Biomarkers and Respiratory Omics as New CHildren Opportunities - Study of Clinical Outcomes and Predictivity Evaluation - a Multi-cohort, Multi-center Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 160
- Locations
- 1
- Primary Endpoint
- Evaluation on microbiome composition and diversity, cellular composition, and metabolomic profile between study groups
Study Overview
Brief Summary
The goal of this observational study is to improve the identification of biomarkers that predict disease progression and to assess the effectiveness of current therapies in children with asthma and protracted bacterial bronchitis.
The main aim of the study is to evaluate the microbiome composition and diversity, cellular composition, and metabolomic profile. In addition, to assess their correlation on subsequent treatment and disease course in children with asthma, protracted bacterial bronchitis, and in those receiving inhaled glucocorticosteroids without a diagnosis of asthma.
Participants will undergo fiberoptic bronchoscopy. During bronchoscopy, the performing physician will collect Bronchoalveolar lavage fluid samples for metagenomic and metabolomic analysis, as well as mucosal biopsies for histopathological evaluation.
Detailed Description
This prospective cohort study will enroll 160 participants and allocate them into study arms according to their medical history. The planned arms include: children with asthma, children with protracted bacterial bronchitis, children without asthma who are exposed to inhaled glucocorticosteroids, children with chronic cough, and a control group.
Participants will be recruited from the Pediatric Pulmonology Departments of the Medical Universities in Warsaw and Lodz. At baseline, investigators will administer a standardized medical questionnaire approved by both medical centers. All participants will undergo a single fiberoptic bronchoscopy during hospitalization according to clinical indications and with informed consent. During bronchoscopy, bronchoalveolar lavage (BAL) fluid samples will be collected for metagenomic, metabolomic, culture, biochemical, and cytological analyses. Additional mucosal biopsies will be obtained with separate consent if applicable.
Follow-up visits will include blood sample collection, sputum sampling (for cooperative children), spirometry, impulse oscillometry, and Fractional Exhaled Nitric Oxide measurements, without repeat bronchoscopy. The bronchoscopy procedure will not be repeated.
The study involves analysis of biological samples obtained during clinically indicated bronchoscopy, followed by a 5-year observation period. The findings will aid in distinguishing asthma phenotypes, identifying risk factors for asthma and protracted bacterial bronchitis, and improving the understanding of factors contributing to poor treatment response in these conditions.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- — to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age at the beginning of the study 0-17 years old
- •Clinical indication and qualification by the attending physician for fiberoptic bronchoscopy under general anesthesia:
- •Obstruction of the airways:
- •Suspicion of foreign body aspiration
- •Persistent stridor
- •Abnormal result of functional tests of respiratory system - flattening of inspiratory or expiratory curve, presence of restriction (tested vital capacity <5 percentile) or irreversible obstruction (persistence of Tiffneau index <5 percentile despite administration of bronchodilators)
- •Radiological findings located in the course of the larynx, trachea or bronchi
- •Persistent atelectasis on subsequent radiological examinations
- •Persistent cough >4 weeks
- •Hemoptysis
- •Suspected laryngomalacia or tracheobronchomalacia
- •Suspected tracheoesophageal fistula
- •Persistent dyspnea unresponsive to anti-asthmatic treatment used for min. 2 months, with no other identifiable causes
- •Radiologically detected mediastinal abnormalities
- •Suspected presence of a vascular ring
- •Presence of excessive secretions that are impossible for the patient to expectorate
- •Fine needle biopsy of cystic lesions
- •Obtained consent from patient/legal guardian for participation in the study
Exclusion Criteria
- •Active acute respiratory infection up to 4 weeks before the procedure
- •Taking antibiotics or systemic glucocorticosteroids up to 4 weeks before the procedure
- •Patients with very severe comorbidities (congenital immunodeficiencies, genetic disorders, neurological or neuromuscular diseases, cancer, severe congenital heart defects, heart failure, liver failure, inflammatory bowel disease, celiac disease)
- •Patients with blood clotting disorders
- •Children with diagnosed respiratory diseases other than asthma and protracted bacterial bronchitis - including interstitial diseases, tuberculosis, inflammation of small and medium-sized blood vessels
- •Patients for whom >48 hours have passed between suspicion of foreign body aspiration and interventional bronchoscopy
- •Children with foreign body aspiration having a foreign body located in the trachea
Arms & Interventions
Control group
Children without underlying diseases who undergo bronchoscopy either for suspected foreign body aspiration or as part of routine diagnostic evaluation
Intervention: fiberoptic bronchoscopy (Procedure)
Control group
Children without underlying diseases who undergo bronchoscopy either for suspected foreign body aspiration or as part of routine diagnostic evaluation
Intervention: blood sample collection (Procedure)
Control group
Children without underlying diseases who undergo bronchoscopy either for suspected foreign body aspiration or as part of routine diagnostic evaluation
Intervention: Respiratory functional tests (Diagnostic Test)
Control group
Children without underlying diseases who undergo bronchoscopy either for suspected foreign body aspiration or as part of routine diagnostic evaluation
Intervention: Sputum culture (Diagnostic Test)
Asthma
Children diagnosed with asthma at the baseline
Intervention: fiberoptic bronchoscopy (Procedure)
Asthma
Children diagnosed with asthma at the baseline
Intervention: blood sample collection (Procedure)
