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

Biomarkers and Respiratory Omics as New CHildren Opportunities - Study of Clinical Outcomes and Predictivity Evaluation - a Multi-cohort, Multi-center Study

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.

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