Antibody response to human papillomavirus vaccination and natural exposure in individuals with Fanconi Anemia.

Fanconi anemia (FA) is a rare genetic disorder associated with predisposition to head and neck and gynecological squamous cell cancers. In the general population, these cancers are commonly linked to human papillomavirus (HPV) infection. Antibodies to natural HPV infection and HPV vaccination were evaluated in 63 individuals with FA while considering host immune factors. Approximately 30% of reportedly unvaccinated participants were seropositive (HPV6-38%, HPV11-25%, HPV16-26%, and HPV18-26%). Seropositivity was significantly associated with having had sex regardless of age (p=.007). Most participants showed seropositivity after HPV vaccination (HPV6-100%, HPV11-100%, HPV16-100% and HPV18-92%). Interestingly, titers for all 4 subtypes were significantly lower in the post-hematopoietic stem cell transplant (HSCT) participants compared to those who received the vaccine, but had not undergone HSCT (HPV6-p=.030, HPV11-p=.003, HPV16-p=.018, HPV18-p=<.001). It is unclear if these titers sufficiently protect from new infection since protective serologic cut offs have not yet been defined for the HPV vaccine. Individual immune functions were not associated with HPV seropositivity, however, underlying heterogeneous immune deficiency may explain higher rates of seropositivity in our younger unvaccinated participants (age 4-13 years). To better measure the efficacy of HPV vaccination in those with FA and other immune-compromised or cancer-prone disorders, future well-controlled vaccine studies are required.

A telephone coaching intervention to improve asthma self-management behaviors.

Long recognizing that asthma, one of the most common chronic childhood diseases, is difficult to manage, the National Asthma Education Prevention Program developed clinical practice guidelines to assist health care providers, particularly those in the primary care setting. Yet, maintenance asthma care still fails to meet national standards. Therefore, in an attempt to improve and support asthma self-management behaviors for parents of children 5 to 12 years of age with persistent asthma, a novel nurse telephone coaching intervention was tested in a randomized, controlled trial. A detailed description of the intervention is provided along with parent satisfaction results, an overview of the training used to prepare the nurses, and a discussion of the challenges experienced and lessons learned.

Telephone coaching for parents of children with asthma: impact and lessons learned.

OBJECTIVE: To determine whether an asthma coaching program can improve parent and child asthma-related quality of life (QOL) and reduce urgent care events. DESIGN: Randomized controlled trial of usual care vs usual care with coaching. Comparisons were made between groups using mixed models. SETTING: A Midwest city. PARTICIPANTS: A community-based sample of 362 families with a child aged 5 to 12 years with persistent asthma. INTERVENTION: A 12-month structured telephone coaching program in which trained coaches provided education and support to parents for 4 key asthma management behaviors. MAIN OUTCOME MEASURES: Parental and child QOL measured with a validated, interview-administered, 7-point instrument and urgent care events in a year (unscheduled office visits, after-hours calls, emergency department visits, or hospitalizations) determined by record audit. RESULTS: Parental asthma-related QOL scores improved by an average of 0.67 units (95% confidence interval [CI], 0.49 to 0.84) in the intervention group and 0.28 units (95% CI, 0.10 to 0.46) in the control group. The difference between study groups was statistically significant (difference, 0.38; 95% CI, 0.14 to 0.63). No between-group difference was found in the change in the child's QOL (difference, -0.17; 95% CI, -0.47 to 0.12) or in the mean number of urgent care events per year (difference, 1.15; 95% CI, 0.82 to 1.61). The proportion of children with very poorly controlled asthma in the intervention group decreased compared with the control group (difference, 0.34; 95% CI, 0.21 to 0.48). CONCLUSIONS: A telephone coaching program can improve parental QOL and can be implemented without additional physician training or practice redesign.

Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis.

