Pulmonary function and bronchopulmonary dysplasia classification: insights from the Spanish Registry.

In 2016, the Spanish Research Group on Bronchopulmonary Dysplasia (BPD) (GEIDIS) established a national registry with participation of 66 hospitals to collect information on clinical characteristics and long-term outcomes of BPD infants into adulthood. The aim of this observational study is to examine forced spirometry data in early childhood and to assess their correlation with the respiratory support required at 36 weeks postmenstrual age (PMA). The study analyzed data from preterm infants with BPD born between January 2016 and December 2017 who underwent forced spirometry at 5-7 years of age. Statistical analyses were conducted to investigate the relationships between spirometry results, perinatal factors, and the required respiratory support at 36 weeks PMA. The study involved 143 patients with a median gestational age (GA) of 27.3 weeks (range 25.7-28.7) and a median weight of 880 g (range 740-1135). Abnormal spirometry results were observed in 39.2% (56) of the patients. Among patients diagnosed with BPD type 3, those requiring over 30% oxygen at 36 weeks PMA exhibited an increased risk of abnormal spirometry results (OR 4.48; 95% CI 1.11-18.13) compared to those requiring positive pressure with less than 30% oxygen. In addition, this subgroup had a higher risk of developing a restrictive-mixed pattern compared to those with BPD type 1 (OR 10.65; 95% CI 2.06-54.98) and BPD type 2 (OR 6.76; 95% CI 1.09-42.06). No significant differences were found in the incidence of an obstructive pattern between BPD types.      Conclusion: The requirement of more than 30% oxygen at 36 weeks PMA serves as a risk indicator for pulmonary function impairment in school-aged children with BPD. These findings suggest persistent airway and parenchymal injury in this specific patient population, and highlight the importance of careful monitoring to evaluate their long-term effects on lung function. What is Known: • Premature patients with bronchopulmonary dysplasia (BPD) may present abnormalities in pulmonary function tests during school age. However, the predictive accuracy of consensus BPD severity classification remains uncertain. What is New: • The requirement of more than 30% oxygen at 36 weeks postmenstrual age (PMA) indicates a potential risk of pulmonary function impairment in school-aged children with BPD. Additionally, a significant correlation has been observed between a restrictive-mixed pattern with exposure to mechanical ventilation and the development of severe forms of BPD.

The Nutrition in Early Life and Asthma (NELA) birth cohort study: Rationale, design, and methods.

BACKGROUND: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. OBJECTIVES: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. POPULATION: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19-22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the "Virgen de la Arrixaca" University Clinical Hospital over a 36-month period, from March 2015 to April 2018. DESIGN: Prospective, population-based, maternal-child, birth cohort study. METHODS: Questionnaires on exposures and outcome variables were administered to mothers at 20-24 gestation week; 32-36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. PRELIMINARY RESULTS: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months' visit and 532 children (72%) attending the 18 months' visit. CONCLUSION: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.

Risk factors and bronchopulmonary dysplasia severity: data from the Spanish Bronchopulmonary Dysplasia Research Network.

GEIDIS is a national-based research-net registry of patients with bronchopulmonary dysplasia (BPD) from public and private Spanish hospitals. It was created to provide data on the clinical characterization and follow-up of infants with BPD until adulthood. The purpose of this observational study was to analyze the characteristics and the impact of perinatal risk factors on BPD severity. The study included 1755 preterm patients diagnosed with BPD. Of the total sample, 90.6% (n = 1591) were less than 30 weeks of gestation. The median gestational age was 27.1 weeks (25.8-28.5) and median birth weight 885 g (740-1,070 g). A total of 52.5% (n = 922) were classified as mild (type 1), 25.3% (n = 444) were moderate (type 2), and 22.2% (n = 389) were severe BPD (type 3). In patients born at under 30 weeks' gestation, most pre-and postnatal risk factors for type 2/3 BPD were associated with the length of exposure to mechanical ventilation (MV). Independent prenatal risk factors were male gender, oligohydramnios, and intrauterine growth restriction. Postnatal risk factors included the need for FiO2 of > 0.30 in the delivery room, nosocomial pneumonia, and the length of exposure to MV. Conclusion: In this national-based research-net registry of BPD patients, the length of MV is the most important risk factor associated with type 2/3 BPD. Among type 3 BPD patients, those who required an FiO2 > .30 at 36 weeks' postmenstrual age had a higher morbidity, during hospitalization and at discharge, compared to those with nasal positive pressure but FiO2 < .30. What is Known: • BPD is a highly complex multifactorial disease associated with preterm birth. What is New: • The length of exposure to mechanical ventilation is the most important postnatal risk factor associated to bronchopulmonary severity which modulate the effect of most pre and postnatal risk factors. • Among patients with BPD, the requirement for FiO2 >.30% at 36 weeks of postmenstrual age is associated with greater morbidity during hospitalization and at discharge.

