Chantel Sloan

Risk of childhood asthma following infant bronchiolitis during the respiratory syncytial virus season

To the Editor: The etiology of asthma remains unclear but is thought to include nonmodifiable risk factors such as family history and genetic predisposition, as well as potentially modifiable risk factors including viral bronchiolitis in infancy. During the winter months, the predominant virus detected in infants with viral bronchiolitis is respiratory syncytial virus (RSV). By age 1 year, approximately 70% of the children have been infected with RSV, and this increases to almost 100% by age 2 years. Infant RSV bronchiolitis is associated with recurrent wheeze or asthma throughout childhood and even into early adulthood, with a dose-response relationship identified between the severity of the bronchiolitis and the risk of developing asthma, and evidence for a causal relationship. The aim of our study was to determine what proportion of childhood asthma is associated with infant bronchiolitis during the RSV season. We analyzed cohort data of children born from 1996 to 2003 and cared for at Northern California Kaiser Permanente (KPNC), an integrated health care delivery system, and children born from 1995 to 2003 and enrolled in Tennessee Medicaid (TennCare). KPNC and TennCare provide health insurance for approximately one-third of Northern California residents and approximately one-half of infants born in Tennessee, respectively. Eligible infants had a minimum gestation age of 32 weeks, had no chronic lung disease, and were continuously enrolled in either TennCare or KPNC during the first year of life. The main predictor variable was infant bronchiolitis during the RSV season defined by International Classification of Diseases, Ninth Revision codes for bronchiolitis and limited to the RSV season, October through March, during the first year of life. The main outcome variable was early childhood asthma determined using an algorithm of International Classification of Diseases, Ninth Revision codes for asthma and asthma-specific medication utilization between ages 4.5 and 6 years. The Vanderbilt University Institutional Review Board and the KPNC Institutional Board for the Protection of Human Subjects approved the study. The Bureau of TennCare approved the use of Tennessee Medicaid data. To ascertain the proportion of childhood asthma in the TennCare or KPNC population that is associated with bronchiolitis exposure during the RSV season, we calculated both the attributable risk of infants with a bronchiolitis event during infancy and the population-attributable risk. We estimated the attributable fraction of bronchiolitis from adjusted risk ratios that were calculated from multivariable Poisson regression models with a robust error variance for the early childhood asthma outcome. Adjustment covariates included gender, race, gestational age, birth weight, siblings, maternal age, and maternal smoking. Statistical analyses were performed with R version 2.12.1 software. A total of 264,010 infant births (KPNC 81,550, TennCare 182,460) were included in this study and followed until age 6 years. Table I highlights key characteristics of the 2 cohorts. Compared with the TennCare population, the KPNC population had more Hispanic and Asian participants, less African American participants, higher rates of maternal education beyond high school, and lower rates of maternal smoking. Overall, 15% of the infants had bronchiolitis during the RSV season. The proportion of children diagnosed with asthma among the KPNC and TennCare cohorts was 8% and 12%, respectively, for those without a history of infant bronchiolitis during the RSV season and 16% and 23%, respectively, for those with a history of infant bronchiolitis during the RSV season. The populationattributable risk for asthma contributed by infant bronchiolitis during the RSV season was 10% for the KPNC cohort, and among the subset of children with infant bronchiolitis during the RSV season, the attributable risk was 49% (95% CI, 47% to 52%); in TennCare, it was 13% and 47% (95% CI, 45% to 48%), respectively (see Fig 1). The unadjusted risk ratio of childhood asthma following infant bronchiolitis during the RSV season for KPNC was 1.97 (95% CI, 1.87-2.09), and the multivariate adjusted risk ratio of childhood asthma following infant bronchiolitis during the RSV season was 1.94 (95% CI, 1.84-2.05); for TennCare, it was 1.87 (95% CI, 1.82-1.92) and 1.81 (95% CI, 1.77-1.86), respectively. In our analysis restricting to term infants (gestational age >_37 weeks), results remain unchanged (data not shown). In both the KPNC and TennCare cohorts, the proportion of children who developed asthma was almost 2 times higher in childrenwith a history of infant bronchiolitis during theRSVseason than in the childrenwhodidnot have a history of infant bronchiolitis during the RSV season. The almost identical attributable risk and population-attributable risk findings are notable given the significant differences between the 2 populations. Adjustment of risk ratios for potential confounders did not change the results. Despite the strengths of our large population-based study, several limitations deserve mention. This study relied on existing electronic data; however, the use of electronic data has been previously validated as both sensitive and specific. Second, the study was unable to detect infants with asymptomatic or mild bronchiolitis during the RSV season as well as those who did not seek treatment. In addition, we were unable to confirm the diagnosis of RSV as the etiology of bronchiolitis events although prior studies support that the majority of infant bronchiolitis events during the RSV season are attributable to RSV. In a retrospective study by Stemple et al in which bronchiolitis was defined by International Classification of Diseases, Ninth Revision codes for bronchiolitis, RSV was detected in the nasal wash samples of 77% of the children younger than age 2 years collected between October and April. By limiting our study to bronchiolitis episodes during the winter months, RSV is likely to be the associated viral pathogen. Last, while human rhinovirus infection has also been implicated in asthma inception, infant rhinovirus bronchiolitis is far less common than infant RSV bronchiolitis, and occurs in older infants, those born to parents with asthma, or those who have already been allergically sensitized, suggesting that rather than being causal, rhinovirus bronchiolitis is a clinical biomarker of future asthma risk. In summary, in 2 representative US populations with significantly varying baseline characteristics, there were consistent findings that nearly 50% of the asthma cases in children with a history of infant bronchiolitis during the RSV season were associated with bronchiolitis. On a population level, 13% of the

