Possible Relation of Toll-Like Receptors and Nitric Oxide to Chronic Lung Disease
| Status: | Completed |
|---|---|
| Conditions: | Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | Any - 1 |
| Updated: | 7/30/2016 |
| Start Date: | January 2002 |
| End Date: | May 2006 |
TLR's, Nitric Oxide and Chronic Lung Disease: Any Connections?
The first objective of this study is to determine if increased expression of one or more
members of the toll-like receptor (TLR) family of receptors that are found on inflammatory
cells (present in the airway) precede development of chronic lung disease (CLD) of
prematurity. The study will also determine if there is a significant correlation between
TLRs and the severity of CLD. The second objective of this study is to determine the impact
of c-administration of inhaled nitric oxide (INO) on TLR expression in infants at risk of
developing CLD or with early CLD.
members of the toll-like receptor (TLR) family of receptors that are found on inflammatory
cells (present in the airway) precede development of chronic lung disease (CLD) of
prematurity. The study will also determine if there is a significant correlation between
TLRs and the severity of CLD. The second objective of this study is to determine the impact
of c-administration of inhaled nitric oxide (INO) on TLR expression in infants at risk of
developing CLD or with early CLD.
BACKGROUND:
This study will examine the role of two members in the family of transmembrane receptors,
TLRs, found on leukocytes and other cells that are upregulated in response to endotoxin and
other stimuli. These substances transfer the signals that propagate inflammation and
production of inflammatory cytokines. CLD of prematurity is characterized by early (first
week of life) evidence of lung airway inflammation. It is unknown if TLR family members
propagate this pathway.
DESIGN NARRATIVE:
This study will involve saving weekly tracheal aspirate fluid samples obtained with routine
airway toilet in infants less than or equal to 1250 gm birth weight, who are admitted to a
Neonatal Intensive Care unit requiring assisted ventilation via an endotracheal tube. The
waste sample will be collected with the cellular contents separated by centrifugation and
placed on Trizol reagent after obtaining a cell count. Later extraction and batch analysis
of TLR, mRNA, and proteins as well as mRNA and protein for housekeeping genes will be
performed. Immunohistochemistry will also be used to semi-quantitate the samples. Samples
will be obtained in the first one to two days, and again at the end of the first week of
life. In infants who were also participating in the related "Low Dose INO in CLD of
Prematurity" study, in which tracheal aspirate samples were collected, when the code is
broken to determine who received nitric oxide versus placebo, the second aim of the study
will be carried out: to determine the impact, if any, of INO.
This study will examine the role of two members in the family of transmembrane receptors,
TLRs, found on leukocytes and other cells that are upregulated in response to endotoxin and
other stimuli. These substances transfer the signals that propagate inflammation and
production of inflammatory cytokines. CLD of prematurity is characterized by early (first
week of life) evidence of lung airway inflammation. It is unknown if TLR family members
propagate this pathway.
DESIGN NARRATIVE:
This study will involve saving weekly tracheal aspirate fluid samples obtained with routine
airway toilet in infants less than or equal to 1250 gm birth weight, who are admitted to a
Neonatal Intensive Care unit requiring assisted ventilation via an endotracheal tube. The
waste sample will be collected with the cellular contents separated by centrifugation and
placed on Trizol reagent after obtaining a cell count. Later extraction and batch analysis
of TLR, mRNA, and proteins as well as mRNA and protein for housekeeping genes will be
performed. Immunohistochemistry will also be used to semi-quantitate the samples. Samples
will be obtained in the first one to two days, and again at the end of the first week of
life. In infants who were also participating in the related "Low Dose INO in CLD of
Prematurity" study, in which tracheal aspirate samples were collected, when the code is
broken to determine who received nitric oxide versus placebo, the second aim of the study
will be carried out: to determine the impact, if any, of INO.
Inclusion Criteria:
- Birth weight less than 1250 gm
- Requiring assisted ventilation
Exclusion Criteria:
- Moribund condition
- Major pulmonary or cardiovascular associated anomaly
We found this trial at
2
sites
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