Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort

Manuel J Rial, Maria J Álvarez-Puebla, Ebymar Arismendi, María L Caballero, José A Cañas, María J Cruz, Francisco J González-Barcala, Juan A Luna, Carlos Martínez-Rivera, Joaquim Mullol, Xavier Muñoz, José M Olaguibel, César Picado, Vicente Plaza, Santiago Quirce, Christian Romero-Mesones, Francisco-Javier Salgado, Beatriz Sastre, Lorena Soto-Retes, Antonio Valero, Marcela Valverde, Joaquín Sastre, Victora Del Pozo, Manuel J Rial, Maria J Álvarez-Puebla, Ebymar Arismendi, María L Caballero, José A Cañas, María J Cruz, Francisco J González-Barcala, Juan A Luna, Carlos Martínez-Rivera, Joaquim Mullol, Xavier Muñoz, José M Olaguibel, César Picado, Vicente Plaza, Santiago Quirce, Christian Romero-Mesones, Francisco-Javier Salgado, Beatriz Sastre, Lorena Soto-Retes, Antonio Valero, Marcela Valverde, Joaquín Sastre, Victora Del Pozo

Abstract

Introduction: The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder.

Material and methods: We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients.

Results: When compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis.

Conclusion: The MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities.

Keywords: Spanish: asma; biomarcadores; asma eosinofílica;inflamación; asma neutrofílica; fenotipos.; asthma; biomarkers; eosinophilic asthma; inflammation; neutrophilic asthma; phenotype.

Conflict of interest statement

Dr. Rial reports nonfinancial support from CIBER de Enfermedades Respiratorias (CIBERES), during the conduct of the study; personal fees from GSK, personal fees from Allergy Therapeutics, personal fees from AstraZeneca outside the submitted work. Dr. González Barcala reports personal fees from ALK, personal fees from AstraZeneca, personal fees from Bial, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from Gebro Pharma, personal fees from GlaxoSmithKline, personal fees from Laboratorios Esteve, Menarini, Mundipharma, Novartis, Rovi, Roxall, Stallergenes‐Greer, Teva, and Grants from Mundipharma outside the submitted work. Dr. Quirce reports personal fees from AstraZeneca, personal fees from Novartis, personal fees from Sanofi, personal fees from Boehringer Ingelheim, personal fees from Teva, personal fees from ALK, personal fees from Mundipharma, personal fees from GSK, personal fees from Chiesi, personal fees from Leti, outside the submitted work. Dr. Romero‐Mesones reports personal fees from Teva, personal fees from GSK, outside the submitted work. Dr. Soto‐Retes reports non‐financial support from CIBER de Enfermedades Respiratorias (CIBERES), during the conduct of the study; personal fees from Stallergennes‐Greer, personal fees from Menarini, personal fees from Novartis, personal fees from GSK, personal fees from Hal Allergy, personal fees from Allergy Therapeutics, personal fees from AstraZeneca, grants from Sociedad Española de Alergologia e Inmunología Clinica SEAIC, grants from Sociedad Española de Neumologia y Cirugia Torácica SEPAR, outside the submitted work. Dr. Martinez Rivera reports grants and personal fees from AstraZeneca, grants and personal fees from Teva, grants and personal fees from GSK, personal fees from Novartis, personal fees from Mundipharma, outsider the submitted work. Dr. Munoz reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, grants and personal fees from GlaxoSmithKline, grants from Menarini, personal fees from Novartis, personal fees from Teva, personal fees from Mundifarma, grants and personal fees from Chiesi, personal fees from Faes, outside the submitted work. Dr. Sastre reports grants from Sanofi, during the conduct of the study; grants and personal fees from Sanofi, personal fees from GSK, personal fees from Novartis, personal fees from AstraZeneca, personal fees from Mundipharma, personal fees from Faes Farma, outside the submitted work. Dr. Luna‐Porta reports other from Astra Zeneca, outside the submitted work. Dr. Olaguibel reports grants from Sanofi during the conduct of the study; personal fees from AstraZeneca, personal fees from Mundipharma, outside the submitted work. Dr. Mullol reports personal fees and other from Sanofi‐Genzyme and Regeneron, personal fees and other from Genentech and Novartis, grants and personal fees from Mylan Pharma, grants and personal fees from Uriach Group, personal fees from Mitsubishi Tanabe, personal fees from Menarini, personal fees from UCB Pharma, personal fees from AstraZeneca, personal fees from GSK, personal fees from MSD, outside the submitted work. Dr. Plaza reports grants and personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Merck, grants and personal fees from Chiesi, personal fees from Novartis, grants from Menarini, personal fees from Sanofi, outside the submitted work. Other authors have no conflicts of interests.

© 2021 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Figures

FIGURE 1
FIGURE 1
Flow chart showing visit schedule. The items appearing in the boxes are defined as follows: Sex; number of patients who completed prebronchodilator spirometry, a specific inhalation challenge with methacholine, exhaled breath condensate, the Asthma Control Test (ACT), induced sputum. Atopy is defined by at least one positive skin prick test (SPT) or detectable levels of specific IgE for any allergen tested. IgE, immunoglobulin E
FIGURE 2
FIGURE 2
Patients with severe exacerbations according to asthma severity and hospital admissions. ER, emergency room admission; HA, hospital admissions; ICU, intensive care unit admission
FIGURE 3
FIGURE 3
Sensitization to aeroallergens and asthma severity levels
FIGURE 4
FIGURE 4
Blood eosinophil count and FENO levels (expressed as mean/median and standard error). No statistically significant differences (p < 0.05) were found between blood eosinophil counts and FeNO levels and the severity of asthma
FIGURE 5
FIGURE 5
Correlation between eosinophilia in peripheral blood and sputum. The best correlation is established between more than 300 cells/mm3 in peripheral blood and more than 2% of eosinophils in sputum (correlation coefficient = 0.5235, p = 0.0002)
FIGURE 6
FIGURE 6
Spirometric, pletismography, and bronchial hyperreactivity data. There are statistically significant differences between FEV1%, FVC%, FEV1/FVC, and asthma severity levels *p < 0.05, **p < 0.01, ***p < 0.001. No statistically significant differences were found in FVC%, RV%, TLC%, and PC20 methacholine and asthma severity. RV, residual volume; TLC, total lung capacity
FIGURE 7
FIGURE 7
ACT and Mini‐AQLQ scores. Patients with severe asthma (191) had worse control with an average ACT score of 18 points (p < 0.001). Statistically significant differences *p < 0.05, **p < 0.01, ***p < 0.001 were found between different levels of asthma severity. ACT, Asthma Control Test; AQLQ, Asthma Quality of Life Questionnaire

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