Characterization of Bronchodilator Response in Children With Bronchiolitis Using Phenotypic and Genotypic Features

May 6, 2026 updated by: Andrea Rivera-Sepulveda, Nemours Children's Clinic
Bronchiolitis is the leading cause of pediatric morbidity and healthcare costs. Despite the commonplace use of bronchodilator treatments, like albuterol, in conditions like asthma, their efficacy in bronchiolitis remains controversial due to the heterogeneity in patient response. Although studies indicate that bronchodilators do not enhance outcomes in bronchiolitis, meta-analyses can obscure the heterogeneity of treatment effects. While bronchodilator response genetics have not been explored in bronchiolitis, treatment effectiveness variations often depend on genomic factors. Genome-wide association studies (GWAS) have linked genetic variants with bronchodilator response and outcomes in childhood asthma, suggesting a bronchodilator-responsive genotype. This proposal aims to extend this paradigm to bronchiolitis, addressing the gap in knowledge where GWAS and clinical characteristics intersect. The proposed study's objective is to characterize phenotypic and genotypic variations of children with bronchiolitis and their association with bronchodilator response. We hypothesize that children with bronchiolitis who exhibit clinical and historical characteristics associated with atopy and specific physical findings have genetic variants linked to bronchodilator response. To achieve this, we propose to (Aim 1) define airway responsiveness to bronchodilator treatment in children with bronchiolitis using the change in respiratory score, (Aim 2a) identify the associations between candidate genetic variants and bronchodilator response among children with bronchiolitis, and (Aim 2b) determine the associations between candidate genetic variants and clinical patient data to identify bronchodilator-responsive children with bronchiolitis. A prospective, double-blind, randomized, placebo-controlled trial of a single albuterol dose in children aged 3 to 24 months presenting with bronchiolitis to the emergency department will be conducted to achieve these aims. Patient information and respiratory assessment outcomes will be collected before and after intervention. Blood, urine, DNA buccal swabs, and nasopharyngeal swabs will also be collected. Completion of these aims will result in a novel clinical prediction model for bronchodilator response determination in bronchiolitis, integrating clinical, physical, and genetic data. Furthermore, this research supports the candidates' career development goals of advancing training in clinical trial research design and execution and becoming an expert in clinical and translational methods to enhance pediatric emergency department health and outcomes. Ultimately, this work will inform an R01 application to validate an evidence-based prediction rule for identifying bronchodilator-responsive children with bronchiolitis through a multi-center emergency medicine research network, optimizing therapeutic approaches, and reducing resource use in those with a low likelihood of bronchodilator response.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32827
        • Recruiting
        • Nemours Children's Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Children between 3 to 24 months of age
  • Clinical diagnosis of bronchiolitis by the treating provider(s), defined by the American Academy of Pediatrics as a clinical syndrome involving lower respiratory tract symptoms
  • Children who either have no history of prematurity or have a history of prematurity but without associated co-morbidities
  • Emergency department (ED) visit to seek care at Nemours Children's Health-Florida (NCH-FL)

Exclusion Criteria:

  • Patients previously enrolled in the PI's K12 study
  • Documented history of asthma or reactive airway disease
  • Co-morbidities affecting airway response (e.g., chronic lung disease, bronchopulmonary dysplasia, bronchiectasis, congenital heart disease, immunodeficiency, neurologic condition)
  • Diagnosis of pneumonia by chest radiography
  • Inhaled, nebulized, or oral corticosteroid use within 72 hours of ED evaluation
  • Inhaled, nebulized, or oral bronchodilator administration within 4 hours of ED arrival

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bronchodilator arm
Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (albuterol sulfate 2.5mg/ 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.
Drug: Albuterol Sulfate, 2.5 Mg/3 mL (0.083%) Inhalation Solution
Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (albuterol sulfate 2.5mg/ 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.
Placebo Comparator: Normal saline arm
Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (sodium chloride 0.9%/ 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.
Drug: Sodium Chloride 0.9% Inhl 3Ml
Children with bronchiolitis will be randomized to an intervention arm to be administered as a nebulization (sodium chloride 0.9% 3mL inhalation solution). The intervention drug will be placed in a sealed manila envelope, randomized in advance by a Nemours Investigational Drug Pharmacist, and stored in the ED pyxis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimum Clinically Important Difference (Aim 1)
Time Frame: Immediately after the intervention

Identify the minimum clinically important difference (MCID) in the modified Tal score (MTS) in children with bronchiolitis from parents/ caregivers and treating providers' perceived improvement in respiratory response. The minimum clinically important difference (MCID) is a 15-point scale, ranging from -7 (very much worse) to +7 (very much improved), as assessed by responses from the caregiver(s) and the treating provider(s). A response of +1 to +2 will be interpreted as a "small" perceived improvement in respiratory function.

The modified Tal score (MTS) includes respiratory parameters documented as part of the ED standard of care. The MTS score ranges from 0 to 12 points, with higher scores indicating greater respiratory distress.
Immediately after the intervention
Candidate genetic variants (Aim 2)
Time Frame: through study completion, an average of 1 year
Identify candidate single nucleotide polymorphisms (SNPs), rank-ordered by the strength of their association with the modified Tal score (delta) respiratory score based on an odds ratio (dichotomous response) or a beta coefficient (continuous response) and filtered by adjusted p-value.
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nemours Children's Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 8, 2022

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

April 11, 2025

First Submitted That Met QC Criteria

April 18, 2025

First Posted (Actual)

April 27, 2025

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1866573

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Clinical data that will be preserved and shared are demographical data, history of prematurity, immunizations, history of corticosteroid use, past medical history, family history, environmental exposure, pulmonary history, randomized drug administered, and physical exam data, among other data pertinent to the study. Clinical data from data collection forms will be preserved and shared. Genomic data that will be preserved and shared will include variant calls from genotyping microarrays with imputation. Clinical data sets will be submitted to the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) in .CSV format. Genomic data sets will be submitted to the Database of Genotypes and Phenotypes (dbGaP, NCBI, NIH) in CRAM, and VCF format.

IPD Sharing Time Frame

The repository will make the data accessible within 2 years of the last patient's enrollment or no later than the date of publication, whichever is sooner.

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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