Effects of dupilumab on mannitol airway hyperresponsiveness in uncontrolled severe asthma.

Background: Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma. However, effects of IL-4/13 blockade with dupilumab (Dupi) on AHR are unknown.

Objectives: This study sought to investigate the effect of 12 weeks of Dupi on AHR, asthma control, and quality of life.

Budesonide/Formoterol or Budesonide/Albuterol as Anti-Inflammatory Reliever Therapy for Asthma.

Overuse of reliever as short-acting beta-agonist and associated underuse of controller as inhaled corticosteroid (ICS) administered via separate inhalers results in worse asthma outcomes. Such discordance can be obviated by combining both controller and reliever in the same inhaler. So-called anti-inflammatory reliever (AIR) therapy comprises the use of a single inhaler containing an ICS such as budesonide (BUD) in conjunction with a reliever as either albuterol (ALB) or formoterol (FORM), to be used on demand, with variable dosing driven by asthma symptoms in a flexible patient-centered regimen.

Should Airway Hyper-Responsiveness Be Included in the Definition of Clinical Remission With Biologic Therapy in Severe Asthma.

Airway hyper-responsiveness (AHR) is a tenet of the persistent asthma phenotype along with reversible airway obstruction and type 2 (T2) inflammation. Indirect acting challenges such as mannitol are more closely related to the underlying T2 inflammatory process as compared with direct challenges. In this review article, we summarise the current literature and explore the future role of mannitol AHR in clinical remission with biologics.

5-Item sino-nasal outcome test and 22-item sino-nasal outcome test relationship with endoscopic and radiologic scores in chronic rhinosinusitis with nasal polyps.

Background: The 22-item sino-nasal outcome test (SNOT-22) is a frequently used patient-recorded outcome measure in patients with chronic rhinosinusitis with nasal polyps (CRSwNPs). Objective findings of nasal polyps and paranasal sinus inflammation are frequently graded using nasal polyp score (NPS) and Lund-Mackay Score (LMS), respectively.

Objective: To evaluate a novel, abbreviated, rhinology-focused, five-domain SNOT-5 questionnaire because we had anecdotally noticed a relative disconnect between SNOT-22 and endoscopy and imaging scores.

Efficacy of biologic therapy on airway hyperresponsiveness in asthma.

Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with mucosal inflammation in asthma. In recent years, the advent of biologics and antialarmins has transformed severe asthma treatment in terms of reducing oral-corticosteroid-requiring exacerbations and improving disease control, asthma quality of life, and spirometry-measured lung function. In contrast, there have been comparatively fewer studies investigating the efficacy of biologics in airway hyperresponsiveness.

Impaired Respiratory System Resistance and Reactance Are Associated With Bronchial Wall Thickening in Persistent Asthma.

Background: A recent study demonstrated a significant correlation between bronchial biopsy airway remodeling and quantitative computed tomography looking at bronchial wall thickness.

Objective: To identify clinical associations with bronchial wall thickness in moderate to severe asthma.

Methods: Ninety-two respiratory physician-diagnosed Global Initiative for Asthma-defined patients with moderate to severe asthma were included in this retrospective cohort study.

Eosinophil depletion with benralizumab is associated with attenuated mannitol airway hyperresponsiveness in severe uncontrolled eosinophilic asthma.

Background: Airway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma.

Objective: We investigated whether eosinophil depletion with benralizumab might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open-label design.

Methods: After a 4-week run-in period with provision of usual inhaled corticosteroids and/or long-acting β-agonist (baseline), adults with mannitol-responsive uncontrolled severe eosinophilic asthma received 3 doses of open-label benralizumab 30 mg every 4 weeks, followed by 16 weeks' washout after the last dose.

Clinical Associations of Mucus Plugging in Moderate to Severe Asthma.

Background: Mucus plugging is recognized as a contributory factor to airway obstruction and symptoms in persistent asthma.

Objective: We aimed to determine phenotypic associations of mucus plugging in patients with moderate to severe asthma in a real-life clinic setting.

Methods: Mucus plugs (MPs) were identified by a thoracic radiologist upon high-resolution computed tomography imaging.

Targeting Downstream Type 2 Cytokines or Upstream Epithelial Alarmins for Severe Asthma.

Biologics, including omalizumab, mepolizumab, benralizumab, and dupilumab, targeting downstream IgE, cytokines IL-5, and IL-4/13, respectively, have shown promising effects in terms of reduction in annualized asthma exacerbation rates (AER), oral corticosteroid-sparing effects, improvements in forced expiratory volume in 1 second, and improved Asthma Control Questionnaire scores. However, despite these welcome advances, approximately 30% of patients with severe asthma receiving biologics tailored to their specific downstream type 2 biomarkers, including total IgE, peripheral blood eosinophils, and fractional exhaled nitric oxide, do not experience meaningful improvements in their AER. Instead of blocking downstream cytokines, targeting upstream epithelial alarmins, including IL-33, thymic stromal lymphopoietin, and IL-25, has been proposed to tackle the immunologic heterogeneity of asthma.