Combined large and small airway obstruction is associated with increased exacerbation frequency and poorer symptom control in persistent asthma

Samruddhi Lele; Anu Pillai; Musab Quayum; Michael E. Wechsler; Praveen Akuthota; Ronald J. Dandurand; Richard Hammond; Atanu Bhattacharjee; Francesco Menzella; Remo Poto; Pasquale Comberiati; Alvise Berti; Carlo Lombardi; Stanley P. Galant; Ophir Freund; Laura Ventura; Andrea Portacci; Giovanna Elisiana Carpagnano; Valeria Ortolani; Brian Lipworth; Salman Siddiqui; Marcello Cottini; Rory Chan

doi:10.1016/j.jaip.2026.06.041

Combined large and small airway obstruction is associated with increased exacerbation frequency and poorer symptom control in persistent asthma

Samruddhi Lele
, Anu Pillai
, Musab Quayum
, Michael E. Wechsler
, Praveen Akuthota
, Ronald J. Dandurand
, Richard Hammond
, Atanu Bhattacharjee
, Francesco Menzella
, Remo Poto
, Pasquale Comberiati
, Alvise Berti
, Carlo Lombardi
, Stanley P. Galant
, Ophir Freund
, Laura Ventura
, Andrea Portacci
, Giovanna Elisiana Carpagnano
, Valeria Ortolani
, Brian Lipworth

Salman Siddiqui, Marcello Cottini, Rory Chan (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

Abstract

Background
Spirometry remains central to the assessment of asthma but may fail to detect small airways dysfunction (SAD), which contributes to considerable symptoms and exacerbation risk.

Objective
We investigated whether integrating oscillometry with spirometry improves physiological phenotyping and risk stratification in asthma.

Methods
In this retrospective multicentre study, data from 1,497 adults with asthma were analysed from the Oscillometry Asthma Registry (OAR). SAD was defined using the (Rrs5-20)/Rrs5 ratio ≥19%, and airflow obstruction as FEV1/FVC <70%. Participants were categorised into four mutually exclusive groups: (a) Group 1 - normal oscillometry and normal spirometry; (b) Group 2 - abnormal oscillometry with normal spirometry; (c) Group 3 - normal oscillometry with abnormal spirometry; and (d) Group 4 - abnormal oscillometry and abnormal spirometry. Associations with symptom control, exacerbations, and type 2 inflammatory biomarkers were assessed using multivariable logistic regression.

Results
For ≥1 exacerbation, the adjusted odds ratio (aORs) (95%CI) for Group 4 were: versus Group 1 3.19 (2.31,4.42); versus Group 2 1.99 (1.46,2.74); and versus Group 3 1.59 (1.07;2.37). Corresponding aOR values for Group 3 were: versus Group 2 1.26 (0.85,1.86); and versus Group 1 2.01 (1.37;2.94). The aOR for ≥1 exacerbation for Group 2 versus Group 1 was 1.60 (1.18,2.16). Results were similar when using FEV1/FVC <LLN instead of traditional predicted values.

Conclusion
The combined use of oscillometry and spirometry identifies distinct physiological phenotypes of asthma with clinically meaningful differences in symptom burden and exacerbation risk.

Original language	English
Journal	The Journal of Allergy and Clinical Immunology: In Practice
Early online date	7 Jul 2026
DOIs	https://doi.org/10.1016/j.jaip.2026.06.041
Publication status	E-pub ahead of print - 7 Jul 2026

Keywords

asthma
exacerbations
oscillometry
spirometry
symptoms

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10.1016/j.jaip.2026.06.041Licence: CC BY-NC

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Lele, S., Pillai, A., Quayum, M., Wechsler, M. E., Akuthota, P., Dandurand, R. J., Hammond, R., Bhattacharjee, A., Menzella, F., Poto, R., Comberiati, P., Berti, A., Lombardi, C., Galant, S. P., Freund, O., Ventura, L., Portacci, A., Carpagnano, G. E., Ortolani, V., ... Chan, R. (2026). Combined large and small airway obstruction is associated with increased exacerbation frequency and poorer symptom control in persistent asthma. The Journal of Allergy and Clinical Immunology: In Practice. Advance online publication. https://doi.org/10.1016/j.jaip.2026.06.041

@article{be7e688540064b8fb33a4940a56b442f,

title = "Combined large and small airway obstruction is associated with increased exacerbation frequency and poorer symptom control in persistent asthma",

abstract = "Background Spirometry remains central to the assessment of asthma but may fail to detect small airways dysfunction (SAD), which contributes to considerable symptoms and exacerbation risk. Objective We investigated whether integrating oscillometry with spirometry improves physiological phenotyping and risk stratification in asthma. Methods In this retrospective multicentre study, data from 1,497 adults with asthma were analysed from the Oscillometry Asthma Registry (OAR). SAD was defined using the (Rrs5-20)/Rrs5 ratio ≥19\%, and airflow obstruction as FEV1/FVC <70\%. Participants were categorised into four mutually exclusive groups: (a) Group 1 - normal oscillometry and normal spirometry; (b) Group 2 - abnormal oscillometry with normal spirometry; (c) Group 3 - normal oscillometry with abnormal spirometry; and (d) Group 4 - abnormal oscillometry and abnormal spirometry. Associations with symptom control, exacerbations, and type 2 inflammatory biomarkers were assessed using multivariable logistic regression. Results For ≥1 exacerbation, the adjusted odds ratio (aORs) (95\%CI) for Group 4 were: versus Group 1 3.19 (2.31,4.42); versus Group 2 1.99 (1.46,2.74); and versus Group 3 1.59 (1.07;2.37). Corresponding aOR values for Group 3 were: versus Group 2 1.26 (0.85,1.86); and versus Group 1 2.01 (1.37;2.94). The aOR for ≥1 exacerbation for Group 2 versus Group 1 was 1.60 (1.18,2.16). Results were similar when using FEV1/FVC Conclusion The combined use of oscillometry and spirometry identifies distinct physiological phenotypes of asthma with clinically meaningful differences in symptom burden and exacerbation risk.",

keywords = "asthma, exacerbations, oscillometry, spirometry, symptoms",

author = "Samruddhi Lele and Anu Pillai and Musab Quayum and Wechsler, \{Michael E.\} and Praveen Akuthota and Dandurand, \{Ronald J.\} and Richard Hammond and Atanu Bhattacharjee and Francesco Menzella and Remo Poto and Pasquale Comberiati and Alvise Berti and Carlo Lombardi and Galant, \{Stanley P.\} and Ophir Freund and Laura Ventura and Andrea Portacci and Carpagnano, \{Giovanna Elisiana\} and Valeria Ortolani and Brian Lipworth and Salman Siddiqui and Marcello Cottini and Rory Chan",

note = "{\textcopyright} 2026 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma \& Immunology",

year = "2026",

month = jul,

day = "7",

doi = "10.1016/j.jaip.2026.06.041",

language = "English",

journal = "The Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "American Academy of Allergy, Asthma and Immunology",

}

Lele, S, Pillai, A, Quayum, M, Wechsler, ME, Akuthota, P, Dandurand, RJ, Hammond, R, Bhattacharjee, A, Menzella, F, Poto, R, Comberiati, P, Berti, A, Lombardi, C, Galant, SP, Freund, O, Ventura, L, Portacci, A, Carpagnano, GE, Ortolani, V, Lipworth, B, Siddiqui, S, Cottini, M & Chan, R 2026, 'Combined large and small airway obstruction is associated with increased exacerbation frequency and poorer symptom control in persistent asthma', The Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2026.06.041

TY - JOUR

T1 - Combined large and small airway obstruction is associated with increased exacerbation frequency and poorer symptom control in persistent asthma

AU - Lele, Samruddhi

AU - Pillai, Anu

AU - Quayum, Musab

AU - Wechsler, Michael E.

AU - Akuthota, Praveen

AU - Dandurand, Ronald J.

AU - Hammond, Richard

AU - Bhattacharjee, Atanu

AU - Menzella, Francesco

AU - Poto, Remo

AU - Comberiati, Pasquale

AU - Berti, Alvise

AU - Lombardi, Carlo

AU - Galant, Stanley P.

AU - Freund, Ophir

AU - Ventura, Laura

AU - Portacci, Andrea

AU - Carpagnano, Giovanna Elisiana

AU - Ortolani, Valeria

AU - Lipworth, Brian

AU - Siddiqui, Salman

AU - Cottini, Marcello

AU - Chan, Rory

PY - 2026/7/7

Y1 - 2026/7/7

N2 - Background Spirometry remains central to the assessment of asthma but may fail to detect small airways dysfunction (SAD), which contributes to considerable symptoms and exacerbation risk. Objective We investigated whether integrating oscillometry with spirometry improves physiological phenotyping and risk stratification in asthma. Methods In this retrospective multicentre study, data from 1,497 adults with asthma were analysed from the Oscillometry Asthma Registry (OAR). SAD was defined using the (Rrs5-20)/Rrs5 ratio ≥19%, and airflow obstruction as FEV1/FVC <70%. Participants were categorised into four mutually exclusive groups: (a) Group 1 - normal oscillometry and normal spirometry; (b) Group 2 - abnormal oscillometry with normal spirometry; (c) Group 3 - normal oscillometry with abnormal spirometry; and (d) Group 4 - abnormal oscillometry and abnormal spirometry. Associations with symptom control, exacerbations, and type 2 inflammatory biomarkers were assessed using multivariable logistic regression. Results For ≥1 exacerbation, the adjusted odds ratio (aORs) (95%CI) for Group 4 were: versus Group 1 3.19 (2.31,4.42); versus Group 2 1.99 (1.46,2.74); and versus Group 3 1.59 (1.07;2.37). Corresponding aOR values for Group 3 were: versus Group 2 1.26 (0.85,1.86); and versus Group 1 2.01 (1.37;2.94). The aOR for ≥1 exacerbation for Group 2 versus Group 1 was 1.60 (1.18,2.16). Results were similar when using FEV1/FVC Conclusion The combined use of oscillometry and spirometry identifies distinct physiological phenotypes of asthma with clinically meaningful differences in symptom burden and exacerbation risk.

AB - Background Spirometry remains central to the assessment of asthma but may fail to detect small airways dysfunction (SAD), which contributes to considerable symptoms and exacerbation risk. Objective We investigated whether integrating oscillometry with spirometry improves physiological phenotyping and risk stratification in asthma. Methods In this retrospective multicentre study, data from 1,497 adults with asthma were analysed from the Oscillometry Asthma Registry (OAR). SAD was defined using the (Rrs5-20)/Rrs5 ratio ≥19%, and airflow obstruction as FEV1/FVC <70%. Participants were categorised into four mutually exclusive groups: (a) Group 1 - normal oscillometry and normal spirometry; (b) Group 2 - abnormal oscillometry with normal spirometry; (c) Group 3 - normal oscillometry with abnormal spirometry; and (d) Group 4 - abnormal oscillometry and abnormal spirometry. Associations with symptom control, exacerbations, and type 2 inflammatory biomarkers were assessed using multivariable logistic regression. Results For ≥1 exacerbation, the adjusted odds ratio (aORs) (95%CI) for Group 4 were: versus Group 1 3.19 (2.31,4.42); versus Group 2 1.99 (1.46,2.74); and versus Group 3 1.59 (1.07;2.37). Corresponding aOR values for Group 3 were: versus Group 2 1.26 (0.85,1.86); and versus Group 1 2.01 (1.37;2.94). The aOR for ≥1 exacerbation for Group 2 versus Group 1 was 1.60 (1.18,2.16). Results were similar when using FEV1/FVC Conclusion The combined use of oscillometry and spirometry identifies distinct physiological phenotypes of asthma with clinically meaningful differences in symptom burden and exacerbation risk.

KW - asthma

KW - exacerbations

KW - oscillometry

KW - spirometry

KW - symptoms

U2 - 10.1016/j.jaip.2026.06.041

DO - 10.1016/j.jaip.2026.06.041

M3 - Article

SN - 2213-2198

JO - The Journal of Allergy and Clinical Immunology: In Practice

JF - The Journal of Allergy and Clinical Immunology: In Practice

ER -

Combined large and small airway obstruction is associated with increased exacerbation frequency and poorer symptom control in persistent asthma

Abstract

Keywords

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