Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study

doi:10.1016/S0140-6736(19)32679-0

The Lancet

Volume 394, Issue 10214, 7–13 December 2019, Pages 2073-2083

https://doi.org/10.1016/S0140-6736(19)32679-0 Get rights and content

Summary

Background

An ongoing outbreak of lung injury associated with e-cigarettes or vaping (also known as E-VALI or VALI) started in March, 2019, in the USA. The cause, diagnosis, treatment, and course of this disease remains unknown.

Methods

In this multicentre, prospective, observational, cohort study, we collected data on all patients with lung injury associated with e-cigarettes or vaping seen in Intermountain Healthcare, an integrated health system based in Utah, USA, between June 27 and Oct 4, 2019. Telecritical care, based in Salt Lake City, UT, USA, was used as the central repository for case validation, public reporting, and system-wide dissemination of expertise, which included a proposed diagnosis and treatment guideline for lung injury associated with e-cigarettes or vaping. We extracted data on patient presentation, treatment, and short-term follow-up (2 weeks after discharge) from chart review and interviews with patients undertaken by the Utah Department of Health (Salt Lake City, UT, USA).

Findings

60 patients presented with lung injury associated with e-cigarettes or vaping at 13 hospitals or outpatient clinics in the integrated health system. 33 (55%) of 60 were admitted to an intensive care unit (ICU). 53 (88%) of 60 patients presented with constitutional symptoms, 59 (98%) with respiratory symptoms, and 54 (90%) with gastrointestinal symptoms. 54 (90%) of 60 were given antibiotics and 57 (95%) were given steroids. Six (10%) of 60 patients were readmitted to an ICU or hospital within 2 weeks, three (50%) of whom had relapsed with vaping or e-cigarette use. Of 26 patients who were followed up within 2 weeks, despite clinical and radiographic improvement in all, many had residual abnormalities on chest radiographs (ten [67%] of 15) and pulmonary function tests (six [67%] of nine). Two patients died and lung injury associated with e-cigarettes or vaping was thought to be a contributing factor, but not the cause of death, for both.

Interpretation

Lung injury associated with e-cigarettes or vaping is an emerging illness associated with severe lung injury and constitutional and gastrointestinal symptoms. Increased awareness has led to identification of a broad spectrum of severity of illness in patients who were treated with antibiotics and steroids. Despite improvement, at short-term follow-up many patients had residual abnormalities. Lung injury associated with e-cigarettes or vaping remains a clinical diagnosis with symptoms that overlap infectious and other lung diseases. Maintaining a high index of suspicion for this disease is important as work continues in understanding the cause or causes, optimal therapy, and long-term outcomes of these patients.

Funding

Intermountain Healthcare.

Introduction

An ongoing outbreak of lung injury associated with e-cigarettes or vaping (also known as E-VALI or VALI) has been reported in the USA, starting in March, 2019, and including 1888 cases as of Oct 29, 2019.¹

An initial case series of 53 patients described severe acute lung injury in those who had vaping exposure in the past 90 days.² The cause of lung injury associated with e-cigarettes or vaping is still unknown, and thus the original case definition described in the case series remains the basis for diagnosing the condition—namely, lung injury associated with e-cigarettes or vaping is a clinical diagnosis that comprises use of an e-cigarette (ie, vaping) in the 90 days before symptom onset, pulmonary infiltrates on plain chest radiograph or chest CT, and absence of another known cause, such as infection.²

Although the cause of lung injury associated with e-cigarettes or vaping remains unclear, patterns consistent with toxic inhalational pulmonary injury suggest direct injury rather than an infectious cause.1, 3 Lipoid pneumonia due to vaping has been previously reported,⁴ and initial reports of this outbreak have reported lipid laden macrophages staining with oil red O on bronchoalveolar lavage samples;⁵ however, the clinical course and radiographic⁶ and pathological samples⁷ do not support lipoid pneumonia as the mechanism of the lung injury in this outbreak of lung injury associated with e-cigarettes or vaping.

Research in context

Evidence before this study

A nationwide outbreak of lung injury associated with e-cigarettes or vaping was first reported in March, 2019, in the USA and more than 1880 cases have been reported to date. Although vaping is widespread globally, almost all cases have been reported in the USA. Initial reports noted severe cases of acute lung injury with constitutional and gastrointestinal symptoms, otherwise negative infectious diagnostic testing, and potential improvement with steroids. Increased disease recognition has led to subsequent small case series outlining the cases assessed at single institutions and public health reports of demographic data and vaping or e-cigarette use information. No pathognomonic test for this disease exists and bronchoscopy findings are non-specific. Uncertainty remains about disease course, appropriate diagnostic testing, the need for invasive testing, and treatment recommendations.

