Craig A. Jones

Undetectable interleukin (IL)-10 and persistent IL-8 expression early in hyaline membrane disease: a possible developmental basis for the predisposition to chronic lung inflammation in preterm newborns.

We are interested in determining whether premature birth alters expression of counterregulatory cytokines which modulate lung inflammation. Production of proinflammatory cytokines tumor necrosis factor α, IL-1β, and IL-8 is regulated in part by the antiinflammatory cytokine IL-10. For preterm newborns with hyaline membrane disease, deficiencies in the ability of lung macrophages to express antiinflammatory cytokines may predispose to chronic lung inflammation. We compared the expression of pro- and antiinflammatory cytokines at the mRNA and protein level in the lungs of preterm and term newborns with acute respiratory failure from hyaline membrane disease or meconium aspiration syndrome. Four sequential bronchoalveolar lavage (BAL) samples were obtained during the first 96 h of life from all patients. All patients rapidly developed an influx of neutrophils and macrophages. Over time, cell populations in both groups became relatively enriched with macrophages. The expression of proinflammatory cytokine mRNA and/or protein was present in all samples from both patient groups. In contrast, IL-10 mRNA was undetectable in most of the cell samples from preterm infants and present in the majority of cell samples from term infants. IL-10 concentrations were undetectable in lavage fluid from preterm infants with higher levels in a few of the BAL samples from term infants. These studies demonstrate that1) IL-10 mRNA and protein expression by lung inflammatory cells is related to gestational age and 2) during the first 96 h of life neutrophil cell counts and IL-8 expression decrease in BAL from term infants, but remain unchanged in BAL samples from preterm infants.

Adherence to Prescribed Treatment for Asthma: Evidence from Pharmacy Benefits Data

Background. Failure to use asthma controller medications as prescribed is associated with more asthma-related adverse events. Medication utilization may vary with ease of drug administration, efficacy, and tolerability as well as other factors. We hypothesized that in usual-care clinical practice settings, there would be greater adherence to oral controller than to inhaled controller asthma medications. Methods. We compared adherence to newly initiated asthma controller therapy among patients initiating monotherapy with leukotriene receptor antagonists (LTRAs), inhaled corticosteroids (ICS), or inhaled long-acting β-agonists (ILBA) from 03 1998 to 07 1999. We measured adherence as the sum of drug supply days between first and last fill dates divided by length of drug therapy. Analyses were stratified by the number of short-acting β-agonists (SBA) prescriptions per year to control for disease severity. Results. Pharmacy claims data from 48,751 subjects (6 to 55 years) were analyzed (mean age 30.4 years; 56% female). Mean adherence to new start monotherapy on LTRA was 67.7%, to ICS was 33.8%, and to ILBA was 40.0%. Adherence to all three controller agents increased with increasing SBA use. The percent of patients persistent to asthma controller monotherapy at both 6 and 9 months was significantly greater among those on LTRA monotherapy than on either ICS or ILBA. Conclusions. In clinical practice settings, patients initiating LTRA monotherapy have about twice the adherence as patients initiating ICS or ILBA monotherapy. Because adherence to treatment is a critical component of treatment response, it is important to consider this factor in the prescription of oral vs. inhaled asthma medications.

Predictive Value of a Cross-Cultural Asthma Case-Detection Tool in an Elementary School Population

