Endotypes of difficult-to-control asthma in inner-city African American children.

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.

Long-term sequelae of postnatal surfactant and corticosteroid therapies for BPD.

OBJECTIVE: This retrospective analysis assessed the relationship between medical treatment (postnatal steroids, surfactant) received neonatally and outcomes at 3 and 8 years using a longitudinal sample of children with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Four groups were formed retrospectively based on the type of neonatal medical treatment received: no drug intervention (n=37), surfactant only (n=29), postnatal steroids only (n=13) and combined surfactant and postnatal steroids (n=16). Groups were compared on neurological and medical outcomes. RESULT: Combined postnatal steroids and surfactant treatment was associated with more days on supplemental oxygen than no intervention or surfactant only. Surfactant replacement therapy alone was not associated with adverse consequences; however, postnatal steroid exposure appeared to be related. CONCLUSION: Although retrospective analyses make statements about causation impossible, the differential relationships of therapies with cognitive outcomes argues for careful monitoring of therapeutic agents with very low birth weight infants.

Are peak flow and symptom measures good predictors of asthma hospitalizations and unscheduled visits?

Epidemiologic studies of pediatric respiratory health often include objective measures such as peak expiratory flow (PEF), and subjective measures such as symptom reports. These measures, however, are poorly correlated with each other, and there is little evidence that PEF is useful in predicting important health outcomes. Within a cohort of 791 inner-city children with asthma, we examined correlations between a series of five peak flow measures and five symptom scores obtained from 2-week diaries. The strongest correlations were found between "total peak flow lability" defined as: [(diary maximum - diary minimum)/diary mean] and "% of days with chest tightness" (r = 0.31). Logistic models evaluated peak flow and symptoms as predictors of an important health outcome: hospitalization or emergency department or unscheduled clinic visit for asthma within 30 days of starting the diary. Each of the peak flow and symptom measures was significantly related to utilization. However, the predictive power of each measure was low (range of area under ROC curve, 0.54-0.67). Models including only peak flow or symptoms had greater prediction than models with risk factors such as atopy, asthma persistence, and age. The prediction from a model with the risk factors and symptoms was not improved by adding a peak flow measure to the model (increase in area under ROC, 0.67-0.68). Stratified analyses suggest that prediction was similar in the fall vs. winter, spring, and summer months. Greater prediction of health outcomes was found among more persistent asthmatics and children who were nonatopic. These findings suggest that in a research setting, peak flow monitoring in children did not add prediction beyond that obtained from symptom reports. Pediatr Pulmonol. 2001; 31:190-197. Published 2001 Wiley-Liss, Inc.

Ipratropium bromide plus nebulized albuterol for the treatment of hospitalized children with acute asthma.

OBJECTIVE: To determine whether the addition of repeated doses of nebulized ipratropium bromide (IB) to a standardized inpatient asthma care algorithm (ACA) for children with status asthmaticus improves clinical outcome. STUDY DESIGN: Children with acute asthma (N = 210) age 1 to 18 years admitted to the ACA were assigned to the intervention or placebo group in randomized double-blind fashion. Both groups received nebulized albuterol, systemic corticosteroids, and oxygen according to the ACA. The intervention group received 250 microg IB combined with 2.5 mg albuterol by jet nebulization in a dosing schedule determined by the ACA phase. The placebo group received isotonic saline solution substituted for IB. Progression through each ACA phase occurred based on assessments of oxygenation, air exchange, wheezing, accessory muscle use, and respiratory rate performed at prescribed intervals. RESULTS: No significant differences were observed between treatment groups in hospital length of stay (P =.46), asthma carepath progression (P =.37), requirement for additional therapy, or adverse effects. Children >6 years (N = 70) treated with IB had shorter mean hospital length of stay (P =.03) and more rapid mean asthma carepath progression (P =.02) than children in the placebo group. However, after adjustment was done for baseline group differences, the observed benefit of IB therapy in older children no longer reached statistical significance. CONCLUSION: The routine addition of repeated doses of nebulized IB to a standardized regimen of systemic corticosteroids and frequently administered beta-2 agonists confers no significant enhancement of clinical outcome for the treatment of hospitalized children with status asthmaticus.

The allocation of family responsibility for asthma management tasks in African-American adolescents.

The allocation of responsibilities for asthma management within African-American families was examined in 60 adolescents and their primary caretakers. Separate structured interviews were conducted with adolescents and primary caretakers, and perceptions of family management, adherence to asthma treatment regimen, and functional morbidity were assessed. Support for the primary hypothesis that higher levels of nonadherence and functional morbidity would be observed in families where caretakers overestimated the level of adolescent involvement in asthma self-care was found. Implications for family-based asthma management in ethnic minority adolescents are discussed.