Secondhand smoke: A new and modifiable prognostic factor in childhood acute lymphoblastic leukemias.

BACKGROUND: The 5-year overall survival (OS) in childhood acute lymphoblastic leukemia (ALL) has reached 90% in high-income countries, levels that can no be longer overcome with strategies based on intensification of treatment. Other approaches in the search for new and modifiable prognostic factors are necessary to continue to improve these rates. The importance of environmental factors in the etiopathogenesis of childhood ALL has been regaining interest but its role in the prognosis and survival of this disease is not well explored. We aim to investigate the association between secondhand smoke (SHS) and survival in children diagnosed with ALL. METHODS: We analyzed survival rates in 146 patients under the age of 15 years diagnosed with ALL between January 1998 and May 2016 in the Region of Murcia, Spain. Evaluation of parental SHS and other known prognostic factors (sex, age, white blood cell count at diagnosis, cytogenetics, NCI/Rome Criteria, early response to therapy, and relapse) were assessed for impact on OS, event-free survival (EFS), cumulative incidence of relapse (CIR), and treatment-related mortality (CITRM) using Kaplan-Meier analysis, Cox regression, and Fine-Gray model. RESULTS: The mean follow-up time was 105.3 months (±66.5). Prenatal exposure to SHS due to parental smoking was highly prevalent. Of the mothers, 44.4% and 55.5% of the fathers smoked at some point during pregnancy. After the child's diagnosis of ALL 39.7% of mothers and 45.9% of fathers reported smoking. The Cox proportional hazards model showed that maternal smoking during pregnancy and after diagnosis (HR = 4.396, 95% CI: 1.173-16.474, p = 0.028); and relapse (HR = 7.919; 95% CI: 2.683-21.868; p < 0.001) are independent prognostic factors in determining survival. The Fine-Gray model showed that maternal smoking during pregnancy and after diagnosis (HR = 14.525, 95% CI: 4.228-49.90, p < 0.001) is an independent prognostic factor in CITRM. CONCLUSIONS: Persistent SHS worsens OS and TRM in children with ALL. This negative impact contributes to a different prognosis and may possibly provide an exceptional insight into new therapeutic approaches, including environmental aspects such as prevention and smoking cessation to improve survival outcomes.

An Integrative Screening Tool of Alcohol Exposure During Early Pregnancy: Combining of the CDT Biomarker with Green Page Questionnaire.

AIMS: In current clinical practice, prenatal alcohol exposure is usually assessed by interviewing the pregnant woman by applying questionnaires. An alternative method for detecting alcohol use is to measure the biomarker carbohydrate-deficient transferrin (CDT). However, few studies measure CDT during pregnancy. This study examines the utility of CDT biomarker in the screening of alcohol exposure during early pregnancy. METHODS: A cohort of 91, first-trimester pregnant women assigned to a public reference maternity hospital, was screened using the Green Page (GP) questionnaire, an environmental exposure tool. CDT levels and other biomarkers of alcohol use were measured and compared with questionnaire data. RESULTS: About 70% of the mothers in the study consumed alcohol during early pregnancy and 22% met high-risk criteria for prenatal exposure to alcohol. CDT measurement showed a statistically significant area under the receiver operating characteristic curve with a value of 0.70. For a value of 0.95% of CDT, a specificity of 93% was observed. The most significant predictors of CDT were the number of binge drinking episodes, women's body mass index and European white race. CONCLUSION: Pregnant women with a CDT value >0.95% would be good candidates for the performance of the GP questionnaire during early pregnancy in order to detect potential high-risk pregnancy due to alcohol exposure.

