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.

On-Demand ICS + FABA Combinations in 6-11-Year-Old Children.

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (ß2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population.

Advances in the Relationship between Respiratory Viruses and Asthma.

Several studies have reported that viral infection is closely associated with the onset, progression, and exacerbation of asthma. The purpose of this review is to summarize the role that viral infections have in the pathogenesis of asthma onset and exacerbations, as well as discuss interrelated protective and risk factors of asthma and current treatment options. Furthermore, we present current knowledge of the innate immunological pathways driving host defense, including changes in the epithelial barrier. In addition, we highlight the importance of the genetics and epigenetics of asthma and virus susceptibility. Moreover, the involvement of virus etiology from bronchiolitis and childhood wheezing to asthma is described. The characterization and mechanisms of action of the respiratory viruses most frequently related to asthma are mentioned.

Effect of Obesity on Lung Function in the Pediatric and Adult Populations with Asthma: A Review.

Obesity and asthma are major global health concerns, particularly in industrialized nations. Obesity has been shown to have detrimental effects on the respiratory system and lung function owing to metabolic issues and immunological consequences. Research has indicated that obese patients with asthma (atopic or T2-high and non-atopic or T2-low) have diminished lung function in terms of functional residual capacity (FRC), residual volume (RV), expiratory reserve volume (ERV), the FEV1/FVC ratio, and FEF 25-75% due to mechanical fat loading on the diaphragm and central adiposity when compared to non-obese asthmatic patients. Therefore, it is plausible that changes in lung function are the result of a combination of mechanical (fat loading on the diaphragm, central adiposity, bronchial hyper-reactivity, and an increase in cholinergic tone), environmental (diet and exercise), and inflammatory factors (local and systemic), which can lead to the obesity-related asthma phenotype characterized by severe asthma symptoms, poor response to corticosteroid treatment, loss of lung function, and poor quality of life from an early age.

Early Prediction of Asthma.

The clinical manifestations of asthma in children are highly variable, are associated with different molecular and cellular mechanisms, and are characterized by common symptoms that may diversify in frequency and intensity throughout life. It is a disease that generally begins in the first five years of life, and it is essential to promptly identify patients at high risk of developing asthma by using different prediction models. The aim of this review regarding the early prediction of asthma is to summarize predictive factors for the course of asthma, including lung function, allergic comorbidity, and relevant data from the patient's medical history, among other factors. This review also highlights the epigenetic factors that are involved, such as DNA methylation and asthma risk, microRNA expression, and histone modification. The different tools that have been developed in recent years for use in asthma prediction, including machine learning approaches, are presented and compared. In this review, emphasis is placed on molecular mechanisms and biomarkers that can be used as predictors of asthma in children.

A dysregulated bile acids pool is associated with metabolic syndrome and gut microbial dysbiosis in early adolescence.

OBJECTIVE: The increased prevalence of childhood metabolic syndrome (MetS) is a public health issue. It has been shown that a dysregulated bile acid (BA) profile could be involved in the development of MetS, in which the gut microbiota could have a significant role in BA levels. This study aimed to evaluate differences in serum BA levels in children with and without MetS and whether these levels were associated with gut microbial composition. METHODS: A total of 100 children aged 10 to 12 years were enrolled in this study, 42 children with MetS (cases) and 58 control participants. Serum BAs were measured by liquid chromatography-tandem mass spectrometry and gut microbiota was determined by 16S ribosomal RNA gene sequencing. RESULTS: Children with MetS showed higher levels of total, secondary, and 12α-hydroxylated BAs, as well as deoxycholic acid, and these were associated with dyslipidemia and insulin resistance markers. Interestingly, total BAs were negatively correlated with gut bacterial diversity (Shannon index: rho = -0.218, p = 0.035), whereas total, 12α-hydroxylated, and secondary BAs, as well as deoxycholic acid, showed negative correlations with genera known for their potential health effects, including Bifidobacterium, Akkermansia, and Faecalibacterium. CONCLUSIONS: This study suggests that childhood MetS is associated with a dysregulated BA pool and that these alterations could influence the abundance of potentially beneficial bacteria, thus contributing to gut microbial dysbiosis.

