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.
Age at the beginning of the study 0-17 years old
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)
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
Participants will be recruited from among patients hospitalized in the University Clinical Center of the Medical University of Warsaw, Department of Pediatric Pulmonology and Allergology, and in the Medical University of Lodz, Department of Pediatric Pulmonology
Cohort
Prospective
fiberoptic bronchoscopy
Procedure/SurgeryDuring procedure performing physician will evaluate respiratory tract anatomy. Samples of bronchoalveolar lavage fluid will be collected for culture, cellular composition analysis, amphiregulin level, cytokine profiling, metagenomic sequencing, metabolomic assessment, additionally mucosal biopsy will be performed using forceps and brush techniques for histopathological evaluation
blood sample collection
Procedure/Surgery5 mL sample of blood will be collected in each individual at baseline and during follow-up visits for complete blood count and Immunoglobulin E levels
Respiratory functional tests
Diagnostic testAt baseline and during each follow-up visit children will perform spirometry, Impulse Oscillometry and Fractional Exhaled Nitric Oxide
Sputum culture
Diagnostic testAt baseline and during first follow-up visit sputum will be collected from each individual for culture
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
Correlation of metagenomic and metabolomic findings on subsequent treatment and disease course between 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, MANOVA and logistic regression, Cox proportional hazards model
Comparison of the previous medical history and demographic characteristics across the study groups
MANOVA, neural networks and logistic regression
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.
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
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
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Medical University of Warsaw
Lead sponsor
Medical University of Lodz
Collaborator
Medical University of Bialystok
Collaborator
