Lipid laden macrophages and electronic cigarettes in healthy adults

Shields, Peter G.; Song, Min-Ae; Freudenheim, Jo L.; Brasky, Theodore M.; McElroy, Joseph P.; Reisinger, Sarah A.; Weng, Daniel; Ren, Rongqin; Eissenberg, Thomas; Wewers, Mark D.; Shilo, Konstantin

doi:10.1016/j.ebiom.2020.102982

Cited by 35 publications

(21 citation statements)

References 24 publications

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“…Shields et al, showed high LLM in the lungs of all conventional smokers and e-cigarettes users, however LLM presence in vape pen users was further associated with elevated levels of the inflammatory cytokines IL-4 and IL-10 in bronchoalveolar lavage fluid. [12] Vitamin E acetate is a thickening chemical agent which is used in THC containing products. Blount et al [13] showed Vitamin E in 94% of patients with THC associated EVALI, an experimental study [14] in rodents has shown EVALI symptoms without the use of THC, vitamin E or nicotine use.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes and lipid-laden macrophages in Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI) in a South Texas population

Mir

Beg

Peters

et al. 2021

DCC

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Objective: To describe the clinical features, proportion of lipid-laden alveolar macrophages in bronchoalveolar lavage (BAL), and short-term and 6-month to 12-month outcomes of patients with Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI).Methods: Retrospective review of clinical characteristics, radiographs, and BAL samples for all patients with a history of vaping who presented with acute hypoxemic respiratory failure to the University Hospital in San Antonio, Texas from 9/2019 to 6/2020 was performed.Results: We report 16 cases (15 men; median age, 30 years [range 19-75]) of EVALI with a history of vaping Tetrahydrocannabinol (THC), nicotine, or both. The most common presenting symptoms were tachycardia, dyspnea, cough, and fever. All patients required supplemental oxygen, including two who required noninvasive positive pressure ventilation, and five who required mechanical ventilation. All 16 patients had bilateral ground-glass opacities (GGO) with peripheral sparing on chest computerizedtomography (CT). Cultures were negative, except for one patient who tested positive for rhinovirus. COVID-19 PCR was done in one individual which was negative. Cytology demonstrated lipid-laden macrophages on Oil-Red-O stain on fresh (i.e., without fixative) BAL in the majority of patients (N = 12) with a mean lipid-saturation percentage of 78% [range, 44%-100%] and the mean Colombo count of 194 [range, 101-359]. Fifteen patients were treated with systemic corticosteroids. The median length of hospital stay was 10 days. At discharge, three patients required supplemental oxygen. Eight of those who had follow-up imaging showed resolution of GGO. One patient had a relapse of symptoms and was again treated with systemic corticosteroids and mycophenolate, with resolution of symptoms. Fourteen patients who were evaluated after discharge denied vaping post-discharge (two patients were not able to be contacted and did not keep follow-up appointments).Conclusions: Successful diagnosis and management of EVALI requires a high clinical suspicion, thorough evaluation to rule out infectious etiologies, and aggressive treatment with systemic corticosteroids, along with sustained abstinence from vaping.

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Section: Discussionmentioning

confidence: 99%

Clinical outcomes and lipid-laden macrophages in Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI) in a South Texas population

Mir

Beg

Peters

et al. 2021

DCC

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“…EVALI pathology was associated with alveolar damage and the presence of lipid-laden macrophages from BAL samples, suggestive of a pathologic role for AMs in the disease (Ref. 56).…”

Section: Environmental Insultsmentioning

confidence: 97%

Alveolar macrophages: novel therapeutic targets for respiratory diseases

Lim

Cervantes

Pham

et al. 2021

Expert Rev. Mol. Med.

