Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative.

IDeA States Pediatric Clinical Trials Network for Underserved and Rural Communities.

The National Institutes of Health's Environmental Influences on Child Health Outcomes (ECHO) program aims to study high-priority and high-impact pediatric conditions. This broad-based health initiative is unique in the National Institutes of Health research portfolio and involves 2 research components: (1) a large group of established centers with pediatric cohorts combining data to support longitudinal studies (ECHO cohorts) and (2) pediatric trials program for institutions within Institutional Development Awards states, known as the ECHO Institutional Development Awards States Pediatric Clinical Trials Network (ISPCTN). In the current presentation, we provide a broad overview of the ISPCTN and, particularly, its importance in enhancing clinical trials capabilities of pediatrician scientists through the support of research infrastructure, while at the same time implementing clinical trials that inform future health care for children.

Heterogeneity of Mild to Moderate Persistent Asthma in Children: Confirmation by Latent Class Analysis and Association with 1-Year Outcomes.

Background: Compared with adults, phenotypic characterization of children with asthma is still limited and it remains difficult to predict which children with asthma are at highest risk for poor outcomes.

Objective: To identify latent classes in a large population of treatment-adherent children with mild to moderate asthma enrolled in clinical trials and determine whether latent class assignment predicts future lung function abnormalities and exacerbation rate.

Methods: Latent class analysis was performed on 2593 children with mild to moderate asthma aged 5 18 years, with 19 variables encompassing demographic characteristics, medical history, symptoms, lung function, allergic sensitization, and type 2 inflammation.

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

Background: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

Methods: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults.

Emerging Therapies in the Treatment of Early Childhood Wheeze.

Phenotypic variation in asthma, especially early childhood asthma, is increasingly recognized. Although inhaled corticosteroids are recommended as first-line therapy, it has less efficacy in controlling intermittent wheeze due to viral-induced symptoms in early childhood. This article reviews 2 emerging therapies in particular for early childhood wheeze: azithromycin and bacterial lysate therapy.

Asthma Guidelines Priority Topics: Intermittent Inhaled Corticosteroid Therapy and Inhaled Corticosteroids with Long Acting Beta-Agonists as Reliever Therapy.

The National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma will update the guidelines on 6 topic areas. This review summarizes the findings for the charge to assess effectiveness of intermittent inhaled corticosteroid therapy with and without long-acting beta-agonist therapy in children 0 to 4 years of age, and children and adults 5 years and older. The complete report can be found on the Agency for Healthcare Research and Quality website.

Challenges in assessing the efficacy of systemic corticosteroids for severe wheezing episodes in preschool children.

This letter addresses the controversial issue of the use of oral corticosteroids during wheezing exacerbations in preschool-aged children by demonstrating findings of a prematurely terminated multi-center clinical trial, discussing lessons learned, and suggesting future directions.

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

Background: Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.

Personalized Medicine in Preschool Children with Asthma.

A growing body of literature has investigated optimizing asthma management by identifying phenotypes and biomarkers to guide the treatment. In particular, management of asthma in preschool children remains challenging due to different phenotype presentation in early life. The focus of this review is to summarize the recent data on personalized medicine in management of preschool children with wheezing.

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.

A randomized study of a method for optimizing adolescent assent to biomedical research.

Purpose: Voluntary consent/assent with adolescents invited to participate in research raises challenging problems. No studies to date have attempted to manipulate autonomy in relation to assent/consent processes. This study evaluated the effects of an autonomy-enhanced individualized assent/consent procedure embedded within a randomized pediatric asthma clinical trial.

Inhaling Essential Oils: Purported Benefits and Harms.

Patients with cystic fibrosis are experimenting with inhaling essential oils (scientifically described as random plant-derived secondary metabolites) through diffusers or nebulizers as a form of natural therapy to treat chronic lung infections. studies are starting to be published on the effects of essential oils (cinnamon, clove, oregano, and thyme) on bacteria commonly found in the lungs of patients with cystic fibrosis. There are no clinical studies and therefore no data are available on a potential placebo effect.

Tiotropium Bromide in Children and Adolescents with Asthma.

Evidence is emerging on the use of long-acting muscarinic antagonists (LAMAs) in the management of asthma. Tiotropium bromide (Spiriva Respimat) is the only LAMA approved in children and adolescents. As the use of tiotropium becomes more common in clinical practice, it is necessary to review the existing data to identify patients who may benefit from the addition of this medication to their daily asthma regimen.

Benefits and Risks of Long-Term Asthma Management in Children: Where Are We Heading?

International guidelines provide recommendations for a stepwise approach to the management of asthma in children 0-4 years old, 5-11 years old, and adolescents who are treated as adults. Therapy is aimed at two domains of control: current impairment and future risk. The long-term controller medications, inhaled corticosteroids (ICSs), ICSs in combination with long-acting β agonists, leukotriene receptor antagonists, and immunomodulators, exhibit different efficacies for these domains.

Individualized therapy for persistent asthma in young children.

Background: Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications.

Methods: The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol.

Management of Acute Cough in Children: Where Do We Go From Here?

The safety of cough and cold products for pediatric use has been a concern of regulatory agencies and advocacy groups for decades. Most recently, the Food and Drug Administration requested input from Pulmonary-Allergy Drugs and Drug Safety and Risk Management advisory committees on the safety of codeine for cough in children aged 18 years and younger. There is little evidence of efficacy for codeine in the treatment of acute cough in children, but mounting evidence for risks of respiratory depression and death.

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

Background: Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking.

Methods: In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids.

Macrolides for Acute Wheezing Episodes in Preschool Children.

The National Asthma Education and Prevention Program's Expert Panel Report 3, Guidelines for the Diagnosis and Management of Asthma does not recommend antibiotics for the management of acute episodes of asthma exacerbation. Macrolides seem to have some potential effect beyond or in addition to their antibacterial effect. It has been reported that macrolides may potentially benefit patients with chronic inflammatory airway diseases due to their antibacterial, antiviral, and/or anti-inflammatory effects.

A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized C-Urea.

This is a "proof of concept" study to determine whether inhalation of C-urea can be safely used to detect the presence of urease producing bacteria in the airways of patients with cystic fibrosis (CF) by detecting CO in breath. This was a prospective, 2-part, open label, single-center, single-arm, single-administration, dose-escalation investigational device exemption trial. First, the safety of 20 and 50 mg inhaled C-urea was evaluated in 6 healthy adult participants.

Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial.

Importance: Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed.

Adolescent Asthma Pharmacotherapy in a State of Flux.

Recently, the United States Food and Drug Administration (FDA) elected not to approve a once-daily inhaled corticosteroid/long-acting β2 agonist combination product in 12-17-year-old patients due to lack of sufficient data, despite approval of previous combination products with similar levels of supporting evidence. As the FDA's stance toward adolescent data is changing, the opportunity to learn about their response to asthma medication has now arisen. A review of the relevant issues pertinent to pharmacotherapy of asthma in the 12-17-year-old population is discussed in this review.

Vitamin D and Asthma: Association, Causality, or Intervention?

Many observational studies have investigated the potential association between vitamin D and asthma. However, it is difficult to find a temporal causal relationship in cross-sectional or observational studies. This review presents recent clinical trials and the evidence of association between vitamin D and asthma in different patient populations and asthma status.