Impact of Pollution, Climate, and Sociodemographic Factors on Spatiotemporal Dynamics of Seasonal Respiratory Viruses

Seasonal viruses present a major cause of morbidity and mortality in temperate climates. Through major pandemics and smaller annual epidemics, viruses such as influenza, respiratory syncytial virus (RSV) and human rhinovirus (HRV) result in lost school and work days for most that are infected and more serious complications for the immunocompromised. The reasons for these viruses showing strict seasonality include but are not limited to the influence of cold weather and humidity on virus particles, human physiology, and human behavior. The relative importance of each is dependent on what geographic scale is being explored as well as the individual region and time period. Theoretical mathematics has also revealed that climatic changes are likely not the only reasons for strong seasonal cycles, but these are also based in periodic resonance with the natural cycles of immunity and antigenic variance, as well as nationwide synchrony through transportation networks. Investigations of seasonality will aid in understanding disease transmission, and thereby effective prevention strategies. The authors present a review of the literature on seasonal viruses, their annual diffusion through populations, and factors that reduce or enhance their seasonal spread. They also offer suggestions for targeted interventions to reduce the disease burden from seasonal viruses. Clin Trans Sci 2011; Volume 4: 48–54

Reactive versus proactive patterns of inhaled corticosteroid use.

For patients with persistent asthma, inhaled corticosteroids (ICS) are a mainstay of controller therapy. These medications are usually prescribed to be taken daily and have been shown to be associated with decreased asthma morbidity. Adherence to daily treatment is very low in many populations in the United States. The purpose of this study is to evaluate the seasonal use of ICS prescription filling as reactive behavior primarily after an asthma exacerbation in a pediatric population. The study population is a subgroup of the Tennessee Asthma and Bronchiolitis Study. The children in this study were enrolled in Tennessee Medicaid (TennCare). The subjects had asthma and were 6 to 9 years of age during the years 2005 to 2010. Prescription filling was determined using claims data, and asthma exacerbations were defined by use of systemic rescue corticosteroids (RCS). In this cohort of 13,114 children with asthma, ICS and RCS filling were highly seasonal and trended with fall and winter peaks in asthma exacerbations. Prescription refilling was very low, with an average of three ICS fills per child who filled at least one during the study period. Among these children, 54.1% (7,096) had an asthma exacerbation during the study period. Among ICS users, 68.5% (3,441/5,020) had a disease exacerbation. ICS filling occurred overwhelmingly on the same day as RCS fills. The seasonal filling patterns of ICS coincide with asthma exacerbations. ICS adherence is low and inconsistent in this population of children with asthma. Increased adherence to ICS, particularly before the seasonal virus epidemics, could greatly reduce asthma morbidity.

Respiratory syncytial virus immunoprophylaxis in high-risk infants and development of childhood asthma.

Background: Respiratory syncytial virus (RSV) lower respiratory tract infection is implicated in asthma development. RSV immunoprophylaxis during infancy is efficacious in preventing RSV‐related hospitalizations and has been associated with decreased wheezing in the first years of life. Objective: We investigated whether greater adherence to immunoprophylaxis in infants at high risk for severe RSV would be associated with decreased childhood asthma. Methods: We conducted a retrospective cohort investigation including children born from 1996‐2003 who were enrolled in Kaiser Permanente Northern California or Tennessee Medicaid and eligible to receive RSV immunoprophylaxis. Asthma was defined at 4.5 to 6 years of age by using asthma‐specific health care visits and medication fills. We classified children into immunoprophylaxis eligibility groups and calculated adherence (percentage receipt of recommended doses). We used a set of statistical strategies (multivariable logistic regression and propensity score [PS]–adjusted and PS‐matched analyses) to overcome confounding by medical complexity because infants with higher adherence (≥70%) have higher prevalence of chronic lung disease, lower birth weight, and longer nursery stays. Results: By using multivariable logistic regression and PS‐adjusted models in the combined group, higher adherence to RSV immunoprophylaxis was not associated with decreased asthma. However, in PS‐matched analysis, treated children with 70% or greater adherence had decreased odds of asthma compared with those with 20% or less adherence (odds ratio, 0.62; 95% CI, 0.50‐0.78). Conclusions: This investigation of RSV immunoprophylaxis in high‐risk children primarily found nonsignificant associations on prevention of asthma in specific preterm groups. Our findings highlight the need for larger studies and prospective cohorts and provide estimates of potential preventive effect sizes in high‐risk children.