Aeroallergen immunotherapy associated with reduced risk of severe COVID-19 in 1095 allergic patients.

Introduction: Allergen immunotherapy (AIT) brings along changes in the immune system, restoring dendritic cell function, reducing T2 inflammation and augmenting the regulatory cell activation. Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, interferes with the immune system causing immune suppression during the first phase and over-activation in more advanced disease. We decided to explore the interaction of both in a real-world observational trial. Methods: We registered COVID-19 outcomes in patients with allergic disorders in Latin America, treated with and without AIT. The registry was conducted during the first 1.3 years of the pandemic, with most of the data collected before COVID-19 vaccination was concluded in most countries. Data collection was anonymous via a web-based instrument. Ten countries participated. Results: 630/1095 (57.6%) of the included patients received AIT. Compared to patients without AIT, those treated with AIT had a reduced risk ratio (RR) for COVID-19 lower respiratory symptoms (RR 0.78, 95% CI: 0.6703-0.9024; p = 0.001662) and need for oxygen therapy (RR 0.65, 95% CI: 0.4217-0.9992; p = 0.048). In adherent patients on maintenance sublingual immunotherapy/subcutaneous immunotherapy (SLIT/SCIT) the RR reduction was larger [RR = 0.6136 (95% CI 0.4623-0.8143; p < 0.001) and RR: 0.3495 (95% CI 0.1822-0.6701; p < 0.005), respectively]. SLIT was slightly more effective (NS). We excluded age, comorbidities, level of health care attendance, and type of allergic disorder as confounders, although asthma was related to a higher frequency of severe disease. When analyzing patients with allergic asthma (n = 503) the RR reduction favoring AIT was more pronounced with 30% for lower respiratory symptoms or worse (RR 0.6914, 95% CI 0.5264 to 0.9081, p = 0.0087) and 51% for need of oxygen therapy or worse (RR 0.4868, 95% CI 0.2829-0.8376, p = 0.0082). Among severe allergic patients treated with biologics (n = 24) only 2/24 needed oxygen therapy. There were no critical cases among them. Conclusion: In our registry AIT was associated with reduced COVID-19 severity.

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.

[Guidelines on atopic dermatitis for Mexico (GUIDAMEX): using the ADAPTE methodology]. / Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE.

With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.

Con el avance de los conocimientos en relación con la fisiopatogenia de la dermatitis atópica (DA) se han desarrollado varias formas terapéuticas nuevas. Asimismo, existen nuevos lineamientos para el autocuidado. Por otro lado, aún existe un subdiagnóstico de la DA en México. Así, se vio la necesidad de desarrollar una guía nacional, con base amplia entre las diferentes agrupaciones médicos que atienden pacientes con DA. Se desarrolló la Guía de DA para México (GUIDAMEX) con la metodología ADAPTE, con el aval y la participación de diez sociedades médicas nacionales, desde médicos del primer contacto hasta alergólogos y dermatólogos. A lo largo del escrito se contestan preguntas clínicas clave que llevan a recomendaciones y sugerencias para el diagnóstico de la DA (incluyendo diagnóstico diferencial con síndromes de inmunodeficiencia), el reconocer de las comorbilidades y complicaciones, las medidas generales (tratamiento no farmacológico) incluyendo la educación terapéutica, el tratamiento de los brotes y el tratamiento de mantenimiento. Este último abarca las medidas generales de evitar agravantes, el tratamiento de primera línea reparador de la barrera cutánea, de segunda línea (manejo proactivo tópico), hasta la fototerapia y el tratamiento sistémico de la tercera línea, incluyendo dupilumab y los inhibidores de la cinasa de Jano.

An independent in-depth analysis proposing adjusted Global Initiative on Asthma Step 1-2 treatment suggestions.