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Alveolar macrophages (AMs) are lung-resident myeloid cells that sit at the interface of the airway and lung tissue. Under homeostatic conditions, their primary function is to clear debris, dead cells and excess surfactant from the airways. They also serve as innate pulmonary sentinels for respiratory pathogens and environmental airborne particles and as regulators of pulmonary inflammation. However, they have not typically been viewed as primary therapeutic targets for respiratory diseases. Here, we discuss the role of AMs in various lung diseases, explore the potential therapeutic strategies to target these innate cells and weigh the potential risks and challenges of such therapies. Additionally, in the context of the COVID-19 pandemic, we examine the role AMs play in severe disease and the therapeutic strategies that have been harnessed to modulate their function and protect against severe lung damage. There are many novel approaches in development to target AMs, such as inhaled antibiotics, liposomal and microparticle delivery systems, and host-directed therapies, which have the potential to provide critical treatment to patients suffering from severe respiratory diseases, yet there is still much work to be done to fully understand the possible benefits and risks of such approaches.

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“…Hence, neither short-term improvements nor the relatively milder changes in some parameters with e-cigarettes versus combustible cigarettes imply unalloyed harm reduction. As reported by several investigators [ 43 •, 100 ••, 104 ], the nature and the type of tissue injury inflicted by e-cigarettes are distinct from that caused by combustible cigarettes. For instance, even though in animal models, e-cigarettes, unlike combustible cigarettes, do not cause emphysematous changes, they stimulate the accumulation of lipid-laden macrophages, which could lead to dysregulation of the pulmonary surfactant and thereby compromise air-exchange and alter innate immunity [ 100 ••], pathological changes distinct from those seen with combustible cigarettes.…”

Section: Perspective and Conclusionmentioning

confidence: 99%

“…Similar lipid-laden macrophages have also been detected in the BAL fluid of EVALI patients [ 103 ]. Although such lipid-laden macrophages have also been found in the lung of smokers, in e-cigarette users, these macrophages are associated with inflammatory cytokines such as IL-4 and IL-10, but not with smoking-related cytokines [ 104 ], suggesting that the pathophysiological changes induced by e-cigarettes in macrophages may be different in nature from that afflicted by combustible cigarettes.…”

Section: E-cigarettes and The Immune Responsementioning

confidence: 99%

Cardiorespiratory and Immunologic Effects of Electronic Cigarettes

Keith

Bhatnagar

2021

Curr Addict Rep

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Purpose of Review Although e-cigarettes have become popular, especially among youth, the health effects associated with e-cigarette use remain unclear. This review discusses current evidence relating to the cardiovascular, pulmonary, and immunological effects of e-cigarettes. Recent Findings The use of e-cigarettes by healthy adults has been shown to increase blood pressure, heart rate, and arterial stiffness, as well as resistance to air flow in lungs. Inhalation of e-cigarette aerosol has been shown to elicit immune responses and increase the production of immunomodulatory cytokines in young tobacco-naïve individuals. In animal models, long-term exposure to e-cigarettes leads to marked changes in lung architecture, dysregulation of immune genes, and low-grade inflammation. Exposure to e-cigarette aerosols in mice has been shown to induce DNA damage, inhibit DNA repair, and promote carcinogenesis. Chronic exposure to e-cigarettes has also been reported to result in the accumulation of lipid-laden macrophages in the lung and dysregulation of lipid metabolism and transport in mice. Although, the genotoxic and inflammatory effects of e-cigarettes are milder than those of combustible cigarettes, some of the cardiorespiratory effects of the two insults are comparable. The toxicity of e-cigarettes has been variably linked to nicotine, as well as other e-cigarette constituents, operating conditions, and use patterns. Summary The use of e-cigarettes in humans is associated with significant adverse cardiorespiratory and immunological changes. Data from animal models and in vitro studies support the notion that long-term use of e-cigarettes may pose significant health risks.

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Lipid laden macrophages and electronic cigarettes in healthy adults

Cited by 35 publications

References 24 publications

Clinical outcomes and lipid-laden macrophages in Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI) in a South Texas population

Clinical outcomes and lipid-laden macrophages in Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI) in a South Texas population

Alveolar macrophages: novel therapeutic targets for respiratory diseases

Cardiorespiratory and Immunologic Effects of Electronic Cigarettes

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