ratio of asthma-like symptoms. However, it's been challenging to nail down why patients are having these symptoms and if it really is "asthma" or some other condition that mimics asthma symptoms, which includes small airway fibrosis that we found in our study. We view this study as a first step towards investigating the cause of these chronic respiratory symptoms. We hope that our findings will light the spark to prioritize investigations into chronic lung diseases associated with vaping. We want to raise awareness so that when clinicians encounter patients who report that they use e-cigarettes, they are reminded to evaluate for signs and symptoms of lung disease and encourage their patients to stop vaping as there is no data to support its safety.

Q: Are you and your team developing further studies on this?

Hariri: We plan to conduct further studies to investigate the changes occurring in the small airways of patients who vape as compared to healthy individuals. We hope that other groups will continue to do larger scale, epidemiologic and basic science studies in this area as well, with a focus on longitudinal studies aimed at assessing long-term disease risks. Hopefully, together, we may be able to shed more light on the short-term and long-term health risks of vaping.

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