Predicting the outcome of respiratory disease in wheezing infants using tidal flow-volume loop shape.

INTRODUCTION AND OBJECTIVES: Wheezing (RW) infants with a positive asthma predictive index (API+) have a lower lung function as measured by forced expiratory techniques. Tidal flow-volume loops (TFVL) are easy to perform in infants, and sedation is not necessary. MATERIALS AND METHODS: A total of 216 wheezing infants were successfully measured, and 183 of them were followed for over a year. TFVL loops were classified into one of three categories depending of their geometric shape (symmetric, convex, and concave). Respiratory rate (Rr), presence of API+, and the number of exacerbations during the following year were also recorded. RESULTS: Children with concave loops had more exacerbations in the following year (OR = 6.8 [IC95% 3.33;13.91]). Infants API + were also significantly more related to concave loops (OR = 10.02 [IC 95% 4.53; 22.15]). Rr was higher in infants with concave loops (44+/-15.5 vs. 36.6 +/-12.6; p < 0.01). CONCLUSION: Infants with a concave TFVL have a higher probability of experiencing exacerbations in the following year, and are at a higher risk of suffering asthma.

Priorities for future research into asthma diagnostic tools: A PAN-EU consensus exercise from the European asthma research innovation partnership (EARIP).

The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two-stage e-Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face-to-face workshop. The three most important diagnostic/predictive tools ranked were as follows: "New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring," "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath."

Cost-utility analysis of Palivizumab for Respiratory Syncytial Virus infection prophylaxis in preterm infants: update based on the clinical evidence in Spain.

BACKGROUND: This study aimed at estimating the efficiency of palivizumab in the prevention of Respiratory Syncytial Virus (RSV) infection and its sequelae in preterm infants (32day 1-35day 0weeks of gestational age -wGA-) in Spain. METHODS: A decision-tree model was developed to compare health benefits (Quality Adjusted Life Years-QALYs) and costs of palivizumab versus a non-prophylaxis strategy over 6 years. A hypothetical cohort of 1,000 preterm infants, 32day 1-35day 0 wGA (4.356 kg average weight) at the beginning of the prophylaxis (15 mg/kg of palivizumab; 3.88 average number of injections per RSV season) was analysed. The model considered the most recent evidence from Spanish observational and epidemiological studies on RSV infection: the FLIP II study provided hospital admission and Intensive Care Unit (ICU) admission rates; in-hospital mortality rate was drawn from an epidemiological study from 2004 to 2012; recurrent wheezing rates associated to RSV infection from SPRING study were adjusted by the evidence on the palivizumab effect from clinical trials. Quality of life baseline value, number of hospitalized infants and the presence of recurrent wheezing over time were granted to estimate QALYs. National Health Service and societal perspective (included also recurrent wheezing indirect cost) were analysed. Total costs (€, 2016) included pharmaceutical and administration costs, hospitalization costs and recurrent wheezing management annual costs. A discount rate of 3.0% was applied annually for both costs and health outcomes. RESULTS: Over 6 years, the base case analysis showed that palivizumab was associated to an increase of 0.0731 QALYs compared to non-prophylaxis. Total costs were estimated in €2,110.71 (palivizumab) and €671.68 (non-prophylaxis) from the National Health System (NHS) perspective, resulting in an incremental cost utility ratio (ICUR) of €19,697.69/QALYs gained (prophylaxis vs non-prophylaxis). Results derived from the risk-factors population subgroups analysed were in line with the total population results. From the societal perspective, the incremental cost associated to palivizumab decreased to an €1,253.14 (ICUR = €17,153.16€/QALYs gained for palivizumab vs non-prophylaxis). One-way and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: The prophylaxis with palivizumab is efficient for preventing from RSV infections in preterm infants 32day 1-35day 0 wGA in Spain.

Is palivizumab effective as a prophylaxis of respiratory syncytial virus infections in cystic fibrosis patients? A meta-analysis.

BACKGROUND: Infections by respiratory syncytial virus (RSV) are more severe in patients with cystic fibrosis (CF), and many CF units use palivizumab as prophylaxis; however, information about palivizumab efficacy in CF patients is almost lacking. METHODS: A literature search up to December 2012 on the morbidity of RSV bronchiolitis in CF patients and on the safety and efficacy of palivizumab in those patients was performed. A random-effects meta-analysis was conducted for those studies meeting pre-specified search criteria. Historical controls were allowed. RESULTS: The number of patients who received palivizumab was 354 and the hospital admission rate was 0.018 (95% CI 0.0077-0.048). The corresponding number in the non-treated groups was 463 patients with an admission rate of 0.126 (95% CI 0.086-0.182) (Q=13.9; p<0.001). CONCLUSION: Palivizumab may have a role in the prevention of severe lower airway infection by RSV in CF patients.

