Justin Panthappattu, B.S.1, Victor Beauvil, R.R.T, PhD.2, Dilbagh Singh, M.D.3, Sameer Verma, M.D.3, 4, Arunabh Talwar, M.D, F.C.C.P.3, 4
- St. George’s University School of Medicine Grenada, West Indies
- Mandl School The College of Allied Health, NY
- Northwell Health Department of Pulmonary, Critical Care and Sleep Medicine 410 Lakeville Rd. Suite 107 New Hyde Park, NY 11040
- Heart and Lung Research Unit The Feinstein Institute for Medical Research
History
Cigarette smoking is injurious to health, affecting every organ of the body. Over the years, various mechanisms of nicotine delivery have been developed. These devices are collectively known as electronic nicotine delivery systems (ENDS).1 In 2003, the first e-cigarette was created, offering an alternative to traditional cigarettes.2 These devices heat special liquid, known as e-liquid, that contains nicotine, flavoring and other substances. The end result is an aerosol which the user then inhales. This behavior is known as “vaping”.
The first-generation device consisted of three main components. The first component is a power source, typically a lithium-ion battery. The second component is an atomizer, which acts as a heat source. The third component of the e-cigarette is a reservoir that houses the e-liquid, commonly in the form of a cartridge. The atomizer heats the liquid and produces an aerosol. Since their introduction, e-cigarettes have seen many changes that have enhanced the user experience, however, the components that allow them to operate have remained the same in modern-day “vape pens” with the addition of a metal sheath and a smart chip.3 The metal sheath encloses the entire device. The smart chip works to allow the user to have more control of the atomizer.
Many consumers believe that vaping entails the inhalation of water vapor after the e-liquid is heated.2 As a result, it is sometimes promoted as a safe alternative to traditional cigarette smoking that can reduce harm. This notion, however, has not effectively been proven true. E-cigarette users inhale an aerosolized spray, not water vapor.
Clinicians should be aware of two things regarding current vape pen usage. First, investigation regarding the safety of ENDS is still lacking. Secondly, vaping is on the rise among certain populations. In recent years, the usage of e-cigarettes among young adults has increased.4 Of these, it is believed that usage is high among lesbian, gay, bisexual and transgender (LGBT) youth.2
Current Generation Devices
Modern vape pens, as opposed to the first e-cigarettes, offer an abundant number of customization options. To date, more than 7000 flavor options exist.2 These options contain varying amounts of compounds such as propylene glycol and glycerin, among others that result in the desired flavor. Additionally, the extensive array of customization options in current devices opens up the possibility of using the device with tetrahydrocannabinol (THC) and cannabinoid (CBD) oils as additives to the e-liquid.
In light of the recent teen vaping epidemic, there has been a push to ban flavored vape fluid though these plans have not gone into effect yet. According to Alex M. Azar II, secretary of the Department of Health and Human Services, “We intend to clear the market of flavored e-cigarettes to reverse the deeply concerning epidemic of youth e-cigarette use that is impacting children, families, schools, and communities”. 5 Ahead of this ban, the Juul Labs has announced that it will be halting online sale of its flavored e-cigarettes temporarily.6
Safety Concerns
A concern regarding current day e-cigarette usage is the relative lack of formal regulation of products. Manufacturer information may not be a reliable indicator of the nicotine content in e-liquid. Even in units of e-liquid from the same provider, there have been disparities in nicotine concentration.7 The expansive array of customization options, including those originating outside of the manufacturing process, pose another safety concern.
What is concerning is the recent outbreak of vaping-associated lung injury. The inhalation of aerosolized particles may play a role in the development of lung injury among individuals using e-cigarettes. Aerosolized particles are able to reach the alveoli as their size allows them to progress down the respiratory tract. The end result is not only inflammation of the airways, but these particles may also translocate into the bloodstream. In some cases, heavy metals are nanoparticles are among the aerosolized matter and consequently cause the formation of reactive oxygen species, which in turn can cause DNA damage.2
Vaping also poses another danger by creating another avenue for environmental nicotine exposure. Vaping carries the same risk of second-hand smoke exposure when compared to traditional smoking. It also, however, carries the risk of third-hand smoke exposure.2 The aerosolized compounds that are exhaled can deposit on surfaces in the environment where they then carry the risk of entering the body through means other than inhalation, such as unintentional ingestion or transdermal absorption.
At present, it is important that clinicians educate themselves with current information regarding the safety and possible risks of e-cigarette usage. Though there is an awareness in the medical of the lack of scientific evidence regarding this topic, many clinicians do not know what information is currently available.2
Mechanisms of Injury
Both cigarette smoking and e-cigarette usage have been shown to cause immune suppression by decreasing the expression of immune-related genes. The result is a decrease in the chemokines required for the activation of immune cells in the nasal epithelium. Another result of smoking in both forms is the activation of pro-inflammatory pathways in the body, which consequently causes tissue injury. Individuals who partake in cigarette smoking or e-cigarette usage are also at higher risk of infection as there is a reduction in host antibacterial defense responses. In the setting of a dampened immune response, there is the risk of increased susceptibility to bacterial colonization and biofilm formation within the respiratory tract. Lastly, smoking increases the expression of genes in the bronchial epithelium that are associated with oxidative stress. Not only does this further contribute to tissue injury, but the changes that result are irreversible.8 It should be noted that recent studies have shown that the changes in the immune response are more pronounced in e-cigarette usage when compared to cigarette smoking.