Prolonged slow expiration technique improves recovery from acute bronchiolitis in infants: FIBARRIX randomized controlled trial.

OBJECTIVE:: To examine the effect of prolonged slow expiration respiratory physiotherapy treatment on the acute bronchiolitis severity scale and O2 saturation at short-time and at medical discharge in infants and the hospital stay. DESIGN:: Randomized controlled trial. SETTING:: Infants' unit of university hospital. PARTICIPANTS:: Infants with acute bronchiolitis ( N = 80). INTERVENTION:: Infants were randomized into respiratory treatment (RT) with prolonged slow expiration or treatment as usual (control) for one-week period. MAIN OUTCOME MEASURES:: The primary outcomes were Acute Bronchiolitis Severity Scale score and O2 saturation, recorded shortly after each intervention during the stay and at medical discharge, and the hospital stay. RESULTS:: The RT had a significantly lower Acute Bronchiolitis Severity Scale 10-minute after the first intervention (mean difference -1.7 points, 95% confidence interval (CI) -3.0 to -0.38), 2 hours after (-2.0 points, 95% CI -3.2 to -0.86) and the last day before medical discharge (-1.3 points, 95% CI -2.1 to 0.51). No changes were detected in O2 saturation. The survival analysis of time at medical discharge showed decrease in the average number of days to achieve an Acute Bronchiolitis Severity Scale of less than 2 points (RT: 2.6 days, 95% CI 2.1-3.1; Control: 4.4 days, 95% CI 3.6-5.1). CONCLUSION:: A prolonged slow expiration physiotherapy reduces Acute Bronchiolitis Severity Scale scores and does not change O2 saturation. Infants in RT group stay less days in hospital than infants in control group and no adverse events were detected.

Long term follow-up of a tobacco prevention and cessation program in cystic fibrosis patients. / Seguimiento a largo plazo de un programa de prevención y cesación tabáquica en pacientes con fibrosis quística.

This study evaluates the impact over time of a telephone-based intervention in tobacco cessation and prevention targeting patients with cystic fibrosis (CF) in the Mediterranean region of Murcia, Spain. We conducted an experimental prospective study with a cohort of CF patients using an integrative smoking cessation programme, between 2008 and 2013. The target population included family members and patients from the Regional CF unit. The study included an initial tobacco exposure questionnaire, measurement of lung function, urinary cotinine levels, anthropomorphic measures and the administered intervention at specific time intervals. Of the 88 patients tracked through follow-up, active smoking rates were reduced from 10.23% to 4.55% (p = 0.06). Environmental tobacco exposure was reduced in non-smoker patients from 62.03% to 36.90% (p < 0.01) during the five year follow-up. Significant reductions in the gradient of household tobacco smoke exposure were also observed with a decrease of 12.60%, from 31.65% (n = 25/79) to 19.05% (n = 16/84) in 2013 (p = <0.01). Cotinine was significantly correlated with both active and passive exposure (p<0.01) with a significant reduction of cotinine levels from 63.13 (28.58-97.69) to 20.56 (0.86-40.27) ng/ml (p<0.01). The intervention to significantly increase the likelihood of family quitting (smoke-free home) was 1.26 (1.05-1.54). Telephone based interventions for tobacco cessation and prevention is a useful tool when applied over time. Trained intervention professionals in this area are needed in the environmental health approach for the treatment of CF.

