Patient- and parent-initiated oral steroids for asthma exacerbations: Review

BACKGROUND: Asthma is a chronic inflammatory disease of the airways affecting an estimated 334 million people worldwide. During severe exacerbations, patients may need to attend a medical centre or hospital emergency department for treatment with systemic corticosteroids, which can be administered intravenously or orally. Some people with asthma are prescribed oral corticosteroids (OCS) for self-administration (i.e. patient-initiated) or to administer to their child with asthma (i.e. parent-initiated), in the event of an exacerbation. This approach to treatment is becoming increasingly common. OBJECTIVES: To evaluate the effectiveness and safety of patient- or parent-initiated oral steroids for adults and children with asthma exacerbations. SEARCH METHODS: We identified trials from Cochrane Airways' Specialised Register (CASR) and also conducted a search of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch). We searched CASR from its inception to 18 May 2016 and trial registries from their inception to 24 August 2016; we imposed no restriction on language of publication. SELECTION CRITERIA: We looked for randomised controlled trials (RCTs), reported as full-text, those published as abstract only, and unpublished data; we excluded cross-over trials.We looked for studies where adults (aged 18 years or older) or children of school age (aged 5 years or older) with asthma were randomised to receive: (a) any patient-/parent-initiated OCS or (b) placebo, normal care, alternative active treatment, or an identical personalised asthma action plan without the patient- or parent-initiated OCS component. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results to identify any studies that met the prespecified inclusion criteria.The prespecified primary outcomes were hospital admissions for asthma, asthma symptoms at follow-up and serious adverse events. MAIN RESULTS: Despite comprehensive searches of electronic databases and clinical trial registries, we did not identify any studies meeting the inclusion criteria for this review. Five potentially relevant studies were excluded for two reasons: the intervention did not meet the inclusion criteria for this review (three studies) and studies had a cross-over design (two studies). Two of the excluded studies asked the relevant clinical question. However, these studies were excluded due to their cross-over design, as per the protocol. We contacted the authors of the cross-over trials who were unable to provide data for the first treatment period (i.e. prior to cross-over). AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials (non-cross-over design) to inform the use of patient- or parent-initiated oral corticosteroids in people with asthma

Cardiovascular disease risk in the offspring of diabetic women: the impact of the intrauterine environment

The incidence of gestational diabetes is increasing worldwide, exposing large numbers of infants to hyperglycaemia whilst in utero. This exposure may have a long-term negative impact on the cardiovascular health of the offspring. Novel methods to assess cardiovascular status in the neonatal period are now available—including measuring arterial intima-media thickness and retinal photography. These measures will allow researchers to assess the relative impact of intrauterine exposures, distinguishing these from genetic or postnatal environmental factors. Understanding the long-term impact of the intrauterine environment should allow the development of more effective health policy and interventions to decrease the future burden of cardiovascular disease. Initiating disease prevention aimed at the developing fetus during the antenatal period may optimise community health outcomes

Mining Medical Data: Bridging the Knowledge Divide

Due to the signi¯cant amount of data generated by modern medicine there is a growing reliance on tools such as data mining and knowledge discovery to help make sense and comprehend such data. The success of this process requires collaboration and interaction between such methods and medical professionals. Therefore an important question is: How can we strengthen the relationship between two traditionally separate fields (technology and medicine) in order to work simultaneously towards enhancing knowledge in modern medicine. To address this question, this study examines the application of data mining techniques to a large asthma medical dataset. A discussion introducing various methods for a smooth approach, straying from the `jack of all trades, master of none' to a modular cooperative approach for a successful outcome is pro-posed. The results of this study support the use of data mining as a useful tool and highlight the advantages on a global scale of closer relations between the two distinct fields. The exploration of CRISP methodology suggests that a `one methodology fits all approach' is not appropriate, but rather combines to create a hybrid holistic approach to data mining

Reproducibility of aortic intima-media thickness in infants using edge-detection software and manual caliper measurements

Background: Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality. Methods. Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. Results: Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was 0.90 (95% CI 0.76, 0.96), mean difference 1.5 μm (95% LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean difference 2 μm (95% LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 μm (95% LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 μm (50) versus mean aIMT 563 μm (49) respectively; p < 0.001, mean difference 44 μm, 95% LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. Conclusion: In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors. © 2014 McCloskey et al.; licensee BioMed Central Ltd

The influence of sighing respirations on infant lung function measured using multiple breath washout gas mixing techniques

There is substantial interest in studying lung function in infants, to better understand the early life origins of chronic lung diseases such as asthma. Multiple breath washout (MBW) is a technique for measuring lung function that has been adapted for use in infants. Respiratory sighs occur frequently in young infants during natural sleep, and in accordance with current MBW guidelines, result in exclusion of data from a substantial proportion of testing cycles. We assessed how sighs during MBW influenced the measurements obtained using data from 767 tests conducted on 246 infants (50% male; mean age 43 days) as part of a large cohort study. Sighs occurred in 119 (15%) tests. Sighs during the main part of the wash‐in phase (before the last 5 breaths) were not associated with differences in standard MBW measurements compared with tests without sighs. In contrast, sighs that occurred during the washout were associated with a small but discernible increase in magnitude and variability. For example, the mean lung clearance index increased by 0.36 (95% CI: 0.11–0.62) and variance increased by a multiplicative factor of 2 (95% CI: 1.6–2.5). The results suggest it is reasonable to include MBW data from testing cycles where a sigh occurs during the wash‐in phase, but not during washout, of MBW. By recovering data that would otherwise have been excluded, we estimate a boost of about 10% to the final number of acceptable tests and 6% to the number of individuals successfully tested

Parent initiated prednisolone for acute asthma in children of school age: randomised controlled crossover trial

Objective To evaluate the efficacy of a short course of parent initiated oral prednisolone for acute asthma in children of school age

The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood

Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 (IGF2) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study (n = 576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Delta = -2.23%;95% CI = -3.68 to -0.77%), and across all six of the individual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower ( 3530 g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Delta = -3.89%;95% CI = -6.06 to -1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Delta = -3.70%;95% CI = -5.90 to -1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2/H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed

Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways

The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103+ dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103+ DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103+ DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens

The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study

As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development