“Inhalation of chemicals via e-devices (vaping and dabbing) is dangerous and can cause acute lung injury, most likely via chemical inhalation” according to Laura Crotty Alexander, an associate professor of medicine at UC San Diego. 9 At the time that this article was written, the CDC has issued a warning regarding vaping in light of the recent outbreak of vaping-associated lung injury. Prior to October 15th, 2019 there have been approximately 1500 cases of lung injury associated with vaping that have been reported in the United States with the exception of Alaska.10 In the majority of these cases, patients reported usage of THC-containing products in addition to nicotine-containing products.
In cases of vaping-associated lung injury, the patient’s presentation may mimic pneumonia. Patients present with dyspnea and chest X-ray /CT scan will show bilateral infiltrates. Even imaging findings, such as chest CT, may appear to suggest pneumonia. In spite of this, it is possible that the root cause of the disease is vaping-associated lung injury. An important distinction is that patients with vaping-associated lung injury may have a picture that resembles pneumonia, though they may not have fever or chills.3,11 Clinicians should be aware of possible mechanisms of vaping-associated lung injury.
Acute Lipoid Pneumonia
Lipoid pneumonia refers to a pattern of inflammation that can occur within the lung when fat particles enter the airways. Patients presenting with this condition typically have a history of e-cigarette usage containing nicotine, THC and marijuana oil or concentrate. Presenting symptoms include acute dyspnea, nausea, vomiting, abdominal discomfort, and fever with a chest X-ray showing bilateral lung infiltrates. Fiber-optic bronchoscopy with bronchoalveolar lavage (BAL), however, is typically performed to reach a definitive diagnosis. BAL in this situation typically reveals reactive bronchial cells, as well as macrophages with vacuolated cytoplasm and chronic inflammatory cells. Staining the lavage sample for cytology with oil red O reveals extensive lipid deposition (the inhaled oil particles) in the alveolar macrophages which confirms the diagnosis. Intravenous corticosteroid therapy has been proven to benefit patients. Timely diagnosis and treatment of this condition is required as these patients carry the risk of progressing to acute respiratory failure without prompt intervention.12,13
Hypersensitivity Pneumonitis
Hypersensitivity pneumonitis is an immune-mediated reaction in response to the inhalation of various antigens containing organic dust and chemicals. Exposure to birds, mycobacteria, isocyanate as well as occupational, socioeconomic and environmental factors contribute to its pathogenesis. Generally, this condition is more common among non-smokers however smokers are more likely to have a chronic variant of the disease. Patients present with non-specific symptoms such as dyspnea, chest tightness and may have inspiratory crackles on physical examination. Typically, these patients will have a history of recurrent episodes of similar symptoms. In acute cases, chest CT may reveal ground-glass opacities in a mosaic pattern. In chronic cases, chest CT is more likely to show a reticular pattern of fibrosis, air trapping and bronchiectasis. BAL may show lymphocytosis though this is a non-specific finding. Due to shared symptoms and chest CT findings, it is important to take an accurate history to differentiate this disease entity from interstitial lung disease. Early treatment with prednisone can improve symptoms rapidly in acute cases, as well as halt the progress to chronic hypersensitivity pneumonitis which is irreversible after development of fibrosis.
Acute Eosinophilic Pneumonia
Eosinophilic pneumonia occurs as a result of eosinophil activation in response to allergens. This condition can be idiopathic or due to environmental exposures. Recent studies have connected diethylene glycol, a breakdown product of propylene glycol commonly used in e-liquid, as a contributor in the pathogenesis of this condition. Patients typically present with non-specific symptoms such as dyspnea, cough, facial flushing and chest pain. In addition to eosinophilia, these patients typically have diffuse patchy reticulonodular opacities which can be seen on chest x-ray. Further investigation by means of chest CT shows diffuse ground-glass opacities. Bronchoscopy with BAL is confirmatory in these patients and will reveal abundant macrophages, eosinophils (>30% on differential) and scattered benign respiratory epithelial cells. Administration of prednisone results in rapid improvement in these patients. However, timely diagnosis and treatment are important in this condition as it may progress to acute respiratory failure.3,14
Bacterial Pneumonia
As a consequence of decreased bacteria, individuals who partake in e-cigarette usage or cigarette smoking are at increased risk of developing bacterial pneumonia. Patients typically present with fever, dyspnea, a productive cough and pleuritic chest pain. Chest X-ray in these patients may reveal consolidations in the lung lobes or infiltrates in the interstitial tissue. This condition is a consequence of bacterial colonization of the lungs. As previously mentioned, e-cigarette usage is associated a decreased immune response. Recent literature has also shown that e-cigarette vapor is associated with an increase in the virulence of bacteria that can colonize the lungs through the resistance to antimicrobial host defenses as well as enhancement of biofilm formation.15 Treatment in these cases should be aimed at managing the underlying infection. Timely diagnosis and treatment are important in this condition as well in order to prevent possible progression to acute respiratory failure.
Conclusion
E-cigarette usage has long been promoted as a safe alternative to cigarette smoking. Recent studies have shown that e-cigarette usage carries significant risk of causing lung injury by multiple mechanisms. Patients may present with progressive dyspnea and bilateral crackles on physical examination. Chest CT may reveal bilateral infiltrates. As such, it is important that clinicians become aware of the current literature and engage their patients in conversation to discover other means of decreasing nicotine dependence.
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