We have previously proposed that the pathogenesis of eosinophilic esophagitis (EE) is mediated by an IL-13-driven epithelial cell response associated with marked gene dysregulation including eotaxin-3 overproduction. In this study, we compared epithelial responses between healthy patients and those with EE, aiming to uncover molecular explanations for EE pathogenesis. Esophageal epithelial cells could be maintained for up to five passages, with 67% and 62% of cell lines reaching confluence in healthy controls and EE cases, respectively. Both sets of epithelial cells avidly responded to IL-13 at similar levels as assessed by eotaxin-3 production. Acidic pH increased cellular release of eotaxin-3 (4.6 +/- 1.98 ng/ml versus 12.46 +/- 2.90 ng/ml at pH 7.4 and 4, respectively; p < 0.05). Numerous epidermal differentiation complex (EDC) genes, such as filaggrin and SPRR3, were downregulated both in IL-13-stimulated esophageal epithelial cells and in EE biopsies specimens compared with healthy controls. Whereas the filaggrin loss of function mutation 2282del4 was overrepresented in EE compared with control individuals (6.1% versus 1.3% respectively; p = 0.0172), the decreased filaggrin expression was uniformly seen in all EE cases in vivo. Indeed, expression of the EDC genes filaggrin and involucrin was strongly decreased directly by IL-13. These results establish that the epithelial response in EE involves a cooperative interaction between IL-13 and expression of EDC genes.

Socioeconomic, family, and pediatric practice factors that affect level of asthma control.

BACKGROUND: Multiple issues play a role in the effective control of childhood asthma. OBJECTIVE: To identify factors related to the level of asthma control in children receiving asthma care from community pediatricians. PATIENTS AND METHODS: Data for 362 children participating in an intervention study to reduce asthma morbidity were collected by a telephone-administered questionnaire. Level of asthma control (well controlled, partially controlled, or poorly controlled) was derived from measures of recent impairment (symptoms, activity limitations, albuterol use) and the number of exacerbations in a 12-month period. Data also included demographic characteristics, asthma-related quality of life, pediatric management practices, and medication usage. Univariable and multivariable analyses were used to identify factors associated with poor asthma control and to explore the relationship between control and use of daily controller medications. RESULTS: Asthma was well controlled for 24% of children, partially controlled for 20%, and poorly controlled for 56%. Medicaid insurance, the presence of another family member with asthma, and maternal employment outside the home were significant univariable factors associated with poor asthma control. Medicaid insurance had an independent association with poor control. Seventy-six percent of children were reported by parents as receiving a daily controller medication. Comparison of guideline recommended controller medication with current level of asthma control indicated that a higher step level of medication would have been appropriate for 74% of these children. Significantly lower overall quality-of-life scores were observed in both parents and children with poor control. CONCLUSIONS: Despite substantial use of daily controller medication, children with asthma continue to experience poorly controlled asthma and reduced quality of life. Although Medicaid insurance and aspects of family structure are significant factors associated with poorly controlled asthma, attention to medication use and quality-of-life indicators may further reduce morbidity.

What constitutes maintenance asthma care? The pediatrician's perspective.

OBJECTIVE: To describe how pediatricians report they provide maintenance care for children with persistent asthma, and to identify opportunities for improvement. METHODS: An anonymous 34-item survey was completed by community pediatricians in St Louis, Missouri, between June 2005 and October 2005. Physicians reported the percentage of patients for whom they would prescribe inhaled corticosteroids, and selected from checklists the activities and questions they would use during a maintenance care visit. RESULTS: A total of 135 (60%) of 225 eligible pediatricians responded. Respondents reported they prescribed inhaled corticosteroids for most patients (median 80% patients, range, 10%-100%). Although most respondents used specific questions to assess recent asthma burden including inquiring about the frequency of daytime (86%) and nighttime (83%) symptoms, fewer asked about activity limitations such as school absences (58%). Some reported using specific questions to assess medication adherence such as how often doses were missed (49%), or included collaborative activities to support daily self-management such as setting asthma care goals (60%), but fewer asked how symptoms were monitored (44%) or assessed the effect of the child's asthma on the parent and family (24%). CONCLUSIONS: Findings from this self-reported physician survey suggest that asthma management practices fall short of optimal standards. Opportunities for improvement include more comprehensive and detailed assessment of asthma control and medication adherence, collaborative goal setting, and better collaboration with the parent to support effective self-management. Further interventions to reduce asthma morbidity need to support physicians with these activities.