Added value of this study

In this study, we report the largest single health system cohort of patients with lung injury associated with e-cigarettes or vaping to date. Public awareness of the outbreak has led to increased recognition, and an evolving clinical picture of disease severity at presentation. Milder disease at presentation, whether due to earlier recognition or other reasons, was associated with less invasive testing (such as bronchoscopy) and shorter courses of lower doses of steroids. Most patients were treated with antibiotics and steroids, with perceived clinical improvement within days. We showed that a system resource (telecritical care) could be used to rapidly identify patients across multiple hospitals in an integrated health system, expediting recognition of this outbreak in one state in the USA. Using a specialised task force, we assessed cases at the system level rather than at individual hospitals, which facilitated validation of cases, shared expertise on the disease across the system, reporting of health outcomes to national bodies, and development of a standardised system approach around a guideline for diagnosis and treatment of lung injury associated with e-cigarettes or vaping. We also developed, and share, a practical clinical guideline for the diagnosis and treatment of lung injury associated with e-cigarettes or vaping.

Implications of all the available evidence

The collective evidence points to a possible opportunity to modify disease course in lung injury associated with e-cigarettes or vaping by faster recognition, cessation of vaping exposure at first symptom onset, and prompt initiation of steroid therapy. Additionally, in less severely ill patients with rapid improvement on steroids, extensive invasive testing, or even admission to hospital might not be necessary. Furthermore, while health systems globally determine whether this outbreak could be affecting their patients, the use of a system resource might help identify and increase the speed of response to an outbreak in which few severe cases accumulate at any single facility.

The prevalence of vaping tetrahydrocannabinol and nicotine compounds has been increasing among children and adults since 2014; however, the scale and severity of this new outbreak of acute lung injury indicates a more recent change in the composition of the e-liquid, and thus e-cigarette vapour, being vaped.1, 8, 9 The number of cases of lung injury associated with e-cigarettes or vaping in Utah, USA, is one of the highest in the USA, despite the state having a similar proportion of adults who use e-cigarettes as the national average and being among the least populated states in the country.¹⁰

In 2017, 5·1% (95% CI 4·5–5·7; age-adjusted 4·9% [4·4–5·5]) of adults in Utah reported currently using e-cigarettes compared with 4·6% nationally.¹¹ The US Centers for Disease Control and Prevention (CDC), the US Food and Drug Administration, and other bodies are attempting to identify the chemical, metal, or other substances newly present in e-devices that might be causing this outbreak.1, 9

Vaping involves heating an e-liquid that contains solvents such as glycol and propylene glycol; active agents, such as nicotine and tetrahydrocannabinol; flavourings; and other additives. The e-liquid is heated and aerosolised, creating an e-cigarette vapour for inhalation.⁸

With increased awareness, clinicians are more consistently obtaining vaping histories in patients who present with acute lung injury in medical centres throughout the USA and building experience with individual case series of patients with lung injury associated with e-cigarettes or vaping.¹² However, individual medical centres are most likely to recognise only the most severe cases in any outbreak and might not have the broader picture of the full range of disease presentations.2, 13

Telehealth has been increasingly implemented across different hospital systems with resulting standardisation of care and intensive care unit (ICU) processes, and improvements in mortality and clinical care have been observed.¹⁴ However, the role of telecritical care in expediting recognition of outbreaks and rapid dissemination in core competencies of treatment has not been previously reported.

The objectives of this study were to report the clinical course, treatment, and outcomes of the largest single health system cohort of patients with lung injury associated with e-cigarettes or vaping to date. Additionally, we note the key role of telecritical care in facilitating the rapid recognition of an outbreak, establishment of a system response via a specialised task force, dissemination of knowledge, and implementation of a proposed guideline for evaluation and treatment of lung injury associated with e-cigarettes or vaping for clinicians in an integrated health system.

Section snippets

Study design and patients

In this prospective observational cohort study, we collected data on all patients with lung injury associated with e-cigarettes or vaping seen at Intermountain Healthcare, Salt Lake City, UT, USA, between June 27 and Oct 4, 2019. Intermountain Healthcare is a Utah-based, not-for-profit, integrated health system comprising 24 hospitals (including one virtual hospital) and approximately 160 clinics serving patients throughout the state of Utah and parts of Idaho, Wyoming, and Nevada. In 2018,

Results

68 patients with suspected lung injury associated with e-cigarettes or vaping were referred to the task force. On review, eight patients did not meet the case definition and were excluded. Thus, 60 patients with confirmed lung injury associated with e-cigarettes or vaping, who presented to 13 hospitals or outpatient clinics in the integrated health system, were included in this analysis (figure 1). This cohort comprises most of the reported cases of the condition in the state of Utah, with 71

Discussion

The rapid recognition of the outbreak in an integrated health system, formation of a specialised task force, and centralisation of data collection and reporting mechanisms led to accumulated experience in diagnosing and treating patients with lung injury associated with e-cigarettes or vaping.

