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Amid a potential menthol ban, electronic cigarette (e-cigarette) companies are incorporating synthetic cooling agents like WS-3 and WS-23 to replicate menthol/mint sensations. This study examines public views on synthetic cooling agents in e-cigarettes via Twitter data. From May 2021 to March 2023, we used Twitter Streaming Application Programming Interface (API), to collect tweets related to synthetic cooling agents with keywords such as ‘WS-23,’ ’ice,’ and ’frozen.’ The deep learning RoBERTa (Robustly Optimized BERT-Pretraining Approach) model that can be optimized for contextual language understanding was used to classify attitudes expressed in tweets about synthetic cooling agents and identify e-cigarette users. The BERTopic (a topic modeling technique that leverages Bidirectional Encoder Representations from Transformers) deep-learning model, specializing in extracting and clustering topics from large texts, identified major topics of positive and negative tweets. Two proportion Z-tests were used to compare the proportions of positive and negative attitudes between e-cigarette users (vapers) and non-e-cigarette-users (non-vapers). Of 6,940,065 e-cigarettes-related tweets, 5,788 were non-commercial tweets related to synthetic cooling agents. The longitudinal trend analysis showed a clear upward trend in discussions. Vapers posted most of the tweets (73.05%, 4,228/5,788). Nearly half (47.87%, 2,771/5,788) held a positive attitude toward synthetic cooling agents, which is significantly higher than those with a negative attitude (19.92%,1,153/5,788) with a P-value < 0.0001. The likelihood of vapers expressing positive attitudes (60.17%, 2,544/4,228) was significantly higher ( P < 0.0001) than that of non-vapers (14.55%, 227/1,560). Conversely, negative attitudes from non-vapers (30%, 468/1,560) were significantly ( P < 0.0001) higher than vapers (16.2%, 685/4,228). Prevalent topics from positive tweets included “enjoyment of specific vape flavors,” “preference for lush ice vapes,” and “liking of minty/icy feelings.” Major topics from negative tweets included “disliking certain vape flavors” and “dislike of others vaping around them.” On Twitter, vapers are more likely to have a positive attitude toward synthetic cooling agents than non-vapers. Our study provides important insights into how the public perceives synthetic cooling agents in e-cigarettes. These insights are crucial for shaping future U.S. Food and Drug Administration (FDA) regulations aimed at safeguarding public health.

Abstract Rationale Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal. Objectives To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma. Methods In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6–17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression. Measurements and Main Results RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, −0.77 to −0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49–0.84). Conclusions In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).

Egg allergy is a common and difficult pediatric problem. In this trial, the investigators found that oral treatment with escalating doses of egg protein enabled about one in four children with known egg allergy to eat egg without allergic symptoms. In the United States, 4% of children have a food allergy, 1 which affects health and quality of life. 2 Egg allergy has a cumulative prevalence of approximately 2.6% by 2.5 years of age, 3 with allergic reactions varying in severity from mild urticaria to systemic anaphylaxis. Severe allergic reactions can occur with a single bite of cooked egg (approximately 70 mg of egg protein). Children with egg allergy are placed on egg-free diets, but total avoidance of egg is difficult. Avoidance places a constant responsibility on patients and caregivers, leaves patients vulnerable to unintentional ingestion and anaphylaxis, and influences quality of life. . . .

In this study, the introduction of guidelines-based therapy in all children decreased the number of days per fortnight that children had asthma symptoms. Treatment with omalizumab resulted in fewer days with asthma symptoms than placebo. Studies of inner-city children, adolescents, and young adults with asthma show that symptom control is improved and exacerbations are decreased when there is either a reduction in household exposure to allergens 1 or aggressive implementation of guidelines-based therapy. 2 Nonetheless, achieving disease control remains difficult, necessitating a need for additional treatment. For patients with allergies who have asthma that is not controlled with implementation of the higher treatment steps of the most recent guidelines from the National Asthma Education and Prevention Program (NAEPP) (Expert Panel Report 3), omalizumab, a humanized monoclonal anti-IgE antibody, is recommended. 3 – 9 Anti-IgE treatment reduces exacerbations, symptoms and, . . .

