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Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity

Domínguez-Ortega J*1,2,3, Luna-Porta JA*1,2,3, Olaguibel JM3,4, Barranco P1,2,3, Arismendi E3,5,6,7, Barroso B3,8, Betancor D3,8, Bobolea I3,5,6,7, Caballero ML1,2,3, Cárdaba B3,9, Cruz MJ3,10,11, Curto E3,12,13,14, González-Barcala FJ3,15,16,17, Losantos-García I2,18, Martínez-Rivera C3,14,19,20, Mendez-Brea P21, Mullol J3,5,6,22, Muñoz X3,11, Picado C3,5,6,7, Plaza V3,12,13,14, del Pozo V3,9, Rial MJ3,23, Sastre J3,8, Soto L3,12,13,14, Valero A3,5,6,7, Valverde-Monge M3,8, Quirce S1,2,3

1Department of Allergy, La Paz University Hospital, Madrid, Spain
2Institute for Health Research IdiPAZ, Madrid, Spain
3CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
4Severe Asthma Unit, Department of Allergy, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain
5Clinical and Experimental Respiratory Immunoallergy (IDIBAPS), Barcelona, Spain
6Universitat de Barcelona, Barcelona, Spain
7Allergy Unit and Severe Asthma Unit, Pneumonology and Allergy Department, Hospital Clínic, Barcelona, Spain
8Department of Allergy, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
9Department of Immunology, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
10Departamento de Biología Celular, Fisiología e Inmunología, Universitat Autónoma de Barcelona, Barcelona, Spain
11Pneumology Department, Hospital Vall d’Hebron, Barcelona, Spain
12Respiratory Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
13Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain
14Universidad Autónoma de Barcelona, Departamento de Medicina, Barcelona, Spain
15Pneumology Department, Complejo Hospitalario Universitario de Santiago, La Coruña, Spain
16Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), La Coruña, Spain
17Universidad de Santiago de Compostela, La Coruña, Spain
18Biostatistics Department, La Paz University Hospital, Madrid, Spain
19Pneumology Department, Hospital Germans Trias i Pujol, Barcelona, Spain
20Institut d’Investigacio Germans Trias I Pujol (IGTP), Badalona, Barcelona, Spain
21Department of Allergy, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, La Coruña, Spain
22Rhinology Unit and Smell Clinic, ENT Department, Hospital Clínic, Barcelona, Spain
23Department of Allergy, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain
*Both authors contributed as equal authors

J Investig Allergol Clin Immunol 2023; Vol 33(4) : 281-288
doi: 10.18176/jiaci.0816

Introduction: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions.
Objective: To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort.
Methods: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient.
Results: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC.
Conclusions: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Key words: Asthma, Exacerbations, MEGA cohort, Asthma control, Multimorbidity