Repeated respiratory hospital encounters among children with asthma and residential proximity to traffic.

OBJECTIVE: The prevalence of adverse respiratory outcomes among children has been frequently associated with measurements of traffic-related exposures, and other data suggest asthma severity is worsened with residence near heavy traffic. We examined the association between neighbourhood traffic burden and repeated acute respiratory illnesses that required emergency department visits and/or hospitalisation for children with a primary or secondary diagnosis of asthma (89% acute bronchitis or pneumonia). METHODS: This is a hospital-based longitudinal study of a southern California urban catchment area around two adjacent children's hospitals. Subjects' home addresses were geocoded and linked to nearby traffic data. Recurrent event proportional hazard analysis was used to estimate the hazard of repeated hospital encounters. RESULTS: We found living within 300 metres of arterial roads or freeways increased risk of repeated hospital encounters in 3297 children age 18 years or less. At highest risk were children in the top quintile of traffic density (HR = 1.21; 95% CL 0.99 to 1.49) and those who had 750 metres or more of arterial road and freeway length within 300 metres of their residence (HR = 1.18; 95% CL 0.99 to 1.41). Associations between repeated hospital encounters and residence near heavy traffic were stronger in females than males and in children without insurance or who required government sponsored insurance than children with private insurance. The gender disparity was most notable among infants (age 0) and children ages 6-18 years. CONCLUSIONS: Results suggest exposure to traffic-related air pollution increases asthma severity as indicated by hospital utilisation. The finding in infants suggests this is an especially vulnerable population, although the validity of asthma diagnosis at this age is unknown. Females and children who do not have private insurance may also be more vulnerable to air pollution from traffic.

The relationship of respiratory and cardiovascular hospital admissions to the southern California wildfires of 2003.

OBJECTIVE: There is limited information on the public health impact of wildfires. The relationship of cardiorespiratory hospital admissions (n = 40 856) to wildfire-related particulate matter (PM(2.5)) during catastrophic wildfires in southern California in October 2003 was evaluated. METHODS: Zip code level PM(2.5) concentrations were estimated using spatial interpolations from measured PM(2.5), light extinction, meteorological conditions, and smoke information from MODIS satellite images at 250 m resolution. Generalised estimating equations for Poisson data were used to assess the relationship between daily admissions and PM(2.5), adjusted for weather, fungal spores (associated with asthma), weekend, zip code-level population and sociodemographics. RESULTS: Associations of 2-day average PM(2.5) with respiratory admissions were stronger during than before or after the fires. Average increases of 70 microg/m(3) PM(2.5) during heavy smoke conditions compared with PM(2.5) in the pre-wildfire period were associated with 34% increases in asthma admissions. The strongest wildfire-related PM(2.5) associations were for people ages 65-99 years (10.1% increase per 10 microg/m(3) PM(2.5), 95% CI 3.0% to 17.8%) and ages 0-4 years (8.3%, 95% CI 2.2% to 14.9%) followed by ages 20-64 years (4.1%, 95% CI -0.5% to 9.0%). There were no PM(2.5)-asthma associations in children ages 5-18 years, although their admission rates significantly increased after the fires. Per 10 microg/m(3) wildfire-related PM(2.5), acute bronchitis admissions across all ages increased by 9.6% (95% CI 1.8% to 17.9%), chronic obstructive pulmonary disease admissions for ages 20-64 years by 6.9% (95% CI 0.9% to 13.1%), and pneumonia admissions for ages 5-18 years by 6.4% (95% CI -1.0% to 14.2%). Acute bronchitis and pneumonia admissions also increased after the fires. There was limited evidence of a small impact of wildfire-related PM(2.5) on cardiovascular admissions. CONCLUSIONS: Wildfire-related PM(2.5) led to increased respiratory hospital admissions, especially asthma, suggesting that better preventive measures are required to reduce morbidity among vulnerable populations.

