Airway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma. We investigated whether eosinophil depletion with benralizumab might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open-label design. 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. The primary outcome was doubling difference (DD) in provocative dose of mannitol required to decrease FEV₁ by 10% (PD₁₀) at the end point after 12 weeks, powered at 90% with 18 patients required to detect 1 DD. Secondary outcomes included measures assessed by the asthma control questionnaire and mini-asthma quality of life questionnaire. Twenty-one patients completed 12 weeks' benralizumab therapy at the end point at week 12. Mean (SEM) age was 53 (4) years, and FEV₁ 80.2% (4.1%) inhaled corticosteroid dose was 1895 (59) μg, with 12 receiving long-acting muscarinic antagonist and 13 leukotriene receptor antagonists. Improvement in AHR was significant by 8 weeks, with a mean 2.1 DD (95% confidence interval 1.0, 3.3; P < .01) change in PD₁₀ at week 12, while mean changes in asthma control questionnaire and mini-asthma quality of life questionnaire were significant by week 2 and sustained over 12 weeks, both exceeding the minimal important difference. Peripheral blood eosinophils were depleted by 2 weeks (439 to 6 cells/μL). No significant improvement occurred in lung function after 12 weeks. Domiciliary peak flow and symptoms also improved with benralizumab. Eosinophil depletion results in clinically meaningful attenuated AHR in severe uncontrolled asthma patients.

The small airways, also referred to as the lung's silent zone, are closely associated with poor symptom control and more frequent asthma exacerbations. The oscillometry technique superimposes sound or airwaves onto normal tidal breathing and provides information on resistance and reactance, that is, obstacles to airflow occurring inside and outside of the bronchi. More recently, a management paradigm based on so-called 'treatable traits' has been proposed to personalize and improve asthma care for individuals by proactively identifying and targeting modifiable pulmonary, extra-pulmonary, and behavioral traits affecting asthma control. In this review article we examine the literature on small airways dysfunction as a potential treatable trait in persistent asthma. Pointedly, we discuss whole- and intra-breath oscillometry as well as the impact of extrafine inhaled corticosteroids and systemic biologics on the peripheral airways.

In the year 2035, projections have estimated that 5% of the Scottish population will be morbidly obese defined as a body mass index (BMI) ≥40kg/m2. Airway oscillometry is an effort-independent test akin to bronchial sonar which measures resistance and compliance. Here, we aim to assess the impact of obesity on lung mechanics using oscillometry. Clinical data for 188 respiratory physician diagnosed moderate-to-severe asthma patients were retrospectively collected and analysed. Obesity (BMI 30 to 39.9kg/m2) and morbid obesity (BMI ≥40kg/m2) were associated with a significantly worse heterogeneity of peripheral resistance between 5 and 20Hz (R5-R20), and peripheral compliance as low frequency reactance at 5Hz (X5) and area under the reactance curve (AX), as compared to normal weight (BMI 18.5 - 24.9kg/m2). Cluster analysis incorporating oscillometry identified a patient cohort who were older, obese and female with combined impairment of spirometry and oscillometry coupled with more frequent severe exacerbations. Obesity is associated with worse peripheral airways dysfunction in moderate-to-severe asthma, including a patient cluster who were older, obese and female with more frequent exacerbations.

The small airways comprise generations 8 to 23 of the bronchial tree, consist of airways with an internal diameter <2mm, and are classically difficult to assess and treat in persistent asthma. Small airways dysfunction (SAD) is integral to the asthma management paradigm as it is associated with poorer symptom control, greater levels of type 2 inflammation, and has been proposed as a potential treatable asthma trait. Although identification of SAD by oscillometry has been found to be clinically useful in managing asthma, very few physicians, including specialists, use this technique as part of standard or adjunct evaluation of lung function to diagnose asthma, grade severity of airway obstruction, ascertain disease control or the risk for future exacerbations or to make management decisions. To rectify the unrecognized value of oscillometry in the asthma community, a consortium of authors who are investigators with knowledge and experience of oscillometry wished to address the most important clinical questions raised by our colleagues who are considering using this technique, including its clinical utility. In this article, we discuss integral concepts including applicability of oscillometry as a predictive tool for asthma exacerbations and disease control; adequacy of spirometry and oscillometry in assessing SAD; potential limitations of oscillometry; as well as treatment options for SAD.

Introduction: Forced vital capacity (FVC) is often preserved in severe asthma unless there is evidence of either airway remodelling or air trapping. Area under the reactance curve (AX) can be used to assess small airways dysfunction related lung stiffness and is related to disease control in severe asthma. Methods: We explore if there may be a potential synergistic interaction between FVC and AX in terms of impaired asthma control as ACQ and exacerbations requiring oral corticosteroids (OCS). We pragmatically defined < 100% and ≥ 1.0 kPa/L/s as impaired FVC or AX, respectively. Results: Patients with combined impairment of FVC and AX had significantly worse asthma control as higher ACQ, more severe exacerbations requiring OCS and worse spirometry (FEV₁ and FEF_25–75) than those with impaired FVC but preserved AX. Conclusion: This in turn supports using both spirometry and oscillometry to characterise airway physiology more comprehensively in patients with more severe asthma.