Response of the Airway in Sinusitis and Asthma

Asthma Clinical Trial

— RAISe  

Official title:

The Role of Nonspecific Immune Response of the Airway Mucosa in Children With Chronic Rhinosinusitis and Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03011632
• Other study ID #: RNN/153/16/KE
• Status: Completed
• Phase: Phase 4
• Start date: January 2017
• Est. completion date: August 2019

Study information

• Verified date: August 2019
• Source: Medical Universtity of Lodz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: August 2019
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 8 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Sinusitis

Intervention

Drug:
• Mometasone Nasal
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
• placebo mometasone
a group of children without 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,

Locations

Country	Name	City	State
Poland	Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland	Lodz

Sponsors (1)

Lead Sponsor	Collaborator
Medical Universtity of Lodz

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Asthma Control Test for children (cACT™)	Childhood Asthma Control Test (cACT™), will be used, which has been recommended by the Global Initiative for Asthma (GINA) Report	12 months
Primary	SN-5	validated questionnaire for the assessment for quality of life in children with CRS (5 symptom-cluster items covering the domains of sinus infection, nasal obstruction, allergy symptoms, emotional distress, and activity limitations)	12 months
Secondary	Spirometry	Respiratory function tests will be performed according to the American Thoracic Society (ATS) standards. The best result of three spirometric maneuvers will be selected for the analysis of obstructive disorders and the level of disease severity according to the standards of the Polish Society of Lung Diseases. The analysis will include FEV1% (A/N% - the percent of the measured to predicted value).	12 months
Secondary	Nasal fraction of exhaled nitric oxide (nFeNO) Measurements	Measurements of nasal fraction of exhaled nitric oxide (nFeNO) will be performed using an electrochemical analyzer (ExpAir) according to the manufacturer's instructions. The detection limit ranged from 1 ppb to 6000 ppb.	12 months
Secondary	Glucose concentration	Glucose concentration in serum and in nasal secretions will be assessed using glucose oxidase sticks (Roche, Lewes, East Sussex, U.K.). Nasal glucose concentration will analyzed in the context of blood glucose level using following ratio: nasal glucose level/blood glucose level.	12 months
Secondary	Immunophenotyping	Mucosa - The nasal mucosa sample will be gently processed (mechanical dissociation, mild enzyme digestion) to produce a single cell suspension. It will be further fixed and stained with specific cocktail of fluorescent dye-stained antibody and then cell identification will be performed by flow cytometry. The relative count of all cell subsets will be determined. All procedures will be performed in buffers containing brefeldin and/or monesin to prevent dislocation of proteins of interest.	12 months
Secondary	quantitative polymerase chain reaction (qPCR)	Total RNA will be isolated from mucosa samples and then reverse-transcribed with e.g. Thermo Scientific Maxima Reverse Transcriptase. qPCR reaction will be performed using house-designed primer sets. Relative expression of genes of interest (involved in innate response) will be analyzed against selected house-keeping gene transcripts.; Manufacturer recommended procedure will be used to quantify Human Epithelial to Mesenchymal Transition gene panel and Multiplex Real-Time PCR for pathogen genes	12 months