Cross-sectional studies suggest an exacerbation-prone asthma (EPA) phenotype and the utility of blood eosinophils and plasma IL-6 as predictive biomarkers.
To prospectively test for EPA phenotype and ...utility of baseline blood measures of eosinophils and IL-6 as predictive biomarkers.
Three-year asthma exacerbation data were analyzed in 406 adults in the Severe Asthma Research Program-3. Transition models were used to assess uninformed and informed probabilities of exacerbation in year 3. Binomial regression models were used to assess eosinophils and IL-6 as predictive biomarkers.
Eighty-three participants (21%) had ≥1 exacerbation in each year (EPA) and 168 participants (41%) had no exacerbation in any year (exacerbation-resistant asthma). The uninformed probability of an exacerbation in Year 3 was 40%, but the informed probability increased to 63% with an exacerbation in Year 2 and 82% with an exacerbation in Years 1 and 2. The probability of a Year 3 exacerbation with no Year 1 or 2 exacerbations was 13%. Compared with exacerbation-resistant asthma, EPA was characterized by lower FEV
and a higher prevalence of obesity, hypertension, and diabetes. High-plasma IL-6 occurred in EPA, and the incident rate ratio for exacerbation increased 10% for each 1-pg/μl increase in baseline IL-6 level. Although high blood eosinophils did not occur in EPA, the incident rate ratio for exacerbations increased 9% for each 100-cell/μl increase in baseline eosinophil number.
Longitudinal analysis confirms an EPA phenotype characterized by features of metabolic dysfunction. Blood measures of IL-6, but not eosinophils, were significantly associated with EPA, and IL-6 and eosinophils predicted exacerbations in the sample as a whole.
The fractional exhaled nitric oxide (FE
) test is a point-of-care test that is used in the assessment of asthma.
To provide evidence-based clinical guidance on whether FE
testing is indicated to ...optimize asthma treatment in patients with asthma in whom treatment is being considered.
An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FE
. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations.
After considering the overall low quality of the evidence, the panel made a conditional recommendation for FE
-based care. In patients with asthma in whom treatment is being considered, we suggest that FE
is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice.
Clinicians should consider this recommendation to measure FE
in patients with asthma in whom treatment is being considered based on current best available evidence.
The programming of sleep architecture begins in pregnancy and depends upon optimal in utero formation and maturation of the neural connectivity of the brain. Particulate air pollution exposure can ...disrupt fetal brain development but associations between fine particulate matter (PM2.5) exposure during pregnancy and child sleep outcomes have not been previously explored.
Analyses included 397 mother-child pairs enrolled in a pregnancy cohort in Mexico City. Daily ambient prenatal PM2.5 exposure was estimated using a validated satellite-based spatio-temporally resolved prediction model. Child sleep periods were estimated objectively using wrist-worn, continuous actigraphy over a 1-week period at age 4–5 years. Data-driven advanced statistical methods (distributed lag models (DLMs)) were employed to identify sensitive windows whereby PM2.5 exposure during gestation was significantly associated with changes in sleep duration or efficiency. Models were adjusted for maternal education, season, child's age, sex, and BMI z-score.
Mother's average age was 27.7 years, with 59% having at least a high school education. Children slept an average of 7.7 h at night, with mean 80.1% efficiency. The adjusted DLM identified windows of PM2.5 exposure between 31 and 35 weeks gestation that were significantly associated with decreased sleep duration in children. In addition, increased PM2.5 during weeks 1–8 was associated with decreased sleep efficiency. In other exposure windows (weeks 39–40), PM2.5 was associated with increased sleep duration.
Prenatal PM2.5 exposure is associated with altered sleep in preschool-aged children in Mexico City. Pollutant exposure during sensitive windows of pregnancy may have critical influence upon sleep programming.
•Prenatal PM2.5 exposure was associated with sleep disruption in preschoolers.•Higher PM2.5 was linked to decreased sleep efficiency and altered sleep duration.•Significant associations were identified during sensitive windows of gestation.
Objective To examine the relationships among obesity, sleep-disordered breathing (SDB, defined as intermittent nocturnal hypoxia and habitual snoring), and asthma severity in children. We ...hypothesized that obesity and SDB are associated with severe asthma at a 1- year follow-up. Study design Children aged 4-18 years were recruited sequentially from a specialty asthma clinic and underwent physiological, anthropometric, and biochemical assessment at enrollment. Asthma severity was determined after 1 year of follow-up and guideline-based treatment, using a composite measure of level of controller medication, symptom burden, and health care utilization. Multivariate logistic regression was used to examine adjusted associations of SDB and obesity with asthma severity at 12-month follow-up. Results Among 108 subjects (mean age, 9.1 ± 3.4 years; 45.4% African-American; 67.6% male), obesity and SDB were common, affecting 42.6% and 29.6% of subjects, respectively. After adjusting for obesity, race, and sex, children with SDB had a 3.62-fold increased odds of having severe asthma at follow-up (95% CI, 1.26-10.40). Obesity was not associated with asthma severity. Conclusion SDB is a modifiable risk factor for severe asthma after 1 year of specialty asthma care. Further studies are needed to determine whether treating SDB improves asthma morbidity.
Morbidity and mortality associated with childhood asthma are driven disproportionately by children with severe asthma. However, it is not known from longitudinal studies whether children outgrow ...severe asthma.
We sought to study prospectively whether well-characterized children with severe asthma outgrow their asthma during adolescence.
Children with asthma were assessed at baseline with detailed questionnaires, allergy tests, and lung function tests and were reassessed annually for 3 years. The population was enriched for children with severe asthma, as assessed by the American Thoracic Society/European Respiratory Society guidelines, and subject classification was reassessed annually.
At baseline, 111 (59%) children had severe asthma. Year to year, there was a decrease in the proportion meeting the criteria for severe asthma. After 3 years, only 30% of subjects met the criteria for severe asthma (P < .001 compared with enrollment). Subjects experienced improvements in most indices of severity, including symptom scores, exacerbations, and controller medication requirements, but not lung function. Surprisingly, boys and girls were equally likely to has resolved asthma (33% vs 29%). The odds ratio in favor of resolution of severe asthma was 2.75 (95% CI, 1.02-7.43) for those with a peripheral eosinophil count of greater than 436 cells/μL.
In longitudinal analysis of this well-characterized cohort, half of the children with severe asthma no longer had severe asthma after 3 years; there was a stepwise decrease in the proportion meeting severe asthma criteria. Surprisingly, asthma severity decreased equally in male and female subjects. Peripheral eosinophilia predicted resolution. These data will be important for planning clinical trials in this population.
Display omitted
Severe Asthma in Childhood Marko, Angela; Ross, Kristie R
Immunology and allergy clinics of North America,
05/2019, Letnik:
39, Številka:
2
Journal Article
Recenzirano
Severe asthma is broadly defined as asthma requiring a high level of therapy, usually high doses of inhaled corticosteroids, to bring under control. Children who remain symptomatic despite such ...treatment are a heterogeneous population, and bear a high burden of disease and require high resource utilization. Children with severe asthma require a comprehensive evaluation, careful consideration of alternative diagnoses and comorbid conditions, assessment of medication adherence and environmental conditions, and frequent disease monitoring.
PDF