Adherence to Immunoprophylaxis Regimens for Respiratory Syncytial Virus Infection in Insured and Medicaid Populations

BACKGROUND Immunoprophylaxis is the only pharmaceutical intervention for mitigating respiratory syncytial virus (RSV) infection. Patient level data on adherence to American Academy of Pediatrics (AAP) immunoprophylaxis recommendations are limited. This study characterizes adherence to AAP guidelines in privately insured and Medicaid populations. METHODS We performed a retrospective birth cohort study of 211 174 privately insured children in Northern California; and 458 837 publicly insured children in Tennessee born between January 1, 1996 and December 31, 2008. Adherence to the AAP guideline was defined for eligible infants as the number of doses of RSV immunoprophylaxis administered over the number recommended for 4 mutually exclusive eligibility groups: chronic lung disease, prematurity <29 weeks, prematurity <32 weeks, and other eligibility. RESULTS We identified 3456 California (Kaiser Permanente Northern California [KPNC]) and 12 251 Tennessee (Tennessee Medicaid [TennCare]) infants meeting AAP eligibility criteria. Immunoprophylaxis administration increased over the study period, from 15% for all eligible groups in 1998 to 54% in 2007. Adherence was highest among babies with chronic lung disease (KPNC 67% and TennCare 55%). Nonadherence (0% adherence) was greatest among infants of African American mothers (adjusted odds ratio [AOR] = 1.32; 95% confidence interval [CI] = .98-1.78); those with mothers with less than a high school education (AOR = 1.58; CI = 1.09-2.30) in KPNC; and in infants of Hispanic mothers in TennCare (AOR = 1.65; CI = 1.24-2.20). In KPNC, 0.11% of ineligible term infants and 5% of ineligible premature infants received immunoprophylaxis; the corresponding proportions in TennCare were 1% and 11%. CONCLUSIONS Overall adherence with AAP guidelines has increased over time. Considerable overuse and underuse of immunoprophylaxis are evident with identifiable risk groups to target for improvement.

Applications of GPS-tracked personal and fixed-location PM2.5 continuous exposure monitoring

ABSTRACT Continued development of personal air pollution monitors is rapidly improving government and research capabilities for data collection. In this study, we tested the feasibility of using GPS-enabled personal exposure monitors to collect personal exposure readings and short-term daily PM2.5 measures at 15 fixed locations throughout a community. The goals were to determine the accuracy of fixed-location monitoring for approximating individual exposures compared to a centralized outdoor air pollution monitor, and to test the utility of two different personal monitors, the RTI MicroPEM V3.2 and TSI SidePak AM510. For personal samples, 24-hr mean PM2.5 concentrations were 6.93 μg/m3 (stderr = 0.15) and 8.47 μg/m3 (stderr = 0.10) for the MicroPEM and SidePak, respectively. Based on time–activity patterns from participant journals, exposures were highest while participants were outdoors (MicroPEM = 7.61 µg/m3, stderr = 1.08, SidePak = 11.85 µg/m3, stderr = 0.83) or in restaurants (MicroPEM = 7.48 µg/m3, stderr = 0.39, SidePak = 24.93 µg/m3, stderr = 0.82), and lowest when participants were exercising indoors (MicroPEM = 4.78 µg/m3, stderr = 0.23, SidePak = 5.63 µg/m3, stderr = 0.08). Mean PM2.5 at the 15 fixed locations, as measured by the SidePak, ranged from 4.71 µg/m3 (stderr = 0.23) to 12.38 µg/m3 (stderr = 0.45). By comparison, mean 24-h PM2.5 measured at the centralized outdoor monitor ranged from 2.7 to 6.7 µg/m3 during the study period. The range of average PM2.5 exposure levels estimated for each participant using the interpolated fixed-location data was 2.83 to 19.26 µg/m3 (mean = 8.3, stderr = 1.4). These estimated levels were compared with average exposure from personal samples. The fixed-location monitoring strategy was useful in identifying high air pollution microclimates throughout the county. For 7 of 10 subjects, the fixed-location monitoring strategy more closely approximated individuals’ 24-hr breathing zone exposures than did the centralized outdoor monitor. Highlights are: Individual PM2.5 exposure levels vary extensively by activity, location and time of day; fixed-location sampling more closely approximated individual exposures than a centralized outdoor monitor; and small, personal exposure monitors provide added utility for individuals, researchers, and public health professionals seeking to more accurately identify air pollution microclimates. Implications: Personal air pollution monitoring technology is advancing rapidly. Currently, personal monitors are primarily used in research settings, but could they also support government networks of centralized outdoor monitors? In this study, we found differences in performance and practicality for two personal monitors in different monitoring scenarios. We also found that personal monitors used to collect outdoor area samples were effective at finding pollution microclimates, and more closely approximated actual individual exposure than a central monitor. Though more research is needed, there is strong potential that personal exposure monitors can improve existing monitoring networks.