[The association of adherence to a Mediterranean diet during early pregnancy and the risk of gastroschisis in the offspring]. / Asociación de la adherencia a la dieta mediterránea al inicio del embarazo y riesgo de gastrosquisis en la descendencia: un estudio de casos-controles.

OBJECTIVES: The aim of this study was to study the association of adherence to the Mediterranean diet in early pregnancy maternal and the offspring's risk of gastroschisis. METHODS: Case-control study. We describe 11 cases of gastroschisis in the region of Murcia from 2007 to 2012 and 34 concurrent controls. At the time of diagnosis each of the cases completed a validated Food Frequency Questionnaire (FFQ) consisting of 98 items on the periconceptional diet. Confounding factors: smoking, exposure to cannabis / marihuana, age of the parents, BMI, income and educational level. We conducted a descriptive and multivariate logistic regression statistical analysis. RESULTS: Mothers of children with gastroschisis were younger (20.8 years, 95% CI 17.3 to 24.2) and their diet consisted of less caloric intake, saturated fat and monounsaturated fats and proteins than controls. The Odds Ratio (OR) in the multivariate model controlling for confounding factors: maternal age (year) 0.70 (95% CI 0.51 to 0.96), monounsaturated fatty acids (oleic acid, g) 0.79 (95% CI 0.65 to 0, 97) and vegetable intake (rations/week) 0.70 (95% CI 0.48 to 1.00). CONCLUSION: A maternal diet rich in oleic acid and vegetable products may prevent vascular risk of onphalomesenteric arteries reducing the risk of gastroschisis.

Head circumference at birth and exposure to tobacco, alcohol and illegal drugs during early pregnancy.

AIMS: We aimed to assess the effects of exposure to tobacco smoke, alcohol and illegal drugs during early pregnancy on the head circumference (HC) at birth of otherwise healthy neonates. METHODS: A follow-up study from the first trimester of pregnancy to birth was carried out in 419 neonates. An environmental reproductive health form was used to record data of substance exposure obtained during the first obstetric visit at the end of the first trimester. A multiple linear regression model was created for this purpose. RESULTS: Alcohol intake during pregnancy and medical ionizing radiation exposure were the most significant predictors of HC. The mothers' alcohol consumption increased with the mothers' and fathers' education level, net family income and fathers' alcohol consumption. In contrast, maternal smoking decreased with increasing mothers' and fathers' education level and net family income. About 13% of the surveyed embryos were exposed to illegal drugs. CONCLUSIONS: Mild to moderate alcohol consumption diminishes the at-birth HC of theoretically healthy newborns in a linear form. There was no threshold dose. We perceived a need for increasing the awareness, and for training, of health care professionals and parents, in regard to risks of alcohol consumption and for recommending abstinence of these substances in both parents during pregnancy. It should also be remembered that medical ionizing radiation should be performed only during the first half of the cycle in fertile women. We think that our study has an important social impact as it affords data for implementing policies for promoting "healthy pregnancies".

Is the effect of prenatal paracetamol exposure on wheezing in preschool children modified by asthma in the mother?

BACKGROUND: There seems to be an association between paracetamol consumption during late pregnancy and the prevalence of wheezing in infancy and childhood. The aim of the present study is to determine whether the aforementioned association is modified by the presence of asthma in the mother. METHODS: A total of 1,741 children aged 3-5 years from an epidemiological survey performed in the province of Murcia (Spain) were included in the analysis. Data on paracetamol consumption (never, at least once during pregnancy or at least once per month during pregnancy), wheezing symptoms in the offspring (according to the International Study of Asthma and Allergies in Childhood protocol) and the presence of asthma in the mother, together with other known risk factors for asthma, were obtained by means of a questionnaire. RESULTS: The mean age of the children was 4.08 +/- 0.8 years and 51.1% were males. The overall prevalence of current wheezing was 20.2%. The frequency of paracetamol usage was similar among asthmatic and non-asthmatic mothers, and only a small proportion of them took this drug at least once a month (13.8% of asthmatics and 11.0% of non-asthmatics). Compared to the mothers who never took paracetamol, there was a significant association between the mother having taken paracetamol at least once per month during pregnancy and the offspring suffering from wheezing at preschool age, but only among non-asthmatic mothers (odds ratio 1.94, 95% confidence interval 1.34-2.79 vs. odds ratio 1.05, 95% confidence interval 0.21-5.08). This association was maintained after controlling for potential confounders (odds ratio 1.74, 95% confidence interval 1.15-2.61). CONCLUSIONS: The frequent usage of paracetamol during pregnancy is associated with the prevalence of wheezing in offspring during preschool years. Asthma in the mother might modify this association.

