Asociación de experiencias adversas en la infancia con síntomas de asma en niños. Revisión bibliográfica / Association of adverse childhood experiences with asthma symptoms in children. A literature review

Las experiencias adversas en la infancia (EAI) tienen un impacto considerable en la salud física y mental de los niños y adolescentes. Esta revisión bibliográfica se centra en la asociación entre estas experiencias y la incidencia de síntomas asmáticos, así como en las alteraciones inmunológicas en la población pediátrica. Los estudios revisados muestran una correlación significativa entre la exposición a EAI y el asma, destacando la importancia de un enfoque biopsicosocial para su manejo. Además, se discuten las implicancias clínicas y las precauciones necesarias al interpretar estos hallazgos.

Adverse childhood experiences (ACEs) have a significant impact on the physical and mental health of children and adolescents. This literature review focuses on the association between these experiences and the incidence of asthma symptoms, as well as immunological alterations in the pediatric population. The reviewed studies show a significant correlation between ACE exposure and asthma, highlighting the importance of a biopsychosocial approach for its management. Additionally, the clinical implications and necessary precautions when interpreting these findings are discussed.

Effect of photobiomodulation in an experimental in vitro model of asthma-Copd overlap.

The objective of the study was to evaluate the effect of photobiomodulation (PBM) with laser on the inflammatory process in an experimental in vitro model of ACO. The groups were: (1) human bronchial epithelial cells (BEAS-2B); (2) BEAS-2B cells treated with dexamethasone; (3) BEAS-2B cells irradiated with laser; (4) BEAS-2B cells stimulated with cigarette smoke extract (CSE) + House Dust Mite (HDM); (5) BEAS-2B cells stimulated with CSE + HDM and treated with dexamethasone; (6) BEAS-2B cells incubated with CSE + HDM and irradiated with laser. After 24 h, cytokines were quantified. There was a reduction in TNF-α, IL-1ß, IL-6, IL-4, IL-5, IL-13, IL-17, IL-21, IL-23, and an increase in IL-10 and IFN-γ in cells from the laser-irradiated ACO group compared to only ACO group. With these results, we can suggest that photobiomodulation acts in the modulation of inflammation observed in ACO, and may be a treatment option.

Genetic polymorphisms (FTO rs9939609 and TMEM18 rs6548238), adipokines (leptin and adiponectin) and adiposity in children and adolescents with asthma.

OBJECTIVE: To describe independent factors related to the interaction of FTO rs9939609, TMEM18 rs6548238, leptin, and adiponectin in children/adolescents with asthma, under the influence of obesity. METHODS: The authors performed a cross-sectional study with 57 children/adolescents, ages 8-19 years, at a tertiary hospital, from 2017 to 2018. Participants were classified by nutritional status, performed spirometry with a bronchodilator test and completed an asthma questionnaire, higher scores indicated more asthma symptoms. Two asthma groups were formed: Group 1(G1)-normal-weight; Group 2(G2)-overweight/obese. Serum was collected for adipokines (n = 32) and genetic polymorphisms (n = 53) dosages. RESULTS: Age and body mass index (BMI) correlated directly in normal-weight (p = 0.009) and obese participants (p = 0.004). Girls reported more asthma complaints (p = 0.044). Participants with negative bronchodilator responses presented lower BMI (14.55-17.16) than responders (19.4-26.84) (p = 0.049). Leptin dosages are related directly to BMI (5,34-40 ng/ml in obese × 0,54-42 ng/ml in nonobese) (p = 0.003). Levels were high in girls (4.78-17.55 µg/ml) (p = 0.029) and low in nonobese boys (0.54-6.92 µg/ml) (p = 0.006). In obese, low leptin levels (< 10 ng/ml) were found in small airway dysfunction carriers (p = 0.025); elevated adiponectin (> 5 µg/ml) correlated with FEV1/FVC > 80 % (p = 0.035) and positive bronchodilator tests (8.84-13 µg/ml) (p = 0.039); and FTO A allele correlated with low adiponectin 0-8.84 µg/ml (p = 0.021) and low FEV1/FVC (46 %-88 %) (p = 0.023). CONCLUSION: BMI correlated directly with age and leptin levels. Obese participants presented high serum levels of leptin and FTO A allele correlated with low FEV1/FVC. Larger cohorts are necessary for better elucidation of the role of adipokines and polymorphisms in the pathophysiology of asthma and obesity.

