Follow-up of Spanish Prospective Asthma and Nasal Polyposis Registry

Overview

Primary objective \- To study the stability of different phenotypes and endotypes of asthma at 3, 5, and 7 years of follow-up and - in MEGA COHORT and in patients on biologic treatment Secondary objective(s) * To study biomarkers variation post-treatment in patients with and without Nasal Polyposis * To demonstrate the existence of different subtypes of eosinophils that may be phenotypically and functionally heterogeneous * To increase the number of patients in the cohort on biologic treatment to reach at least 900 (400 over the current cohort).

Detailed description

Open-labeled National, Multicenter Non-interventional on the therapeutic strategy, Prospective (longitudinal) Disease registry, 3 years of follow-up

1. Correlation between non-invasive T2 markers (FeNO, blood eosinophils) versus inflammatory markers in sputum (eosinophils, periostin, NO, etc.) 2. Cluster analysis in both cohorts. 3. Analysis of some treatable traits on asthma control in MEGA cohort (BMI, anxiety and depression scale, exercise). 4. To characterize exacerbations (numbers, ICU admissions, treatments compliance, etc). 5. Analysis of compliance with asthma medications. 6. Analysis of patients with phenotype T2-LOW in MEGA cohort. 7. Analysis of patients with undetectable total IgE ( \< 10 UI/L). 8. Role of microRNA in diagnosis, follow-up and variations after treatments. 9. Analysis of alarmins (TSLP, IL-33 e IL-25) and IL-6 in blood and sputum. 10. To Immunophenotype eosinophils by single-cell analysis in blood and sputum at baseline and post-biological treatment.

Interventions

• Drug Antiasthmatic
  real-life

Primary outcome measures

• Correlation between non-invasive T2 biomarkers versus biomarkers in sputum [Time frame: at date of randomization and after one year of follow-up]

Secondary outcome measures (9)

• Analysis of treatable traits on asthma control by ACT questionnaire [Time frame: at date of randomization and after one, two and three years of follow-up]
• To characterize asthma exacerbations. [Time frame: at date of randomization and after one, two and three years of follow-up]
• Analysis of withdrawing asthma medications [Time frame: at date of randomization and after one, two and three years of follow-up]
• Analysis of patients with phenotype T2-LOW (IgE less than 75 kU/L, blood eosinophils less than 150 cells/μL, and FeNO less than 20 ppb) [Time frame: at date of randomization and after one year of follow-up]
• Analysis of clinical outcomes, pulmonary function tests, biomarkers patients with very low total IgE ( < 10 UI/L) [Time frame: at date of randomization and after one year of follow-up]
• Role of alarmins and IL-6 in the component of inflammation in asthma [Time frame: at date of randomization and after one year of follow-up]
• Role of microRNAs in asthma diagnosis and variations after different treatments [Time frame: 1 year]
• Immunophenotype eosinophils [Time frame: 1 year]
• Stability of asthma phenotypes along the follow-up [Time frame: at date of randomization and after one, two and three years of follow-up]

Eligibility criteria

Inclusion criteria

For the general asthma cohort (MEGA):

• Age from 18 to 80 y.o. with asthma with and without nasal polyposis based on GINA guidelines (compatible clinical symptoms+reversibility of at least 12% and 200 mL in FEV1 after the administration of 200-400 μg albuterol/salbutamol or positive methacholine test) of several severities attended at participant centres
• Already in follow-up in MEGA cohort
• To participate in the study
• Signed informed consent

Inclusion criteria for asthma patients treated with biologics

• Patients from 18 to 80 y.o. with uncontrolled asthma with and without nasal polyposis that fulfil criteria to be treated with biological drugs (Existing treatment with medium-to-high-dose ICS (≥ 250 μg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 μg/day of fluticasone propionate or equivalent) in combination with a second controller (e.g., LABA, LTRA) for at least 3 months+ airflow limitation- FEV1 <80%/FEV1/FVC <70+ACQ-5 score ≥ 1.5/ ACT < 19 at inclusion and/or have experience any of the following events on the last year: treatment with systemic steroids/ hospitalization or emergency medical care visit for worsening asthma.
• When planning dupilumab, mepolizumab, benralizumab or reslizumab, biomarker levels, and exacerbation in the previous year will be considered according to the Spanish Ministry of Health recommendations for reimbursement of any biological drug in severe asthma. In the case of Omalizumab allergic asthma and IgE > 75 and < 1500 UI
• Patients already in follow-up in the cohort of patients treated with biologics
• Willing to participate in the study
• Sign informed consent

Exclusion criteria

• Exclusion criteria for MEGA COHORT

• Diagnosis of chronic obstructive pulmonary disease or other lung disease that may impair lung function
• Comorbid disease that might interfere with the evaluation, e.g. psychiatric disorders
• Patients participating in other clinical trials
• Patients without the capacity to understand the aim of the study
• Exclusion criteria for asthma patients treated with biologics