Este estudio evalúa el impacto en el tiempo de una intervención telefónica de prevención y cesación tabáquica dirigida a pacientes con fibrosis quística (FQ) en la Región de Murcia, España. Estudio prospectivo experimental en una cohorte de pacientes con FQ utilizando un programa integrativo de cesación tabáquica, entre 2008 y 2013. La población diana incluye a pacientes y familiares de la unidad regional de FQ. El estudio incluyó un cuestionario inicial de exposición al tabaco, medición de la función pulmonar, niveles de cotinina en orina, medidas antropomórficas y la intervención realizada en intervalos de tiempo.De los 88 pacientes seguidos, la tasa de fumadores activos se redujo de 10,23% a 4,55% (p = 0,06). La exposición al humo ambiental de tabaco se redujo en los pacientes no fumadores de 62,03% a 36,90% (p < 0,01) durante los cinco años de seguimiento. Se observaron reducciones significativas en la exposición al humo ambiental de tabaco en los hogares, de 31,65% (n = 25/79) a 19,05% (n = 16/84) en 2013 (p = <0,01). La cotinina se correlacionó significativamente con la exposición al tabaco activa y pasiva (p < 0,01) con una reducción significativa de los niveles de cotinina de 63,13 (28,58-97,69) a 20,56 (0,86-40,27) ng/ml (p < 0,01). La intervención para aumentar significativamente la probabilidad de abandono familiar (hogar libre de humo) fue de 1,26 (1,05-1,54). La intervención telefónica mantenida en el tiempo es una herramienta útil para la prevención y cesación tabáquica. Profesionales entrenados en este modelo de intervención con enfoque en salud medioambiental son necesarios para mejorar el tratamiento de FQ.

Role of body mass index in unbalanced (dysanaptic) lung growth of healthy infants.

RATIONALE: Imbalance between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) (dysanapsis) has been reported in children who are obese. This dysanaptic growth might begin at an early age, although there are no data on children younger than 6 years. OBJETIVES: To assess whether body mass index (BMI) and early weight gain, in healthy infants born at term, plays a significant role in the imbalance between FEV1 and FVC, even in the absence of obesity. METHODS: Lung function was measured by means of raised volume rapid thoracic compression in 69 healthy infants born at term from the Nutrition in Early Life and Asthma cohort. Dysanapsis was defined as zFVC >0.674, zFEV0 .5 ≥-1.645, and FEV0 .5/FVC ≤-1.645. Weight gain (g/day) and growth rate (cm/year) were calculated as the difference between weight and length on the test date and those at birth. To assess the relationship between zBMI and dysanapsis, a receiver operating characteristic curve was performed. Multivariable analysis was carried out by means of linear regressions (one for each lung function index) and by logistic regression for dysanapsis (yes/no). RESULTS: Higher zBMI was associated with risk of dysanapsis (odds ratio: 3.53, [95% confidence interval: 1.30; 9.66]; p = .014): Each additional zBMI unit was associated with ~10 mL higher FVC and with ~3.5% lower FEV0.5/FVC. Weight gain was associated with lower FEV0.5/FVC ratio. CONCLUSION: Dysanaptic development of lung function begins very early in infancy and is related with weight gain and body mass index, even in the absence of obesity.

Influence of gestational diabetes on circadian rhythms of children and their association with fetal adiposity.

OBJECTIVE: To analyse the circadian rhythm maturation of temperature, activity and sleep during the first year of life in offspring of diabetic mothers (ODM) and its relationship with obesity markers. METHODS: A prospective analysis of the children of 63 pregnant women (23 controls, 21 gestational diabetes mellitus (GDM) controlled with diet and 19 GDM with insulin). Fetal abdominal circumference was evaluated ecographically during gestation. Skin temperature and rest-activity rhythms were monitored for 3 consecutive days in children at 15 days and 1, 3 and 6 months. Anthropometrical parameters of the children were evaluated during the first year of life. RESULTS: Children from the GDM groups tended to higher fetal abdominal circumference z-score than controls at the beginning of the last trimester (p = 0.077) and at delivery (p = 0.078). Mean skin temperature or activity was not different among the groups. The I < O sleep index pointed to increasing concordance with parental sleeping at 3 and 6 months but no significant GDM-dependent differences. However, some of the parameters that define temperature maturation and also the circadian function index from the temperature-activity variable were significantly lower at 6 months in the GDM + insulin group. Fetal abdominal circumference z-score, as a predictor of fetal adiposity, correlated negatively with parameters related to circadian rhythm maturation as the circadian/ultradian rhythm (P1 /Pult ratio). CONCLUSIONS: Fetal adiposity correlated with a worse circadian rhythm regulation in ODM. In addition, ODM insulin-treated showed a disturbed pattern of the circadian function index of temperature activity at 6 months of age.

