Asthma Phenotypes in Childhood

INTRODUCTION: Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment. Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods. Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes. In return, this would lead to better patient stratification and disease management, thereby providing true personalised medicine

Evolution of IgE responses to multiple allergen components throughout childhood

BACKGROUND: There is a paucity of information about longitudinal patterns of IgE responses to allergenic proteins (components) from multiple sources. OBJECTIVE: To investigate temporal patterns of component-specific IgE responses from infancy to adolescence, and their relationship with allergic diseases. METHODS: In a population-based birth cohort, we measured IgE to 112 components at 6 follow-ups during childhood. We used a Bayesian method to discover cross-sectional sensitization patterns and their longitudinal trajectories, and related these patterns to asthma and rhinitis in adolescence. RESULTS: We identified one sensitization cluster at age one, 3 at age three, 4 at ages five and eight, 5 at age 11, and six at age 16 years. "Broad" cluster was the only cluster present at every follow-up, comprising of components from multiple sources. "Dust mite" cluster formed at age three and remained unchanged to adolescence. At age three, a single-component "Grass" cluster emerged, which at age five absorbed additional grass components and Fel d 1 to form the "Grass/cat" cluster. Two new clusters formed at age 11: "Cat" cluster and "PR-10/profilin" (which divided at age 16 into "PR-10" and "Profilin"). The strongest contemporaneous associate of asthma at age 16 years was sensitization to "Dust mite" cluster (OR [95% CI]: 2.6 [1.2-6.1], P<0.05), but the strongest early-life predictor of subsequent asthma was sensitization to "Grass/cat" cluster (3.5 [1.6-7.4], P<0.01). CONCLUSIONS: We describe the architecture of the evolution of IgE responses to multiple allergen components throughout childhood, which may facilitate development of better diagnostic and prognostic biomarkers for allergic diseases

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Suboptimal geographic accessibility to comprehensive HIV care in the US: regional and urban–rural differences

Achieving US state and municipal benchmarks to end the HIV epidemic and promote health equity requires access to comprehensive HIV care. However, this care may not be geographically accessible for all people living with HIV (PLHIV). We estimated county-level drive time and suboptimal geographic accessibility to HIV care across the contiguous US, assessing regional and urban–rural differences. We integrated publicly available data from four federal databases to identify and geocode sites providing comprehensive HIV care in 2015, defined as the co-located provision of core HIV medical care and support services. Leveraging street network, US Census and HIV surveillance data (2014), we used geographic analysis to estimate the fastest one-way drive time between the population-weighted county centroid and the nearest site providing HIV care for counties reporting at least five diagnosed HIV cases. We summarized HIV care sites, county-level drive time, population-weighted drive time and suboptimal geographic accessibility to HIV care, by US region and county rurality (2013). Geographic accessibility to HIV care was suboptimal if drive time was \u3e30 min, a common threshold for primary care accessibility in the general US population. Tests of statistical significance were not performed, since the analysis is population-based. We identified 671 HIV care sites across the US, with 95% in urban counties. Nationwide, the median county-level drive time to HIV care is 69 min (interquartile range (IQR) 66 min). The median county-level drive time to HIV care for rural counties (90 min, IQR 61) is over twice that of urban counties (40 min, IQR 48), with the greatest urban–rural differences in the West. Nationally, population-weighted drive time, an approximation of individual-level drive time, is over five times longer in rural counties than in urban counties. Geographic access to HIV care is suboptimal for over 170,000 people diagnosed with HIV (19%), with over half of these individuals from the South and disproportionately the rural South. Nationally, approximately 80,000 (9%) drive over an hour to receive HIV care. Suboptimal geographic accessibility to HIV care is an important structural barrier in the US, particularly for rural residents living with HIV in the South and West. Targeted policies and interventions to address this challenge should become a priority

Risk aversion in a performativity culture – what can we learn from teachers’ curriculum decision making in history?

Using the notion of risk aversion, this study explores the decisions teachers make when constructing a curriculum. Adopting a qualitative, grounded approach, this study used semi-structured interviews with nine history teachers to examine the decisions they were making during a period of considerable curriculum change in England. Five key categories were identified, which were then defined as risk averse or high risk. The findings show that teachers largely adopt a low risk approach when constructing a curriculum. In particular choice of content, pedagogical and assessment approaches are affected. Also, changes to the curriculum in high stakes examination courses have a major distorting impact on the curriculum choices for the phase of schooling prior to the examination course. This study would suggest that teachers generally aim to maximise examination outcomes through adopting a low risk approach to curriculum change. However, according to the literature, these low risk approaches appear unlikely to improve examination outcomes, whilst at the same time narrowing students’ experience of the curriculum

Intergenerational Communication – an interdisciplinary mapping review of research between 1996 and 2017

Concerns have been raised regarding the limited opportunities for intergenerational communication both outside and within the family. This “mapping review” draws together empirical literature in the topic published since 1996. Three hundred and twenty-four published studies met inclusion criteria, based on abstract review. The contents of each study were subjected to thematic analysis and nine broad themes emerged. These were (1) Dynamics of relationships, (2) Health & Well-being, (3) Learning & Literacy, (4) Attitudes, (5) Culture, (6) Digital, (7) Space, (8) Professional Development, and (9) Gender & Sexual Orientation. Studies commonly intersected disciplinary research areas. There was a marked rise across three key academic journals since 2007. An emergent finding was that a third of the studies relate to programs addressing intergenerational interventions, but many of these were primarily descriptive and failed to specify a primary outcome. Review implications and future research directions are discussed

Depression and loneliness in Jamaicans with sickle cell disease

<p>Abstract</p> <p>Background</p> <p>Sickle cell disease (SCD) is the commonest genetic disorder in Jamaica, and has life-long implications for those afflicted with it. It is well known that depression and loneliness may exist in those with chronic diseases, but the coexistence of depression and loneliness in people with sickle cell disease is not clear. The aim of this study is to determine the prevalence of and factors associated with depression and loneliness in the Jamaica Sickle Cell Cohort Study and its age and sex matched controls.</p> <p>Methods</p> <p>277 patients with SCD and 65 controls were administered a questionnaire that studied demographics, disease severity, depression, and loneliness. Regression analyses were done to examine relationships between outcomes and associated variables.</p> <p>Results</p> <p>Depression was found in 21.6% of patients and 9.4% in controls. Loneliness scores were also significantly higher in patients (16.9 ± 5.1) than in controls (14.95 ± 4.69). Depression was significantly associated with unemployment [OR = 2.9, p-value: < 0.001], whereas unemployment (p-value: 0.002), and lower educational attainment were significantly associated with loneliness.</p> <p>In patients with SCD, depression was significantly associated with being unemployed (OR 2.4, 95% CI 1.2,4.6, p-value:0.01), presence of a leg ulcer (OR = 3.8, 95% CI: 1.7, 8.4, p-value: 0.001), frequent visits (OR = 3.3, 95% CI: 1.2, 8.9, p-value: 0.019), and frequent painful crises (OR = 2.5, 95% CI: 1.1, 5.8, p-value: 0.035). Not being employed (Coef.: 2.0; p-value: 0.004) and higher educational attainment (tertiary vs. primary education, Coef.: -5.5; p-value: < 0.001) were significant associations with loneliness after adjusting for genotype.</p> <p>Conclusions</p> <p>Health workers need to actively look for and manage these problems to optimize their patients' total biopsychosocial care.</p

Trajectories of childhood immune development and respiratory health relevant to asthma and allergy.

Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk 'atopic' cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma