International variation in severe exacerbation rates in patients with severe asthma

Tae Yoon Lee, David Price, Chandra Prakash Yadav, Rupsa Roy, Laura Lim Huey Mien, Eileen Wang, Michael E Wechsler, David J Jackson, John Busby, Liam G Heaney, Paul E Pfeffer, Bassam Mahboub, Diahn-Warng Perng Steve, Borja G Cosio, Luis Perez-de-Llano, Riyad Al-Lehebi, Désirée Larenas-Linnemann, Mona Al-Ahmad, Chin Kook Rhee, Takashi IwanagaEnrico Heffler, Giorgio Walter Canonica, Richard Costello, Nikolaos G Papadopoulos, Andriana I Papaioannou, Celeste M Porsbjerg, Carlos A Torres-Duque, George C Christoff, Todor A Popov, Mark Hew, Matthew Peters, Peter G Gibson, Jorge Maspero, Celine Bergeron, Saraid Cerda, Elvia Angelica Contreras Contreras, Wenjia Chen, Mohsen Sadatsafavi

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma.

RESEARCH QUESTION: What is the extent of the variability of exacerbations rate across countries and its implications in disease management?

STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients ≥ 18 years of age who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naïve model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables.

RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39).

INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

Original languageEnglish
Early online date21 Feb 2024
Publication statusEarly online date - 21 Feb 2024

Bibliographical note

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.


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