Impact of Nonpharmaceutical Interventions during the COVID-19 Pandemic on the Prevalence of Respiratory Syncytial Virus in Hospitalized Children with Lower Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

During the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were implemented in order to control the transmission of SARS-CoV-2, potentially affecting the prevalence of respiratory syncytial virus (RSV). This review evaluated the impact of NPIs on RSV-related hospitalizations in children during the lockdown (2020-2021) compared to the pre-pandemic (2015-2020) and post-lockdown (2021-2022) periods. In this systematic review and meta-analysis, we searched through PubMed, Scopus, and Web of Science for studies published in English between 1 January 2015 and 31 December 2022. Additionally, we conducted hand searches of other records published between 1 January 2023 and 22 January 2024. Our target population was hospitalized children aged 0-18 years with RSV-related lower respiratory tract infections confirmed through immunofluorescence, antigen testing, or molecular assays. We focused on peer-reviewed observational studies, analyzing the primary outcome of pooled RSV prevalence. A generalized linear mixed model with a random-effects model was utilized to pool each RSV prevalence. Heterogeneity was assessed using Cochran's Q and I2 statistics, while publication bias was evaluated through funnel plots and Egger's tests. We identified and analyzed 5815 publications and included 112 studies with 308,985 participants. Notably, RSV prevalence was significantly lower during the lockdown period (5.03% [95% CI: 2.67; 9.28]) than during the pre-pandemic period (25.60% [95% CI: 22.57; 28.88], p < 0.0001). However, RSV prevalence increased notably in the post-lockdown period after the relaxation of COVID-19 prevention measures (42.02% [95% CI: 31.49; 53.33] vs. 5.03% [95% CI: 2.67; 9.28], p < 0.0001). Most pooled effect estimates exhibited significant heterogeneity (I2: 91.2% to 99.3%). Our findings emphasize the effectiveness of NPIs in reducing RSV transmission. NPIs should be considered significant public health measures to address RSV outbreaks.

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation.

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.

Whole Blood Expression Levels of Long Noncoding RNAs: HOTAIRM1, GAS5, MZF1-AS1, and OIP5-AS1 as Biomarkers in Adolescents with Obesity-Related Asthma.

Asthma is a heterogeneous entity encompassing distinct endotypes and varying phenotypes, characterized by common clinical manifestations, such as shortness of breath, wheezing, and variable airflow obstruction. Two major asthma endotypes based on molecular patterns are described: type 2 endotype (allergic-asthma) and T2 low endotype (obesity-related asthma). Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides in length, currently involved in many diverse biological functions, such as chromatin remodeling, gene transcription, protein transport, and microRNA processing. Despite the efforts to accurately classify and discriminate all the asthma endotypes and phenotypes, if long noncoding RNAs could play a role as biomarkers in allergic asthmatic and adolescent obesity-related asthma, adolescents remain unknown. To compare expression levels of lncRNAs: HOTAIRM1, OIP5-AS1, MZF1-AS1, and GAS5 from whole blood of Healthy Adolescents (HA), Obese adolescents (O), allergic asthmatic adolescents (AA) and Obesity-related asthma adolescents (OA). We measured and compared expression levels from the whole blood of the groups mentioned above through RT-q-PCR. We found differentially expressed levels of these lncRNAs between the groups of interest. In addition, we found a discriminative value of previously mentioned lncRNAs between studied groups. Finally, we generated an interaction network through bioinformatics. Expression levels of OIP5-AS1, MZF1-AS1, HOTAIRM1, and GAS5 in whole blood from the healthy adolescent population, obese adolescents, allergic asthma adolescents, and obesity-related asthma adolescents are differently expressed. Moreover, these lncRNAs could act as molecular biomarkers that help to discriminate between all studied groups, probably through molecular mechanisms with several genes and miRNAs implicated.

Negative Effects of Chronic High Intake of Fructose on Lung Diseases.

In the modern diet, excessive fructose intake (>50 g/day) had been driven by the increase, in recent decades, of the consumption of sugar-sweetened beverages. This phenomenon has dramatically increased within the Caribbean and Latin American regions. Epidemiological studies show that chronic high intake of fructose related to sugar-sweetened beverages increases the risk of developing several non-communicable diseases, such as chronic obstructive pulmonary disease and asthma, and may also contribute to the exacerbation of lung diseases, such as COVID-19. Evidence supports several mechanisms­such as dysregulation of the renin−angiotensin system, increased uric acid production, induction of aldose reductase activity, production of advanced glycation end-products, and activation of the mTORC1 pathway­that can be implicated in lung damage. This review addresses how these pathophysiologic and molecular mechanisms may explain the lung damage resulting from high intake of fructose.

Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma.

