An Unexpected Consequence of Electronic Cigarette UseUnforeseen Risk of Electronic Cigarette Use FREE TO VIEW

A 42-year-old woman was admitted to the hospital with a 7-month history of dyspnea, productive cough, and subjective fevers. She had been seen multiple times in the ED with similar complaints and had received several courses of antibiotics.

The patient had recently started using electronic cigarettes (e-cigarettes), about 7 months prior, which coincided with the onset of her respiratory symptoms. Her past medical history also was significant for asthma, reported rheumatoid arthritis, fibromyalgia, schizoaffective disorder, and hypertension. Her medications included amlodipine, albuterol metered dose inhaler, lovastatin, lisinopril, multiple vitamins, cyclobenzaprine, citalopram, and multiple psychiatric medications.

The patient reported a recent exposure to fumigation chemicals, as the result of a bedbug infestation of her apartment building 2 weeks prior to her hospitalization. She had no pets. There was no other history of significant exposures, illicit drug use, or recent travel. She denied any dysphagia or aspiration.

On presentation, her vital signs were notable for mild tachycardia and a pulse oximetric saturation of 94% while breathing room air. Her physical examination was normal except for bilateral rales.

Laboratory findings showed a WBC count of 18.0 (×10³) with a normal differential and hemoglobin level of 11.2 g/dL. The chemistry panel and brain natriuretic peptide levels were normal. Chest radiographic imaging showed new multifocal bilateral opacities. CT images (Fig 1) revealed extensive bilateral upper- and lower-lobe patchy ground glass pulmonary opacities in a “crazy paving” pattern. Results of an HIV test were negative. Results of a nasal Pertussis polymerase chain reaction swab were negative. Results of urine Legionella antigen and serum Mycoplasma IgG and IgM tests were negative. Results of a hypersensitivity pneumonitis panel, extracted nuclear antigen panel, and tests for antinuclear antibody, cyclic citrullinated peptide, and rheumatoid factor were negative. A bird fancier’s panel showed trace reactivity to pigeon and parrot droppings.

Bronchoscopy and BAL were performed. The cell count showed 48% neutrophils, 8% lymphocytes, 43% monocytes, and 1% eosinophils. Results of all bacterial and viral cultures remained negative; fungal cultures showed light growth of Candida. Results of a viral DFA panel, Pneumocystis jeroveci DFA, and Legionella antigen tests were negative. BAL cytologic examination revealed abundant lipid-laden macrophages (Fig 2).

Lipoid pneumonia is a rare, primarily chronic inflammatory reaction secondary to the presence of lipid substances in the lungs, with subsequent uptake by alveolar macrophages and accumulation in the interstitium. The endogenous form occurs when fat is deposited into the lung tissue in vivo, typically from proximal obstructive lesions, fat embolism, necrotic tissue, lipid storage disease, or hyperlipidemia. The exogenous form develops from inhaling or aspirating lipids, such as those seen in animal, vegetable, or mineral oil. Classically, exogenous lipoid pneumonia is associated with aspiration of mineral oil-based laxatives in the pediatric population or with occupational exposures. The incidence is also higher in older patients with underlying debility, achalasia, reflux, and other neuromuscular disorders of the pharynx and esophagus.

Most patients are asymptomatic; however, symptoms may include cough, dyspnea, fever, weight loss, chest pain, pleurisy, hemoptysis, chills, and night sweats. Findings on physical examination may be normal or nonspecific, such as tachypnea and adventitious breath sounds. Thus, a high clinical suspicion is required to make the diagnosis of exogenous lipoid pneumonia.

Depending on the severity of the disease, exogenous lipoid pneumonia may present with hypoxia or respiratory alkalosis. Results of pulmonary function tests typically show a restrictive ventilatory defect and/or diffusion impairment, but they may be normal.

The most frequent chest radiographic findings are extensive bilateral alveolar consolidations and ground glass opacities in the dependent portions of the lungs. However, unilateral involvement may be seen, affecting the right and left lungs equally. Adenopathy is rare. Fibrosis may occur and lead to volume loss. Solid lesions may also develop, resembling bronchogenic carcinoma.

High-resolution CT imaging plays an important role in the diagnosis of lipoid pneumonia. The most frequent findings are bilateral posterior and lower-lobe-predominant alveolar consolidation, ground glass opacities, and the “crazy paving” pattern. Consolidated areas are typically hypodense (−30 to −75 HU), with similar attenuation to the surrounding adipose tissue. The use of CT scan angiography may help confirm these findings, with the consolidated lung having a considerably lower attenuation than the enhancing vessels.

A key component to making a true diagnosis of exogenous lipoid pneumonia is the presence of lipid-laden macrophages in the sputum or BAL fluid. These vacuolated macrophages stain orange with Sudan stain or red with Oil-Red-O stain. No clear cytologic profile has been found to be more suggestive of the disease. Histologic examination shows an inflammatory landscape, similar to that seen with a foreign body reaction. In severe disease, a proliferative fibrosis and disorganization of the pulmonary architecture can occur. A biopsy may be necessary to confirm the diagnosis in certain cases.

Once the diagnosis has been identified, all efforts should be made to avoid recurrent oil exposures and stop aspiration. Expectorants and repeat therapeutic BAL have not been shown to offer any benefit. Systemic corticosteroids have been recommended; however, they lack proven efficacy. Therefore, their use should be limited to severe cases.

For this patient, the suspected source of her exogenous lipoid pneumonia was recurrent exposure to glycerin-based oils found in e-cigarette nicotine vapor. Since the 1980s, there has been an ever-increasing development of electronic nicotine-delivery systems. The e-cigarette comprises a plastic tube and a battery-powered electronic heating device that vaporizes a liquid nicotine cartridge. E-cigarettes are advertised as an alternative to smoked tobacco and as a smoking cessation aide.

However, health analysis and empirical research on e-cigarettes is sparse. Recent evaluation of the nicotine solution and vapor content of e-cigarettes found primary components of propylene glycol, glycerin, and nicotine. Other chemicals identified in trace amounts include N-nitrosamines, diethylene glycol, polycyclic aromatic hydrocarbons, anabasine, myosmine, and β-nicotyrine. Many of these compounds are carcinogenic and harmful to humans.

Vegetable glycerin is often added to the nicotine solutions used in e-cigarettes to make the visual smoke when the solution is vaporized. Glycerin is produced by heating palm or coconut oil; however, it can also be produced from animal fat and soap through a fatty-acid splitting operation.

As discussed, most cases of exogenous lipoid pneumonia are associated with aspiration of mineral oil or lipid-based preparations. There is one published case of exogenous lipoid pneumonia due to inhaling vaporized weed oil. Other cases have been reported involving inhalation of crack cocaine mixed with petroleum jelly. To our knowledge, there are no prior published cases of exogenous lipoid pneumonia due to the use of glycerin-based e-cigarettes. Importantly, this case highlights harm caused by the nicotine-solution carrier and the delivery system of the e-cigarette. Prior discussion regarding the safety of e-cigarettes has primarily focused on nicotine and other carcinogenic components. Certainly, the risk of lipoid pneumonia adds another dimension to the supercharged social, political, and medical debate surrounding the regulation and legality of e-cigarette use.

The patient was instructed to avoid the use of e-cigarettes, and, subsequently, her symptoms improved. A follow-up chest radiograph was normal, and pulmonary function testing showed mild diffusion impairment but no obstructive or restrictive defects.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: This work was performed at Legacy Good Samaritan Medical Center, Portland, OR.