Objective. Bronchial asthma, which affects ∼5 million US children, is vastly underdiagnosed and treated, particularly among minorities and those of low socioeconomic status. Because current methods of detecting those at greatest risk of asthma in a multicultural setting appear inadequate, we assessed the validity and reliability of a new asthma questionnaire across 3 dominant cultures in Orange County, California (white, Hispanic, and Vietnamese). Methods. Children in grades 1, 3, and 5 and their families, in 3 different schools representative of these major ethnic groups, were randomly selected to participate in the validation process. Two schools with low socioeconomic status and dominant Hispanic or Vietnamese minorities were designated inner-city schools, whereas the third school was a suburban school with predominately white students. Participants completed a 7-question, 11-element questionnaire in their primary language, followed by an asthma evaluation (history, physical examination, and spirometry) by an asthma specialist (who was blinded with respect to the results of the questionnaire), at their respective schools. The physician then made a determination regarding the presence and severity (according to National Institutes of Health guidelines) of asthma. Several weeks later, the entire student body was asked to complete the questionnaire at home and return it to school for analysis. Validation of each item was evaluated for sensitivity, specificity, and positive and negative predictive values, and application of univariate analyses provided an estimated probability of an asthma diagnosis by the asthma specialist. A “best-fit” algorithm was determined with all 11 elements, if possible, and an abbreviated algorithm that selected the fewest-question combination that yielded the best asthma predictability was established. Reliability was established with the percent agreement between the 2 questionnaires and the κ statistic. Results. Of the 401 children/families who participated in the validation analysis, 45% were Hispanic, 22% white, 19% Vietnamese, and 15% other. The overall prevalence of asthma specialist-diagnosed asthma was 28%, with 65% of cases being graded as intermittent and 35% as persistent. Sixty-two percent of the children had not been previously diagnosed with asthma. There were no significant differences among cultures in sensitivity or specificity for any of the individual questions or the complete or abbreviated algorithms. The abbreviated algorithm with 3 questions, ie, question 1 (asthma in the past 2 years), question 4 (cough, chest tightness, trouble breathing, or wheezing with exercise), and question 6 (same symptoms in the morning or day in the past 4 weeks) yielded comparable sensitivity and specificity for the complete algorithm in all groups. The abbreviated algorithm had >86% predictability in detecting children with persistent asthma and 56% predictability in detecting children with intermittent asthma. Reliability was also excellent, with percent agreement usually > 80% and κ values of >.70. Conclusions. This asthma detection tool has been shown to be suitable for detecting persistent asthma in a multicultural inner-city population, as well as in a suburban setting. An abbreviated algorithm with 3 questions and >80% predictability in detecting persistent asthma seems ideal for evaluating large numbers of school-aged children. The school setting is an excellent site for identifying children with asthma. Although there is concern that subjects detected in the school setting might not have access to ongoing medical care, case detection is an important first step that could lead to earlier diagnosis and treatment. Reducing the barriers to good care in inner-city environments is the next step.

Educational intervention to control cockroach allergen exposure in the homes of hispanic children in Los Angeles: results of the La Casa study

Background Cockroach allergy is common among inner city children with asthma, and exposure to cockroach allergen is associated with more severe disease. However, there has been little evaluation of educational approaches for controlling cockroach infestations and reducing allergen exposure.

Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) study.

BACKGROUND Uncontrolled asthma remains prevalent in the United States and confers a substantial burden on the health care system. OBJECTIVES To evaluate the association between uncontrolled asthma and activity limitations in a nationally representative sample of patients with moderate-to-severe-treated asthma and to assess the degree to which demographics and comorbidities were associated with activity limitations. METHODS Patients who participated in the Real-world Evaluation of Asthma Control and Treatment study were surveyed regarding type and degree of activity limitations in 4 categories: outdoor activity, physical activity, daily activity, and environmental triggers. Information about asthma control, demographics, and comorbidities was collected. Multivariable regression was used to assess the association between uncontrolled asthma and activity limitations while adjusting for demographic characteristics and comorbid conditions. RESULTS Uncontrolled asthma was associated with a greater than 2-fold risk of outdoor (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.90-3.51) or physical (OR, 2.62; 95% CI, 1.90-3.61) activity limitations and a 66% increased risk of daily activity limitations (OR, 1.66; 95% CI, 1.09-2.51). Comorbidities associated with activity limitation included hives, chronic sinusitis, arthritis, gastroesophageal reflux disease, hypercholesterolemia, and depression. The observed associations between uncontrolled asthma and activity limitation remained significant after controlling for demographic characteristics and comorbid conditions. CONCLUSIONS Compared with patients with controlled asthma, those with uncontrolled asthma are at higher risk for limitations in outdoor activity, physical activity, and daily activity. To help patients achieve optimal health, asthma management should include routine assessment of activity limitations and assessment and coordinated care for comorbid conditions.

Cockroach counts and house dust allergen concentrations after professional cockroach control and cleaning

BACKGROUND It is known that cockroach allergen exposure is both frequent in inner-city homes and associated with asthma severity in children living in those homes. However, there have been few studies of interventions to reduce exposures in this setting. OBJECTIVE To evaluate the effect of short-term professional cockroach control and intensive cleaning on allergen concentrations. METHODS Families of children from a school-based asthma treatment program who had skin test results positive to cockroach allergen were enrolled if the home had cockroaches. Forty-nine homes were randomly assigned to receive professional cleaning with bait traps containing insecticide, professional cleaning with bait traps without insecticide, or no cleaning or bait traps. In all homes, dust was collected repeatedly to evaluate cockroach allergen Bla g 2 in the kitchen and bedroom, and cockroaches were trapped and counted repeatedly for more than 11 weeks. RESULTS Median cockroach counts were reduced in the homes treated with insecticide bait traps but not in other groups. There were significant reductions in allergen concentration in the kitchen in homes that received professional cleaning and had higher initial cockroach counts (54), regardless of whether bait traps had insecticide or not. CONCLUSIONS We conclude that intensive cleaning can produce significant reductions in cockroach allergen in homes with heavy initial cockroach infestations.