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Glutathione S-transferase polymorphisms and outcome of chemotherapy in childhood acute myeloid leukemia.

PURPOSE: Glutathione S-transferase theta (GSTT1) and mu (GSTM1) genes are polymorphic, the genes being absent in approximately 15% and 50% of the population, respectively. Because glutathione S-transferases may be involved in the metabolism of chemotherapy drugs, we hypothesized that presence or absence of the genes may influence the outcome of treatment for childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: We genotyped GSTT1 and GSTM1 in 306 children with AML receiving chemotherapy on Children's Cancer Group therapeutic studies. Outcomes were compared in those with and without GSTT1 and GSTM1 genes. RESULTS: Patients with the GSTT1-negative genotype had reduced survival compared with those with at least one GSTT1 allele (GSTT1 positive) (52% v 40% at 5 years; log-rank P =.05). A multivariate model of survival adjusted for age group, sex, WBC count, chloroma, CNS involvement, and French-American-British group confirmed the increased risk of death in the GSTT1-null cases (relative risk, AQ 1.6; P =.02). The frequency of death in remission was increased in GSTT1-negative cases compared with GSTT1-positive cases (24% v 12%, log-rank P =.05). The frequency of relapse from end of induction was similar in GSTT1-negative and GSTT1-positive cases (38% v 35%, log-rank P =.5). CONCLUSION: Children who lacked GSTT1 had greater toxicity and reduced survival after chemotherapy for AML compared with children with at least one GSTT1 allele. If confirmed in further studies, GSTT1 genotype might be useful in selecting appropriate chemotherapy regimens for children with AML.

Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia.

The Flt3 gene encodes a tyrosine kinase receptor that regulates proliferation and differentiation of hematopoietic stem cells. An internal tandem duplication of the Flt3 gene (Flt3/ITD) has been reported in acute myelogenous leukemia (AML) and may be associated with poor prognosis. We analyzed diagnostic bone marrow specimens from 91 pediatric patients with AML treated on Children's Cancer Group (CCG)-2891 for the presence of the Flt3/ITD and correlated its presence with clinical outcome. Fifteen of 91 samples (16.5%) were positive for the Flt3/ITD. Flt3/ITD-positive patients had a median diagnostic white count of 73 800 compared with 28 400 for the Flt3/ITD-negative patients (P =.05). The size of the duplication ranged from 21 to 174 base pairs (bp). Nucleotide sequencing of the abnormal polymerase chain reaction products demonstrated that all duplications involved exon 11 of the Flt3 gene and also preserved the reading frame. Lineage restriction analysis revealed that Flt3/ITD was not present in the lymphocytes, suggesting a lack of stem cell involvement for this mutation. None of the Flt3/ITD-positive patients had unfavorable cytogenetic markers, and there was no predominance of a particular FAB class. The remission induction rate was 40% in Flt3/ITD-positive patients compared with 74% in Flt3/ITD-negative ones (P =.005). The Kaplan-Meier estimates of event-free survival at 8 years for patients with and without Flt3/ITD were 7% and 44%, respectively (P =.002). Multivariate analysis demonstrated that presence of the Flt3/ITD was the single most significant, independent prognostic factor for poor outcome (P =.009) in pediatric AML.

Exposure to immunization media messages among African American parents.

