Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry

Background: Investigation for the presence of asthma comorbidities is recommended by the Global Initiative for
Asthma because their presence can complicate asthma management.
Objective: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe
asthma and their association with asthma-related outcomes.
Methods: This was a cross-sectional study using data from the International Severe Asthma Registry from 22
countries. A total of 30 comorbidities were identified and categorized a priori as any of the following: (1) poten-
tially type 2−related comorbidities, (2) potentially oral corticosteroid (OCS)−related comorbidities, or (3) comor-
bidities mimicking or aggravating asthma. The association between comorbidities and asthma-related outcomes
was investigated using multivariable models adjusted for country, age at enrollment, and sex (ie male or female).
Results: Of the 11,821 patients, 69%, 67%, and 55% had at least 1 potentially type 2−related, potentially OCS-related,
or mimicking or aggravating comorbidities, respectively; 57% had 3 or more comorbidities, and 33% had comorbid-
ities in all 3 categories. Patients with allergic rhinitis, nasal polyposis, and chronic rhinosinusitis experienced 1.12
(P = .003), 1.16 (P < .001), and 1.29 times (P < .001) more exacerbations per year, respectively, than those without.
Patients with nasal polyposis and chronic rhinosinusitis were 40% and 46% more likely (P < .001), respectively, to
have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated
with a greater likelihood of LTOCS use (odds ratios [ORs]: 1.23-2.77) and, except for dyslipidemia, with a greater like-
lihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking or aggravating comorbidities assessed were associated
with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled
asthma (ORs: 1.57-1.81), and all (except chronic obstructive pulmonary disease) with increased likelihood of LTOCS
use (ORs: 1.37-1.57). A greater number of comorbidities was associated with worse outcomes.
Conclusion: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and
is associated with poorer asthma-related outcomes.
Clinical Trial Registration: The International Severe Asthma Registry database has ethical approval from the
Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the
European Union Electronic Register of Post-Authorization Studies (European Network Centres for Pharmacoepi-
demiology and Pharmacovigilance [ENCEPP]/DSPP/23720). The study was designed, implemented, and reported
in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP)
Code of Conduct (EMA 2014; EUPAS44024) and with all applicable local and international laws and regulations,
and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=48848). Governance was
provided by ADEPT (registration number: ADEPT1121).