Clinical trial NCT02047877: Airway Inflammatory Response During Illness in Children With Respiratory Failure
Official title: Investigation of Airway Inflammatory Response During an Acute Respiratory Illness in Pediatric Patients With Respiratory Failure
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Acute Respiratory Failure
Acute Respiratory Infection
Acute Respiratory Distress Syndrome
Keywords: Respiratory Secretions
Tracheal Secretions
Bronchial Secretions
NonBronchoscopic BAL
Interleukin 10
Interleukin 12p70
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2014-01-28
Enrollment: 0
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Previously healthy patients presenting to UNC with respiratory failure presumptively caused by a primary lung infection will be screened. Only those patients intubated within 48-hours of potential enrollment and between the ages of ≥37 weeks gestation and 17 years will be considered. For purposes of this study, acute respiratory illness is defined as having upper respiratory infection symptoms and/or lower respiratory tract infection. Patient should have fever (\>38 oC) OR leukocytosis / leukopenia (\>10,000 or \<2,000) AND any of the following: tachypnea, hypoxia (saturation \<97%), cough, congestion, rhinorrhea, abnormal lung exam findings, or infiltrate on chest x-ray.

Brief summary: The purpose of this study has two major goals: 1) to measure the amount of two specific hormones interleukin (IL)-10 and interleukin (IL)-12p70 in mucous and blood; and 2) compare the hormone levels in two specific areas of the lung called the trachea (upper airway) and the bronchioles (lower airway). The hormones IL-10 and IL-12p70 are cytokines, special hormones cells use to communicate with each other during inflammation or infection. Cytokines can be measured in mucous and blood. The balance of one cytokine compared to another help doctors to understand how people respond differently to infection. Unfortunately, the amount of IL-10 and IL-12p70 is not known in children, especially children with a lung infection. In addition, we do not know if the balance of these cytokines differ in various regions of the lung. We believe the balance of IL-10 and IL-12p70 is similar whether measured in the upper or lower airways.

Detailed description: This study is designed to measure the concentration and describe the distribution of cytokine IL-10 and IL-12p70 in a previously healthy pediatric population suffering direct lung injury by an infectious etiology, not yet described in the literature.

In addition, this study seeks to determine whether tracheal aspirates (TA) obtained in early acute respiratory failure can be substituted for distal airway aspirates, obtained by non-bronchoscopic broncho-alevolar lavage (nb-BAL), for the purposes of investigating markers of inflammation. We will compare the ratio of IL-10 to IL-12p70 at each time point measured in tracheal secretion, bronchial secretion, and blood to assess for sample equivalence.

Finally, this study will affirm the safety profile for repeated nb-BAL, establish a protocol for respiratory sample collection and storage for future larger scale studies, and generate feasibility data regarding consent rate, estimates of data completion, and fraction of missing data for us to determine whether a future study involving the ratio of IL-10 to IL-12p70 can be used as a predictor of acute respiratory distress syndrome (ARDS) in this population.

The data generated by this study regarding safety, comparison of nb-BAL and TA, and cytokine concentrations will be used as preliminary data informing the design of a larger multicenter study testing the hypothesis that IL-10 and IL-12p70 levels in airway secretions can predict risk for ARDS in this population. This may be approached via application to the Pediatric Acute Lung Injury and Sepsis (PALISI) clinical research network group.

Eligibility criteria: Inclusion Criteria:

* Previously healthy
* Age 37 weeks gestation through 17 years
* Presumed respiratory infection
* Intubated \<48 hours

Exclusion Criteria:

* Trauma, Drowning, Pancreatitis, or Sepsis not originating from a pulmonary infection.
* Pre-existing chronic disease including:
* congenital heart disease or acquired cardiomyopathy
* pulmonary hypertension
* restrictive lung disease
* cystic fibrosis
* asthma controlled with chronically inhaled steroids
* Tracheostomy
* Immunocompromised including chronic steroid use within last month
* Oncological condition except conditions in active remission not requiring maintenance chemotherapy.
* Intubated patient with an endotracheal tube \<3.5 mm
* Patients with persistent SpO2 \<90% despite adequate ventilator support, or patients deemed too unstable to undergo mini-BAL by the clinical care team

Primary outcomes:
measure: Mean log transformed IL-10:IL-12p70 ratio in tracheal secretion, bronchial secretion, and serum within 48-hours of mechanical ventilation
timeFrame: Within 48 hours of mechanical ventilation
Secondary outcomes:
measure: Blood oxygenation saturation and hemodynamic changes following non-bronchoscopic BAL
timeFrame: Baseline through 1-hour post procedure
measure: Mean log transformed IL-10:IL-12p70 ratio in tracheal secretion, bronchial secretion, and serum between days 3-4
timeFrame: Days 3 to 4 of mechanical ventilation
measure: Mean log transformed IL-10:IL-12p70 ratio in tracheal secretion, bronchial secretion, and serum between days 5-7
timeFrame: Days 5 to 7 of mechanical ventilation
Other outcomes:
measure: Fraction of screened patients enrolled, fraction of patients with complete sample collection, and fraction of patients with complete clinical data
timeFrame: 1-Year from Initial Enrollment
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina Hospital at Chapel Hill
name: Daniel Lercher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Benny Joyner, MD, MPH
role: STUDY_DIRECTOR
affiliation: University of North Carolina, Chapel Hill
name: Benny L Joyner, Jr., MD, MPH
role: STUDY_CHAIR
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