Mepolizumab (anti-IL5 therapy) reduces asthma exacerbations in urban children with exacerbation-prone eosinophilic asthma. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with asthma exacerbations despite this therapy. In this study, we applied differential gene correlation analysis on these targeted gene co-expression modules to gain better insight into the treatment effects on correlation structure within gene networks. Mepolizumab treatment resulted in loss of correlation amongst eosinophil-specific genes but conservation and even strengthening of correlation amongst mast cell-specific genes, T2 cytokines, and airway epithelial inflammatory genes. Notably, mepolizumab induced significant gain in correlation of genes associated with multiple aspects of airway epithelial inflammation including those related to extracellular matrix production and nitric oxide synthesis, and this change was associated with a poor clinical response to mepolizumab. These findings highlight that using differential gene correlation analysis offers insight into the molecular regulatory effects of treatment on gene interactions and may lead to better understanding of disease mechanisms and therapeutic responses. ClinicalTrials.gov ID: NCT03292588. Mepolizumab (anti-IL-5 therapy) has been shown to reduce type 2 inflammation in asthma. Here the authors use bulk transcriptomics from nasal samples before and after mepolizumab treatment to assess the changes and associations with treatment outcomes.

Background Respiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections ( CCL8 / CXCL11 ), we screened 92 asthmatic and 69 healthy children without illness for respiratory virus infections. Results We found 21 viral qPCR-positive and 2 suspected virus-infected subjects with high expression of CCL8/CXCL11 . We applied a dual RNA-seq workflow to these subjects, together with 25 viral qPCR-negative subjects, to compare qPCR with sequencing-based virus detection and to generate the airway transcriptome for analysis. RNA-seq virus detection achieved 86% sensitivity when compared to qPCR-based screening. We detected additional respiratory viruses in the two CCL8/CXCL11 -high subjects and in two of the qPCR-negative subjects. Viral read counts varied widely and were used to stratify subjects into Virus-High and Virus-Low groups. Examination of the host airway transcriptome found that the Virus-High group was characterized by immune cell airway infiltration, downregulation of cilia genes, and dampening of type 2 inflammation. Even the Virus-Low group was differentiated from the No-Virus group by 100 genes, some involved in eIF2 signaling. Conclusions Respiratory virus infection without illness is not innocuous but may determine the airway function of these subjects by driving immune cell airway infiltration, cellular remodeling, and alteration of asthmogenic gene expression.

Background Air pollution is associated with poor asthma outcomes in children. However, most studies focus on ambient or indoor monitor pollution levels. Few studies evaluate breathing zone exposures, which may be more consequential for asthma outcomes. Methods We measured personal exposures to NO 2 , O 3 , PM 10 and PM 10 constituents, including black carbon (BC), brown carbon (BrC), environmental tobacco smoke (ETS), endotoxins, and 𝛽-glucan, in a cohort of children with exacerbation-prone asthma for 72 h using wearable monitors. Personal exposures were compared to concentrations from in-home monitors in the child’s bedroom and ambient EPA air quality monitoring using correlation analyses. Personal exposures were tested for association with lung function and compared between participants with and without well-controlled asthma and signs of exacerbation in the prior 60 days using censored regression with robust standard errors. Results 81 children completed 219 monitoring sessions. Personal NO 2 , O 3 , and PM 10 exposures ranged from < 2 to 99.1 parts per billion (ppb), < 1.5 to 23.3 ppb, and < 1 to 141.9 𝜇g/m 3 , respectively. Personal endotoxin ranged from 0.04 to 101.3 EU/m 3 , 𝛽-glucan from 18.5 to 1,162 pg/m 3 , BC from < 0.3 to 46.9 𝜇g/m 3 , BrC from < 0.3 to 6.1 𝜇g/m 3 , and ETS from < 0.3 to 56.6 𝜇g/m 3 . Correlations between personal and ambient PM 10 , NO 2 , and O 3 concentrations were poor, whereas personal PM 10 and NO 2 correlated with in-home concentrations. In-home monitoring less frequently detected BrC (Personal:79% > lower limit of detection, Home:36.8%) and ETS (Personal:83.7%, Home:4.1%) than personal exposures, and detected BC in participants without personal exposure (Personal: 26.5%, Home: 96%). Personal exposures were not significantly associated with lung function or daily asthma control. Children requiring corticosteroid treatment for asthma exacerbation within 60 days of exposure monitoring had 1.98, 2.21 and 2.04 times higher personal exposures to BrC ( p  < 0.001; 95% CI: 1.43–2.37), ETS ( p  = 0.007; 95% CI: 1.25–3.91), and endotoxin ( p  = 0.012; 95% CI: 1.14–3.68), respectively. Conclusions Although in-home monitoring was correlated with personal exposure to PM 10 and NO 2 , in-home detection of ETS and BrC was not associated with personal exposures. Personal PM 10 exposures in general, as well as BrC, ETS, and endotoxin levels were associated with recent childhood asthma exacerbations. Clinical trial number Not applicable.

