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).

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.

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

Patients with asthma (intermittent, mild, moderate or severe asthma according to the GINA classification), with or without nasal polyposis attended third-level hospitals of the Spanish National Health System.