Early-life external exposome in children 2-5 years old in Colombia.

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.

STK4 deficiency and epidermodysplasia verruciformis-like lesions: A case report.

Serine/threonine kinase 4 deficiency (STK4 or MST1, OMIM:614868) is an autosomal recessive (AR) combined immunodeficiency that can present with skin lesions such as epidermodysplasia verruciformis-like lesions (EVLL). Herein, we describe a 17-year-old male patient born from consanguineous parents presenting with recurrent respiratory infections, verruciform plaques, poikiloderma, chronic benign lymphoproliferation, and Sjögren syndrome with suspected interstitial lymphocytic pneumonia.

Multilevel analysis identifying the factors associated with RSV detection in infants admitted for viral bronchiolitis in the era of the COVID-19 pandemic.

OBJECTIVES: To identify factors independently associated with respiratory syncytial virus (RSV) detection in infants admitted for viral bronchiolitis during 3 consecutive years, before and during the COVID-19 pandemic, in Bogota, Colombia, a middle-income country with a subtropical highland climate. METHODS: An analytical cross-sectional study was conducted before and during the COVID-19 pandemic, including patients with a diagnosis of viral bronchiolitis admitted to all the hospitals of the city between January 2019 and November 2021. We evaluated a set of a priori-selected predictor variables that included individual, healthcare system, meteorological, air pollutant, and COVID-19 variables. Since the variables analyzed are hierarchical in nature, multilevel modeling was used to identify factors independently associated with detection of RSV as the causative agent of viral bronchiolitis. RESULTS: A total of 13,177 patients were included in the study. After controlling for potential confounders, it was found that age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.76-0.97), a third level of medical care institution (OR 3.05; 95% CI 1.61-5.76), temperature (OR 1.60; 95% CI 1.24-2.07), rainfall (OR 1.003, 95% CI 1.001, 1.005), NO2 (OR 0.97; 95% CI 0.95-0.99), CO (OR 0.99; 95% CI 0.99-0.99), and COVID-19 pandemic period (OR 0.84, 95% CI 0.71-0.99) were independently associated with RSV detection in our sample of patients. CONCLUSIONS: The identified factors associated with RSV detection provide additional scientific evidence that may be useful in the development of specific interventions aimed at ameliorating or preventing the impact of RSV in Bogota and probably other similar low- to middle-income countries in high-risk infants.

Characterization of the external exposome and its contribution to the clinical respiratory and early biological effects in children: The PROMESA cohort study protocol.

BACKGROUND: Air pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known. OBJECTIVE: This study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children. MATERIALS AND METHODS: A cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana. EXPECTED STUDY OUTCOMES/FINDINGS: To estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children's health.

Predictors of severity in severe respiratory infection in children with COVID-19 respiratory infection in a developing country.

On March 11, 2020, the WHO declared the COVID-19 pandemic. This name was given to the disease caused by the SARS-CoV 2 virus at its outbreak in December 2019 in Wuhan, Hubei, China. In Colombia, a significant number of cases have been confirmed. The aim of this study was to evaluate children with respiratory symptoms caused by SARS-CoV2 infection, identifying independent predictors of risk of having a severe illness, thus leading to an early approach and intervention in our patients, especially in children with comorbidities. An analytical cross-sectional study was conducted between April 1, 2020 and March 31, 2021 at a fourth-level referral institution in Bogotá on patients under 18 years of age with respiratory symptoms and a COVID-19 diagnosis confirmed in the laboratory. An explanatory binary logistic regression model was performed with an outcome variable of admission to the intensive care unit. A total of 385 children were included in the study, with ages between 9 months and 17 years of age; 50.1% were male, and the ICR was 9.75 years. 41.6% had some comorbidity, 13.5% were admitted to the pediatric ICU, and 3.6% of the total number of patients died. The predictor variables were: use of antibiotics in the first 24 h, neurological comorbidity, and consolidation shown in the chest X-ray. This explains 38.7% of the variability of the variable. In this cohort of patients with COVID-19-associated respiratory symptoms, we identified predictors of severity, so we consider that these patients require a risk approach that allows timely and adequate care.

Pulmonary nodule in pediatrics: Beyond the infection. / Nódulo pulmonar en pediatría: Más allá de la infección.

