A similar pattern was demonstrated in a clinically relevant model of pneumococcal pneumonia after antibiotic treatment,and other animal models have also shown that cigarette smoke increases alveolar epithelial-capillary permeability and susceptibility to lung injury.The relationship between cigarette smoking and COVID-19, which in 2020 was the leading cause of ARDS in the United States,is unclear. There is evidence that the receptor for severe acute respiratory syndrome coronavirus 2 , angiotensin-converting enzyme 2 , is more highly expressed in the lung epithelium of smokers than in nonsmokers. It is not obvious from the available data, however, that this leads to an increased risk of SARS-CoV-2 infection or worse outcomes from COVID-19. In fact, smokers are disproportionately underrepresented among patients with COVID-19.It has been proposed that nicotine as an isolated substance may have a protective effect in COVID-19.The relationships among cigarette smoking, ACE2, nicotine, and inflammation are complex, and a full understanding of the implications of smoking on COVID-19 pathogenesis and outcomes requires further study.E-cigarette use has increased among young people in recent years.Furthermore, using e-cigarettes increases the likelihood of future cigarette smoking among children and adolescents,is associated with increased rates of smoking initiation in adults, and increases the risk of relapse among former cigarette smokers.Therefore,rolling grow tables promoting vaping as a harm reduction strategy from traditional cigarettes may be misguided. E-cigarette use likely has negative implications for long-term health based on the cellular and molecular mechanisms it affects, although confirming this will require longitudinal studies.
In addition, e-cigarettes pose an increased public health risk as a direct cause of ALI. An outbreak of EVALI, mostly among patients younger than 35 years, emerged in the United States in the spring and summer of 2019. The Centers for Disease Control and Prevention has reported more 2800 cases and 68 deaths.The diagnostic criteria are vaping within the prior 90 days and a new infiltrate on chest imaging in the absence of pulmonary infection.EVALI most commonly presents as acute to sub-acute constitutional and respiratory symptoms with radiographic findings of bilateral ground glassopacities .In one case series, 26% of patients required mechanical ventilation, and approximately 12% of patients met the Berlin criteria for ARDS by chart review. Vitamin E acetate is likely the major causative agent among patients with EVALI. In one case series of patients from 16 different states, VEA was found in 94% of BAL fluid samples from patients with EVALI and in none of the samples from healthy comparators.Most patients report using tetrahydrocannabinol products, in which VEA is frequently used as a diluent,although some report exclusively using nicotine-based products.The effect of VEA was recently studied in a murine model and in primary alveolar type II cell culture.In the mouse model, exposure to aerosolized VEA resulted in significantly increased BAL protein, excess lung water, and BAL biomarkers of alveolar epithelial damage and inflammation when compared with aerosolized tobacco or vegetable glycerin and propylene glycol. Histologic patterns closely mirrored those found in patients with EVALI.VEA was also found to cause direct, dose-dependent ATII toxicity.Because of the many ingredients found in e-cigarettes and the use of unregulated products,however, identifying a single culprit in EVALI is difficult.
It is unknown whether chronic e-cigarette use also increases the risk of developing ARDS from other causes. Studies of cigarette smoke exposure and ARDS using biomarkers for nicotine may have included patients who were using both traditional cigarettes and e-cigarettes, and smoking histories in medical records do not always describe whether patients also vape. E-cigarette vapor both with and without nicotine increases rat endothelial cell permeability in vitro, although the effect is more pronounced with nicotine.Mice chronically exposed to e-cigarette vapor with and without nicotine demonstrate altered lipid homeostasis in alveolar macrophages and changes to ATII lamellar body ultrastructure, which may indicate that e-cigarettes disrupt surfactant production.Chronic e-cigarette exposure also delays the immune response and results in worse lung injury in mice exposed to influenza.Similar changes in humans could plausibly prime the lung for injury as with cigarette use.Further studies should examine whether e-cigarettes increase the risk of developing ARDS from infection, trauma, or other causes.Regardless of the environmental risk factors for ARDS, the cornerstones of diagnosis and management remain the same. None of the aforementioned exposures, includinge-cigarettes, results in a unique radiographic appearance,and clinicians should use the Berlin criteria for ARDS for diagnosis.Workup should include a thorough investigation of possible pulmonary and extrapulmonary infections, including viral pneumonia, and bronchoscopy may be warranted.Understanding the environmental risk factors for ARDS underscores the importance of an accurate exposure history. For example, patients or surrogates should be asked about both personal use of cigarettes and passive cigarette smoke exposure.