Relation between air quality and asthma in high-altitude places, La Paz, Bolivia (3,600 m a.s.l.) / Relación entre la calidad del aire y el asma en habitantes de grandes altitudes, La Paz, Bolivia (3.600 m.s.n.m.).

Introduction. Asthma is a chronic disease affecting millions of people around the world. Air quality is a major factor in triggering asthma symptoms. Objective. To analyze air quality and asthma in high-altitude residents of La Paz, Bolivia. Materials and methods. In this analytical, descriptive, and retrospective study, we collected data from patients diagnosed with asthma at the Instituto Nacional del Tórax and the Instituto Boliviano de Biología de Altura. In addition, air quality monitoring of particulate matter was carried out at the stations of the Red de Monitoreo de la Calidad del Aire. Results. Women represented 56.9% of cases at the Instituto Nacional del Tórax and the Instituto Boliviano de Biología de Altura. In both institutions, the average age was 47 years and patients were overweight or obese. Increases in PM2.5 were recorded in autumn, winter and spring from 2014, 2016 to 2019 and 2015 in all four seasons. PM10 showed increases in autumn and winter from 2014 to 2020 within the established limits. We observed a positive and significant association between PM2,5 concentration and the spirometry parameters of forced vital capacity, peak expiratory flow, and "reversibility percentage" or "bronchodilator response percentage". The association of PM10 and forced vital capacity, forced expiratory volume in the first second, and peak expiratory flow, was also statistically significant. Conclusion. Asthma cases occur on average at 47 years of age in overweight or obese people. We observed a positive association between particles PM2,5 and PM10 with spirometric parameters, stronger with particulate matter PM2,5.

Introducción. El asma es una enfermedad crónica que afecta a millones de personas en todo el mundo. La calidad del aire es uno de los factores clave que puede desencadenar los síntomas del asma. Objetivo. Analizar la calidad del aire y su relación con el asma en habitantes de grandes altitudes en La Paz (Bolivia). Materiales y métodos. Se desarrolló un estudio analítico, descriptivo y retrospectivo. Se recolectaron datos de pacientes con diagnóstico de asma en el Instituto Nacional del Tórax y en el Instituto Boliviano de Biología de Altura. Además, se monitoreó la calidad del aire y su material particulado en las estaciones de la "Red de monitoreo de la calidad del aire". Resultados. El 56,9 % de los casos fueron mujeres del Instituto Nacional del Tórax y el 45,7 % del Instituto Boliviano de Biología de Altura. En ambas instituciones, la media de edad fue de 47 años y los pacientes presentaban sobrepeso u obesidad. Se registraron incrementos de material particulado fino (PM2,5) en otoño, invierno y primavera, en 2014, 2016-2019 y en las cuatro estaciones del 2015. El material particulado inhalable grueso (PM10) se incrementó en otoño e invierno del 2014 al 2020, dentro de los límites establecidos. Se observó una asociación positiva y significativa entre la concentración de material particulado PM2,5 y los parámetros espirométricos de capacidad vital forzada, flujo espiratorio máximo y el porcentaje de reversión. La relación de partículas PM10 y los parámetros espirométricos de capacidad vital forzada, volumen espiratorio máximo en el primer segundo y flujo espiratorio máximo, también fue estadísticamente significativa. Conclusión. Los casos de asma se presentaron en promedio a los 47 años y en personas con sobrepeso u obesidad. Se observó una asociación positiva entre el material particulado, PM2,5 y PM10, con los parámetros espirométricos, la cual fue más marcada con las partículas PM2,5.

Introducing the concept of loss of corticosteroid credit in asthma.

The widespread use of systemic corticosteroids (SCS) in asthma is associated with significant comorbidities and mortality. A dose-response relationship for cumulative SCS exposure with most adverse outcomes began at cumulative exposures of 1.0-<2.5 g, equivalent to four lifetime SCS courses. The purpose of creating the SCS credit concept was to increase awareness of the risks of SCS exposure and to promote better therapeutic alternatives. Consuming the lifetime SCS credit of 1.5 g/yr significantly increased morbidity and mortality.

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.

C-Phycocyanin Prevents Oxidative Stress, Inflammation, and Lung Remodeling in an Ovalbumin-Induced Rat Asthma Model.

Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling.

Unhealthy habits and comorbidities associated with uncontrolled asthma in young people.