• Diagnosis of chronic obstructive pulmonary disease or other lung disease that may impair lung function
• Comorbid disease that might interfere with the evaluation, e.g. psychiatric disorders
• Patients participating in other clinical trials
• Patients without the capacity to understand the aim of the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Spain · 8 centers

• Hospital Universitario Santiago de Compostela — Santiago de Compostela
• Hospital Universitario Germans Trias — Badalona
• Hospital Universitari Vall de Hebron — Barcelona
• Hospital Clinic — Barcelona
• Hospital Universitario Sant Pau — Barcelona
• Hospital Del Ferrol — A Coruña
• Hospital Universitario La Paz — Madrid
• Hospital Universitario de Navarra — Pamplona

Publications

• Dominguez-Ortega J, Luna-Porta JA, Olaguibel JM, Barranco P, Arismendi E, Barroso B, Betancor D, Bobolea I, Caballero ML, Cardaba B, Cruz MJ, Curto E, Gonzalez-Barcala FJ, Losantos-Garcia I, Martinez-Rivera C, Mendez-Brea P, Mullol J, Munoz X, Picado C, Plaza V, Del Pozo V, Rial MJ, Sastre J, Soto L, Valero A, Valverde-Monge M, Quirce S. Exacerbations Among Patients With Asthma Are Largely Depende PMID 35503227
• Matabuena M, Salgado FJ, Nieto-Fontarigo JJ, Alvarez-Puebla MJ, Arismendi E, Barranco P, Bobolea I, Caballero ML, Canas JA, Cardaba B, Cruz MJ, Curto E, Dominguez-Ortega J, Luna JA, Martinez-Rivera C, Mullol J, Munoz X, Rodriguez-Garcia J, Olaguibel JM, Picado C, Plaza V, Quirce S, Rial MJ, Romero-Mesones C, Sastre B, Soto-Retes L, Valero A, Valverde-Monge M, Del Pozo V, Sastre J, Gonzalez-Barcala PMID 36732158
• Rodrigo-Munoz JM, Canas JA, Sastre B, Rego N, Greif G, Rial M, Minguez P, Mahillo-Fernandez I, Fernandez-Nieto M, Mora I, Barranco P, Quirce S, Sastre J, Del Pozo V. Asthma diagnosis using integrated analysis of eosinophil microRNAs. Allergy. 2019 Mar;74(3):507-517. doi: 10.1111/all.13570. Epub 2018 Oct 11. PMID 30040124
• Romero-Mesones C, Cruz MJ, Alobid I, Barroso B, Arismendi E, Barranco P, Betancor D, Bobolea I, Cardaba B, Curto E, Domenech G, Dominguez-Ortega J, Espejo D, Gonzalez-Barcala FJ, Luna-Porta JA, Martinez-Rivera C, Mendez-Brea P, Mullol J, Olaguibel JM, Picado C, Plaza V, Del Pozo V, Quirce S, Rial MJ, Rodrigo-Munoz JM, Sastre J, Serrano S, Soto-Retes L, Valero A, Valverde-Monge M, Munoz X. Disposit PMID 37391017
• Barroso B, Valverde-Monge M, Betancor D, Gomez-Lopez A, Villalobos-Vilda C, Gonzalez-Cano B, Sastre J. Improvement in Smell Using Monoclonal Antibodies Among Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review. J Investig Allergol Clin Immunol. 2023 Dec 14;33(6):419-430. doi: 10.18176/jiaci.0939. Epub 2023 Sep 4. PMID 37669083
• Baos S, Calzada D, Cremades-Jimeno L, de Pedro M, Sastre J, Picado C, Quiralte J, Florido F, Lahoz C, Cardaba B. Discriminatory Molecular Biomarkers of Allergic and Nonallergic Asthma and Its Severity. Front Immunol. 2019 May 9;10:1051. doi: 10.3389/fimmu.2019.01051. eCollection 2019. PMID 31143187
• Baptista-Serna L, Rodrigo-Munoz JM, Minguez P, Valverde-Monge M, Arismendi E, Barranco P, Barroso B, Bobolea I, Canas JA, Cardaba B, Cruz MJ, Curto E, Dominguez-Ortega J, Garcia-Latorre R, Gonzalez-Barcala FJ, Martinez-Rivera C, Mullol J, Munoz X, Olaguibel JM, Picado C, Plaza V, Quirce S, Rial MJ, Sastre B, Soto L, Valero A, Del Pozo V, Sastre J. Anxiety and body mass index affect asthma control: PMID 34673289
• Rial MJ, Alvarez-Puebla MJ, Arismendi E, Caballero ML, Canas JA, Cruz MJ, Gonzalez-Barcala FJ, Luna JA, Martinez-Rivera C, Mullol J, Munoz X, Olaguibel JM, Picado C, Plaza V, Quirce S, Romero-Mesones C, Salgado FJ, Sastre B, Soto-Retes L, Valero A, Valverde M, Sastre J, Pozo VD. Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort. Clin Transl Allerg PMID 33900052

Identifiers

NCT: NCT06163807 · SGZ-2022-13739

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