The Global Initiative on Asthma (GINA) strategy included major changes for the treatment of mild asthma in the 2020 version that are even taken to the next level in 2021, leaving a preferred track with only rescue therapy with inhaled corticosteroid and formoterol (ICS-FORM) for steps 1-2 in 12+ years old. It has been questioned how solid the evidence behind these recommendations is. We decided to independently conduct an in-depth analysis of published evidence based on a comprehensive evaluation of original articles and related appendices and publications, including quality of evidence and risk of bias per article. We first defined the major asthma treatment goals and proceeded to review how these were met in publications referenced in the main asthma guidelines. For patients with GINA (2021) Step 1 characteristics, the analysis supports GINA's decision to avoid SABA monotherapy and to prefer ICS-FORM rescue with an alternative ICS rescue every time a SABA is used for ≥12 years, even though evidence is extrapolated from step 2 patients. For 6- to 11-year-olds, we propose to consider ICS-FORM rescue as an alternative, as its use has been approved in this age group, be it not as rescue medication. For patients with GINA 2021 Step 2 characteristics, our proposal slightly differs from GINA 2021. We propose to continue avoiding the separate use of SABA, using ICS rescue whenever a fast-acting bronchodilator is taken (even with ICS maintenance). Also, the superiority of ICS-FORM rescue over classical step 2 treatment is not uniform and year-long experience is lacking. Consequently, for now, both treatment options seem equal: ICS-FORM rescue or ICS maintenance with SABA (+ICS) rescue. For 6- to 11-year-olds, ICS rescue every time a SABA is used has the advantage of lower total ICS dose; as alternative we suggest ICS-FORM rescue. The best treatment option depends on patient characteristics and treatment goals. Recommendations should be reviewed as soon as new evidence becomes available.

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.

Effect of Gut Microbial Enterotypes on the Association between Habitual Dietary Fiber Intake and Insulin Resistance Markers in Mexican Children and Adults.

Dietary fiber (DF) is a major substrate for the gut microbiota that contributes to metabolic health. Recent studies have shown that diet-metabolic phenotype effect might be related to individual gut microbial profiles or enterotypes. Thus, the aim of this study was to examine whether microbial enterotypes modify the association between DF intake and metabolic traits. This cross-sectional study included 204 children (6-12 years old) and 75 adults (18-60 years old). Habitual DF intake was estimated with a Food Frequency Questionnaire and biochemical, clinical and anthropometric data were obtained. Gut microbiota was assessed through 16S sequencing and participants were stratified by enterotypes. Correlations adjusting for age and sex were performed to test the associations between dietary fiber components intake and metabolic traits. In children and adults from the Prevotella enterotype, a nominal negative correlation of hemicellulose intake with insulin and HOMA-IR levels was observed (p < 0.05), while in individuals of the other enterotypes, these associations were not observed. Interestingly, the latter effect was not related to the fecal short-chain-fatty acids profile. Our results contribute to understanding the enterotype influence on the diet-phenotype interaction, which ultimate could provide evidence for their use as potential biomarkers for future precision nutrition strategies.

A higher bacterial inward BCAA transport driven by Faecalibacterium prausnitzii is associated with lower serum levels of BCAA in early adolescents.

BACKGROUND: Elevations of circulating branched-chain amino acids (BCAA) are observed in humans with obesity and metabolic comorbidities, such as insulin resistance. Although it has been described that microbial metabolism contributes to the circulating pool of these amino acids, studies are still scarce, particularly in pediatric populations. Thus, we aimed to explore whether in early adolescents, gut microbiome was associated to circulating BCAA and in this way to insulin resistance. METHODS: Shotgun sequencing was performed in DNA from fecal samples of 23 early adolescents (10-12 years old) and amino acid targeted metabolomics analysis was performed by LC-MS/MS in serum samples. By using the HUMAnN2 algorithm we explored microbiome functional profiles to identify whether bacterial metabolism contributed to serum BCAA levels and insulin resistance markers. RESULTS: We identified that abundance of genes encoding bacterial BCAA inward transporters were negatively correlated with circulating BCAA and HOMA-IR (P < 0.01). Interestingly, Faecalibacterium prausnitzii contributed to approximately ~ 70% of bacterial BCAA transporters gene count. Moreover, Faecalibacterium prausnitzii abundance was also negatively correlated with circulating BCAA (P = 0.001) and with HOMA-IR (P = 0.018), after adjusting for age, sex and body adiposity. Finally, the association between Faecalibacterium genus and BCAA levels was replicated over an extended data set (N = 124). CONCLUSIONS: We provide evidence that gut bacterial BCAA transport genes, mainly encoded by Faecalibacterium prausnitzii, are associated with lower circulating BCAA and lower insulin resistance. Based on the later, we propose that the relationship between Faecalibacterium prausnitzii and insulin resistance, could be through modulation of BCAA.