INTRODUCTION: Asthma is a chronic inflammatory disease of the lower airways that affects more than 260 million people worldwide and has been related to more than 460,000 deaths a year. It is estimated that in 60% of asthma cases, the symptoms are not adequately controlled. The objective of this study was to determine the association between some comorbidities, habits, and health risk behaviors with uncontrolled asthma in a sample of young people with asthma. METHODS: Through a cross-sectional study, data from 1,078 young people aged 17 to 19 years were analyzed. Information was collected through physical examination, direct questioning, and the application of a self-administered questionnaire. RESULTS: In the group of young people with asthma, the prevalence of uncontrolled asthma was 20.6%, of which 53.8% were women, 76.9% suffered from rhinitis, 46.2% were overweight and 23.1% were obese. In the group of young with uncontrolled asthma, gingivitis was detected in 53.8% and alcohol consumption in 84.6%. Logistic regression analysis showed a significant association between allergic rhinitis, gingivitis, carbohydrate intake, alcohol consumption, overweight, and obesity with uncontrolled asthma. CONCLUSIONS: Parents and members of the health team need to identify on time the risk factors associated with uncontrolled asthma in young people with asthma to limit its development and the negative effects it generates. The results of this study should be used to strengthen programs that promote the comprehensive health of adolescents.

Ecuadorian Provinces with High Morbidity and Mortality Rates Due to Asthma among the Working-Age Population: An Ecological Study to Promote Respiratory Health.

Asthma is a significant public health concern. This study identified the provinces with the highest morbidity and mortality rates due to asthma among the working-age population (15-69 years) in the Republic of Ecuador. The secondary objective was to explain the possible differences attributable to occupational exposure. This nationwide ecological study was conducted in 24 provinces between 2016 and 2019. Government databases were used as sources of information. Age-standardized rates were calculated for codes J45 and J46. The hospitalization morbidity rate for asthma decreased from 6.51 to 5.76 cases per 100,000 working-age population, and the mortality rate has consistently been low and stable from 0.14 to 0.15 deaths per 100,000 working-age population. Geographic differences between the provinces were evident. The risk of hospitalization and death due to asthma was higher in the Pacific coast (Manabí with 7.26 and 0.38, Esmeraldas with 6.24 and 0.43, Los Ríos with 4.16 and 0.40, El Oro with 7.98 and 0.21, Guayas with 4.42 and 0.17 and the Andean region (Azuay with 6.33 and 0.45, Cotopaxi (5.84 and 0.48)). The high rates observed in provinces with greater agricultural and industrial development could be national heterogeneity's main determinants and act as occupational risk factors. The contribution of occupational hazards in each province should be examined in depth through ad hoc studies. The findings presented here provide valuable information that should prompt further detailed studies, which will assist in designing public policies aimed at promoting and safeguarding the respiratory health of the population, particularly that of workers. We believe that this study will inspire the creation of regional networks for the research and surveillance of occupational health.

A critical analysis of the effect of OM-85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta-analysis.

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.

INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system. RESULTS: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress. CONCLUSIONS: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.

Londrina Activities of Daily Living Protocol: validity, reliability, minimal detectable change, and standard error of measurement in adults with asthma.

INTRODUCTION: Asthma symptoms are dyspnea, chronic cough, wheezing, chest tightness, or chest discomfort, which can directly limit the activities of daily living (ADL), which is frequently reported by adults with asthma. Evaluating ADL with a reliable protocol at the usual speed is necessary. OBJECTIVES: To investigate the validity, reliability, minimal detectable change (MDC), and standard error of measurement (SEM) of the Londrina ADL Protocol (LAP) for adults with asthma. METHODS: Adults with asthma were evaluated with the LAP test. Spearman's correlation coefficient was used to verify validity with the 6-min walk test (6MWT), Glittre-ADL test, and London Chest Activity of Daily Living (LCADL). To test the reliability, the test was reapplied in at least 30 min; the Wilcoxon test and Intraclass Correlation Coefficient (ICC), SEM, MDC, and learning effect were performed. RESULTS: Fifty-three individuals were included (26% men, 43 ± 15 years, BMI 28 ± 8 kg/m2, FEV1 70 ± 24%predicted). For convergent validity, the LAP test was correlated with the 6MWT, Glittre-ADL, and LCADL scale (r = -0.49, 0.71, and 0.30, respectively; p < 0.03). There was a difference in test-retest (p < 0.0001) and reliability analysis shows ICC3 of 0.94, SEM of 14.88 s (22%), and MDC of 41.23 s (15%). Furthermore, the individuals performed the second test with -23 ± 19 (7.9%) s. CONCLUSION: The LAP test is valid and reliable for assessing limitations during ADL in adults with asthma. Considerable learning effect was observed, therefore, the best of two measures may avoid underestimation.