BACKGROUND: African Americans have low immunization rates, yet little is known about their immunization knowledge, attitudes, and practices or about the effect of outreach to this audience. In Spring 1997, the California Department of Health Services (CDHS) launched a statewide culturally sensitive and ethnically specific media campaign directed toward African Americans. This campaign was preceded by a major Los Angeles County Department of Health Services media campaign. OBJECTIVES: The objectives of this study were to (a) estimate exposure to immunization media messages among African Americans; (b) determine sources of immunization information; and (c) assess various immunization attitudes and beliefs in order to refine future outreach efforts. METHODS: Following the CDHS media campaign, a random digit dial survey was conducted with 801 African American families with children under age 10. The sample was drawn from the four California regions with the highest African American birth rates. It included all zip codes in these regions with greater than 150 African American births per year. Lower bound response rates ranged from 62.5 to 76.1%. Higher income and education levels were overrepresented. Results were weighted to adjust for this. RESULTS: Over 88% remembered seeing or hearing some form of immunization information. Exposure to television ads was reported by 63% followed by billboards (51%) and radio (42%). Sixty-two percent thought mild disease was possible after shots; 27% feared HIV from needles and 19% thought pain was a barrier. Respondents who cited money as a barrier (26%) were less likely to believe that shots were available for free (P = 0.02). CONCLUSIONS: Media advertising is an effective tool for reaching African Americans. Addressing specific concerns (e.g., clarification of the circumstances and likelihood of getting a mild case of the disease following an immunization, availability of free shots, and risk of HIV) may contribute to increased immunization rates for this population.

Children's cancer group trials of interleukin-2 therapy to prevent relapse of acute myelogenous leukemia.

PURPOSE: Up to 80% of children with acute myelogenous leukemia treated with intensive chemotherapy achieve remission; however, a large proportion of patients develops recurrent disease. Because interleukin (IL)-2 can induce remission in patients with overt evidence of acute myelogenous leukemia, we hypothesized that it might prevent relapse when administered to patients in first remission after intensive consolidation chemotherapy. A pilot Children's Cancer Group (CCG) trial (CCG-0941) demonstrated the feasibility of this approach, and we initiated a prospective randomized trial (CCG-2961) to further evaluate the safety and potential efficacy of IL-2 therapy in preventing relapse of acute myelogenous leukemia. PATIENTS AND METHODS: In trial CCG-0941, 21 pediatric patients in complete remission following induction and consolidation chemotherapy on protocol CCG-2941 received IL-2 therapy. In CCG-2961, 79 patients in complete remission were randomized as of February 1999 to receive either IL-2 (n = 39) or no further therapy. In both trials, recombinant IL-2 was given at a dose of 9 million IU/m2/d by continuous intravenous infusion for 4 days. After 4 days of rest, IL-2 was resumed at a dose of 1.6 million IU/m2/d for 10 days by continuous infusion. We monitored patients for toxicity and relapse. RESULTS: The majority of patients treated with IL-2 in these two trials experienced some degree of fever. Seven of 60 patients (12%) had clinically significant rashes, and grade 3 vascular leak syndrome and hypotension have each been observed in five patients (8%). Hypotension resolved promptly after treatment with intravenous fluids. No patients have experienced renal toxicity or required cardiac vasopressors or transfer to an intensive care unit; there have been no treatment-related deaths. Overall, the incidence and severity of adverse events remain similar in the two trials. Total projected accrual to the IL-2 randomization is anticipated to be 326 patients, and relapse and survival data remain blinded. CONCLUSION: The dose and schedule of IL-2 used in these two trials continue to be reasonably well tolerated by children with acute myelogenous leukemia in first remission. Any conclusions with regard to efficacy must await completion of the randomized trial.

Pretesting Spanish-language educational radio messages to promote timely and complete infant immunization in California.

California's Hispanic infants have lower immunization levels than non-Latino white infants, 53.7% versus 65.2%, respectively. Spanish-language radio is an effective mass media venue for imparting information to Latino populations. It has been demonstrated that lack of parental knowledge of infant immunization timing is associated with delayed immunization coverage. In an effort to improve Latino parent knowledge of immunization timing, two Spanish-language radio commercials were developed to be used in conjunction with community-based educational efforts. In order to gage the potential educational impact of the two commercials, they were pretested with a group of low-income Spanish-speaking Latino parents who represented members of the target population for whom the commercials were created. Both commercials were rated favorably by parents, and elicited immunization-specific responses. Although correct recall of the simplified, basic immunization schedule was low, the level of immunization response consistency and overall approval of both commercials appear to support their use as part of Latino infant immunization educational outreach in California.