INTRODUCTION: The study of a pulmonary nodule in pediatrics is a diagnostic challenge where multiple pathologies must be taken into account, especially infections. In developing countries, where tuberculosis infec tion is endemic, it is one of the most likely diagnoses; however, the diagnostic possibility of malig nancy should never be overlooked. OBJECTIVE: To describe a case report of a patient with a pulmonary nodule, that after ruling out the most frequent causes, a primary malignant tumor was diagnosed. CLINICAL CASE: 17-year-old female patient with a one-month history of cough, dyspnea, and hemop tysis, without other symptoms. Since she did not respond to conventional antibiotic management, a chest CT scan with contrast was performed which showed a pulmonary nodule with irregular con tours, and with the bronchoalveolar lavage pulmonary infections were ruled out (pulmonary tuber culosis, fungal infection, and others bacteria). Biopsy of the lesion was performed to complete the study which histopathology was compatible with a mucoepidermoid carcinoma (MEC). The patient underwent right low lobectomy and lymph node resection with good clinical response during three years of follow-up. CONCLUSION: Pulmonary nodule in pediatrics is a finding usually associated with infection, nevertheless, neoplastic conditions have to be considered, not only metastasis but also pri mary pulmonary malignant lesions due to prognosis implications.

Prediction of normal values for central apnea-hypopnea index at different ages and altitudes above sea level in healthy children.

BACKGROUND: There is a critical need for studies aimed to help clinicians to establish the normal/expected central apnea-hypopnea index (CAHI) at altitudes above sea level and ages other than those reported in the current available studies. The aim of the present study was to develop predictive models useful for determining the normal/expected CAHI in children of different ages born and living at various altitudes above sea level. METHODS: A systematic review of the literature was performed in order to identify all available studies that reported on CAHI values measured in healthy children of different ages and living at various levels above sea level. In order to identify factors independently associated with CAHI values, they were fit to multiple linear and quantile regression models. RESULTS: A total of 16 studies that reported on CAHI values measured in healthy children living at various levels above sea level were included in the analyses. Out of the 16 studies, 12 (75%) were conducted in low-altitude cities, 1 (6.2%) was conducted in a medium-altitude city, 2 (12.5%) in high-altitude cities, and 1 (6.2%) in both low- and high-altitude cities. Age and altitude above sea level are independent predictors of CAHI values in the linear regression analysis and in the quantile regression at the ninetieth percentile. CONCLUSIONS: The best-fitting prediction equations were obtained with linear regression and quantile regression at the ninetieth percentile analyses, and either of the two models could be used to predict the normal/expected CAHI values in healthy children.

[Brain-lung-thyroid syndrome in a newborn with deletion 14q12-q21.1]. / Síndrome cerebro-pulmón-tiroides en un recién nacido con deleción 14q12-q21.1.

INTRODUCTION: In newborns with respiratory failure and interstitial lung disease, it should be approached as chILD (Childhood Interstitial Lung Disease) syndrome to rule out alterations in surfactant metabolism and brain-lung-thyroid syndrome caused by pathogenic variants in the NKX2-1 gene. OBJECTIVE: To pre sent a newborn with chILD syndrome and a large deletion in chromosome 14q12-q21.1. CLINICAL CASE: Newborn patient with respiratory distress since birth, chILD syndrome, and hypothyroidism, in which brain-lung-thyroid syndrome was suspected. He also presented seizures, minor and ma jor abnormalities on physical examination. Microarray analysis revealed a 14.7 Mb deletion in the chromosome 14q12-q21.1, which includes the NKX2-1 gene. CONCLUSION: The brain-lung-thyroid syndrome should be considered in newborns with respiratory distress syndrome and diffuse lung disease (chILD syndrome), especially if they present hypotonia, choreoathetosis, or hypothyroidism. Diagnosis confirmation requires genetic analysis, even more, when there are other abnormalities not explained by the suspected syndrome.

Challenges and Clinical Implications of the Diagnosis of Cytomegalovirus Lung Infection in Children.

PURPOSE OF REVIEW: Pulmonary cytomegalovirus (CMV) infection is a potential lethal disease in children, but it remains a diagnostic challenge. The differentiation between latent CMV infections with viral shedding and active infections is difficult and may lead to false positives in bronchoalvolar lavage (BAL) PCR detection. This review summarizes current diagnostic approaches for CMV lung infection in children including progress in the identification of underlying immune defects linked to this condition. RECENT FINDINGS: There is increasing literature supporting that the combined assessment of host risk factors and lung disease pattern is essential for the diagnosis of pulmonary CMV infection in children. The most important host risk factor is an immunecompromised state that has expanded from primary or acquired immunodeficiency (e.g., HIV) to include a myriad of immune-dysregulation syndromes (e.g., CTLA4, PIK3 defects). Newborns, paricularly those born premature, are also a high-risk group. At the pulmonary level, active CMV infection is typically characterized by alveolar compromise leading to hypoxemia, ground-glass opacities, and intra-alveolar infiltrates with CMV inclusions in lung biopsy. The identification of active CMV lung infection should trigger additional evaluation of immune defects (primary or secondary) impairing T and NK cell function or innate antiviral responses as well as other immune dysregulation disorders. Lung CMV infections in children are more prevalent in immunocompromised hosts and premature newborns. Lung CMV infections should prompt further investigation into conditions altering immune mechanisms usually in place to contain CMV infections. Common clinical and radiological patterns such as hypoxemia and ground-glass pulmonary opacities may allow early identification and treatment of CMV lung infection and underlying causes in the pediatric population.

