Novel Inflammatory Markers in Different Phenotypes of Severe Asthma

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.

Study Overview

• Status: Recruiting
• Conditions: Asthma; Nasal Polyps
• Intervention / Treatment: Other: observational

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Ilaria Puxeddu, MD, PhD; Phone Number: +393394740912; Email: ilaria.puxeddu@unipi.it

Study Locations

• Italy
  • Tuscany
    • Pisa, Tuscany, Italy, 56126
      • Recruiting
      • Pisa University
      • Contact: Ilaria Puxeddu, MD, PhD; Phone Number: +393394740912; Email: ilaria.puxeddu@unipi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
asthma with nasal polyps; severe asthma with involvement of the upper airways (chronic rhinosinusitis with nasal polyps)	Other: observational; observation of biomarkers in different asthma groups
severe asthma without nasal polyps; severe asthma without involvement of the upper airways	Other: observational; observation of biomarkers in different asthma groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Pisa

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): August 31, 2022
• Study Completion (Anticipated): February 28, 2023

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): May 21, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: asthma; neutrophils; eosinophils
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Polyps; Asthma; Nasal Polyps
• Other Study ID Numbers: NIMISA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No