HLA-DRB1 and HLA-DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA-DRB1 alleles have previously been associated with ABPA-CF susceptibility; however, HLA-DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA-CF and determine their roles in susceptibility or protection. Patients with ABPA-CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA-DRB1 and -DQB1 genotyping was performed by the Luminex PCR-SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR-SSP was also performed by high-resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA-DRB1*5:01 and -DRB1*11:04 alleles occurred with greater frequency in patients with ABPA-CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA-CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA-DQB1 region, the HLA-DQB1*06:02 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*02:01 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.

Effects of infant cereals with different carbohydrate profiles on colonic function--randomised and double-blind clinical trial in infants aged between 6 and 12 months--pilot study.

Infant cereals are often the elected foodstuff for beginning complementary feeding and provide carbohydrates which are different to those found in maternal milk. The objective of this preliminary study was to ascertain the colonic effects of two infant cereals, with different carbohydrate profiles, in a randomised and double-blind trial in healthy infants. Nineteen term infants between 6.3 and 9.8 months of age were enrolled, after written informed consent was obtained from parents. Ten subjects were allocated to take infant cereal A and nine, infant cereal B. An intervention period was 2 months, with five visits every 15 days, to take anthropometric measurements and faeces samples for the analysis of microbiota, short-chain fatty acids concentration (SCFA), pH value and secretory immunoglobulin A (sIgA). An adequate growth and stool frequency was registered in both intervention groups. Faecal counts of Bifidobacterium, Lactobacillus, Enterobacteriaceae, Enterococcus, Clostridium and Bacteroides did not show any statistical differences. However, a significantly (P < 0.05) higher butyric acid and sIgA, and lower faecal pH were observed in infants who had ingested infant cereal A, with a higher ratio complex/simple carbohydrates. In conclusion, small changes in the carbohydrate profile of infant cereals could lead to significant differences in parameters related to fermentative activity of intestinal microbiota.

Enterovirus reverse transcriptase polymerase chain reaction assay in cerebrospinal fluid: an essential tool in meningitis management in childhood.

BACKGROUND: Enteroviruses (EV) are the main aetiological agents of aseptic meningitis in children and a common cause of febrile illnesses in young infants in summer. A rapid diagnosis is essential to rule out other conditions. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay performed in cerebrospinal fluid (CSF) has proved to be a very fast and useful tool. METHODS: We collected demographic, clinical and laboratory data of children (aged 11-years or younger) with EV RT-PCR (Cepheid(®) Xpert EV) positive in CSF from December 2007 to July 2010, to describe EV meningitis in children and to determine the role of this assay. RESULTS: We included 92 children (mean age 2.5 years), 32% of whom were neonates. There was no pleocytosis in the CSF of 18.5% (36% in newborn) of the patients, and 23 (25%) were discharged to home from the Emergency Room after the positive results. Length of hospital stay was 2 days (>2 years) versus 4.5 days in newborns (P<0.0001). Antibiotic treatment was prescribed in 38% (75% <3 months), but in 40% of these, it was stopped after the positive results. Mean EV RT-PCR information time was 7h (4-18h). All children had a good clinical outcome. CONCLUSIONS: EV RT-PCR assay in CSF has played an essential role in the management of children with EV meningitis, allowing earlier discharges and decreasing avoidable inappropriate antibiotic treatments. This test should be considered as part of the initial study of children with aseptic meningitis, especially during epidemic seasons.

Dissecting Airborne Allergens.