Asthma
Children diagnosed with asthma at the baseline
Intervention: Respiratory functional tests (Diagnostic Test)
Asthma
Children diagnosed with asthma at the baseline
Intervention: Sputum culture (Diagnostic Test)
Protracted Bacterial Bronchitis
Children diagnosed with Protracted Bacterial Bronchitis at the baseline
Intervention: fiberoptic bronchoscopy (Procedure)
Protracted Bacterial Bronchitis
Children diagnosed with Protracted Bacterial Bronchitis at the baseline
Intervention: blood sample collection (Procedure)
Protracted Bacterial Bronchitis
Children diagnosed with Protracted Bacterial Bronchitis at the baseline
Intervention: Respiratory functional tests (Diagnostic Test)
Protracted Bacterial Bronchitis
Children diagnosed with Protracted Bacterial Bronchitis at the baseline
Intervention: Sputum culture (Diagnostic Test)
Children without asthma who have been exposed to inhaled glucocorticosteroids
Children without asthma who have been exposed to inhaled glucocorticosteroids for at least 4 weeks during the 2 months preceeding bronchoscopy
Intervention: fiberoptic bronchoscopy (Procedure)
Children without asthma who have been exposed to inhaled glucocorticosteroids
Children without asthma who have been exposed to inhaled glucocorticosteroids for at least 4 weeks during the 2 months preceeding bronchoscopy
Intervention: blood sample collection (Procedure)
Children without asthma who have been exposed to inhaled glucocorticosteroids
Children without asthma who have been exposed to inhaled glucocorticosteroids for at least 4 weeks during the 2 months preceeding bronchoscopy
Intervention: Respiratory functional tests (Diagnostic Test)
Children without asthma who have been exposed to inhaled glucocorticosteroids
Children without asthma who have been exposed to inhaled glucocorticosteroids for at least 4 weeks during the 2 months preceeding bronchoscopy
Intervention: Sputum culture (Diagnostic Test)
Non inflammatory causes of chronic cough
Children diagnosed with: laryngomalacia, tracheobronchomalacia adenoid hypertrophy, gastroesophageal reflux disease, habitual cough
Intervention: fiberoptic bronchoscopy (Procedure)
Non inflammatory causes of chronic cough
Children diagnosed with: laryngomalacia, tracheobronchomalacia adenoid hypertrophy, gastroesophageal reflux disease, habitual cough
Intervention: blood sample collection (Procedure)
Non inflammatory causes of chronic cough
Children diagnosed with: laryngomalacia, tracheobronchomalacia adenoid hypertrophy, gastroesophageal reflux disease, habitual cough
Intervention: Respiratory functional tests (Diagnostic Test)
Non inflammatory causes of chronic cough
Children diagnosed with: laryngomalacia, tracheobronchomalacia adenoid hypertrophy, gastroesophageal reflux disease, habitual cough
Intervention: Sputum culture (Diagnostic Test)
Outcomes
Primary Outcomes
Evaluation on microbiome composition and diversity, cellular composition, and metabolomic profile between study groups
Time Frame: Index hospitalization, immediately after the procedure
16S rRNA targeted sequencing, Shannon index, Chao1, and Pielou's evenness, Bray-Curtis dissimilarity, weighted UniFrac and unweighted UniFrac measures, PERMANOVA, principal coordinate analysis, ANCOM-BC2, ASVs tables generated by QIIME2 will be used as input for PICRUSt2 to infer functional profiles of the microbiomes, Biocrates' MetIDQ and MetaboAnalystR R package
Correlation of metagenomic and metabolomic findings on subsequent treatment and disease course between groups
Time Frame: 2 years
16S rRNA targeted sequencing, Shannon index, Chao1, and Pielou's evenness, Bray-Curtis dissimilarity, weighted UniFrac and unweighted UniFrac measures, PERMANOVA, principal coordinate analysis, ANCOM-BC2, ASVs tables generated by QIIME2 will be used as input for PICRUSt2 to infer functional profiles of the microbiomes, Biocrates' MetIDQ and MetaboAnalystR R package, MANOVA and logistic regression, Cox proportional hazards model
Secondary Outcomes
- Comparison of the previous medical history and demographic characteristics across the study groups(At baseline)
- Assessment of the degree of asthma control among children diagnosed with asthma according to Global Initiative for Asthma(5 years)
- Evaluation how the place of residence influences the incidence and clinical course of the studied diseases(5 years)
- Assessment of exposure to PM10 dust at the place of residence during the year preceding study inclusion in children from each group(At baseline)
- Comparison of the normalized difference vegetation index (NDVI) and chlorophyll index (CI) green levels between study groups at baseline(At baseline)
- Comparison of the sputum culture at baseline and at the control visit(2 years)
- Comparison of the baseline sputum culture findings with BALF culture and metagenomic results(2 years)
- Evaluation of the initial Immunoglobulin E (IgE) concentrations and their dynamics of change between groups(5 years)
- Comparison of the eosinophil concentrations according to disease type and course(5 years)
- Assessment of the correlation between ICS used without an asthma diagnosis and airway dysbiosis(2 years)
- Evaluation of asthma treatment response, exacerbation rates, and need for bronchodilators according to airway metabolome profiles(5 years)
- Comparison of the asthma subtypes and evaluate possibilities for developing personalized treatment in selected pediatric groups(2 years)
- Identification of the most common pathogens cultured from BALF samples in children with asthma, PBB, chronic cough, and in those taking ICS without an asthma diagnosis(Index hospitalization, immediately after the procedure)
- Analysis of the frequency and type of antibiotic therapy in each study group and correlate these findings with the total number of respiratory diseases in individual participants.(5 years)
- Evaluation of the recurrence rates of PBB and development of CSLD and BE based on identified airway pathogens(5 years)
- Assessment of the prevalence of antibiotic-resistant strains among patients with PBB(5 years)
- Assessment of the time to PBB development in previously healthy children based on metagenomic and metabolomic findings(5 years)