Novel Inflammatory Markers in Different Phenotypes of Severe Asthma

NCT04888910 | Unknown

• 1 other identifier: NIMISA
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Nasal Polyps

Keywords

asthma; eosinophils; neutrophils

Outcome Measures

Primary Outcomes (2)

• cell receptors

  to identify neutrophil- and eosinophil-receptors in the airways of severe asthmatic patients with or without involvement of the upper airways

  2 years

• cell mediators

  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

  2 years

Study Arms (2)

asthma with nasal polyps

severe asthma with involvement of the upper airways (chronic rhinosinusitis with nasal polyps)

Other: observational

severe asthma without nasal polyps

severe asthma without involvement of the upper airways

Other: observational

Interventions

observational OTHER

observation of biomarkers in different asthma groups

asthma with nasal polyps; severe asthma without nasal polyps

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

severe asthmatic patients referred to the asthma clinic with or without upper airways involvement. Some of them are currently under biological therapies according to their grade of disease in addition to inhaled therapies.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

Pisa University

Pisa, Tuscany, 56126, Italy

RECRUITING

Related Publications (3)

• Wu W, Bleecker E, Moore W, Busse WW, Castro M, Chung KF, Calhoun WJ, Erzurum S, Gaston B, Israel E, Curran-Everett D, Wenzel SE. Unsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data. J Allergy Clin Immunol. 2014 May;133(5):1280-8. doi: 10.1016/j.jaci.2013.11.042. Epub 2014 Feb 28.

  PMID: 24589344 RESULT

• Wenzel SE, Jayawardena S, Graham NM, Pirozzi G, Teper A. Severe asthma and asthma-chronic obstructive pulmonary disease syndrome - Authors' reply. Lancet. 2016 Dec 3;388(10061):2742. doi: 10.1016/S0140-6736(16)31720-2. Epub 2016 Dec 2. No abstract available.

  PMID: 27924776 RESULT

• Ray A, Kolls JK. Neutrophilic Inflammation in Asthma and Association with Disease Severity. Trends Immunol. 2017 Dec;38(12):942-954. doi: 10.1016/j.it.2017.07.003. Epub 2017 Aug 4.

  PMID: 28784414 RESULT

MeSH Terms

Conditions

Asthma; Nasal Polyps

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Central Study Contacts

Ilaria Puxeddu, MD, PhD

CONTACT

+393394740912; ilaria.puxeddu@unipi.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: May 17, 2021
• Study Start: March 1, 2021
• Primary Completion: August 31, 2022
• Study Completion: February 28, 2023
• Last Updated: May 21, 2021

Record last verified: 2021-05

Locations

IT (1)