Rhinovirus as a Driver of Airway T-Cell Dynamics in Children with Severe Asthma.

Severe asthma in children is notoriously difficult to treat, and its immunopathogenesis is complex. In particular, the contribution of T cells and relationships to anti-viral immunity, remain enigmatic. Here, we coupled deep phenotyping with machine learning methods to resolve the dynamics of T cells in the diseased lower airways, and examined rhinovirus (RV) as a driver.

A novel syndrome of silent rhinovirus-associated bronchoalveolitis in children with recurrent wheeze.

Background: Rhinovirus (RV) infections trigger wheeze episodes in children. Thus, understanding of the lung inflammatory response to RV in children with wheeze is important.

Objectives: This study sought to examine the associations of RV on bronchoalveolar lavage (BAL) granulocyte patterns and biomarkers of inflammation with age in children with treatment-refractory, recurrent wheeze (n = 616).

Further evidence of a type 2 inflammatory signature in chronic obstructive pulmonary disease or emphysema.

Background: There is increasing recognition of a type 2 (T2) inflammatory pattern in a subset of patients with chronic obstructive pulmonary disease (COPD) or emphysema, characterized by blood and airway eosinophilia. The mechanism underlying this is not well established. The recognition that CD125 (interleukin [IL]-5 receptor alpha) is expressed on some lung neutrophils and eosinophils in patients with asthma led us to speculate that CD125 may also be expressed on lung neutrophils in patients with COPD or emphysema.

Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3.

Background: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete.

Objective: We sought to determine phenotypic factors associated with FEV throughout childhood in the Severe Asthma Research Program 3 pediatric cohort.

Methods: Lung function was measured at baseline and annually.

Interleukin-5 receptor alpha (CD125) expression on human blood and lung neutrophils.

Background: Our previous studies revealed the presence of interleukin-5 (IL-5) receptor alpha chain (IL-5Rα, CD125) on neutrophils in a murine model of influenza and in the lung fluid of children with severe asthma.

Objective: To further evaluate the functional characteristics and effects of clinical factors and inflammatory variables on neutrophil surface IL-5Rα abundance in lung fluid and blood.

Methods: IL-5Rα expression was quantified by flow cytometry performed on purified neutrophils from blood and bronchoalveolar lavage fluid samples obtained from healthy controls and individuals with asthma.

Prevention and Outpatient Treatment of Asthma Exacerbations in Children.

Acute exacerbations cause significant morbidity and mortality in children with asthma worldwide. Although exacerbations can be minor and transient, in some children they are recurrent and significantly adversely impact quality of life. Children with frequent exacerbations account for a disproportionate amount of unscheduled care in nonprimary health facilities.

Novel Treatment-Refractory Preschool Wheeze Phenotypes Identified by Cluster Analysis of Lung Lavage Constituents.

Background: Preschool children with treatment-refractory wheeze often require unscheduled acute care. Current guidelines advise treatment of persistent wheeze with inhaled corticosteroids. Alternative treatments targeting structural abnormalities and specific inflammatory patterns could be more effective.

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.

Measures of ventilation heterogeneity mapped with hyperpolarized helium-3 MRI demonstrate a T2-high phenotype in asthma.

Background: Hyperpolarized gas with helium (HHe-3) MR (magnetic resonance) is a noninvasive imaging method which maps and quantifies regions of ventilation heterogeneity (VH) in the lung. VH is an important feature of asthma, but little is known as to how VH informs patient phenotypes.

Purpose: To determine if VH indicators quantified by HHe-3 MR imaging (MRI) predict phenotypic characteristics and map to regions of inflammation in children with problematic wheeze or asthma.

Characteristics Relevant To Respiratory Health Among African Americans Attending Church-based Asthma Programs in Atlanta.

Background: Not One More Life (NOML), a health and faith partnership, aims to engage African Americans at risk for asthma morbidity into community-partnered asthma programs.

Methods: Not One More Life programs consisted of interactive presentations, a questionnaire, and spirometry.

Results: 4,522 individuals attended NOML programs at 136 Atlanta churches over nine years.

Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory in Adults with Moderate-to-Severe Asthma.

It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function. To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline.

The Added Burden of Allergen Sensitization Among Children with Severe or Poorly Controlled Asthma.

Background: Allergen sensitization (AS) may negatively affect asthma outcomes in children with severe or poorly controlled (SPC) asthma.

Objectives: To examine the impact of AS on asthma exacerbations, health care use, and costs among children with SPC asthma in private and public insurance settings.

Methods: This retrospective study analyzed children with SPC asthma aged 6 to 11 years from the MarketScan Commercial (private insurance) and Medicaid databases.

The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations.

The Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) study is an adaptive platform trial designed to investigate novel interventions to severe asthma. The study is conducted under a master protocol and utilizes a crossover design with each participant receiving up to five interventions and at least one placebo. Treatment assignments are based on the patients' biomarker profiles and precision health methods are incorporated into the interim and final analyses.

Bronchoalveolar lavage cytokine patterns in children with severe neutrophilic and paucigranulocytic asthma.

Background: Asthma is a complex heterogeneous disease occurring in adults and children that is characterized by distinct inflammatory patterns. While numerous studies have been performed in adults, little is known regarding the heterogeneity of severe asthma in children, particularly inflammatory signatures involving the air spaces.

Objective: We sought to determine the relationship of bronchoalveolar lavage (BAL) cytokine/chemokine expression patterns in children with severe therapy-resistant asthma stratified according to neutrophilic versus nonneutrophilic BAL inflammatory cell patterns.