One ubiquitous and modifiable environmental factor associated with both significant infant morbidity, as well as asthma development, is infant respiratory syncytial virus (RSV) infection. While most children who experience RSV infection have mild symptoms, a significant minority experience more severe disease, often requiring hospitalization and sometimes intensive care. We, and others, have shown that, among children with RSV infection severe enough to require medical attention, the severity of the infection has a strong association with subsequent development and severity of asthma. In addition, we have shown a causal relationship between RSV-attributable infant illness and childhood asthma inception. Because an RSV vaccine is not currently available, RSV immunoprophylaxis is the only currently available alternative approach, licensed for use in preventing RSV-attributable morbidity in high-risk infant groups. RSV immunoprophylaxis been evaluated in children who experience excessive RSV morbidity. While there have been a number of randomized clinical trials that have enrolled selective populations investing significant resources to ensure adherence that have established """"""""efficacy"""""""" (can it work?), the """"""""effectiveness"""""""" (does it work?) data are limited and conflicting. No investigations have assessed patterns of use, adherence, and effectiveness in US Medicaid and insured """"""""real world"""""""" populations. Neither are there any investigations of the impact of reducing RSV infant morbidity on long-term outcomes such as asthma. These are critically important questions to answer in informing policy for the most costly preventive therapy in pediatrics, and in assessing effectiveness of our only currently available """"""""tool"""""""" for decreasing infant RSV morbidity. Lastly, neither are there investigations of the more long-term impact of reducing RSV infant morbidity on the development of asthma, a lifelong chronic disease known to be more common among most groups of children considered high-risk for RSV. In three specific aims utilizing two denominator-based study populations of children enrolled in Tennessee Medicaid and six Kaiser Permanente-Northern California integrated medical care practices, we will study infants born between 1995 and 2008 and followed longitudinally to: (1) Determine RSV immunoprophylaxis utilization patterns and adherence;(2) Determine the effectiveness of RSV immunoprophylaxis on RSV hospitalizations and outpatient visits as well as comparative effectiveness with birth timing;and (3) assess the impact of RSV immunoprophylaxis on asthma inception, estimate the effect size, and compare the impact of RSV immunoprophylaxis on asthma inception with the effect we have shown of timing of birth on reducing childhood asthma.
Lay Summary The objectives of this study are to determine the disparities in use, adherence and real-world effectiveness, and whether there are any important long-term protective effects on preventing diseases such as asthma, of a medication to prevent severe infant viral respiratory tract infections from a virus known as RSV. While there have been a number of clinical trials that have enrolled very select populations that have established efficacy (can it work?), the effectiveness (does it work?) data are limited and conflicting. We need to understand who gets this highly costly medication, who doesn't, does it work in the real-world, and can it prevent childhood asthma.