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV 1 ) (p = 2.4x10 -9 ; β z = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV 1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV 1 -associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV 1 risk alleles (p = 1.3x10 -5 ; β = 0.12, 95% CI = 0.06–0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure.

Asthma afflicts an estimated 339 million people globally and is associated with ill health, disability, and early death. Strong risk factors for developing asthma are genetic predisposition and environmental exposure to inhaled substances that may provoke allergic reactions. Asthma guidelines recommend identifying causal or trigger allergens with specific IgE (slgE) testing after a diagnosis of asthma has been made. Allergy testing with slgE targets subpopulations of patients considered at high risk, such as those with frequent exacerbations, emergency visits or hospitalizations, or uncontrolled symptoms. Specific recommendations apply to preschool children, school-age children, patients with persistent or difficult-to-control asthma, patients needing oral corticosteroids or high-dose inhaled steroids, patients seeking understanding and guidance about their disease, and candidates for advanced therapies (biologics, allergen immunotherapy). Allergen skin testing is common in specialized settings but less available in primary care. Blood tests for total and slgE are accessible and yield quantifiable results for tested allergens, useful for detecting sensitization. Results are interpreted in the context of the patient's clinical presentation, age, and relevant allergen exposures. Incorporating slgE testing into asthma management adds objective information to identify specific allergies and can guide personalized treatment plans, which reinforce patient-doctor communication. Test results can also be used to predict exacerbations and response to therapies. Additional diagnostic information can be gleaned from (i) eosinophil count >300 [micro]L, which significantly increases the odds of having exacerbations, and emerging eosinophil biomarkers (eg, eosinophil-derived neurotoxin), which can be measured in plasma or serum samples, and (ii) fractional exhaled nitric oxide (FeNO), with values >25 ppb regarded as the cutoff for diagnosis, evaluating inhaled corticosteroid response, and of probable response to anti-IgE, anti-IL4 and anti-IL5 receptor biologics. Referral to asthma/allergy specialists is warranted when the initial diagnosis is uncertain, and when asthma symptoms, impairment, or exacerbations are repeated or severe. Keywords: primary care, allergy, asthma, sensitization, specific IgE, component resolved diagnostics

Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently, no effective treatment for RV infection is available. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), are potent regulators of inflammatory processes and exert antiviral activity against respiratory syncytial virus (RSV) and influenza A viruses (IAV). In the current study, we examined the potencies of POPG and PI against rhinovirus A16 (RV-A16) in primary human airway epithelial cells (AECs) differentiated at an air–liquid interface (ALI). After AECs were infected with RV-A16, PI reduced the viral RNA copy number by 70% and downregulated (55–75%) the expression of antiviral (MDA5, IRF7, and IFN-lambda) and CXCL11 chemokine genes. In contrast, POPG only slightly decreased MDA5 (24%) and IRF7 (11%) gene expression but did not inhibit IFN-lambda gene expression or RV-A16 replication in AECs. However, both POPG and PI inhibited (50–80%) IL6 gene expression and protein secretion and CXCL11 protein secretion. PI treatment dramatically attenuated global gene expression changes induced by RV-A16 infection alone in AECs. The observed inhibitory effects were indirect and resulted mainly from the inhibition of virus replication. Cell-type enrichment analysis of viral-regulated genes opposed by PI treatment revealed the PI-inhibited viral induction of goblet cell metaplasia and the virus-induced downregulation of ciliated, club, and ionocyte cell types. Notably, the PI treatment also altered the ability of RV-A16 to regulate the expression of some phosphatidylinositol 4-kinase (PI4K); acyl-CoA-binding, domain-containing (ACBD); and low-density lipoprotein receptor (LDLR) genes that play critical roles in the formation and functioning of replication organelles (ROs) required for RV replication in host cells. These data suggest PI can be used as a potent, non-toxic, antiviral agent for RV infection prophylaxis and treatment.