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Abstract Portable air purifiers help improve indoor air quality by neutralizing allergens, including animal dander proteins. However, there are limited in-vivo models to assess the efficacy of these devices. Here, we developed a novel animal model of experimental asthma using aerosolized cat dander extract (CDE) exposure and compared the efficacy of select air purification technologies. Mice were exposed to CDE aerosols for 6 weeks in separate custom-built whole-body exposure chambers equipped with either a photoelectrochemical oxidative (PECO) Molekule filtration device (PFD) or a HEPA-assisted air filtration device (HFD) along with positive (a device with no filtration capability) and negative controls. Compared to the positive control group, the CDE-induced airway resistance, and plasma IgE and IL-13 levels were significantly reduced in both air purifier groups. However, PFD mice showed a better attenuation of lung tissue mucous hyperplasia and eosinophilia than HFD and positive control mice, indicating a better efficacy in managing CDE-induced allergic responses. Cat dander protein destruction was evaluated by LCMS proteomic analysis, which revealed the degradation of 2731 unique peptides on PECO media in 1 h. Thus, allergen protein destruction on filtration media enhances air purifier efficacy that could provide relief from allergy responses compared to traditional HEPA-based filtration alone.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Electronic cigarette (e-cig) aerosol exposures are strongly associated with pulmonary dysfunctions, and the airway epithelial cells (AECs) of respiratory passages play a pivotal role in understanding this association. However, not much is known about the effect of synthetic cooling agents such as WS-23 on AECs. WS-23 is a synthetic menthol-like cooling agent widely used to enhance the appeal of e-cigs and to suppress the harshness and bitterness of other e-cig constituents. Using primary human AECs, we compared the effects of aerosolized WS-23 with propylene glycol/vegetable glycerin (PG/VG) vehicle control and nicotine aerosol exposures. AECs treated with 3 % WS-23 aerosols showed a significant increase in viable cell numbers compared to PG/VG-vehicle aerosol exposed cells and cell growth was comparable following 2.5 % nicotine aerosol exposure. AEC inflammatory factors, IL-6 and ICAM-1 levels were significantly suppressed by WS-23 aerosols compared to PG/VG-controls. When differentiated AECs were challenged with WS-23 aerosols, there was a significant increase in secretory mucin MUC5AC expression with no discernible change in airway inflammatory SCGB1A1 expression. Compared to PG/VG-controls, WS-23 or nicotine aerosols presented with increased MUC5AC expression, but there was no synergistic effect of WS-23 + nicotine combination exposure. Thus, WS-23 and nicotine aerosols modulate the AEC responses and induce goblet cell hyperplasia, which could impact the airway physiology and susceptibility to respiratory diseases.

There has been a substantial rise in e-cigarette (e-cig) use or vaping in the past decade, prompting growing concerns about their adverse health effects. Recently, e-cig manufacturers have been using synthetic cooling agents, like WS-23 and WS-3, to provide a cooling sensation without the “menthol taste”. Studies have shown that aerosols/vapes generated by e-cigs can contain significant levels of reactive oxygen species (ROS). However, studies investigating the role of synthetic coolants in modulating ROS levels generated by e-cigs are lacking. This study seeks to understand how synthetic coolants, e-cig additives that have become increasingly prevalent in e-liquids sold in the United States (US), impact acellular ROS production from e-liquid aerosols as well as cellular ROS levels from pulmonary epithelial cells exposed to these e-liquids. To further explain, our study aims to understand whether the addition of WS-3 and WS-23 to e-liquid base and e-liquid base with nicotine significantly modifies generated acellular ROS levels within aerosolized e-liquids, as well as cellular ROS within BEAS-2B cells treated with these same e-liquids. Aerosols were generated from e-liquids with and without synthetic coolants through a single-puff aerosol generator; subsequently, acellular ROS was semi-quantified in H2O2 equivalents via fluorescence spectroscopy. Our acellular ROS data suggest that adding WS-3 to e-liquid base (PG:VG), regardless of nicotine content, has a minimal impact on modifying e-cig generated acellular ROS levels. Additionally, we also measured cellular ROS in lung epithelial cells using both e-liquids containing and not containing synthetic coolants via the CellROX Green fluorescent sensor. Similar comparable results were found in BEAS2B cells though ROS was increased by WS-3 and WS-23 treated in e-cig nicotine groups. Altogether, our data suggest that neither the addition of WS-23 nor WS-3 to e-liquid base solution, with and without nicotine, significantly modifies e-cig generated acellular ROS levels within aerosolized e-liquids and cellular ROS levels within treated BEAS-2B cells. Together, our data provide insight into whether synthetic coolants added to e-liquids could impact vaping-induced oxidative stress in the lungs.

SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and the generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting in the emergence of several lineages and variants of concern (VOC) that have gained more efficient transmission, severity, and immune evasion properties. The World Health Organization has given these variants names according to the letters of the Greek Alphabet, starting with the Alpha (B.1.1.7) variant, which emerged in 2020, followed by the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. This review explores the genetic variation among different VOCs of SARS-CoV-2 and how the emergence of variants made a global impact on the pandemic.

Summary: Noncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression of IL-6, ICAM-1, CXCL-8, and SCGB1A1 inflammatory factors; MUC5AC and MUC5B mucins; and SPDEF, FOXA3, and FOXJ1 transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 or LASI was induced 2-fold in COVID-19 patients, and its expression was directly correlated with viral loads. A SARS-CoV-2-infected 3D-airway model largely recapitulated these clinical findings. RNA microscopy and molecular modeling indicated a possible interaction between viral RNA and LASI lncRNA. Notably, blocking LASI lncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and select LASI-dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus, LASI lncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response.

Research ImpactCigarette smoke (CS) exposure is strongly associated with chronic obstructive pulmonary disease (COPD). In respiratory airways, CS exposure disrupts airway barrier functions, mucous/phlegm production, and basic immune responses of airway epithelial cells. Based on our recent identification of a specific immunomodulatory long noncoding RNA (lncRNA), we investigated its role in CS-induced responses in bronchial airways of cynomolgus macaque model of CS-induced COPD and in former smokers with and without COPD. The lncRNA was significantly upregulated in CS-induced macaque airways and in COPD airways that exhibited higher mucus expression and goblet cell hyperplasia. Experimental models of cells derived from COPD subjects recapitulated the augmented inflammation and mucus expression following the smoke challenge. Blocking of lncRNA expression in cell culture setting suppressed the smoke-induced and COPD-associated dysregulated mucoinflammatory response suggesting that this airway specific immunomodulatory lncRNA may represent a novel target to mitigate the smoke-mediated inflammation and mucus hyperexpression.RationaleIn conducting airways, CS disrupts airway epithelial functions, mucociliary clearances, and innate immune responses that are primarily orchestrated by human bronchial epithelial cells (HBECs). Mucus hypersecretion and dysregulated immune response are the hallmarks of chronic bronchitis (CB) that is often exacerbated by CS. Notably, we recently identified a long noncoding RNA (lncRNA) antisense to ICAM-1 (LASI) that mediates airway epithelial responses.ObjectiveTo investigate the role of LASI lncRNA in CS-induced airway inflammation and mucin hyperexpression in an animal model of COPD, and in HBECs and lung tissues from former smokers with and without COPD. To interrogate LASI lncRNA role in CS-mediated airway mucoinflammatory responses by targeted gene editing.MethodsSmall airway tissue sections from cynomolgus macaques exposed to long-term mainstream CS, and those from former smokers with and without COPD were analyzed. The structured-illumination imaging, RNA fluorescence in-situ hybridization (FISH), and qRT-PCR were used to characterize lncRNA expression and the expression of inflammatory factors and airway mucins in a cell culture model of CS extract (CSE) exposure using HBECs from COPD (CHBEs) in comparison with cells from normal control (NHBEs) subjects. The protein levels of mucin MUC5AC, and inflammatory factors ICAM-1, and IL-6 were determined using specific ELISAs. RNA silencing was used to block LASI lncRNA expression and lentivirus encoding LASI lncRNA was used to achieve LASI overexpression (LASI-OE).ResultsCompared to controls, LASI lncRNA was upregulated in CS-exposed macaques and in COPD smoker airways, correlating with mucus hyperexpression and mucus cell hyperplasia in severe COPD airways. At baseline, the unstimulated CHBEs showed increased LASI lncRNA expression with higher expression of secretory mucin MUC5AC, and inflammatory factors, ICAM-1, and IL-6 compared to NHBEs. CSE exposure of CHBEs resulted in augmented inflammation and mucus expression compared to controls. While RNA silencing-mediated LASI knockdown suppressed the mucoinflammatory response, cells overexpressing LASI lncRNA showed elevated mRNA levels of inflammatory factors.ConclusionsAltogether, LASI lncRNA may represent a novel target to control the smoke-mediated dysregulation in airway responses and COPD exacerbations.