Available online 10 July 2025

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What is already known about this topic?

Small airways dysfunction (SAD) is prevalent across all severities of asthma and is associated with worse symptom control and a greater exacerbation frequency.•

What does this article add to our knowledge?

To our knowledge, this is the first report of an association between greater exacerbation frequency and small airways dysfunction in patients with mild well-controlled asthma.•

How does this study impact current management guidelines?

Healthcare professionals should consider a detailed assessment of the small airways even in those with perceived mild well-controlled asthma.

AbstractBackground

Although current guidelines for asthma diagnosis and management have proven relatively successful, many asthmatics continue to experience poor asthma control and exacerbations. This may be due to a failure to recognize that mild, well-controlled asthmatics commonly have small airway dysfunction (SAD), which is associated with a significant exacerbation risk.

Objective

We aimed to better characterize how well SAD, determined by impulse oscillometry (IOS), is associated with prior exacerbations in the GINA defined mild, well-controlled asthma phenotype.

Methods

In 170 adults with mild, well-controlled asthma we determined the presence of SAD by IOS metrics of peripheral airway resistance between 5Hz and 20Hz (Rrs5 - Rrs20) and peripheral airway reactance as area under the reactance curve (AX) at cut points of 0.10 kPa/L/s and 1.0 kPa/L respectively. We also assessed the association between SAD, FEV1, FeNO, blood eosinophilia, and extra fine inhaled corticosteroids (ICS) with prior exacerbations. A multivariate analysis evaluated which variables were independently associated with prior exacerbations.

Results

SAD was present in 27.6% and prior exacerbations in 34.1% of the population. Exacerbations were greater in those with SAD (82.9% versus 15.4%, p < .001), lower in those receiving extra fine ICS (27.7% versus 55.3% p< .05). SAD and extra fine ICS were both independently associated with prior exacerbations, with SAD increasing and extra fine ICS decreasing exacerbation risk.

Conclusions

In the mild, well-controlled asthmatic, SAD and prior exacerbations are common. SAD and extra fine ICS are independently associated with increased or decreased exacerbations respectively. Detecting SAD could result in early extra fine ICS intervention potentially preventing future exacerbations in this phenotype.

Key words

asthma

small airways dysfunction

exacerbations

AbbreviationsAX

area under the reactance curve

FeNO

fractional exhaled nitric oxide

FEV1

forced expiratory volume in 1 second

GINA

Global Initiative for Asthma

ICS

inhaled corticosteroid

ROC

receiver operator characteristics

Rrs5-20

resistance between 5 and 20Hz

SAD

small airway dysfunction

TH2

T helper 2 inflammation

© 2025 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology