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Exacerbations among patients with asthma are largely dependent on the presence of multimorbidity

Domínguez-Ortega J1,2*, Luna-Porta JA1,2*, Olaguibel JM2,3, Barranco P1,2, Arismendi E2,4, Barroso B2,5, Betancor D2,5, Bobolea I2,4, Caballero ML1,2, Cárdaba B2,6, Cruz MJ2,7,8, Curto E2,9, González-Barcala FJ2,10, Losantos-García I11, Martínez-Rivera C2,12, Mendez-Brea P13, Mullol J2,14, Muñoz X2,8, Picado C2,4, Plaza V2,9, del Pozo V2,6, Rial MJ2,15, Sastre J2,5, Soto L2,9, Valero A2,4, Valverde-Monge M2,5 , Quirce S1,2

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

*Both authors have contributed as equals

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

Introduction: Comorbidities can influence asthma control and promote asthma exacerbations (AE). However, the impact of multimorbidity in AE, through long-term follow-up in patients with asthma of different severity has been scarcely studied in real-life conditions.
Objective: To describe the epidemiological and clinical characteristics and predictive factors of AE in patients who had presented at least one AE in the last year among patients recruited in the MEchanism of Genesis and Evolution of Asthma (MEGA) project.
Methods: We carried out a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and multimorbidity assessment. For each subject, the number of moderate-severe AE in the preceding year was registered.
Results: 486 patients with asthma were included (23.7% mild, 35% moderate, 41.3% severe). 41.9% remained uncontrolled. 47.3% presented ≥1 moderate-severe AE, with mean annual exacerbation rate of 0.47±0.91 vs 2.11±2.82 in mild and severe asthma, respectively. 56.4% (66.6% among severe asthmatics) presented some comorbidity. Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidaemia and hypertension were significantly related with AE. No associations were found for FeNO, blood eosinophils and total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AE. Multivariable regression analysis showed significant association with asthma severity, uncontrolled disease and low pre-bronchodilator FEV1/FVC.
Conclusions: The MEGA cohort found a high AE rate, which 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