Interference between respiratory syncytial virus and human rhinovirus infection in infancy

Background Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines. Methods To study viral interference, we evaluated cases of RSV and HRV codetection by polymerase chain reaction in 2 prospective birth cohort studies (the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure [INSPIRE] study and the Tennessee Childrens Respiratory Initiative [TCRI]) and a double-blinded, randomized, controlled trial (MAKI), using adjusted multivariable regression analyses. Results Among 3263 respiratory tract samples, 24.5% (798) and 37.3% (1216) were RSV and HRV positive, respectively. The odds of HRV infection were significantly lower in RSV-infected infants in all cohorts, with adjusted odds ratios of 0.30 (95% confidence interval [CI], .22-.40 in the INSPIRE study, 0.18 (95% CI, .11-.28) in the TCRI (adjusted for disease severity), and 0.34 (95% CI, .16-.72) in the MAKI trial. HRV infection was significantly more common among infants administered RSV immunoprophylaxis, compared with infants who did not receive immunoprophylaxis (OR, 1.65; 95% CI, 1.65-2.39). Conclusions A negative association of RSV on HRV codetection was consistently observed across populations, seasons, disease severity, and geographical regions. Suppressing RSV infection by RSV immunoprophylaxis might increase the risk of having HRV infection.

Socioeconomic Disparities and Influenza Hospitalizations, Tennessee, USA

High rates of poverty, low education, and female single-parent households are associated with these hospitalizations.

Pollen Count and Presentation of Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema

BACKGROUND The incidence of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema is increased in patients with seasonal allergies. OBJECTIVE We tested the hypothesis that patients with ACE inhibitor-associated angioedema present during months when pollen counts are increased. METHODS Cohort analysis examined the month of presentation of ACE inhibitor-associated angioedema and pollen counts in the ambulatory and hospital setting. Patients with ACE inhibitor-associated angioedema were ascertained through (1) an observational study of patients presenting to Vanderbilt University Medical Center, (2) patients presenting to the Marshfield Clinic and participating in the Marshfield Clinic Personalized Medicine Research Project, and (3) patients enrolled in The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Measurements include date of presentation of ACE inhibitor-associated angioedema, population exposure to ACE inhibitor by date, and local pollen counts by date. RESULTS At Vanderbilt, the rate of angioedema was significantly associated with tree pollen months (P = .01 from χ(2) test). When separate analyses were conducted in patients with a history of seasonal allergies and patients without, the rate of ACE inhibitor-associated angioedema was increased during tree pollen months only in patients with a history of seasonal allergies (P = .002). In Marshfield, the rate of angioedema was significantly associated with ragweed pollen months (P = .025). In ONTARGET, a positive trend was observed between the ACE inhibitor-associated angioedema rate and grass season, although it was not statistically significant (P = .057). CONCLUSIONS Patients with ACE inhibitor-associated angioedema are more likely to present with this adverse drug event during months when pollen counts are increased.

Identifying and Reducing Disparities in Mental Health Outcomes Among American Indians and Alaskan Natives Using Public Health, Mental Healthcare and Legal Perspectives

The purpose of this paper was to investigate disparities in mental healthcare delivery in American Indian/Alaska Native populations from three perspectives: public health, legal policy and mental healthcare and provide evidence-based recommendations toward reducing those disparities. Data on mental health funding to tribes were obtained from the Substance Abuse and Mental Health Services Administration. As a result of analysis of these data, vital statistics and current literature, we propose three recommendations to reduce mental health disparities. First, where possible, increase mental health funding opportunities for federally-recognized tribes. Second, model funding practices on principles of tribal self-determination. Finally, support diverse interventions that are culturally-based and culturally-appropriate.