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| Name | Class |
|---|---|
| Medical University of Lodz | OTHER |
| Medical University of Bialystok | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Asthma | Children diagnosed with asthma at the baseline |
| |
| Protracted Bacterial Bronchitis | Children diagnosed with Protracted Bacterial Bronchitis at the baseline |
| |
| 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 |
| |
| Non inflammatory causes of chronic cough | Children diagnosed with: laryngomalacia, tracheobronchomalacia adenoid hypertrophy, gastroesophageal reflux disease, habitual cough |
| |
| Control group |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fiberoptic bronchoscopy | Procedure | During 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Index hospitalization, immediately after the procedure |
| 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 | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of the previous medical history and demographic characteristics across the study groups | MANOVA, neural networks and logistic regression | At baseline |
| Assessment of the degree of asthma control among children diagnosed with asthma according to Global Initiative for Asthma |
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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:
Obtained consent from patient/legal guardian for participation in the study
Exclusion Criteria:
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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
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tomasz Kopiec, MD | Contact | +48505300599 | tomasz.kopiec@wum.edu.pl | |
| Aleksander Adamiec, MD | Contact | +48606349502 | aleksander.adamiec@wum.edu.pl |
| Name | Affiliation | Role |
|---|---|---|
| Wojciech Feleszko, MD, PhD | Medical University of Warsaw | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35648804 | Background | Martin J, Townshend J, Brodlie M. Diagnosis and management of asthma in children. BMJ Paediatr Open. 2022 Apr;6(1):e001277. doi: 10.1136/bmjpo-2021-001277. | |
| 38413121 | Background | Thomas R, Marchant JM, Goyal V, Masters IB, Yerkovich ST, Chang AB. Clinical utility of elective paediatric flexible bronchoscopy and impact on the quality of life: protocol for a single-centre, single-blind, randomised controlled trial. BMJ Open Respir Res. 2024 Feb 26;11(1):e001704. doi: 10.1136/bmjresp-2023-001704. |
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IPD may be available upon request, by default IPD sharing is not planned.
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bronchoalveolar lavage fluid; sputum; mucosal biopsy; whole blood sample
Children without underlying diseases who undergo bronchoscopy either for suspected foreign body aspiration or as part of routine diagnostic evaluation |
|
|
| blood sample collection | Procedure | 5 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 Test | At baseline and during each follow-up visit children will perform spirometry, Impulse Oscillometry and Fractional Exhaled Nitric Oxide |
|
| Sputum culture | Diagnostic Test | At baseline and during first follow-up visit sputum will be collected from each individual for culture |
|
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. |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 5 years |
| Assessment of the correlation between ICS used without an asthma diagnosis and airway dysbiosis | PERMANOVA and logistic regression | 2 years |
| Evaluation of asthma treatment response, exacerbation rates, and need for bronchodilators according to airway metabolome profiles | PERMANOVA and logistic regression | 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 | 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 | 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 | 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 | 5 years |
| Assessment of the prevalence of antibiotic-resistant strains among patients with PBB | descriptive statistics | 5 years |
| Assessment of the time to PBB development in previously healthy children based on metagenomic and metabolomic findings | Cox proportional hazards model | 5 years |
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| ID | Term |
|---|---|
| D000096822 | Chronic Cough |
| D001249 | Asthma |
| ID | Term |
|---|---|
| D003371 | Cough |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001982 | Bronchial Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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