Electronic cigarettes (e-cigarettes or e-cigs) are designed to heat and aerosolize mixtures of vegetable glycerin, propylene glycol, nicotine, and flavoring additives, thus delivering nicotine by inhalation in the absence of combustion. These devices were originally developed to facilitate smoking cessation and have been available in the United States for over a decade. Since 2010, e-cig use has expanded rapidly, especially among adolescents, despite a paucity of short- and long-term safety data. Patterns of use have shifted to include never smokers and many dual users of e-cigs and combustible tobacco products. Over the last several years, research into the potential toxicities of e-cig aerosols has grown exponentially. In the interim, regulatory policymakers across the world have struggled with how to regulate an increasingly diverse array of suppliers and products, against a backdrop of strong advocacy from users, manufacturers, and tobacco control experts. Herein we provide an updated review of the pulmonary toxicity profile of these devices, summarizing evidence from cell culture, animal models, and human subjects. We highlight the major gaps in our current understanding, emphasize the challenges confronting the scientific and regulatory communities, and identify areas that require more research in this important and rapidly evolving field.

Stimulation of the antiviral response depends on the sensing of viral pathogen-associated molecular patterns (PAMPs) by specialized cellular proteins. During infection with RNA viruses, 5′-di- or -triphosphates accompanying specific single or double-stranded RNA motifs trigger signaling of intracellular RIG-I-like receptors (RLRs) and initiate the antiviral response. Although these molecular signatures are present during the replication of many viruses, it is unknown whether they are sufficient for strong activation of RLRs during infection. Immunostimulatory defective viral genomes (iDVGs) from Sendai virus (SeV) are among the most potent natural viral triggers of antiviral immunity. Here we describe an RNA motif (DVG70-114) that is essential for the potent immunostimulatory activity of 5′-triphosphate-containing SeV iDVGs. DVG70-114 enhances viral sensing by the host cell independently of the long stretches of complementary RNA flanking the iDVGs, and it retains its stimulatory potential when transferred to otherwise inert viral RNA. In vitro analysis showed that DVG70-114 augments the binding of RIG-I to viral RNA and promotes enhanced RIG-I polymerization, thereby facilitating the onset of the antiviral response. Together, our results define a new natural viral PAMP enhancer motif that promotes viral recognition by RLRs and confers potent immunostimulatory activity to viral RNA.

IntroductionHeated tobacco products are being touted as novel reduced-harm tobacco products by tobacco companies. In the USA, Philip Morris International submitted a modified risk tobacco product (MRTP) application to the US Food and Drug Administration in 2016 in which it purports that its heated tobacco product, I-Quit-Ordinary-Smoking (IQOS), is associated with reduced harm compared with conventional cigarettes.MethodsWe reviewed Philip Morris International’s MRTP application to assess the pulmonary and immune toxicities associated with IQOS use in both animal and human studies.ResultsAmong rats exposed to IQOS, there was evidence of pulmonary inflammation and immunomodulation. In human users, there was no evidence of improvement in pulmonary inflammation or pulmonary function in cigarette smokers who were switched to IQOS.ConclusionIQOS is associated with significant pulmonary and immunomodulatory toxicities with no detectable differences between conventional cigarette smokers and those who were switched to IQOS in Philip Morris International’s studies. Philip Morris International also failed to consider how dual use and secondhand aerosol exposure may further impact, and likely increase, the harms associated with these products.

Key Points Question Did the delivery of services within a cancer system change during the first year of the COVID-19 pandemic? Findings This population-based cohort study conducted in Ontario, Canada, found a total of 4 476 693 cancer care services during the first year of the COVID-19 pandemic, compared with 5 644 105 services in the year prior, representing a reduction of 20.7% and suggesting a backlog of 1 167 412 cancer services during the first pandemic year. Limited change was observed in systemic treatments and emergency or urgent imaging examinations and surgical procedures, while major reductions were observed in cancer screening tests, biopsies, surgical treatments, and new consultations for systemic and radiation treatment. Meaning These findings provide evidence on the deficits in cancer care that occurred during the first year of the COVID-19 pandemic that are likely to inform continued delivery of care, recovery, and future pandemic planning.