A thorough history should also include questions about e-cigarette use , regardless of whether patients also use combustible cigarettes. Providers should ask about product type; duration and frequency of use; use of nicotine-based products, cannabis products, or both; additives; and where the patient obtains their product.Although corticosteroids are frequently used in EVALI,this treatment has not been assessed in prospective randomized trials. Similarly, there is no pharmacotherapy specific to patients who smoke or who have been exposed to environmental pollutants. Management should therefore be based on the evidence-supported strategies of lung protective ventilation,conservative fluid management,and early prone positioning when PaO2/ fraction of inspired oxygen is less than 150 mm Hg.The period during and after critical illness may be a unique opportunity for clinicians to encourage smoking and vaping cessation. Behavioral counseling for hospitalized patients, including critically ill patients, can lead to increased abstinence from smoking.Providers caring for ICU survivors may also have an opportunity to encourage smoking cessation or continued abstinence.Current American Thoracic Society guidelines recommend pharmacologic therapy with varenicline and nicotine replacement for smoking cessation in adults.Initiating varenicline therapy in critically ill patients has not been studied, and the role of nicotine replacement therapy in critically ill patients is not well established.Research about pharmacologic therapy for teenagers who use cigarettes or electronic cigarettes is limited. The American Academy of Pediatrics recommends behavioral interventions, adding pharmacologic therapy depending on the severity of tobacco dependence.The best approach for addressing tobacco dependence or e-cigarette use in patients with ARDS requires further investigation. Other exposures such as pollution and wildfire smoke are best addressed by public policy, which also plays a crucial role in smoking and vaping cessation.The emerging data about chronic exposures and the risk of ARDS underscores how policy-level interventions impact the practice of critical care. Policy provides opportunities to fill current knowledge gaps through research funding and to limit risks of environmental exposures on a population level. Air quality measures and wildfire mitigation largely depend on public health and policy strategies. Upholding safe air quality standards is necessary to limit population-level exposure, but ambient pollution and the risk of wildfires will continue to increase as climate change progresses. The ATS has made climate change a priority for its public health and research agenda,4×8 grow tables citing the risk posed to cardiopulmonary health.Patient-level interventions are important for smoking and vaping cessation, but they should be part of a larger policy agenda . Declining smoking rates are one of the great public health achievements of the twentieth and twenty-first centuries, and there are still many opportunities for progress such as expanded laws mandating smoke-free public environments, ongoing public awareness campaigns, and widespread adoption of evidence-based treatment of tobacco users.The emergence of e-cigarettes and other alternative nicotine and cannabis delivery systems require new regulatory efforts. The Food and Drug Administration has recently started enforcing regulations of flavored e-cigarette cartridges, for example, but many products still fall outside of this enforcement effort.
