We have demonstrated that respiratory syncytial virus (RSV) infection during infancy is in the causal pathway of the development of childhood wheezing and asthma. Currently, RSV immunoprophylaxis is the only available pharmacologic preventive strategy for severe RSV infection, and is licensed for use only in high-risk infants. Whether prevention of RSV infection during infancy through RSV immunoprophylaxis will reduce the risk of subsequent development of childhood wheezing and asthma is unknown.
Specific Aims : We hypothesize that healthy preterm infants with a gestational age of 33 to 36 6/7 weeks will experience a measureable reduction in RSV-attributable healthcare visits after RSV immunoprophylaxis administration, and this reduction will subsequently result in a reduced risk of recurrent wheeze and asthma. To determine whether RSV prevention reduces the risk of asthma, we will 1) demonstrate that healthy preterm infants experience a measurable reduction in RSV-attributable healthcare visits if they receive RSV immunoprophylaxis;2) determine the effect of RSV immunoprophylaxis on reducing the risk of wheezing in infancy, childhood wheezing between age 2 to 4 years, and childhood asthma by age 6 years. Research Design: We will conduct a retrospective birth cohort study of infants who were born at 33 to 36 6/7 weeks of gestation and were continuously enrolled in an established birth cohort, PRIMA (Prevention of RSV: Impact on Morbidity and Asthma).
In Aim 1, the effectiveness of RSV immunoprophylaxis on bronchiolitis healthcare visits during infancy will be analyzed accounting for the temporal relationship between RSV immunoprophylaxis administration and bronchiolitis healthcare visits.
In Aim 2, we will determine the effect of RSV immunoprophylaxis on reducing RSV morbidity during infancy and on the development of infant wheezing at 1-year, childhood wheezing between age 2 to 4 years, and childhood asthma by age 6 years. For both aims, propensity score methods will be applied to adjust for confounding by indication (selection) bias, and various sensitivity analyses will be conducted to test the accuracy and the robustness of the effect estimates. Impact: Infant RSV infection represents a ubiquitous and modifiable environmental factor associated with wheezing and asthma, the most common and significant diseases of infancy and childhood. Currently no prevention strategy has been proven effective for these diseases. Palivizumab, the only available prevention strategy for RSV-attributable morbidity, will be off patent and be more affordable soon. The results of the proposed study may demonstrate an effective preventive strategy of a lifelong disease, and thus have significant clinical and public health impact.

Public Health Relevance

As the only available prophylactic pharmacologic strategy for severe respiratory syncytial virus (RSV) infection, RSV immunoprophylaxis administration to healthy preterm infants might decrease the risk of recurrent wheeze and childhood asthma through prevention of RSV infection during infancy. Until a vaccine for RSV is available, the results of this study may impact infant morbidity, healthcare utilization, and be a first step in developing a much needed asthma primary prevention strategy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL123829-01
Application #
8757597
Study Section
Special Emphasis Panel (ZRG1-PSE-Q (56))
Program Officer
Freemer, Michelle M
Project Start
2014-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$131,360
Indirect Cost
$47,691
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212