The effects of violence and related stress on asthma.

In the United States, people living in deprived urban areas and persons in certain minoritized groups are often exposed to violence and affected with asthma, and epidemiologic studies have shown a link between exposure to violence (ETV) and asthma throughout the lifespan. Indeed, ETV at the individual, intrafamilial and community levels has been linked to asthma in children and adults. In this review, we discuss the evidence for a causal relation between ETV and asthma, emphasizing findings published in the last five years. Interpretation of the available evidence is limited by variable quality of the assessment of ETV or asthma, potential recall and selection bias, inability to estimate the relative contribution of various types of violence to the observed associations, lack of objective biomarkers of asthma or asthma endotypes, and inconsistent consideration of potential confounders or modifiers of the ETV-asthma link. Despite such limitations, the aggregate evidence from studies conducted in different locations and populations suggests that ETV affects asthma and asthma outcomes, and that this is explained by direct physiologic effects of violence-related distress and indirect effects (e.g., through risky health behaviors or co-morbidities). Thus, large prospective studies with careful assessment of specific types of ETV, key covariates and comorbidities (including mental illness), and asthma are needed to advance this field. Such research efforts should not preclude screening for maltreatment in children with asthma and ETV-related depression and anxiety in adolescents and adults with asthma. Further, vigorous policies are needed to curtail violence, as such policies could benefit patients with asthma while saving lives.

Nonelective cesarean section is associated with the prevalence of asthma among Mexican children who attended childcare centers.

Background: The cesarean section (CS) mode of delivery can influence the prevalence of bronchial asthma (BA), allergic rhinitis (AR), or atopic dermatitis (AD) by promoting modifications in the infantile microbiome. Objective: To analyze the prevalence of asthma in children who were born through CS and attended childcare centers. Methods: The data were obtained through an online survey that was answered anonymously by one of the parents; the survey inquired about the route of delivery of the child and the prevalence of BA, AR, and AD. Results: A total of 525 children were included. The frequency of births by vaginal, elective CS, or nonelective CS was 34.1%, 37.9%, and 28.0%, respectively, and the prevalence of BA, AR, and AD was 4.8%, 19.8%, and 12.4%, respectively. Multivariate analyses identified nonelective CS as a factor associated with the prevalence of BA (odds ratio: 3.51, P = 0.026). Conclusion: Our study shows that being born through nonelective CS can increase the probability of BA in children who attended daycare centers.

IgE-Mediated Sensitization to Blo t 21 and Blo t 5 Is Associated With Asthma in the Tropics: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Sensitization to Blomia tropicalis is associated with asthma in various tropical and subtropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. RESULTS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. CONCLUSION: Although Blo t 5 and Blo t 21 are considered common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for diagnosis of allergy in the tropics.

Childhood severe asthma: relationship among asthma control scores, FeNO, spirometry and impulse oscillometry.

INTRODUCTION: The evaluation of the asthmatic patient is usually based on clinical and functional parameters that do not necessarily evidence the degree of airway inflammation. The aim of this study was to analyze whether clinical scores (CS) correlate with spirometry (S), impulse oscillometry (IO) and FeNO, in severe asthmatic children. MATERIAL AND METHODS: A multicentric, prospective, cross-sectional study was conducted over a 12-month period. All SA patients (6-18 years old) followed-up in the Pulmonology Department were recruited. CS, FeNO measurements, IO and S were consecutively performed on the same day. Asthma control was ascertained using ACT and GINAq. A cut-off value of ≥ 25 parts per billion (ppb) was used to define airway inflammation. RESULTS: Eighty-one patients were included. ACT: 75% (n 61) were controlled; GINAq: 44.5% (n 36) were controlled; 39.5% (n 32) were partly controlled, and 16% (n 13) were uncontrolled. FeNO had a median value of 24 ppb (IQR 14-41); FeNO ≥ 25 ppb was observed in 49% of patients (n 39). ROC AUC for FeNO vs. ACT was 0.71 (95%CI 0.57-0.86), PPV 0.47, NPV 0.87, SE 0.61, SP 0.80; FeNO vs. GINAq was ROC AUC 0.69 (95%CI 0.54-0.85), PPV 0.34, NPV 0.91, SE 0.62, SP 0.77; Youden cut-off FeNO > 39 ppb for both CS. CONCLUSION: In severe asthmatic children, current symptoms control as evidenced by ACT and GINA correlates with low FeNO values. Clinical scores showed good correlation with airway inflammation.