Asthma genetics and personalised medicine

Super User Monday, 05 May 2014 14:31

Prof Deborah A Meyers PhD aProf Eugene R Bleecker MD aProf John W Holloway PhD aProf Stephen T Holgate DSc b Corresponding AuthorThis email address is being protected from spambots. You need JavaScript enabled to view it.

Summary

Unbiased genetic approaches, especially genome-wide association studies, have identified novel genetic targets in the pathogenesis of asthma, but so far these targets account for only a small proportion of the heritability of asthma. Recognition of the importance of disease heterogeneity, the need for improved disease phenotyping, and the fact that genes involved in the inception of asthma are likely to be different from those involved in severity widens the scope of asthma genetics. The identification of genes implicated in several causal pathways suggests that genetic scores could be used to capture the effect of genetic variations on individuals. Gene—environment interaction adds another layer of complexity, which is being successfully explored by epigenetic approaches. Pharmacogenetics is one example of how gene—environment interactions are already being taken into account in the identification of drug responders and non-responders, and patients most susceptible to adverse effects. Such applications represent one component of personalised medicine, an approach that places the individual at the centre of health care.
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Drs. Hershey and Brandt JACI interview on diesel exhaust and asthma

Super User Thursday, 27 March 2014 15:08

Study of urinary leukotriene E4 levels in children with acute asthma

Super User Monday, 17 March 2014 00:26
Int J Gen Med. 2014; 7: 131–135.
Published online Mar 3, 2014. doi:  10.2147/IJGM.S56660
PMCID: PMC3949722
 Abstract - Objective: The goal of this study was to evaluate the impact of urinary leukotriene E4 (ULTE4) in asthmatic children during acute asthma exacerbation. Also, we wanted to correlate it with the total serum (TS) immunoglobulin (Ig) E level in relation to asthma severity. Methods: This prospective study was conducted in the emergency room of the Department of Pediatrics, Benha University Hospital in Benha, Egypt, from November 2011 to May 2012. In this study, 63 children with acute asthma exacerbation (group I) and 25 healthy children as the control (group II) were included. Their ages ranged between 3–14 years. All children were subjected to a full medical history, and an emphasis was placed on the symptoms of asthma exacerbation and a complete clinical examination. TS IgE and ULTE4 were measured by an enzyme-linked immunosorbent assay after receiving the parents’ consent. The LTE4 concentration was measured in urine samples obtained at the onset of admission and adjusted by urinary creatinine concentrations. Results: The ULTE4 levels were significantly higher in cases compared to the controls (309.7±97.1 versus 14.5±5.7 pg/mg creatinine, respectively). It correlated positively to both the TS IgE and asthma severity in the cases. Also, the TS IgE levels increased significantly in cases (392.1±309.7 IU/mL), when compared to the controls (45.5±22.1 IU/mL). Conclusion: The ULTE4 and the TS IgE levels are significantly elevated during acute asthma episodes in children. The significant positive correlation between the severity of these attacks and the ULTE4 levels makes it a good noninvasive marker for monitoring acute asthma exacerbations and follow-up of the inflammatory process in asthmatic children.
 

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Validation of Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) – a prospective multicenter study

Super User Monday, 24 March 2014 21:17

Abstract - Background: Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross-sectional validity, and longitudinal validity. Methods: A prospective observational study was conducted in 11 Portuguese centers. During two visits separated by 6 wk, CARATKids, visual analog scale scales and childhood asthma control test were completed, and participant's asthma and rhinitis were evaluated by his/her physician without knowing the questionnaires’ results. Data-driven item reduction was conducted, and internal consistency, responsiveness analysis, and associations with external measures of disease status were assessed. Results: Of the 113 children included, 101 completed both visits. After item reduction, the final version of the questionnaire has 13 items, eight to be answered by the child and five by the caregiver. Its Cronbach's alpha was 0.80, the Guyatt's responsiveness index was −1.51, and a significant (p < 0.001) within-patient change of CARATKids score in clinical unstable patients was observed. Regarding cross-sectional validity, correlation coefficients of CARATKids with the external measures of control were between 0.45 and −0.69 and met the a prioripredictions. In the longitudinal validity assessment, the correlation coefficients between the score changes of CARATKids and those of external measures of control ranged from 0.34 to 0.46. Conclusion: CARATKids showed adequate psychometric properties and is ready to be used in clinical practice.

Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis

Juan Carlos Ivancevich Thursday, 13 March 2014 11:29

Abstract Background: Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth. Methods and Findings: Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%. Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding. Conclusions: There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions.

Full Text - Open Access - PLoS Med. 2014 Jan 28;11(1):e1001596. doi: 10.1371/journal.pmed.1001596. eCollection 2014.

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Editor: Juan C. Ivancevich, MD

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