The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of Network organization, procedures, and interventions.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden.

Use of Fractional Exhaled Nitric Oxide to Guide the Treatment of Asthma: An Official American Thoracic Society Clinical Practice Guideline.

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.

Factors Associated with Persistence of Severe Asthma from Late Adolescence to Early Adulthood.

Rationale: Asthma severity in children generally starts mild but may progress and stay severe for unknown reasons.

Objectives: Identify factors in childhood that predict persistence of severe asthma in late adolescence and early adulthood.

Methods: The Childhood Asthma Management Program is the largest and longest asthma trial in 1041 children aged 5-12 years with mild to moderate asthma.

PrecISE: Precision Medicine in Severe Asthma: An adaptive platform trial with biomarker ascertainment.

Severe asthma accounts for almost half the cost associated with asthma. Severe asthma is driven by heterogeneous molecular mechanisms. Conventional clinical trial design often lacks the power and efficiency to target subgroups with specific pathobiological mechanisms.

Lung mechanical properties distinguish children with asthma with normal and diminished lung function.

Background: Children with asthma, even those with severe persistent disease, can have forced expiratory volume in 1 second (FEV ) values ≥100% of predicted, while others have diminished FEV .

Objective: We sought to characterize the lung mechanical properties underlying these two asthma phenotypes and the mechanisms explaining the paradox of severe asthmatic children, whom when clinically stable can have an FEV >100% of predicted, but during an acute bronchospastic episode can experience a life-threatening asthma event.

Methods: Lung mechanics were evaluated in three groups of children: asthmatics with FEV ≥100% (HFEV ; n = 13), asthmatics with FEV ≤80% (LFEV ; n = 14) and non-asthmatic controls (n = 10).

Bronchoprovocation Testing in Asthma: An Update.

Bronchial hyperresponsiveness (BHR) is defined as a heightened bronchoconstrictive response to airway stimuli. It complements the cardinal features in asthma, such as variable or reversible airflow limitation and airway inflammation. Although BHR is considered a pathophysiologic hallmark of asthma, it should be acknowledged that this property of the airway is dynamic, because its severity and even presence can vary over time with disease activity, triggers or specific exposure, and with treatment.

Overweight/obesity status in preschool children associates with worse asthma but robust improvement on inhaled corticosteroids.

Background: Overweight/obesity (OW) is linked to worse asthma and poorer inhaled corticosteroid (ICS) response in older children and adults.

Objective: We sought to describe the relationships between OW and asthma severity and response to ICS in preschool children.

Methods: This post hoc study of 3 large multicenter trials involving 2- to 5-year-old children compared annualized asthma symptom days and exacerbations among normal weight (NW) (body mass index: 10th-84th percentiles) versus OW (body mass index: ≥85th percentile) participants.

Pivotal efficacy trials of inhaled corticosteroids in asthma.

Background: Inhaled corticosteroids (ICSs) are the mainstay of daily controller treatment for persistent and uncontrolled asthma. However, many clinicians are wary of ICSs because of safety concerns. Clinicians need to know the underlying efficacy data that support the use of ICSs to weigh efficacy against safety.

Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma.

Objective: To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma.

Study Design: This was a Phase IIb, multicenter, stratified, randomized, double-blind, double-dummy, parallel-group, placebo- and active-controlled study in children aged 5-11 years with inadequately controlled asthma. The study comprised a 4-week run-in period, 12-week treatment period, and 1-week follow-up period.

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma.

Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease.

Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma.

Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline).

Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy.

Background: Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.

Asthma phenotypes in childhood.

Purpose Of Review: This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area.

Recent Findings: Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma.

Markers of Differential Response to Inhaled Corticosteroid Treatment Among Children with Mild Persistent Asthma.

Background: Inhaled corticosteroids are recommended as first-line therapy for children with mild persistent asthma; however, specific patient characteristics may modify the treatment response.

Objective: Identify demographic, clinical, and atopic characteristics that may modify the inhaled corticosteroid treatment response among children enrolled in the Treating Children to Prevent Exacerbations of Asthma trial.

Methods: Children aged 6 to 18 years with mild persistent asthma were randomized to 44 weeks of combined, daily, rescue, or placebo treatment.

The chitinase-like protein YKL-40 is not a useful biomarker for severe persistent asthma in children.

Background: The chitinase-like protein YKL-40 is thought to play a role in inflammation and tissue remodeling. In adults with severe asthma, YKL-40 is expressed in the airway and YKL-40 levels are elevated in the serum.

Objective: To compare YKL-40 levels in children with severe persistent asthma with those in adults with severe persistent asthma and to determine whether YKL-40 levels correlate with increasing asthma severity in childhood asthma.

The Childhood Asthma Management Program (CAMP): Contributions to the Understanding of Therapy and the Natural History of Childhood Asthma.

The Childhood Asthma Management Program (CAMP) has been in continuous existence for almost two decades, which makes it the largest randomized, placebo-controlled clinical trial with extended follow-up for children with mild to moderate asthma. As such, its cumulative data from baseline, active treatment, and post-treatment have proved to be an invaluable resource for not only assessing the efficacy and safety of long-term inhaled corticosteroid therapy in childhood, but for discovery of many other aspects of childhood asthma, including genetics and biomarkers.

Predictors for asthma at age 7 years for low-income children enrolled in the Childhood Asthma Prevention Study.

Objective: To identify the predictive factors of early childhood wheezing in children of low socioeconomic status.

Study Design: The Childhood Asthma Prevention Study enrolled 177 low-income children (9-24 months old) with frequent wheezing. At age 7 years, presence of asthma was assessed through caregiver reports of physician diagnosis of asthma (CRPDA) and corroborated by assessment of bronchial hyperresponsiveness (BHR).

Bronchoprovocation testing in asthma.

This article covers the relationships between BHR and airway inflammation. Recent evidence suggests that various commonly used bronchoprovocation challenges (BPCs) differ in their potential to serve as inflammatory biomarkers. The response to direct stimuli depends on the smooth muscle's response to the chemical, whereas in indirect challenges, the reaction is caused by the smooth muscle's responsiveness to the mediators induced by the stimuli.

Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial.

Background: Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment.

Methods: In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5-18 years from five clinical centres in the USA.

Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids.

Background: For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.

Methods: We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.

Predictors of remitting, periodic, and persistent childhood asthma.

Background: The course of mild to moderate persistent asthma in children is not clearly established.

Objective: To determine the rate and predictors for remitting, periodic, and persistent asthma in adolescence.

Methods: The Childhood Asthma Management Program (CAMP) was a 4.

Relationship between infant weight gain and later asthma.

Like obesity, the prevalence of asthma has increased over the past several decades. Accelerated patterns of infant growth have been associated with obesity and its co-morbidities. We aimed to determine if infant weight gain pattern is associated with asthma development later in childhood.

Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children.

Background: Asthma exacerbations are a common cause of critical illness in children.

Objective: To determine factors associated with exacerbations in children with persistent asthma.

Methods: Regression modeling was used to identify historical, phenotypic, treatment, and time-dependent factors associated with the occurrence of exacerbations, defined by need for oral corticosteroids or emergency or hospital care in the 48-week Pediatric Asthma Controller Trial study.