Moduladores CFTR (cystic fibrosis transmembrane conductance regulator): presente y futuro en la terapia de fibrosis quística. Revisión / Cystic fibrosis transmembrane conductance regulator modulators: Present and future in cystic fibrosis treatment. A review

Los moduladores cystic fibrosis transmembrane conductance regulator (CFTR) representan el presente y el futuro del manejo farmacológico para los pacientes con fibrosis quística. El objetivo de esta publicación es realizar una revisión de esta opción terapéutica. Se revisaron artículos científicos consultando las bases de datos MedLine, información disponible a través de la página oficial Cystic Fibrosis Foundation, desde 2009 hasta 2018, en el idioma inglés. Sin restricciones respecto al tipo de estudio, se seleccionaron 12 artículos que incluyeron información sobre el estado actual de la investigación sobre moduladores CFTR. Actualmente, están aprobados por la Food and Drug Administration tres moduladores: ivacaftor, lumacaftor + ivacaftor y tezacaftor + ivacaftor, y hay otros 11 en diferentes fases de estudio. La terapia con moduladores CFTR es una realidad en desarrollo que apunta al máximo objetivo de la medicina personalizada y que promete mejorar la calidad de vida de pacientes con fibrosis quística.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are the present and future of drug management for patients with cystic fibrosis. The objective of this article is to review this therapeutic option. Scientific articles were reviewed by searching the MedLine database, which is available through the Cystic Fibrosis Foundation's official website, from 2009 to 2018, in English. Twelve articles about the current status of research in CFTR modulators were selected without restrictions regarding the type of study. To date, the United States Food and Drug Administration has approved three modulators: ivacaftor, lumacaftor + ivacaftor, and tezacaftor + ivacaftor, while other 11 drugs are being studied in different investigation phases. CFTR modulator therapy is a developing reality aimed at the highest goal of personalized medicine and promises to improve the quality of life of cystic fibrosis patients.

Cystic fibrosis transmembrane conductance regulator modulators: Present and future in cystic fibrosis treatment. A review. / Moduladores CFTR (cystic fibrosis transmembrane conductance regulator): presente y futuro en la terapia de fibrosis quística. Revisión.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are the present and future of drug management for patients with cystic fibrosis. The objective of this article is to review this therapeutic option. Scientific articles were reviewed by searching the MedLine database, which is available through the Cystic Fibrosis Foundation's official website, from 2009 to 2018, in English. Twelve articles about the current status of research in CFTR modulators were selected without restrictions regarding the type of study. To date, the United States Food and Drug Administration has approved three modulators: ivacaftor, lumacaftor + ivacaftor, and tezacaftor + ivacaftor, while other 11 drugs are being studied in different investigation phases. CFTR modulator therapy is a developing reality aimed at the highest goal of personalized medicine and promises to improve the quality of life of cystic fibrosis patients.

Los moduladores cystic fibrosis transmembrane conductance regulator (CFTR) representan el presente y el futuro del manejo farmacológico para los pacientes con fibrosis quística. El objetivo de esta publicación es realizar una revisión de esta opción terapéutica. Se revisaron artículos científicos consultando las bases de datos MedLine, información disponible a través de la página oficial Cystic Fibrosis Foundation, desde 2009 hasta 2018, en el idioma inglés. Sin restricciones respecto al tipo de estudio, se seleccionaron 12 artículos que incluyeron información sobre el estado actual de la investigación sobre moduladores CFTR. Actualmente, están aprobados por la Food and Drug Administration tres moduladores: ivacaftor, lumacaftor + ivacaftor y tezacaftor + ivacaftor, y hay otros 11 en diferentes fases de estudio. La terapia con moduladores CFTR es una realidad en desarrollo que apunta al máximo objetivo de la medicina personalizada y que promete mejorar la calidad de vida de pacientes con fibrosis quística.