Predictive genetic panel for adult asthma using machine learning methods.

Background: Asthma is a chronic inflammatory disease of the airways that is heterogeneous and multifactorial, making its accurate characterization a complex process. Therefore, identifying the genetic variations associated with asthma and discovering the molecular interactions between the omics that confer risk of developing this disease will help us to unravel the biological pathways involved in its pathogenesis. Objective: We sought to develop a predictive genetic panel for asthma using machine learning methods. Methods: We tested 3 variable selection methods: Boruta's algorithm, the top 200 genome-wide association study markers according to their respective P values, and an elastic net regression. Ten different algorithms were chosen for the classification tests. A predictive panel was built on the basis of joint scores between the classification algorithms. Results: Two variable selection methods, Boruta and genome-wide association studies, were statistically similar in terms of the average accuracies generated, whereas elastic net had the worst overall performance. The predictive genetic panel was completed with 155 single-nucleotide variants, with 91.18% accuracy, 92.75% sensitivity, and 89.55% specificity using the support vector machine algorithm. The markers used range from known single-nucleotide variants to those not previously described in the literature. Our study shows potential in creating genetic prediction panels with tailored penalties per marker, aiding in the identification of optimal machine learning methods for intricate results. Conclusions: This method is able to classify asthma and nonasthma effectively, proving its potential utility in clinical prediction and diagnosis.

Aeroallergen sensitization patterns among patients with chronic rhinitis with or without concomitant asthma.

OBJECTIVES: The aim of this study was to explore the differences in the pattern of allergen sensitization in CR individuals without or with asthma, according to asthma severity. METHODS: A total of 1066 adults were evaluated. Asthma and chronic/allergic rhinits were identified by specialists, questionnaries and skin-prick test. The phenotypic characterization was avaliable from skin-prick test to an aeroallergen extended panel, total IgE and pulmonary function. Using questionnaires and clinical evaluation, participants were classified into the groups: chronic rhinitis alone (CRA) and chronic rhinitis + asthma, the latter subdivided into CR + mild asthma (CRMA) and CR + moderate to severe asthma (CRMSA). Aerollergen sensitization was defined by a positive prick test to one or more allergens associated with nasal symptoms and/or asthma. The association between CR and asthma was evaluated by multivariable logistic regression. The evidence of effect modification of pattern of sensitization in CR on the association with asthma severity and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. RESULTS: Frequency of sensitization to aeroallergens was higher in association with asthma in comparison to CRA (CRMA 70.4%; CRMSA 65.0%; CRA 47.0%; p = 0.000). Similarly, the presence of asthma was associated to aeroallergen multiple sensitization (51.5%) (OR = 2.10, 95% CI 1.27-3.50). Additionally, the sensitization to mites, cockroaches, animal epithelium, grasses, and molds, were higher in asthma (56.8%, 24.3%, 12%, 7.13% and 10.3%, respectively). Sensitization to Alternaria alternata, Cladosporium herbarum and dog epithelium was exclusive in asthma groups. A concomitant asthma diagnosis was directly associated with a positive allergen sensitization at least one allergen (62.7%, OR = 2.45, 95% CI 1.80-3.34) and polissensitization (51.5%, OR = 2.10, 95% CI 1.27-3.50). CONCLUSION: Asthma is associated with multiple allergen sensitization among patients with CR. Some unique profiles of aeroallergen sensitization were observed in patients with CR and asthma. Nevertheless, no difference was found in the sensitization in relation to asthma severity, which suggest atopy is not the main underlying mechanism for asthma severity among patients with CR. LEVEL OF EVIDENCE: Level 3.

Aeroallergen sensitization patterns among patients with chronic rhinitis with or without concomitant asthma

Abstract Objectives The aim of this study was to explore the differences in the pattern of allergen sensitization in CR individuals without or with asthma, according to asthma severity. Methods A total of 1066 adults were evaluated. Asthma and chronic⁄allergic rhinits were identified by specialists, questionnaries and skin-prick test. The phenotypic characterization was avaliable from skin-prick test to an aeroallergen extended panel, total IgE and pulmonary function. Using questionnaires and clinical evaluation, participants were classified into the groups: chronic rhinitis alone (CRA) and chronic rhinitis + asthma, the latter subdivided into CR + mild asthma (CRMA) and CR + moderate to severe asthma (CRMSA). Aerollergen sensitization was defined by a positive prick test to one or more allergens associated with nasal symptoms and/or asthma. The association between CR and asthma was evaluated by multivariable logistic regression. The evidence of effect modification of pattern of sensitization in CR on the association with asthma severity and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. Results Frequency of sensitization to aeroallergens was higher in association with asthma in comparison to CRA (CRMA 70.4%; CRMSA 65.0%; CRA 47.0%; p= 0.000). Similarly, the presence of asthma was associated to aeroallergen multiple sensitization (51.5%) (OR = 2.10, 95% CI 1.27-3.50). Additionally, the sensitization to mites, cockroaches, animal epithelium, grasses, and molds, were higher in asthma (56.8%, 24.3%, 12%, 7.13% and 10.3%, respectively). Sensitization to Alternaria alternata, Cladosporium herbarum and dog epithelium was exclusive in asthma groups. A concomitant asthma diagnosis was directly associated with a positive allergen sensitization at least one allergen (62.7%, OR = 2.45, 95% CI 1.80-3.34) and polissensitization (51.5%, OR = 2.10, 95% CI 1.27-3.50). Conclusion Asthma is associated with multiple allergen sensitization among patients with CR. Some unique profiles of aeroallergen sensitization were observed in patients with CR and asthma. Nevertheless, no difference was found in the sensitization in relation to asthma severity, which suggest atopy is not the main underlying mechanism for asthma severity among patients with CR. Level of evidence: Level 3.

