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Changes in Small Airway Physiology Measured by Impulse Oscillometry in Subjects with Allergic Asthma Following Methacholine and Inhaled Allergen Challenge

Stenberg, Henning LU ; Chan, Rory ; Abd-Elaziz, Khalid ; Pelgröm, Arjen ; Lammering, Karin ; Kuijper-De Haan, Gerda ; Weersink, Els ; Lutter, René ; Zwinderman, Aeilko H. and de Jongh, Frans , et al. (2025) In Journal of Clinical Medicine 14(3).
Abstract

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18–55 years, FEV1 > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS... (More)

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18–55 years, FEV1 > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV1 ≥ 20% (PC20) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV1 from post-diluent baseline during 0–3 h and 3–8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV1 and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV1 % predicted did not differ between MR and DR at baseline, but DR had lower median PC20M (0.84 (range 0.07–7.51) vs. MR (2.15 (0.53–11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV1), the maximal % change from baseline following M and HDM challenge were correlated. PC20M was inversely correlated with the % change in FEV1 and the % change in Xrs5 during the LAR (r= −0.443; p = 0.0018 and r= −0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
allergen bronchoprovocation test, asthma, impulse oscillometry, lung function, methacholine challenge, small airways
in
Journal of Clinical Medicine
volume
14
issue
3
article number
906
publisher
MDPI AG
external identifiers
  • scopus:85217639889
  • pmid:39941577
ISSN
2077-0383
DOI
10.3390/jcm14030906
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 by the authors.
id
e97d8744-8a1b-4f90-b926-ed3c069c8074
date added to LUP
2025-06-23 14:40:31
date last changed
2025-07-07 15:17:55
@article{e97d8744-8a1b-4f90-b926-ed3c069c8074,
  abstract     = {{<p>Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18–55 years, FEV<sub>1</sub> &gt; 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV<sub>1</sub> ≥ 20% (PC<sub>20</sub>) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV<sub>1</sub> from post-diluent baseline during 0–3 h and 3–8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV<sub>1</sub> and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV<sub>1</sub> % predicted did not differ between MR and DR at baseline, but DR had lower median PC<sub>20</sub>M (0.84 (range 0.07–7.51) vs. MR (2.15 (0.53–11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV<sub>1</sub>), the maximal % change from baseline following M and HDM challenge were correlated. PC<sub>20</sub>M was inversely correlated with the % change in FEV<sub>1</sub> and the % change in Xrs5 during the LAR (r= −0.443; p = 0.0018 and r= −0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease.</p>}},
  author       = {{Stenberg, Henning and Chan, Rory and Abd-Elaziz, Khalid and Pelgröm, Arjen and Lammering, Karin and Kuijper-De Haan, Gerda and Weersink, Els and Lutter, René and Zwinderman, Aeilko H. and de Jongh, Frans and Diamant, Zuzana}},
  issn         = {{2077-0383}},
  keywords     = {{allergen bronchoprovocation test; asthma; impulse oscillometry; lung function; methacholine challenge; small airways}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{MDPI AG}},
  series       = {{Journal of Clinical Medicine}},
  title        = {{Changes in Small Airway Physiology Measured by Impulse Oscillometry in Subjects with Allergic Asthma Following Methacholine and Inhaled Allergen Challenge}},
  url          = {{http://dx.doi.org/10.3390/jcm14030906}},
  doi          = {{10.3390/jcm14030906}},
  volume       = {{14}},
  year         = {{2025}},
}