[MIA 2021, Comprehensive Asthma Management. Guidelines for Mexico]. / MIA 2021, Manejo Integral del Asma. Lineamientos para México.

BACKGROUND: Asthma continues to be one of the most frequent chronic respiratory diseases in our country. New methods for diagnosis and treatment have been described; accordingly, the international guidelines were renewed. OBJECTIVE: To create a national platform for the development of updated guidelines, solidly based on evidence: Comprehensive Asthma Management (Spanish acronym: MIA). METHODS: MIA uses the ADAPTE method. The MIA development group consists of experts in pulmonology-allergology-methodology and representatives of 13 institutions and societies of specialties that manage asthma. The international reference guidelines (selected with AGREE-II): GINA 2020, GEMA 5.0, BTS/SIGN 2019 and ATS/ERS consensus document 2014-2019 on severe asthma. MIA covers suspected asthma, diagnosis, treatment, and special groups. Key clinical questions were formulated on treatment steps 1-3, biomarkers and severe asthma. RESULTS: Based on evidence, safety, cost and local reality, the core group developed responses. Through a Delphi process the broad MIA development group suggested adjustments until consensus was reached. CONCLUSION: A document was generated with multiple figures and algorithms, solidly based on evidence about asthma management, adjusted for Mexico with a broad base among different societies that participated in its development. It does not include guidelines for acute asthma.

Antecedentes: El asma sigue siendo una patología respiratoria crónica frecuente en México. Se han descrito nuevos métodos para el diagnóstico y tratamiento conforme se renuevan las guías internacionales. Objetivo: Crear la plataforma nacional Manejo Integral del Asma (MIA), para el desarrollo de lineamientos actualizados con base en evidencia. Métodos: Se utilizó el método ADAPTE. El grupo de desarrollo de MIA estuvo integrado por expertos en neumología, alergología y metodología y representantes de 13 instituciones y sociedades de especialidades que manejan asma. Las guías internacionales de referencia (seleccionadas con AGREE-II) fueron GINA 2020, GEMA 5.0, BTS/SIGN 2019 y consenso ATS/ERS 2014-2019. En MIA se aborda sospecha de asma, diagnóstico, tratamiento y grupos especiales. Se formularon preguntas clínicas clave sobre tratamiento en los pasos 1 a 3, biomarcadores y asma grave. Resultados: Con base en evidencia, seguridad, costo y realidad local, el grupo nuclear desarrolló respuestas. Mediante proceso Delphi, el grupo amplio de desarrollo sugirió ajustes hasta que se logró el consenso. Conclusión: El documento generado contiene múltiples figuras y algoritmos, está sólidamente basado en evidencia acerca del manejo del asma y fue ajustado para México con participación de diferentes sociedades para su desarrollo; no se incluyeron lineamientos para la crisis asmática.

Genome-Wide Association Study Identifies a Functional SIDT2 Variant Associated With HDL-C (High-Density Lipoprotein Cholesterol) Levels and Premature Coronary Artery Disease.

Objective: Low HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population. Approach and Results: A genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP, ABCA1, LIPC, and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts (P=5.9×10−18 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism. Conclusions: This is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans.

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.

Coronavirus disease 2019, allergic diseases, and allergen immunotherapy: Possible favorable mechanisms of interaction.

Background: Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease. Objective: To review immune changes brought along by each of these entities and how they might interrelate. Methods: We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection. Results: We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation. Conclusion: As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.

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.