Clinical trial NCT03011632: Response of the Airway in Sinusitis and Asthma
Official title: The Role of Nonspecific Immune Response of the Airway Mucosa in Children With Chronic Rhinosinusitis and Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sinusitis
Asthma
Lead sponsor: Medical University of Lodz
Sponsor class: OTHER
First posted: 2017-01-05
Enrollment: 150
Sex: ALL
Minimum age (years): 4
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The project is intended to be realised in two phases. In the first stage, a case control study will be performed. In the second phase, double-blind, placebo controlled study will be conducted. In the first phase 3 groups of children will be compare: i) a group of children suffering from chronic rhinosinusitis (CRS) (fulfilling the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria) and asthma (fulfilling the Asthma Predictive Index (API) criteria) (CRS+/asthma+, n=90), ii) a group of children suffering from CRS (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria) (CRS+/asthma-, n=30) and iii) a group of children without symptoms of CRS (negative EPOS criteria) and without asthma symptoms (negative API criteria) (CRS-/asthma-, n=30). In the second phase the effect of intranasal glucocorticosteroids will be assessed. The following research methods will be used: CRS-symptom score questionnaire (SN-5) and Childhood Asthma Control Test (cACT) questionnaires, skin prick test, spirometry, measurement of nitric oxide NO in exhaled breath (FeNO), taste perception test, eosinophil morphology assessment, ratio: glucose concentration in nasal secretion/serum glucose level, concentration of specific immunoglobulin (Ig) E, total immunoglobulin G (IgG) and immunoglobulin A (IgA), the proportion of innate lymphoid cells (ILC) and regulatory lymphocytes cells in the peripheral blood. Endoscopic examination of the upper airways will be performed and samples of the mucosa will be taken. The mucosal examination will be as follows: i) polymerase chain reaction (PCR) examination for the detection of the presence of viral and bacterial genetic material, ii) measurement of the expression of the various messenger ribonucleic acid (mRNA), iii) measurement of the expression of mRNA for the Epithelial-Mesenchymal Transition (EMT) genes and iv) percentage of ILCs.

Detailed description: Persistence of CRS and asthma require multiple interconnected feedback and feed-forward circuits between ILCs and epithelial cells. It seems that type 2 ILCs (ILC2) are the most important accelerators of type II immune response that prepare cytokine microenvironment for Th2 cells chronic activation. What decide on ILC2 accumulation - this is an urgent question. The aim of the proposed project is to examine the role of the innate immune response of airways in children suffering from chronic rhinosinusitis and asthma.

The project is intended to be realised in two phases. In the first stage, a case control study will be performed. In the second phase, double-blind, placebo controlled study will be conducted. In the first phase 3 groups of children will be compare: i) a group of children suffering from CRS (fulfilling the EPOS criteria) and asthma (fulfilling the API criteria) (CRS+/asthma+, n=90), ii) a group of children suffering from CRS (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria) (CRS+/asthma-, n=30) and iii) a group of children without symptoms of CRS (negative EPOS criteria) and without asthma symptoms (negative API criteria) (CRS-/asthma-, n=30). In the second phase the effect of intranasal glucocorticosteroids will be assessed. The following research methods will be used: SN-5 and cACT questionnaires, skin prick test, spirometry, measurement of NO in exhaled breath, taste perception test, eosinophil morphology assessment, ratio: glucose concentration in nasal secretion/serum glucose level, concentration of specific immunoglobulin E, total IgG and IgA, the proportion of ILC2 cells and regulatory cells in the peripheral blood. Endoscopic examination of the upper airways will be performed and samples of the mucosa will be taken. The mucosal examination will be as follows: i) PCR examination for the detection of the presence of viral and bacterial genetic material, ii) measurement of the expression of the various mRNA types, iii) measurement of the expression of mRNA for the Epithelial-Mesenchymal Transition (EMT) genes and iv) percentage of ILC 1, 2 and 3 cells and regulatory cells.

Eligibility criteria: Inclusion Criteria:

* a group of children (n=90) suffering from CRS (fulfilling the EPOS criteria, European Position Paper on Rhinosinusitis and Nasal Polyps) and asthma (fulfilling the API criteria, Asthma Predictive Index), including a 30-person subgroup diagnosed with clinically significant IgE-dependent hypersensitivity (accordance between symptoms and current exposure to sensitizing allergen),
* a group of children (n=30) suffering from CRS (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria), including a 15-person subgroup diagnosed with clinically significant IgE-dependent hypersensitivity (accordance between symptoms and current exposure to sensitizing allergen),
* a group of children (n=30) without symptoms of CRS (negative EPOS criteria) and without asthma symptoms (negative API criteria).

Exclusion Criteria:

* food allergy with symptoms affecting the respiratory tract
* contraindication to nasal endoscopy or contraindication to nasal mucosa biopsy
* hypertrophy of the third tonsil exceeding 60% of the nasopharynx (the criterion of obstruction being an indication for adenoidectomy). In these patients, the anatomical nasal obstruction may be the single cause of chronic inflammation in the airways, and hence verification of the hypotheses is impossible
* confirmed immunodeficiency
* exacerbation of asthma requiring systemic administration of glucocorticosteroids
* obesity, exposure to tobacco smoke
* other chronic illnesses and clinical conditions, which in the opinion of the researcher may influence the evaluation and the course of the study.

Primary outcomes:
measure: Asthma Control Test for children (cACT™)
timeFrame: 12 months
measure: SN-5
timeFrame: 12 months
Secondary outcomes:
measure: Spirometry
timeFrame: 12 months
measure: Nasal fraction of exhaled nitric oxide (nFeNO) Measurements
timeFrame: 12 months
measure: Glucose concentration
timeFrame: 12 months
measure: Immunophenotyping
timeFrame: 12 months
measure: quantitative polymerase chain reaction (qPCR)
timeFrame: 12 months
Other outcomes:
Locations:
city: Lodz
country: Poland
facility: Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland
Study officials:
affiliation: Department of Internal Medicine, Asthma and Alergology, Barlicki Hospital,
name: Pawel Majak, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Molinska K, Latek M, Rychlik B, Lach J, Strapagiel D, Majak J, Blazowski L, Jerzynska J, Kuna P, Majak P. House dust mite sensitization and frequent antibiotic courses may suppress remission of rhinosinusitis and asthma symptoms in young children. Allergy. 2022 Jan;77(1):301-304. doi: 10.1111/all.15085. Epub 2021 Sep 17. No abstract available.
citation: Majak P, Molinska K, Latek M, Rychlik B, Wachulec M, Blauz A, Budniok A, Gruchala M, Lach J, Sobalska-Kwapis M, Baranowska M, Krolikowska K, Strapagiel D, Majak J, Czech D, Palczynski C, Kuna P. Upper-airway dysbiosis related to frequent sweets consumption increases the risk of asthma in children with chronic rhinosinusitis. Pediatr Allergy Immunol. 2021 Apr;32(3):489-500. doi: 10.1111/pai.13417. Epub 2020 Dec 18.