Novel Inflammatory Markers in Different Phenotypes of Severe Asthma

• Conditions: Asthma; Nasal Polyps
• Interventions: Other: observational

• Registration Number: NCT04888910
• Lead Sponsor: University of Pisa

Brief Summary

Asthma is a highly prevalent chronic airway inflammatory disease characterized by airway hyper-responsiveness, reversible airflow obstruction and increased mucus secretion, involving large and small airways. An emerging sub-phenotype of severe asthma is the late onset disease associated with nasal polyposis, a frequent co-morbidity that significantly impacts lung function and symptom control. On the basis of the infiltrate found in the sputum, asthma can be divided into four distinct phenotypes: eosinophilic, neutrophilic, mixed granulocytic and pauci-granulocytic. The majority of patients with eosinophilic asthma are sensitive to corticosteroids, and biological therapies targeting eosinophils (anti-Interleukin (IL)-5 and anti-IL5R) have been recently approved. However, it is known that some asthmatics, particularly those who have severe disease and are resistant to corticosteroids, have elevated neutrophil counts in the airway where they play a vital role in the exacerbation of the disease. However, the precise role of neutrophils in severe asthma and the mechanisms involved in neutrophil-induced tissue damage have not been clarified yet.

The hypothesis of the study is that neutrophils and eosinophils can contribute to the severity of asthma by changing their phenotypes according to the airway environment. Thus, a better understanding of the roles of neutrophils and eosinophils in severe asthma may lead to the identification of novel biomarkers and the development of new therapeutic approaches in different phenotypes of severe asthma.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-01
• Status Verified: 2021-05
• Study First Submitted: 2021-05-11
• Study First Submitted QC: 2021-05-11
• Study First Posted: 2021-05-17
• Last Update Submitted: 2021-05-18
• Last Update Posted: 2021-05-21
• Primary Completion: 2022-08-31
• Study Completion: 2023-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Male or female
• age (18-65 years)
• Diagnosis of severe asthma according to the European Respiratory Society (ERS) and American Thoracic Society (ATS) definition, with and without nasal symptoms
• normal pulmonary function post-therapy (FEV1 post-bronchodilation: greater than 80% of the predicted value, with FEV1/ vital capacity (VC) > 88-89% - for males and females, respectively - of the predicted value)
• non reversible chronic airflow limitation (FEV1 post-bronchodilation: lower than 70% of the predicted value, with FEV1/VC < 88-89% of the predicted value)
• Signing of the informed consent

Exclusion Criteria

• Referred Pregnancy
• Use of therapy with beta-blockers
• Smoking (current or within the previous 3 months)
• Negation to participate to the study
• Current upper and lower airways infectious diseases
• Current systemic infectious diseases

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
asthma with nasal polyps	observational	severe asthma with involvement of the upper airways (chronic rhinosinusitis with nasal polyps)
severe asthma without nasal polyps	observational	severe asthma without involvement of the upper airways

Primary Outcome Measures

Name	Time	Method
cell receptors	2 years	to identify neutrophil- and eosinophil-receptors in the airways of severe asthmatic patients with or without involvement of the upper airways
cell mediators	2 years	to identify soluble and matrix-derived mediators from neutrophils and eosinophils in the airways of severe asthmatic patients with or without involvement of the upper airways

Trial Locations

Locations (1)

Pisa University; 🇮🇹 Pisa, Tuscany, Italy