While each individual physician might have seen fewer than ten patients with the condition, as a system many more were seen. To disseminate this expertise, we developed a proposed guideline for diagnosis

Data sharing

To protect patient privacy and comply with relevant regulations, identified data are unavailable. Requests from qualified researchers with appropriate ethics board approvals and relevant data use agreements for de-identified data will be processed by the Intermountain Healthcare Office of Research. To request access please contact the office by email: [email protected].

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Four databases were systematically searched for literature investigating the impact of cannabis, and evidence for its therapeutic use, in adult ICU patients.
Of 2589 articles screened, 22 articles were included for analysis. Cannabis-associated admissions were primarily related to an outbreak of vaping associated lung injury, and synthetic cannabinoid toxicity. Studies on the impact of cannabis use on outcomes were mostly limited to trauma and burns populations, with an inconsistent mortality benefit, and a trend towards increased pain scores and analgesic requirements found. There is minimal research on its therapeutic uses in ICU, with two trials investigating the use of a synthetic cannabinoid in patients with severe traumatic brain injury, with ultimately no significant effect on intracranial pressure found.
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To date, very few cannabis-based specialities are authorised on the French market despite a growing demand from patients and health professionals. The objective of this study is to review the tolerance profile and the French legislative status of the two main cannabinoids used for therapeutic purposes: tetrahydrocannabiol (THC) associated with psychoactive effects and non-psychoactive cannabidiol (CBD).
This review is based on relevant articles retrieved by a search in Google Scholar and PubMed databases and on an assessment of the legal texts and summaries of product characteristics available in France.
Evidence for the tolerability of CBD during chronic use is reassuring, but a significant risk of drug interactions exists. THC use appears to be associated with a higher proportion of serious adverse effects, including neuropsychological and cardiovascular effects. Inhaled cannabis appears to be associated with greater toxicity than the oral route. These data are presented together with the pharmacokinetic and pharmacodynamic data of THC and CBD.
The literature reports several frequent but rarely serious adverse effects of CBD during chronic use as well as a significant risk of drug interactions. THC use seems to be associated with a higher proportion of serious adverse effects compared to CBD, particularly at the neuropsychological and cardiovascular levels. Health professionals should be up to date on the particularities of therapeutic cannabis in terms of efficacy, safety and drug interactions.
Très peu de spécialités à base de cannabis sont autorisées sur le marché français. L’objectif de cette étude est de réaliser une revue de la littérature sur le profil de tolérance et le statut législatif français des deux principaux cannabinoïdes utilisés à des fins thérapeutiques: le tétrahydrocannabiol (THC) associé à des effets psychoactifs et le cannabidiol (CBD) non psychoactif.
Cette revue est basée sur des articles pertinents retrouvés dans les bases de données Google Scholar et PubMed et sur une évaluation des textes législatifs au regard des produits disponibles en France.
Les données de tolérance du CBD lors d’un usage chronique sont rassurantes, mais un risque important d’interactions médicamenteuses existe. La consommation de THC semble être associée à une proportion plus élevée d’effets indésirables graves, incluant des effets neuropsychologiques et cardiovasculaires. Le cannabis inhalé semble être associé à une plus grande toxicité que la voie orale. Ces données sont présentées parallèlement aux données pharmacocinétiques et pharmacodynamiques du THC et du CBD.
La littérature rapporte plusieurs effets indésirables fréquents mais rarement graves du CBD lors d’une utilisation chronique ainsi qu’un risque important d’interactions médicamenteuses. La consommation de THC semble être associée à une proportion plus élevée d’effets indésirables graves par rapport au CBD, notamment au niveau neuropsychologique et cardiovasculaire. Les professionnels de santé doivent être au courant des particularités du cannabis thérapeutique en termes d’efficacité, de tolérance et d’interactions médicamenteuses.
Impact of COVID-19 lockdown on smoking and vaping: systematic review and meta-analysis
2023, Public Health
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This was a systematic review and meta-analysis.
A systematic literature search was conducted up to 28 April 2022 in the following databases: PubMed, Embase and Web of Science.
In total, 77 studies met the inclusion criteria for this review. In 34 studies, an increase in smoking behaviour was reported for the majority of participants; however, in 21 and 18 studies, ‘no change’ and ‘decrease’ in smoking were the predominant responses, respectively. The results from the meta-analysis, which examined the change in the number of cigarettes smoked per day, showed no difference between the pre- and post-lockdown periods: 0.81 weighted mean difference (95% confidence interval, −0.59 to 2.21). Regarding vaping, three of seven studies reported an increase in smoking for the majority of participants, whereas ‘no change’ and ‘decrease’ were the predominant answers in the other four studies.
