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Introduction <p>Small airways disease (SAD) is increasingly recognized as a relevant trait in severe asthma, but its influence on outcomes with biologic therapies remains uncertain. We assessed the prevalence of SAD and its association with real-world treatment response in a severe asthma cohort. We hypothesized that baseline SAD, particularly when identified by oscillometry, would be associated with non-response to biologic therapy over 12 months.</p> Methods <p>This single-center, retrospective cohort included adult severe asthma outpatients initiating biologic therapy. At enrolment, participants underwent clinical and biomarker evaluation, complete lung function testing (spirometry/plethysmography), and the Forced Oscillation Technique. SAD was defined by the coexistence of ≥ 1 oscillometry abnormality and ≥ 1 spirometry/plethysmography abnormality. “Non-responders” were defined as patients experiencing ≥ 2 exacerbations during 12-month follow-up. Multivariable logistic regression was used to identify independent predictors of response, adjusting for biologic therapy and key confounders (including BMI).</p> Results <p>The analytic sample comprised 156 patients (aged 55 ± 18 years, 91 females) treated with omalizumab (<i>n</i> = 60), benralizumab (<i>n</i> = 23), mepolizumab (<i>n</i> = 32), or dupilumab (<i>n</i> = 41). After 12&#xa0;months, 24/156 patients (15%) were classified as non-responders. At baseline, SAD was present in 69/156 patients (44%) and was more prevalent in non-responders than in responders (75% vs. 40%, <i>p</i> &lt; 0.01). Non-responders showed worse spirometric indices (FEV<sub>1</sub>% and FEV<sub>1</sub>/VC) and more abnormal oscillometry (lower X5exp and higher ΔXrs, R5exp, and R5-R19). In multivariable models adjusted for biologic and key confounders, baseline oscillometry abnormalities were independently associated with a reduced odds of response (adjusted OR 0.08, 95% CI 0.02–0.37; <i>p</i> = 0.001).</p> Conclusions <p>In a real-world severe asthma cohort, baseline SAD, particularly when identified by oscillometry, was associated with subsequent non-response to biologic therapy, suggesting potential value for risk stratification.</p>

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Small Airways Disease Adversely Impacts the Response to Biologic Therapies in Severe Asthma

  • 期刊论文

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  • 发表日期：

    2026年2月28日

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  • Chiara Allegrini,
  • Elisa Bentivegna,
  • Alessia Catalisano,
  • Greta Insalata,
  • Rubina Giulia Girolamo,
  • Martina Maria Marinato,
  • Luca Paita,
  • Alessandra Sorano,
  • Chiara Marzi,
  • Clara De Filippis,
  • Federico Lavorini,
  • Gianna Camiciottoli

摘要

Introduction

Small airways disease (SAD) is increasingly recognized as a relevant trait in severe asthma, but its influence on outcomes with biologic therapies remains uncertain. We assessed the prevalence of SAD and its association with real-world treatment response in a severe asthma cohort. We hypothesized that baseline SAD, particularly when identified by oscillometry, would be associated with non-response to biologic therapy over 12 months.

Methods

This single-center, retrospective cohort included adult severe asthma outpatients initiating biologic therapy. At enrolment, participants underwent clinical and biomarker evaluation, complete lung function testing (spirometry/plethysmography), and the Forced Oscillation Technique. SAD was defined by the coexistence of ≥ 1 oscillometry abnormality and ≥ 1 spirometry/plethysmography abnormality. “Non-responders” were defined as patients experiencing ≥ 2 exacerbations during 12-month follow-up. Multivariable logistic regression was used to identify independent predictors of response, adjusting for biologic therapy and key confounders (including BMI).

Results

The analytic sample comprised 156 patients (aged 55 ± 18 years, 91 females) treated with omalizumab (n = 60), benralizumab (n = 23), mepolizumab (n = 32), or dupilumab (n = 41). After 12 months, 24/156 patients (15%) were classified as non-responders. At baseline, SAD was present in 69/156 patients (44%) and was more prevalent in non-responders than in responders (75% vs. 40%, p < 0.01). Non-responders showed worse spirometric indices (FEV1% and FEV1/VC) and more abnormal oscillometry (lower X5exp and higher ΔXrs, R5exp, and R5-R19). In multivariable models adjusted for biologic and key confounders, baseline oscillometry abnormalities were independently associated with a reduced odds of response (adjusted OR 0.08, 95% CI 0.02–0.37; p = 0.001).

Conclusions

In a real-world severe asthma cohort, baseline SAD, particularly when identified by oscillometry, was associated with subsequent non-response to biologic therapy, suggesting potential value for risk stratification.