Another case of preventable death from asthma.

INTRODUCTION: Asthma prevalence is 262 million globally, with more than 1,000 deaths each day, most of them preventable. We were performing a longitudinal study, in Brazil, with the objective to following up patients who had a severe asthma attack and attended an emergency room (ATTACK Study). Here we present a case of a 28-year-old woman presenting what was considered moderate asthma, enrolled in ATTACK, who subsequently died of asthma. CASE STUDY: The patient was initially evaluated at an emergency room (ER) with uncontrolled asthma and no regular treatment. She had an asthma diagnosis just before this visit to the ER, despite presenting symptoms of asthma since childhood. She was subsequently evaluated by a specialist, who prescribed a treatment with regular inhaled corticosteroid and an inhaled bronchodilator, if necessary. The patient was systematically monitored by telephone for six months. RESULTS: The patient did not adhere to the treatment, in spite of repeated warnings, and 6 months later had an asthma attack resulting in her death. CONCLUSION: It is important to prioritize asthma in primary health care, including building capacity health care professionals for early diagnosis, asthma management, and to educate patients with asthma patients for the identification of worsening and signs of severity, to manage the exacerbations according to a written asthma plan. This may reduce the number of premature and preventable asthma deaths.

Variants in interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes that modulate inflammatory response are associated with periodontitis.

OBJECTIVE: Evaluate the association of genetic variants of the interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes with periodontitis. METHODS: The study involved 117 individuals with periodontitis and 389 without periodontitis, all Brazilians, miscegenated. Individuals with periodontitis presented at least 4 teeth with ≥ 1 site with probing depth ≥ 4 mm; clinical attachment level ≥ 3 mm on the same site and bleeding upon stimulus. Genotyping was performed using the Infinium Multi-Ethnic AMR/AFR-8 Bead Chip focused on Hispanic and African American populations with approximately 2 million markers of the human genome. Multivariate logistic regression was performed to identify associations in additive, dominant and recessive models adjusted for covariates age, obesity, mouth breathing, flossing, asthma, and ancestry. RESULTS: In IFI16, the rs75985579-A is positively associated with periodontitis in the additive (Odds Ratio adjusted (ORadjusted) 2.65, 95% confidence interval (CI):1.25-5.60, p value: 0.007) and dominant models (ORadjusted 2.56, 95%CI:1.13-5.81, p value: 0.017). In AIM2, the rs76457189-G, is associated negatively with periodontitis in two genetic models evaluated, additive (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022) and dominant (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022). CONCLUSIONS: These results have shown that variants in the IFI16 and AIM2 genes are associated with periodontitis. Individuals with at least one A (adenine) allele of the rs75985579 (IFI16) are more than twice as likely to have periodontitis, while individuals with the G (guanine) allele of rs76457189 (AIM2) are less likely to be diagnosed with periodontitis, providing a negative association with periodontitis.

Lipid mediators are detectable in the nasal epithelium and differ by asthma status in female subjects.

BACKGROUND: Lipid mediators, bioactive products of polyunsaturated fatty acid metabolism, contribute to inflammation initiation and resolution in allergic diseases; however, their presence in lung-related biosamples has not been fully described. OBJECTIVE: We aimed to quantify lipid mediators in the nasal airway epithelium and characterize preliminary associations with asthma. METHODS: Using liquid chromatography-mass spectrometry, we conducted a pilot study to quantify 56 lipid mediators from nasal epithelial samples collected from 11 female participants of an outpatient asthma clinic and community controls (aged 30-55 years). We examined the presence of each compound using descriptive statistics to test whether lipid mediators could distinguish subjects with asthma (n = 8) from control subjects (n = 3) using linear regression and partial least squares discriminant analysis. RESULTS: Fifteen lipid mediators were detectable in all samples, including resolvin (Rv) D5 (RvD5), with the highest median concentrations (in pg/µg protein) of 13-HODE (126.481), 15-HETE (32.869), and 13-OxoODE (13.251). From linear regression adjusted for age, prostaglandin E2 (PGE2) had a trend (P < .1) for higher concentrations in patients with severe asthma compared to controls (mean difference, 0.95; 95% confidence interval, -0.04 to 1.95). Asthma patients had higher scores on principal component 3 compared to controls (mean difference, 2.42; 95% confidence interval, 0.89 to 3.96), which represented lower levels of proresolving 15-HEPE, 19,20-DiHDPA, RvD5, 14-HDHA, 17-HDHA, and 13-HOTrE. Most of these compounds were best at discriminating asthma cases from controls in partial least squares discriminant analysis. CONCLUSION: Lipid mediators are detectable in the nasal epithelium, and their levels distinguish asthma cases from controls.