Illicit products necessarily are not subject to FDA regulations. Rates of EVALI may be higher in regions where cannabis is illegal,and because it remains so on a federal level, there are no federal guidelines for the safe manufacturing or use of cannabis vaping products. There are also federal limitations on cannabis research, which restrict opportunities to study short- and long term pulmonary effects of THC exposure. Future research and policy priorities should focus on continuing to limit exposures that increase ARDS risk on both an individual and the population level. Researchers should investigate the optimum timing and method for encouraging smoking cessation after critical illness, including whether it may be appropriate to initiate pharmacologic therapy in the ICU. Priorities for e-cigarettes include strict safety standards, investigating whether e-cigarette exposure increases the risk of ARDS from other causes, and expanding research of potentially harmful electronic marijuana delivery systems. Public messaging about air quality standards should be expanded, and the medical community should continue to raise awareness about the impact of climate change on pollutants that threaten cardiopulmonary health. In summary, the scientific understanding of how environmental exposures increase the risk of ARDS is well established, but there is much to be learned. There are many opportunities to expand our knowledge and implement policy-level changes to continue combat this deadly syndrome.In the USA, synthetic cannabinoids have been detected in products obtained via smoke shops, gas stations and the Internet . Many of these substances are surmised to be full agonists of cannabinoid receptor 1 and cannabinoid receptor 2 . The consumption of synthetic cannabinoids and related products has been linked to adverse effects including agitation, confusion, hypertension, respiration issues, seizures, tachycardia, paranoia, hallucinations, psychoses and acute kidney injury . They have also been associated with several driving under the influence or impairment cases and have been implicated in human deaths . During the summer of 2012, President Obama signed legislation which placed 15 synthetic cannabinoid compounds and 5 overall cannabinoid structural classes into Schedule I of the Controlled Substances Act . These compounds include, but are not limited to, AM-2201, JWH-018, JWH-019, JWH-073 and JWH-122 . The tetramethylcyclopropylindole cannabinoids, UR-144 and XLR-11, became prevalent for much of the remaining portion of 2012 and were ultimately controlled by the Federal government in April 2013 . In early 2013, a new wave of compounds that contained a large change in chemical structure emerged and are classified as quinolinyl carboxylate derivatives. 1–1H-indole-3-carboxylic acid 8-quinolinyl ester, also known as 5F-PB-22, is a quinolinyl carboxylate derivative that differs from the earlier generation naphthoylindole, AM-2201, by replacing the naphthalene group with an 8-hydroxyquinoline moiety . Pharmacological and toxicological data for this compound do not currently exist, but similar to other synthetic cannabinoids, it is expected to be a CB1 and CB2 receptor agonist. Currently, this compound is considered a controlled substance in the states of Minnesota and Florida. On 10 January 2014, the US government temporarily placed four synthetic cannabinoids, including 5F-PB-22, into Schedule I of the CSA via emergency schedule . We describe a liquid chromatography with tandem mass spectrometry method for the quantitation of 5F-PB-22 in blood and report a series of four fatalities involving these compounds.Forensic pathologists collected blood specimens in polypropylene tubes containing sodium fluoride and EDTA during standard autopsy procedures before transporting to the laboratory at ambient temperature for toxicological analyses. Methodologies utilized in the analyses include an enzyme-linked immunosorbent assay screen for classical cannabinoids and opiates/ opioids, a liquid chromatography– time-of-flight mass spectrometry screen for other abused drugs and therapeutic agents, and a headspace-gas chromatography with flame ionization detection screen for volatile compounds. Synthetic cannabinoids were analyzed via a directed analysis by LC–MS-MS.Here, we describe four postmortem case reports that include the detection and quantitative determination of the synthetic cannabinoid, 5F-PB-22, in blood or antemortem serum. The cases were received by our laboratory during a 4-month period , prior to 5F-PB-22, and three other synthetic cannabinoid compounds, gaining the designation as Schedule I in the CSA. The decedents in all cases were young males; three teenage and one 27 year old. Three cases presented as relatively sudden or abrupt episodes following a history of ‘partying’ in the company of others. In Case 2, the decedent presented with several acute medical problems which progressively became worse during an intensive care unit hospital stay. The most prominent autopsy findings were associated with Case 2 ; Cases 3 and 4 exhibited relatively nonspecific findings . The observed concentration range of 5F-PB-22 is 1.1 –1.5 ng/mL for three postmortem blood specimens and one antemortem serum specimen. Other remarkable toxicology findings included ethanol and THCCOOH ; other findings were consistent with medical intervention .