The results show that lockdowns led most participants to increase smoking/vaping, whereas a decrease or cessation of smoking/vaping was only reported in the minority of participants. Attention should be given to the non-communicable diseases that could arise as a result of the increase in smoking/vaping during lockdowns, and further research in this area is needed.
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Aggressive, albeit false marketing of electronic nicotine delivery systems (ENDS) or vaping devices as safer alternatives to cigarette smoking, combined with lack of regulations, has led to its mass adoption, especially among youth. A sudden increase in acute lung injuries was noted in 2019 which was linked to ENDS. It was termed by the Centers for Disease Control and Prevention (CDC) as electronic cigarette or vaping product use-associated lung injury (EVALI). Analysis of bronchoalveolar lavage fluid samples linked EVALI to vitamin E acetate (VEA), which is used as a diluting agent for marijuana oils. Patients with EVALI present with a combination of non-specific respiratory, gastrointestinal, and systemic symptoms. Laboratory results may show elevated inflammatory biomarkers. EVALI is a diagnosis of exclusion and must meet the following criteria: i) history of vaping within last 90 days, ii) abnormal chest imaging, iii) negative evaluation for infection, and iv) no other plausible diagnosis. A spectrum of computed tomography (CT) chest findings has been reported in EVALI, ranging from diffuse alveolar damage to organizing pneumonia, characterized by bilateral ground-glass opacities, consolidation, and septal thickening. A similar spectrum is seen on histopathology, characterized by lipid-laden alveolar macrophages, with varying degrees of infiltrative inflammatory cells and fibrin deposition. Early and accurate identification of the EVALI pattern can help optimize patient care. For example, in diffuse alveolar damage (DAD), a lower threshold for ventilation support and corticosteroid may improve outcomes. Here, we review the etiopathogenesis, clinical management, histopathology, and imaging features of EVALI.
Pulmonary and Critical Care Considerations for e-Cigarette, or Vaping, Product Use-Associated Lung Injury
2022, Chest
Citation Excerpt :
Pneumomediastinum, pleural effusions, and pneumothorax have been seen in a minority of patients; a published description of 34 cases reported a variety of imaging patterns that correlated with pathologic investigations, including acute eosinophilic pneumonia, diffuse alveolar damage, organizing pneumonia, and lipoid pneumonia, but noted that most of the patterns identified had basilar-predominant consolidation and ground-glass opacity, often with areas of lobular or subpleural sparing.20 In one case series from Utah of 60 patients with EVALI, pneumothorax or pneumomediastinum was identified in 18%.28 When evaluating a patient with suspected EVALI, the principal alternative diagnosis to consider is an infectious agent presenting with diffuse lung involvement.
In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU.
What are the recent literature and expert opinions which inform the diagnosis and management of patients with critical illness with EVALI?
To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, this study examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts.
Of the 2,708 patients with confirmed or probable EVALI requiring hospitalization as of January 21, 2020, a total of 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%) and in severe cases required intubation (36.1%) or extracorporeal membrane oxygenation (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antiviral agents, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and extracorporeal membrane oxygenation; and patient outcomes.
Review of the clinical course of patients with EVALI requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. Because a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI.

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^†: Contributed equally

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ArticlesClinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and patients

Results

Discussion

Data sharing

Chest

Outbreak of lung injury associated with e-cigarette use, or vaping

Pulmonary illness related to e-cigarette use in Illinois and Wisconsin—preliminary report

N Engl J Med

Vaping-induced lung injury

N Engl J Med

Pulmonary lipid-laden macrophages and vaping

N Engl J Med

Imaging of vaping-associated lung disease

N Engl J Med

Pathology of vaping-associated lung injury

N Engl J Med

About electronic cigarettes (e-cigarettes)

Characteristics of a multistate outbreak of lung injury associated with e-cigarette use, or vaping—United States, 2019

MMWR Morb Mortal Wkly Rep

Quickfacts: Utah

National Center for Chronic Disease Prevention and Health Promotion, Division of Population Health

Vaping-associated acute lung injury: a case series

Am J Respir Crit Care Med

Articles
Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study