A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of RORC, IL17A, and TNFA. However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between RORC, IL17A, and TNFA methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11-18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of RORC, IL17A, and TNFA than the HP group. Notably, the OAP group presents lower RORC promoter methylation status than the OP group. Interestingly, RORC promoter methylation status was moderately negatively associated with gene expression of RORC (r s = -0.39, p < 0.001) and IL17A (r s = -0.37, p < 0.01), respectively. Similarly, the promoter methylation pattern of IL17A was moderately negatively correlated with IL17A gene expression (r s = -0.3, p < 0.01). There is also a moderate inverse relationship between TNFA promoter methylation status and TNFA gene expression (r s = -0.3, p < 0.01). The present study suggests an association between lower RORC, IL17A, and TNFA gene promoter methylation status with obesity-related asthma and allergic asthma. RORC, IL17A, and TNFA gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate RORC, IL17A, and TNF gene expression in both asthmatic phenotypes.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents.

BACKGROUND: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. OBJECTIVE: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. METHODS: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). RESULTS: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8-76.0] vs. 23.5 ng/mL [95% CI: 3.2-33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7-26.5] vs. 15.9 ng/mL [95% CI: 9.4-18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599-0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554-0.819, p = 0.008), considered fair. CONCLUSIONS: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents

Background: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. Objective: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. Methods: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). Results: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8–76.0] vs. 23.5 ng/mL [95% CI: 3.2–33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7–26.5] vs. 15.9 ng/mL [95% CI: 9.4–18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599–0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554–0.819, p = 0.008), considered fair Conclusions: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice (AU)

Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents.

Obesity is associated with a unique non-T2 asthma phenotype, characterised by a Th17 immune response. Retinoid-related orphan receptor C (RORC) is the master transcription factor for Th17 polarisation. We investigated the association of TNFA, IL17A, and RORC mRNA expression levels with the non-T2 phenotype. We conducted a cross-sectional study in adolescents, subdivided as follows: healthy (HA), allergic asthma without obesity (AA), obesity without asthma (OB), and non-allergic asthma with obesity (NAO). TNFA, IL17A, and RORC mRNA expression in peripheral blood leukocytes were assessed by RT-PCR. NAO exhibited higher TNFA mRNA expression levels than HA or OB, as well as the highest IL17A and RORC mRNA expression levels among the four groups. The best biomarker for discriminating non-allergic asthma among obese adolescents was RORC mRNA expression levels (area under the curve: 0.95). RORC mRNA expression levels were associated with the non-T2 asthma phenotype, hinting at a therapeutic target in obesity-related asthma.

IL-17A and TNF-α as potential biomarkers for acute respiratory distress syndrome and mortality in patients with obesity and COVID-19.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and international health emergency by the World Health Organization. Patients with obesity with COVID-19 are 7 times more likely to need invasive mechanical ventilation than are patients without obesity (OR 7.36; 95% CI: 1.63-33.14, p = 0.021). Acute respiratory distress syndrome (ARDS) is one of the main causes of death related to COVID-19 and is triggered by a cytokine storm that damages the respiratory epithelium. Interleukins that cause the chronic low-grade inflammatory state of obesity, such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant peptide (MCP)-1, and, in particular, IL-17A and tumour necrosis factor alpha (TNF-α), also play very important roles in lung damage in ARDS. Therefore, obesity is associated with an immune state favourable to a cytokine storm. Our hypothesis is that serum concentrations of TNF-α and IL-17A are more elevated in patients with obesity and COVID-19, and consequently, they have a greater probability of developing ARDS and death. The immunobiology of IL-17A and TNF-α opens a new fascinating field of research for COVID-19.

Decreased methylation profiles in the TNFA gene promoters in type 1 macrophages and in the IL17A and RORC gene promoters in Th17 lymphocytes have a causal association with non-atopic asthma caused by obesity: A hypothesis.

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.

Effect of supplementation with omega-3 fatty acids on hypertriglyceridemia in pediatric patients with obesity.

Background The beneficial effects of treating hypertriglyceridemic adults with omega-3 fatty acids have been reported. However, information regarding omega-3 treatment of pediatric patients is limited. To evaluate the efficacy and safety of administering omega-3 fatty acids (3 g/day for 12 weeks) to children/adolescents with obesity and hypertriglyceridemia. Methods A randomized, double-blind, placebo-controlled, parallel study involving pediatric patients (10-16 years old) with obesity and hypertriglyceridemia was conducted. The National Center for Health Statistics (CDC) defines obesity as a body mass index (BMI) ≥95th percentile. Subjects with triglyceride concentrations ranging from 150 to 1000 mg/dL were randomized into two groups: those receiving omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) (n = 65) and those receiving a placebo (n = 65) for 12 weeks. Serum triglyceride concentrations were always measured from 8 to 9 am after a 12-h fast. Results By the end of treatment, triglyceride concentrations had decreased by 39.1% in the omega-3 group and 14.6% in the placebo group (p < 0.01). The incidence of adverse gastrointestinal events (e.g. flatulence, belching) was 41.2% and 6.2% in the omega-3 and placebo groups, respectively (p < 0.01). There were no serious drug-related adverse events. Conclusions Supplementation with 3 g/day of omega-3 fatty acids is a safe and effective option for treating hypertriglyceridemia in children and adolescents with obesity.