Biomarkers and Respiratory Omics as New CHildren Opportunities - Study of Clinical Outcomes and Predictivity Evaluation

N/ANot Yet RecruitingNCT07232550

Medical University of Warsaw160 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

Eligibility

Sex: ALLMax age: 17 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Evaluation on microbiome composition and diversity, cellular composition, and metabolomic profile between study groups

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

Time frame: Index hospitalization, immediately after the procedure

Correlation of metagenomic and metabolomic findings on subsequent treatment and disease course between groups

Time frame: 2 years

Secondary Outcomes

Comparison of the previous medical history and demographic characteristics across the study groups

MANOVA, neural networks and logistic regression

Time frame: At baseline

Assessment of the degree of asthma control among children diagnosed with asthma according to Global Initiative for Asthma

In children aged ≥5 years using the Asthma Control Questionnaire (ACQ) numeric scale, and in children \<5 years using a questionnaire assessing the preceding month for asthma symptoms occurring more than twice per week, nocturnal cough or insomnia caused by dyspnea, need for short-acting β-mimetics more than twice per week, and physical activity limitations due to dyspnea.

Time frame: 5 years

Evaluation how the place of residence influences the incidence and clinical course of the studied diseases

Residence classified as urban (\>100,000 inhabitants), town (\<100,000 inhabitants), or rural area logistical regression

Time frame: 5 years

Assessment of exposure to PM10 dust at the place of residence during the year preceding study inclusion in children from each group

Data will be obtained from the Chief Environmental Protection Inspectorate website and will include average, minimum, and maximum monthly and annual concentrations, ANOVA/non-parametric tests

Time frame: At baseline

Comparison of the normalized difference vegetation index (NDVI) and chlorophyll index (CI) green levels between study groups at baseline

At place of residence

Time frame: At baseline

Comparison of the sputum culture at baseline and at the control visit

Comparison of fact of growth and number of CFU with Fisher's exact or χ² test

Time frame: 2 years

Comparison of the baseline sputum culture findings with BALF culture and metagenomic results

Comparison of fact of growth and number of CFU with Fisher's exact or χ² test, logistical regression

Time frame: 2 years

Evaluation of the initial Immunoglobulin E (IgE) concentrations and their dynamics of change between groups

Using medians with interquartile ranges and compared using the Mann-Whitney U or Kruskal-Wallis tests

Time frame: 5 years

Comparison of the eosinophil concentrations according to disease type and course

Using medians with interquartile ranges and compared using the Mann-Whitney U or Kruskal-Wallis tests

Time frame: 5 years

Assessment of the correlation between ICS used without an asthma diagnosis and airway dysbiosis

PERMANOVA and logistic regression

Time frame: 2 years

Evaluation of asthma treatment response, exacerbation rates, and need for bronchodilators according to airway metabolome profiles

PERMANOVA and logistic regression

Time frame: 5 years

Comparison of the asthma subtypes and evaluate possibilities for developing personalized treatment in selected pediatric groups

An attempt to assess the presence and relationship of asthma subtypes in relation to metagenomic and metabolomic findings PERMANOVA and logistic regression

Time frame: 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

descriptive statistics

Time frame: 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.

Cox proportional hazards model

Time frame: 5 years

Evaluation of the recurrence rates of PBB and development of CSLD and BE based on identified airway pathogens

Cox proportional hazards model, descriptive statistics

Time frame: 5 years

Assessment of the prevalence of antibiotic-resistant strains among patients with PBB

descriptive statistics

Time frame: 5 years

Assessment of the time to PBB development in previously healthy children based on metagenomic and metabolomic findings

Cox proportional hazards model

Time frame: 5 years

Biomarkers and Respiratory Omics as New CHildren Opportunities - Study of Clinical Outcomes and Predictivity Evaluation

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts