Impact of Biologic Therapy on the Small Airways Asthma Phenotype

Rory Chan, Brian J. Lipworth (Lead / Corresponding author)

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Abstract

The small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree. Recently, this has become particularly relevant as measurements of small airways using airway oscillometry for example, are strong determinants of asthma control and exacerbations in moderate-to-severe asthma. The small airways can be assessed using spirometry as forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF 25–75) and has been deemed more accurate in detecting small airways dysfunction than forced expiratory volume in 1 s (FEV 1). Oscillometry as the heterogeneity in resistance between 5 and 20 Hz (R5–R20), low frequency reactance at 5 Hz (X5) or area under the reactance curve between 5 Hz and the resonant frequency can also be used to assess the small airways. The small airways can also be assessed using the multiple breath nitrogen washout (MBNW) test giving rise to values including functional residual capacity, lung clearance index and ventilation distribution heterogeneity in the conducting (Scond) and the acinar (Sacin) airways. The ATLANTIS group showed that the prevalence of small airways disease in asthma defined on FEF 25–75, oscillometry and MBNW all increased with progressive GINA asthma disease stages. As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti–alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma.

Original languageEnglish
Pages (from-to)691-696
Number of pages6
JournalLung
Volume200
Early online date14 Oct 2022
DOIs
Publication statusPublished - Dec 2022

Keywords

  • Benralizumab
  • Dupilumab
  • FEF
  • Itepekimab
  • Mepolizumab
  • Multiple breath nitrogen washout
  • Omalizumab
  • Oscillometry
  • Reslizumab
  • Severe asthma
  • Small airways
  • Tezepelumab

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