Asthma is a heterogeneous and very complex group of diseases, and includes different clinical phenotypes depending on symptoms, progression, exacerbation patterns, or responses to treatment, among other characteristics. The allergic phenotype is the most frequent, especially in pediatric asthma. It is characterized by sensitization (the production of specific IgEs) to allergens and frequent comorbidity with rhinitis as well as atopic dermatitis. Given the complexity of allergic asthma, knowledge of it must be approached from different points of view: clinical, histological, physiological, epidemiological, biochemical, and immunological, among others. Since partial approaches do not allow for the understanding of this complexity, it is necessary to have multidimensional knowledge that helps in performing the optimal management of each case, avoiding a "blind men and elephant parable" approach. Allergens are antigens that trigger the production of specific IgE antibodies in susceptible individuals, who present symptoms that will depend on the type and intensity of the allergenic load as well as the tissue where the interaction occurs. Airborne allergens cause their effects in the respiratory tract and eyes, and can be indoor or outdoor, perennial, or seasonal. Although allergens such as mites, pollens, or animal dander are generally considered single particles, it is important to note that they contain different molecules which could trigger distinct specific IgE molecules in different patients. General practitioners, pediatricians, and other physicians typically diagnose and treat asthma based on clinical and pulmonary function data in their daily practice. This nonsystematic and nonexhaustive revision aims to update other topics, especially those focused on airborne allergens, helping the diagnostic and therapeutic processes of allergic asthma and rhinitis.

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.

Severe Asthma and Biological Therapies: Now and the Future.

Recognition of phenotypic variability in pediatric asthma allows for a more personalized therapeutic approach. Knowledge of the underlying pathophysiological and molecular mechanisms (endotypes) of corresponding biomarkers and new treatments enables this strategy to progress. Biologic therapies for children with severe asthma are becoming more relevant in this sense. The T2 phenotype is the most prevalent in childhood and adolescence, and non-T2 phenotypes are usually rare. This document aims to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of biological drugs, focusing on the pediatric population. The drugs currently available are omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, with some differences in administrative approval prescription criteria between the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Previously, we described the characteristics of severe asthma in children and its diagnostic and therapeutic management.

Inherited Epigenetic Hallmarks of Childhood Obesity Derived from Prenatal Exposure to Obesogens.

Childhood obesity has reached epidemic levels in developed countries and is becoming a major cause for concern in the developing world. The causes of childhood obesity are complex and multifactorial, involving the interaction between individual genetics and environmental and developmental factors. Among the environmental factors, there is a growing interest in understanding the possible relationship between the so-called environmental obesogens and the development of obesity in children. Exposure to these obesogens such as phthalates, bisphenol A, or parabens, has been identified as a promoter of obesity through different mechanisms such as the alteration of adipocyte development from mesenchymal progenitors, the interference with hormone receptors, and induced inflammation. However, less attention has been paid to the inheritance of epigenetic modifications due to maternal exposure to these compounds during pregnancy. Thus, the aim of this review is to summarize the current knowledge of epigenetic modifications due to maternal exposure to those obesogens during pregnancy as well as their potential implication on long-term obesity development in the offspring and transgenerational inheritance of epiphenotypes.

SARS-CoV-2 infection in children with cystic fibrosis: A cross-sectional multicenter study in Spain. New waves, new knowledge.

INTRODUCTION: The association between viral infections and pulmonary exacerbations in children with cystic fibrosis (cwCF) is well established. However, the question of whether cwCF are at a higher risk of COVID-19 or its adverse consequences remains controversial. METHODS: We conducted an observational, multicenter, cross-sectional study of cwCF infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between March 2020 and June 2022, (first to sixth COVID-19 pandemic waves) in Spain. The study aimed to describe patients' basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. RESULTS: During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (sixth wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). Infection occurring along the sixth wave was the only independent risk factor for being symptomatic. Just eight cwCF needed hospital admission. No multisystem inflammatory syndrome, persisting symptoms, long-term sequelae, or deaths were reported. CONCLUSIONS: Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients' basal characteristics, clinical courses, and outcomes were detected across waves. While the pandemic continues, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

Relationship between lung function and exhaled volatile organic compounds in healthy infants.

OBJECTIVE: The aim of this study is to assess, for the first time, the relationship between the volatilome and lung function in healthy infants, which may be of help for the early detection of certain respiratory diseases. Lung function tests are crucial in chronic respiratory diseases diagnosis. Moreover, volatile organic compounds (VOCs) analysis in exhaled breath is a noninvasive technique that enables the monitorization of oxidative stress, typical of some forms of airway inflammation. METHODS: Lung function was studied in 50 healthy infants of 3-8 months of age and the following parameters were obtained: forced vital capacity (FVC), forced expiratory volume at 0.5 s (FEV0.5 ), forced expiratory flow at 75% of FVC (FEF75 ), forced expiratory flow at 25%-75% of FVC (FEF25-75 ), and FEV0.5 /FVC. Lung function was measured according to the raised volume rapid thoracoabdominal compression technique. In addition, a targeted analysis of six endogenous VOCs (acetone, isoprene, decane, undecane, tetradecane, and pentadecane) in the exhaled breath of the children was carried out by means of thermal desorption coupled gas chromatography-single quadrupole mass spectrometry system. RESULTS: A negatively significant relationship has been observed between levels of acetone, tetradecane, and pentadecane in exhaled breath and several of the lung function parameters. Levels of acetone (feature m/z = 58) were significantly negatively associated with FVC and FVE0.5 , levels of tetradecane (feature m/z = 71) with FEV0.5, and levels of pentadecane (feature m/z = 71) with FEV0.5 and FEF25-75 . CONCLUSION: The findings of this study highlight a significant association between VOCs related to oxidative stress and lung function in healthy infants.

Development of Lung Function in Preterm Infants During the First Two Years of Life.

INTRODUCTION: It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size. AIM: To assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period. METHODS: This observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks' gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V'maxFRC and FEF25-75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age. RESULTS: Lung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V'maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants. CONCLUSION: When compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.

Geographic distribution and phenotype of European people with cystic fibrosis carrying A1006E mutation.

BACKGROUND: A1006E is a Cystic Fibrosis (CF) mutation that is still not widely known. We report phenotypic features and geographic distribution of the largest cohort of people with CF (pwCF) carrying A1006E to date. METHODS: Study of European pwCF carrying A1006E mutation, included in the European CF Society Patient Registry (ECFSPR). Genotype, ancestries and all variables recorded were compared to a cohort of F508del/F508del patients. Rate of decline in percentage-of-predicted FEV1 (ppFEV1) was also analyzed using the 2010-2017 ECFSPR. RESULTS: 44 pwCF carrying A1006E were reported (59% males), median age 33 years old (3-58), 54.5% Spanish and 40.9% Italian, most with ancestry in Murcia (Spain) and Lazio (Italy) regions. Compared to F508del homozygous, A1006E-pwCF were significantly older (75% vs. 52.5% ≥ 18 years old) and diagnosed at later median age (6.98 vs. 0.29 years); showed lower rates of meconium ileus (2.33% vs. 17.7%), pancreatic insufficiency (27.91% vs. 99.26%), diabetes (2.33% vs. 21.98%), liver disease (6.98% vs. 36.72%) and Pseudomonas aeruginosa chronic colonization (30.95% vs. 42.51%); and presented better nutrition (BMI z-score 0.44 vs. -0.43) and ppFEV1 (90.8% vs. 78.6%), with 18.9% (most >40 years old) having a ppFEV1<70%. Additional ppFEV1 decline (0.96% per year) was attributed to F508del/F508del genotype (p = 0.0007). None died or needed organ transplantation during the study period. CONCLUSIONS: A1006E-pwCF are mainly of Western Mediterranean Spanish and Italian descent. When compared with F508del/F508del-pwCF, they usually have a milder form of the disease, associated with pancreatic sufficiency and slower FEV1 decline. However, some will develop progressive respiratory impairment during adulthood.