Ability to control persistent asthma in obese versus non-obese children enrolled in an asthma-specific disease management program (breathmobile).

To determine if asthma control was more difficult to achieve in obese versus non-obese asthmatic children, retrospective analysis was performed on obese and non-obese Los Angeles inner-city children (2 to 18 years of age) with persistent asthma. No difference in time required to achieve control of asthma, ability to maintain control of asthma, baseline pulmonary functions, and number of controllers prescribed was found between the two groups. We conclude that in a Los Angeles inner-city pediatric population, obesity is not a factor in the ability to control asthma.

Children's exposure to environmental tobacco smoke in the home: Comparison of urine cotinine and parental reports

Abstract The authors examined the relationship between parent-reported estimates of childrens exposure to environmental tobacco smoke (ETS) in the home and childrens urinary cotinine levels. Data were collected from a largely ethnic minority, low-income, urban sample of households in which a child had asthma and at least 1 household member smoked. Information about level of household smoking restriction, parental smoking status, and number of cigarettes smoked per day accounted for approximately 45% of the variance in cotinine concentration. Detailed information about the duration of household smoking or childrens ETS exposure added no additional significant information. Questionnaires eliciting detailed information about smoking habits and childrens ETS exposure may be no better at predicting childrens urinary cotinine levels than simpler surveys that inquire about smoking restrictions in the home, parental smoking status, and number of cigarettes smoked at home per day.

Asthma control and future asthma-related morbidity in inner-city asthmatic children

BACKGROUND Asthma guidelines recommend routine evaluation of asthma control, which includes measurements of impairment and risk. It is unclear whether rigorous asthma control changes risk of asthma morbidity. OBJECTIVE To examine whether the degree of asthma control in inner-city asthmatic children results in differential risk reduction of future asthma-related morbidity. METHODS This retrospective observational study examines 960 inner-city children with asthma who were highly engaged in an asthma-specific disease management program for a minimum of 2 years. Degree of asthma control was determined during the first year of enrollment and was categorized as well controlled (> or = 80% of visits in control), moderately controlled (50%-79% of visits in control), or difficult to control (< 50% of visits in control). Risk and probability of asthma-related morbidity at each visit were determined during the second year of enrollment and included self-reported asthma exacerbations requiring systemic corticosteroid rescue and emergency department visits or hospitalizations. RESULTS Increasing the degree of asthma control measured during the first year of enrollment led to statistically significant incremental reductions in risk of acute asthma exacerbations and emergency department visits or hospitalizations during the second year of enrollment. CONCLUSIONS Achieving and maintaining asthma control in inner-city children with asthma results in significant reductions in asthma-related morbidity. Systematic assessments of asthma control may be useful for predicting future risk in children with asthma.

Constitutive IL-10 expression by lung inflammatory cells and risk for bronchopulmonary dysplasia.

Expression of IL-10 is decreased in lungs of preterm infants. We determined the constitutive and lipopolysaccharide (LPS)-induced IL-10 synthesis by lung inflammatory cells from preterm and term infants and examined their relationship to gestational age and/or incidence of bronchopulmonary dysplasia (BPD). A total of 37 infants; preterm neonates at gestational ages of 23–27 wk (group 1); 28–34 wk (group 2), and four full-term infants with meconium aspiration (group 3) were enrolled. One sample of lung inflammatory cells, obtained during postnatal d 1–3, and another during postnatal d 4–7 were cultured in vitro in presence or absence of 100 μg/mL of LPS. Secreted IL-10 was measured by ELISA. A positive relationship was found between gestational age and LPS-induced, but not constitutive IL-10 production within 1–3 d of life; group 1 on d 1–3 had a significant number of IL-10 nonresponders compared with group 2. All term neonates in group 3 had positive LPS-induced IL-10 response. Thus, in utero maturation of IL-10 gene expression is due to acquisition of inducibility. In contrast, constitutive IL-10 production within d 1–3 of life correlated with, and predicted the incidence of BPD in the highly vulnerable very premature infants.