Clinical trial NCT04888910: Novel Inflammatory Markers in Different Phenotypes of Severe Asthma
Official title: Novel Inflammatory Markers in Different Phenotypes of Severe Asthma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthma
Nasal Polyps
Keywords: asthma
eosinophils
neutrophils
Lead sponsor: University of Pisa
Sponsor class: OTHER
First posted: 2021-05-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: cell receptors
timeFrame: 2 years
measure: cell mediators
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: Pisa University
state: Tuscany
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.