Bronchodilator Dose Responsiveness in Children and Adolescents: Clinical Features and Association with Future Asthma Exacerbations.

BACKGROUND: Bronchodilator reversibility measures are often associated with poor asthma outcomes in children. Whether bronchodilator dose responsiveness is similarly useful in children is unclear. OBJECTIVE: We hypothesized that children and adolescents requiring higher doses of bronchodilator to achieve maximal bronchodilation would have unique risk factors and increased risk of future exacerbation. METHODS: Children (6-11 years, N = 299) and adolescents (12-21 years, N = 331) with confirmed asthma underwent clinical phenotyping procedures and a test of maximal bronchodilation with escalating doses of albuterol sulfate up to 720 mcg. Outcome measures were assessed at 12 months and included exacerbations treated with systemic corticosteroids, emergency department (ED) visits, and hospitalizations for asthma. RESULTS: A total of 6.7% of children and 9.3% of adolescents had poor bronchodilator dose responsiveness, defined as attainment of maximal forced expiratory volume in 1 second with 720 mcg albuterol. Risk factors included type 2 inflammation, prior exacerbations, and greater asthma severity; historical pneumonia and tobacco exposure were also risk factors in children. Children and adolescents with poor bronchodilator dose responsiveness did not have increased current symptoms or impaired quality of life, but had approximately 2-fold increased odds of exacerbation or ED visit and approximately 3-fold increased odds of hospitalization by 12 months, independent of airflow obstruction. CONCLUSIONS: Bronchodilator dose responsiveness may be useful for phenotyping and may be of utility in practice and future studies focused on asthma outcomes or quantification of treatment responses. In children and adolescents, this phenotype of poor bronchodilator responsiveness may be associated with periods of relatively stable disease yet marked airway constriction in response to triggers, including tobacco smoke, respiratory infections/pneumonia, and aeroallergens.

Procedural Sedation Outside the Operating Room and Potential Neurotoxicity: Analysis of an At-Risk Pediatric Population.

OBJECTIVES: To determine the characteristics of children who met the risk criteria for potential neurotoxicity defined by the US Food and Drug Administration (FDA; 2016 warning) in a procedural sedation (PS) service. STUDY DESIGN: A single-center retrospective review of all infants and children aged <3 years receiving PS outside the operating room from 2014 to 2016. Demographics, duration of, and the reason for PS were analyzed. RESULTS: A total of 2950 patients with 3653 sedation encounters were included. Median age was 19 (range, 11-26) months. Most PS (86.4%) were for magnetic resonance imaging (MRI). The median number of sedation procedures per patient was 1 (25th-75th: 1-7), and median duration of sedation was 72 minutes (25th-75th: 55-98 minutes). Forty patients (1.4%) required prolonged sedations >3 hours, in a single encounter (median, [25th-75th] of 196 minutes [185-214 minutes]), and 298 patients (10.1%) had multiple sedation exposures during the study period. Overall, 327 patients, 11.1% (95% confidence interval, 10.0%-12.3%) required repeated and/or prolonged sedation. The most common reasons for repeated or prolonged sedation were MRI of the brain and neurologic concerns. CONCLUSIONS: Multiple and prolonged PS commonly occurs outside the operating room in this young and potentially vulnerable population. Although certain imaging cannot be avoided, other cases may have the potential to be delayed until the child is >3 years old or to have alternate imaging that may not require prolonged PS. Family and provider awareness of the FDA warnings regarding potential neurotoxicity of sedation in all settings, both inside and outside the operating room, is critical.

Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features.

BACKGROUND: Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking. OBJECTIVE: This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response. METHODS: Asthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups. RESULTS: Three groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, AIMP1, CCR2, IL10RB, and IL5, strongly differentiated children who failed to achieve control with triamcinolone administration. CONCLUSIONS: Systemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects.

First report of Streptococcus parauberis in wild finfish from North America.

Streptococcosis is a common cause of pathology and mortality in fishes resulting in significant economic losses for the aquaculture industry. One etiologic agent of the disease, Streptococcus parauberis, has been associated with fish mortalities in Spain and Korea. Here we report the first identification of S. parauberis in wild finfish in Chesapeake Bay, USA. Gram-positive cocci were isolated from the spleens of striped bass, Morone saxatilis, and identified via species-specific primers and 16S rRNA gene sequencing. Biochemical characterization and antibiotic susceptibility tests were used to compare local isolates to isolates infecting aquacultured fishes and dairy cattle. This is also the first report of a plasmid in S. parauberis from any host.