[Consensus-based approach for severe paediatric asthma in routine clinical practice]. / Consenso para el abordaje del asma grave pediátrica en la práctica clínica habitual.

INTRODUCTION: Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. MATERIAL AND METHODS: An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. RESULTS: Eleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. CONCLUSIONS: This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma.

Ontogeny and aging of the distal skin temperature rhythm in humans.

In circadian terms, human ontogeny is characterized by the emergence of a daily pattern, from a previous ultradian pattern, for most variables during the first 6 months of life. Circadian aging in humans is characterized by a phase advance, accompanied by rhythm fragmentation and flattening. Despite an expanding body of literature focused on distal skin temperature, little information is available about the ontogeny and practically nothing about age-related changes in this rhythm. Thus, the aim was to evaluate the degree of maturation and aging of the circadian pattern of distal skin temperature to identify those parameters that are modified throughout life and could be used to differentiate subjects according to their age. For this, distal skin temperature was measured in 197 volunteers (55 % women), including babies aged 15 days (30 subjects), 1 month (28 subjects), 3 months (31 subjects), and 6 months (10 subjects); young adults aged 19 years (37 subjects); middle-aged persons aged 46 years (27 subjects); older people aged 72 (34 subjects). Circadian system maturation was associated with an increase in amplitude and a reduction in skin temperature during sleep. During adulthood, women showed a more robust pattern (lower fragmentation, and higher night-time temperature, amplitude, circadian function index, and first harmonic relative power); however, these differences were lost with aging, a period of life that was consistently associated with a phase advance of the rhythm. In summary, distal skin temperature pattern can be used as a robust variable to discern between different ages throughout the life.

Is low docosahexaenoic acid associated with disturbed rhythms and neurodevelopment in offsprings of diabetic mothers?

BACKGROUND/OBJECTIVE: To evaluate the relation between docosahexaenoic acid (DHA) status and neurodevelopment in the offsprings of gestational diabetic mothers (ODMs). SUBJECTS/METHODS: A prospective cohort study was performed. The offspring of 63 pregnant women (23 controls, 21 diet-controlled gestational diabetes mellitus (GDM) and 19 insulin-treated GDM) were recruited. Maternal and venous cord plasma DHA percentages were analyzed. Skin temperature and activity in children were recorded for 72 h at 3 and 6 months of life. Neurodevelopment was assessed using the Bayley Scale of Infant Development II (BSID II) at 6 and 12 months of age. RESULTS: Cord plasma DHA percentage was significantly lower in the ODMs compared with that in the controls (Control 6.43 [5.04-7.82](a); GDM+diet 5.65 [4.44-6.86](ab); GDM+insulin 5.53 [4.45-6.61](b)). Both mental (Control 102.71 [97.61-107.81](a); GDM+diet 100.39 [91.43-109.35](a); GDM+insulin 93.94 [88.31-99.57](b)) and psychomotor (Control 91.52 [81.82-101.22](a); GDM+diet 81.67 [73.95-89.39](b); GDM+insulin 81.89 [71.96-91.85](b)) scores evaluated by the BSID II were significantly lower at 6 months in ODMs, even after adjusting for confounding factors such as breastfeeding, maternal educational level and gender. Cord plasma DHA percentage correlated with the psychomotor score from BSID II (r=0.27; P=0.049) and with the intra-daily variability in activity (r=-0.24; P=0.043) at 6 months. Maternal DHA was correlated with several sleep rhythm maturation parameters at 6 months. CONCLUSIONS: Lower DHA levels in cord plasma of ODMs could affect their neurodevelopment. Maternal DHA status was also associated with higher values in the sleep rhythm maturation parameters of children.

Validity of parent-reported height and weight for defining obesity among asthmatic and nonasthmatic schoolchildren.

BACKGROUND: The relationship between parent-reported and measured height and weight is not well established in schoolchildren. This relationship has never been studied in asthmatic children. The objective of this study is to test the validity of the parent-reported weight and height for defining obesity by BMI and to know whether the perception of this height and weight changes when the child suffers from asthma. METHODS: All classes of children of the target ages of 6-8 years (n = 1,672, participation rate 70.2%) of all schools in four municipalities of Murcia (Spain) were included. Parents were asked about their children's weight and height using a questionnaire which included the International Study of Asthma and Allergies in Childhood (ISAAC) core questions on asthma. Parents were not aware that their children were going to be weighed and measured within 1 week's time. Measurements were performed using a rigid stadiometer to the nearest 0.1 cm and a scale to the nearest 0.1 kg. RESULTS: The bias (reported minus real) was, respectively, for nonasthmatics and asthmatics: weight +0.42 kg (95% CI +0.24; +0.59 kg) versus +0.97 kg (+0.50; +1.44 kg), height +2.37 cm (+2.06; +2.68 cm) versus +2.87 cm (+1.87; +3.87 cm); BMI -0.39 kg/m(2) (-0.52; -0.23 kg/m(2)) versus -0.23 kg/m(2) (-0.58; +0.13 kg/m(2)). Diagnostic accuracy of obesity calculated from reported measurements was, respectively, for nonasthmatics and asthmatics: sensitivity 78.0 versus 77.8%, specificity 96.2 versus 94.5%, positive predictive value 77.2 versus 73.7% and negative predictive value 96.4 versus 91.7%. CONCLUSIONS: Reported weights and heights had large biases, comparable between parents of both asthmatic and those of nonasthmatic children. However, this information could be reasonably valid for classifying children as obese or nonobese in large epidemiological studies.

Novel HMBS founder mutation and significant intronic polymorphism in Spanish patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis, caused by a partial deficiency of hydroxymethylbilane synthase (HMBS). Knowledge of the nature of the HMBS mutations causing AIP in Spanish families is very limited. Here we report a novel 669_698del of the HMBS gene in twenty-two individuals from five independent Spanish AIP families, settled in Murcia (southeastern region of Spain). All mutation carriers shared a common disease associated haplotype indicating an ancestral founder effect. Identification of the 669_698del founder mutation allowed rapid and simple molecular diagnosis of AIP in families from this region in Spain. In addition, 771 + 58C>T in intron 12 on the non-669_698del allele was identified in six AIP patients, which promoted homozygous AIP misdiagnosis.

Penetrating craniocerebral injury from an underwater fishing harpoon.

Weapon injuries other than gunshot wounds or low-velocity stab wounds to the head are extremely rare. We report the case of a 6-year-old girl who sustained a penetrating craniocerebral injury after being accidentally shot with an underwater fishing harpoon. This mechanism of injury seems to share characteristics of both high- and low-velocity projectiles. We discuss the management of this unusual injury in a child, remarking that foreign body removal in these cases must be carried out following the original direction of the projectile trajectory. We review the current literature on craniocerebral injuries caused by similar objects, especially those occurring in children.

[Importance of childhood accidents. Results of a regional study]. / Importancia de los accidentes en la infancia. Datos de un estudio regional.

In order to know the importance and epidemiology of childhood accidents, a prospective study was made in a Spanish region, this study was founded in death certificates and 3,344 questionnaires from children under 7 years old, accidented in 1986 and attended in emergency departments in our region. The information was coded and analysed by computer of the Murcia University. Accidents are the main cause of death in children aged over 1 year, as a common cause of assistance in emergency departments. Its characteristic are common to most countries, but the authors find some differences in our region. It is necessary to dedicate bigger effort to study and prevention of childhood accidents.

Exercise-induced asthma in children: a comparative study of free and treadmill running.

BACKGROUND: Exercise is one of the most common precipitating factors of acute asthmatic crises in childhood. Although it has been described as more frequent among children, this is probably due to their more abundant physical activity. Nevertheless, it also occurs at other ages. OBJECTIVE: The aim of this study is to assess possible differences in postexercise spirometry after treadmill and free running provocation tests. METHODS: We compared the results obtained in a treadmill test performed by 30 asthmatic children and 30 healthy children with the results obtained with these same children in a free running test, keeping similar environmental conditions (temperature and humidity), exercise intensity (assessed by heart rate), and airway status at the time of the test. RESULTS: Seventy-three percent of the patients had positive treadmill tests and 63.3% had positive free running tests. For the spirometric parameters studied, there were no significant differences in the percent decrease in postexercise performance after either of the provocation tests. For FEV1, which is the most sensitive diagnostic parameter, the sensitivity was 53.3% in treadmill running and 56.7% in free running, with a specificity of 100% in both tests. CONCLUSIONS: If environmental conditions, exercise intensity, and airway status are controlled at the time of the test, treadmill and free running can be used indistinctly as asthma-inducing exercises.

[Alcohol consumption in children: polling the parents]. / Consumo de alcohol en niños: encuesta realizada a los padres.

Alcoholism is a major health problem in Spain. Frequently, the first drink is offered in the home. We report the results of a poll in which parents were asked when they offer alcohol to their children. We found that 76.1% offered alcohol anytime. Furthermore, 15% of the mothers answered that this may be of benefit to their children. Drinks with a higher level of alcohol (brandy, punch, anis) were offered more frequently after seven years of age and to those children whose mother had offered the first alcoholic beverage at an earlier age.