Kimberly B. Woodward

Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years.

Background: Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness (URI) in infants are limited. Methods: This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute URI or bronchiolitis during September to May 2004 to 2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time reverse-transcriptase polymerase chain reaction. Results: Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup and 27% URI. Among infants with bronchiolitis, 76% had respiratory syncytial virus (RSV), 18% human rhinovirus (HRV), 10% influenza, 2% coronavirus, 3% human metapneumovirus and 1% parainfluenza virus. Among infants with croup, 39% had HRV, 28% parainfluenza virus, 28% RSV, 11% influenza, 6% coronavirus and none human metapneumovirus. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% parainfluenza virus and 4% human metapneumovirus. Individual viruses exhibited distinct seasonal, demographic and clinical expression. Conclusions: The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.

The Tennessee Children's Respiratory Initiative: Objectives, design and recruitment results of a prospective cohort study investigating infant viral respiratory illness and the development of asthma and allergic diseases.

Background and objective:  The ‘attack rate’ of asthma following viral lower respiratory tract infections (LRTI) is about 3–4 fold higher than that of the general population; however, the majority of children who develop viral LRTI during infancy do not develop asthma, and asthma incidence has been observed to continuously decrease with age. Thus, we do not understand how viral LRTI either predispose or serve as a marker of children to develop asthma. The Tennessee Childrens Respiratory Initiative has been established as a longitudinal prospective investigation of infants and their biological mothers. The primary goals are to investigate both the acute and the long‐term health consequences of varying severity and aetiology of clinically significant viral respiratory tract infections on early childhood outcomes.

Mechanisms of allergy and clinical immunologyEstrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma

BACKGROUND Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA. OBJECTIVE We sought to Determine the mechanism by which 17β-estradiol (E2) and progesterone (P4) increase IL-17A production. METHODS IL-17A production was determined by using flow cytometry in TH17 cells from women (n = 14) and men (n = 15) with severe asthma. Cytokine levels were measured by using ELISA, and IL-23R and let-7f expression was measured by using quantitative PCR in TH17-differentiated cells from healthy women (n = 13) and men (n = 14). In sham-operated or ovariectomized female mice, 17β-E2, P4, 17β-E2+P4, or vehicle pellets were administered for 3 weeks before ex vivo TH17 cell differentiation. Airway neutrophil infiltration and CXCL1 (KC) expression were also determined in ovalbumin (OVA)-challenged wild-type female recipient mice with an adoptive transfer of OVA-specific TH17 cells from female and male mice. RESULTS In patients with severe asthma and healthy control subjects, IL-17A production was increased in TH17 cells from women compared with men. IL-23R expression was increased and let-7f expression was decreased in TH17-differentiated cells from women compared with men. In ovariectomized mice IL-17A and IL-23R expression was increased and Let-7f expression was decreased in TH17 cells from mice administered 17β-E2+P4 compared with those administered vehicle. Furthermore, transfer of female OVA-specific TH17 cells increased acute neutrophil infiltration in the lungs of OVA-challenged recipient mice compared with transfer of male OVA-specific TH17 cells. CONCLUSIONS 17β-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men.

Increased healthcare resource utilization for acute respiratory illness among Latino infants.

OBJECTIVE To examine healthcare resource utilization for acute respiratory illness in Latino infants compared with other racial/ethnic groups. STUDY DESIGN We studied 674 term-born, previously healthy infants brought in for an unscheduled healthcare visit for an acute respiratory illness. The predictor variable was infant race/ethnicity, and the primary outcome was healthcare resource utilization, adjusted for age and disease severity. RESULTS The cohort was 14% Latino, 52% white, 22% African American, and 12% other race/ethnicity. More than one-third (37%) of the mothers of Latino infants were Spanish-speaking. The bronchiolitis severity score was higher (indicating more severe disease) in white infants (median, 6.0; IQR, 3.0-9.0 on a scale of 0-12) compared with Latino (median, 3.0; IQR, 1.0-6.0) and African American (median, 3.5; IQR, 1.0-6.0) infants (P < .001 for the comparison of all groups). Disease severity was similar in Latino and African American infants (P = .96). Latino infants were the most likely to receive antibiotics (58%, compared with 47% of whites and 34% of African Americans; P = .005) and to have body fluid cultures drawn. Latino infants also were more likely than African American infants to undergo chest radiography and respiratory virus rapid antigen testing (P ≤ .01). Latino infants from Spanish-speaking families had a higher rate of respiratory syncytial virus testing compared with those from English-speaking families (76% vs 51%; P = .016). CONCLUSION Providers caring for Latino infants with acute respiratory illness ordered more antibiotics and diagnostic testing for this group, particularly compared with African Americans, even though the 2 groups had similar disease severity and socioeconomic disparities. Language barrier may be a possible explanation for these differences.

Association between breast-feeding and severity of acute viral respiratory tract infection.

In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever vs. never) was associated with decreased relative odds of a lower versus upper respiratory tract infection (adjusted odds ratio: 0.64; 95% confidence interval: 0.42–0.99). There was not a significant association between breast-feeding and bronchiolitis severity score or length of hospital stay.

Prevalence and characteristics of medication sharing behavior in a pediatric Medicaid population with asthma

Few studies have examined sharing or borrowing of non-addicting prescription medications (references 1–6; reviewed in reference 7) and no study has looked at this behavior in patients with asthma. We hypothesized that medication sharing/borrowing would be common in families with children with asthma and be associated with worsened asthma control, and undertook this investigation to describe features surrounding this behavior and examine its effect on adverse asthma outcomes. We studied 112 children enrolled from primary care or pediatric pulmonology clinic at the Vanderbilt University site of a larger study regarding barriers to asthma medication adherence. Eligible children were aged 4–11 years, insured under Tennessee Medicaid (TennCare), and carried a chart reviewed physician’s diagnosis of asthma, with a controller medication prescribed in the previous year. The child and caregiver completed an interview including an Asthma Control Test (ACT) score (for ages 4–11 years),8 and questions about asthma adverse events, asthma controller adherence, and medication sharing/borrowing behaviors. Medication sharing (“Sometimes patients share medicine that a doctor prescribed with someone else. In the last year, have you ever given your child’s prescription medicine for asthma or allergy to someone else?”) and borrowing (“In the last year, has your child ever taken a dose of a medicine for asthma or allergy that was prescribed for someone else?”) were determined by parental report, using questions modeled on those utilized in previous studies.3,6,7 We examined, by sharing/borrowing status, subjects’ ACT scores, reported emergency department (ED) or asthma acute care visits in the past 6 months, rescue inhaler usage, and reported asthma controller medication adherence in the past week. Parents provided written informed consent, and the protocol was approved by the Institutional Review Board of Vanderbilt University. A total of 112 children were studied. The cohort was 52% African-American, 29% white, 3% Asian, and 14% other or >1 race; 20% were of Latino ethnicity. The cohort had a slight male predominance (64%), and mean age was 7.8 years (range 4–11 years). Sixty percent of families had yearly income <

Host and viral factors associated with severity of human rhinovirus–associated infant respiratory tract illness

20,000, and 92% had yearly income <

Influence of maternal asthma on the cause and severity of infant acute respiratory tract infections

40,000. Parents of 18 children (16%) reported that their child either shared or borrowed prescription asthma or allergy medication in the preceding year; parents of 13 children (12%) reported borrowing someone else’s medication, and parents of 11 children (10%) reported sharing their child’s medication with someone else. (Table 1) The most common medications to share/borrow were short acting beta agonists (SABA), leukotriene antagonists, inhaled corticosteroids (ICS), and inhaled corticosteroid-long acting beta agonists (ICS-LABA); no subjects reported sharing/borrowing antibiotics or oral corticosteroids. Sharing/borrowing among siblings or with other family members accounted for nearly all reported instances. Reasons cited for sharing/borrowing medication are listed in Table 1. Table 1 Features of asthma and allergy medication sharing/borrowing in the preceding year among 18 asthmatic children whose parent reported this behavior. Among those who shared/borrowed asthma/allergy medication, median ACT (interquartile range) was 17 (13.2–21.5) compared with 20 (17–22) among those who did not share/borrow, p=0.14 (Table 2). Among those who shared/borrowed, 67% had an ACT ≤19 (suggesting uncontrolled asthma8) compared with 43% of those who did not share/borrow, p=0.066. Rate of reporting one or more ED or acute care visits for asthma in the previous 6 months, and reported usage of rescue inhalers in the previous 14 days, did not differ by medication sharing/borrowing status. Finally, there was no difference by sharing/borrowing status in reported adherence to asthma controller medications over the week preceding the survey (median reported usage of ICS, ICS-LABA, and leukotriene modifier medications among those who did and those who did not share/borrow was 7 out of 7 days). Table 2 Measures of asthma control by asthma/allergy medication sharing/borrowing status. Asthma is a major cause of childhood morbidity, and disproportionately affects disadvantaged persons, including minorities and those of low socioeconomic status.9 A factor that has not been studied previously that might influence asthma outcomes is sharing or borrowing of prescription asthma and allergy medications. Among a population of Medicaid-enrolled children with asthma, 16% of families reported engaging in this behavior in the year preceding the survey. Nearly all sharing/borrowing was among family members, particularly between siblings, and most frequently involved rescue inhalers and asthma controllers. Previous studies2,4,6–7 of non-recreational medication sharing/borrowing found that one-time or short duration medications (e.g. antibiotics, oral antihistamines, pain medications) were most frequently shared; interestingly no family reported sharing/borrowing antibiotics or oral corticosteroids. This may relate to the cohort being of lower socioeconomic status, since previous studies of medication sharing have suggested that young adult, white, more educated individuals comprise the group that feels most competent to self-medicate.6 For reasons that likely include that the cohort is of low socioeconomic status and most subjects qualify for free or very low co-pay prescriptions10, asthma and allergy medication sharing/borrowing was somewhat less frequent than in previous studies, impacting our ability to detect differences in asthma control and controller medication adherence. There was a trend toward decreased ACT and a higher proportion with ACT ≤19 among those who shared/borrowed medication, although not significant at the 0.05 level. This study has several limitations. First, sharing/borrowing behavior, asthma adverse events, and controller medication adherence were based upon parental report. Language validating sharing/borrowing behavior was included in the questionnaire (“Sometimes patients share medicine…”), and questions were modeled on those used in previous studies3,6,7 that have examined medication sharing/borrowing, but it is likely that this practice is underreported. Asthma controller medication adherence was likely overreported, and future studies may benefit from inhaler dose counters or other confirmatory measures. Regarding asthma adverse events, a validated objective measure of asthma control (ACT) was included, and questions about sharing/borrowing were asked last, to minimize recall bias. Finally, this study was intended to be primarily descriptive about the prevalence and features of medication sharing/borrowing among children with asthma, and the sample size did not allow for detection of small differences in asthma control. Nevertheless, this is the first study to our knowledge to examine prescription asthma and allergy medication sharing/borrowing among any population with asthma, and suggests that this is a relatively common issue, even when self-reported. Future studies should examine the prevalence of this practice among other populations of asthmatics, and define whether this practice impacts asthma control and asthma controller medication adherence.