Dupilumab Induces Long-term On-Treatment Clinical Remission in Patients With Type 2 Asthma.

Background: Remission is proposed as a multicomponent outcome for patients with severe asthma.

Objective: This post hoc analysis of QUEST (NCT02414854) and TRAVERSE (NCT02134028) evaluated whether dupilumab treatment leads to clinical asthma remission (≥12 months with no severe exacerbations, zero oral corticosteroid use, stabilized or improved lung function, patient-reported asthma control <1.5) and assessed its durability in patients with uncontrolled, moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb at parent-study baseline) who are not receiving maintenance oral corticosteroids.

The role of biologics in inducing remission in asthma.

Asthma remissions have been identified as a new treatment outcome and as based on experience with biologics. Remissions are defined as no symptoms, no exacerbations, no use of systemic corticosteroids, and stabilization (optimization) of lung functions; all these criteria need to be sustained for at least 1 year. This study discussed the evolution of remissions, the evolving criteria, and experiences in achieving remission after treatment with biologics.

Home and school pollutant exposure, respiratory outcomes, and influence of historical redlining.

Background: The discriminatory and racist policy of historical redlining in the United States during the 1930s played a role in perpetuating contemporary environmental health disparities.

Objective: Our objectives were to determine associations between home and school pollutant exposure (fine particulate matter [PM], NO) and respiratory outcomes (Composite Asthma Severity Index, lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods.

Methods: Children ages 6 to 17 with moderate-to-severe asthma (N = 240) from 9 US cities were included.

Alzheimer incidence and prevalence with and without asthma: A Medicare cohort study.

Background: International data suggest that asthma, like other inflammatory diseases, might increase Alzheimer disease (AD) risk.

Objective: We sought to explore risk pathways and future mitigation strategies by comparing diagnostic claims-based AD incidence and prevalence among US patients with asthma with those without asthma.

Methods: This cohort study included a national Medicare 20% random sample (2013-2015).

Dupilumab Reduces Exacerbations Independent of Changes in Biomarkers in Moderate-to-Severe Asthma.

Background: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma.

Objective: This post hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854).

Methods: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV) at week 52 were performed as a function of the fold change in FeNO at week 52 and the maximum fold change in Eos over weeks 0-12 (also change from baseline in pre-BD FEV at week 12).

Activated sputum eosinophils associated with exacerbations in children on mepolizumab.

Background: MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations.

Targeting Asthma Remission as the Next Therapeutic Step Toward Improving Disease Control.

The long-term goal of asthma management is to achieve disease control, comprising the assessment of 2 main domains: (1) symptom control and (2) future risk of adverse outcomes. Decades of progress in asthma management have correlated with increasingly ambitious disease control targets. Moreover, the introduction of precision medicines, such as biologics, has further expanded the limits of what can be achieved in terms of disease control.

Resting state functional connectivity changes following mindfulness-based stress reduction predict improvements in disease control for patients with asthma.

Background: The staggering morbidity associated with chronic inflammatory diseases can be reduced by psychological interventions, including Mindfulness-Based Stress Reduction (MBSR). Proposed mechanisms for MBSR's beneficial effects include changes in salience network function. Salience network perturbations are also associated with chronic inflammation, including airway inflammation in asthma, a chronic inflammatory disease affecting approximately 10% of the population.

Efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma with fungal sensitization.

Background: Fungal sensitization (FS) exacerbates asthma in patients who have elevated type 2 inflammatory response. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases.

Objective: This post hoc analysis, funded by the manufacturers of dupilumab, was conducted to assess dupilumab efficacy in patients from the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) and TRAVERSE open-label extension (NCT02134028) study who had uncontrolled, moderate-to-severe asthma with type 2 inflammatory phenotype (defined as blood eosinophil count ≥150 cells/μL or FeNO ≥25 ppb) and with FS (defined as IgE specific to Alternaria alternata, Aspergillus fumigatus or Cladosporium herbarum >0.

Molecular pathways underlying lung-brain axis signaling in asthma: Relevance for psychopathology and neuroinflammation.

Background: Accumulating evidence indicates that asthma has systemic effects and affects brain function. Although airway inflammation is proposed to initiate afferent communications with the brain, the signaling pathways have not been established.

Objective: We sought to identify the cellular and molecular pathways involved in afferent lung-brain communication during airway inflammation in asthma.

Dupilumab efficacy in high sleep disturbance management among patients with type 2 asthma.

Background: Patients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD.

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood.