Response of the Airway in Sinusitis and Asthma (RAISe)

Medical University of Lodz

Status and phase: Completed; Phase 4

Conditions: Asthma; Sinusitis

Treatments: Drug: Mometasone Nasal; Drug: placebo mometasone

Study type: Interventional

Funder types: Other

Identifiers

NCT03011632

RNN/153/16/KE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 patients

Sex: All

Ages: 4 to 8 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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150 participants in 2 patient groups, including a placebo group

mometasone nasal

Experimental group

Description:

a group of children who will receive a nasal mometasone in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% sodium chloride (NaCl) solution in a nasal nebuliser once a day for 3 months,

Treatment:

Drug: Mometasone Nasal

placebo mometasone

Placebo Comparator group

Description:

a group of children without immunoglobulin E (IgE) - dependent hypersensitivity who will receive nasal mometasone placebo in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% NaCl solution in a nasal nebuliser once a day for 3 months,

Treatment:

Drug: placebo mometasone