Acute inpatient care of status asthmaticus.

The hospital management of status asthmaticus includes aggressive use of a limited armamentarium of medications. Understanding the appropriate use of available medications is key. Proper assessment of the severity of an acute episode and response to applied therapies is essential for optimum outcomes without undue delays in treatment and excessive costs. Ensuring that all patients discharged from the hospital receive an individualized treatment plan for the management of chronic stable, worsening, and acute asthma can help prevent future hospitalizations.

A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study.

OBJECTIVE: To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma. STUDY DESIGN: Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk profile assessed at baseline. RESULTS: Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P =.004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14. 8%), a decrease of 4.19% (CI, -8.75 to 0.36, P =.071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor. CONCLUSIONS: We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city.

Pitfall in the use of genotype analysis as the sole diagnostic criterion for cystic fibrosis.

In this report, we present an asymptomatic infant, seen for a second opinion, who was given the diagnosis of cystic fibrosis (CF) as a neonate based on the presence of two mutant alleles, DeltaF508 and R117H. The diagnosis of CF adversely affected the family's emotional, employment, and financial statuses. Our evaluation included sweat chloride, nasal transepithelial potential difference, and bronchoscopy with bronchoalveolar lavage measurements, all which were consistent with findings expected from an individual without CF. Genotype analysis for the sequence polymorphism in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene revealed the 7 thymidines and 9 thymidines alleles. We conclude that this patient probably expresses enough epithelial cell surface CFTR function such that she has a normal phenotype. Based on our evaluation, she does not meet the current diagnostic criteria for CF. Although genotype analysis can be an useful adjunct, it should not be the sole diagnostic criterion for CF.

Pediatric asthma care in the emergency department: measuring the quality of history-taking and discharge planning.

The National Asthma Education and Prevention Program NAEPP Guidelines include recommendations for history-taking and discharge planning during an asthma visit, but there are no tools to measure performance. The objectives of this study were to define and operationalize key elements of history-taking and discharge planning, to develop a tool for measuring these elements, and to evaluate the quality of history-taking and discharge planning in the emergency department (ED) during visits for asthma using the new tool. Expert opinion and extensive literature review were used to develop a 13-item checklist containing items that should be documented during history-taking and provided during discharge planning for an ED visit for an acute asthma exacerbation by children. A convenience sample of 90 pediatric emergency medicine physicians and allergists rated each item in the checklist. The checklist was used to score audiotapes of asthma visits in the ED. Subjects were 154 parents of asthmatic children aged 4-9 years seeking care in nine inner-city EDs affiliated with asthma centers participating in the National Cooperative Inner-City Asthma Study and the physician/providers who delivered care. Seven of the 13 items on the checklist were rated as required to be performed by more than 90% of the allergist/pediatric emergency medicine physicians. Only 10% of the 154 visits included all seven of the highly rated items, whereas 19% of the visits included three or fewer. Only 7 of the 13 items (54%) were performed in more than 50% of the visits, and 4 items were performed in fewer than 25% of visits. Based on expert ratings, the checklist for measuring elements of history-taking and discharge planning during asthma visits appears to have considerable face validity. In the visits studied, the overall performance of these elements was low. Interventions to improve performance on the checklist might lead to improved care for children with asthma who frequent the ED.

Patient-provider communication during the emergency department care of children with asthma. The National Cooperative Inner-City Asthma Study, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD.

OBJECTIVES: Poor children's reliance on emergency facilities is one factor implicated in the rise of morbidity attributed to asthma. Although studies have examined doctor-patient communication during routine pediatric visits, little data are available about communication during emergency care. This study sought to describe communication during emergency treatment of childhood asthma to learn if a "patient-centered" provider style was associated with increased parent satisfaction and increased parent and child participation. METHODS: This cross-sectional, observational study examined 104 children aged 4 to 9 years and their guardian(s) attending emergency departments in seven cities. Quantitative analysis of provider-family dialogue was performed. Questionnaires measured satisfaction with care, provider informativeness, and partnership. RESULTS: Providers' talk to children was largely supportive and directive; parents received most counseling and information. Children spoke little to providers (mean: 20 statements per visit versus 156 by parents). Providers made few statements about psychosocial aspects of asthma care (mean: three per visit). Providers' patient-centered style with parents was associated with more talk from parents and higher ratings for informativeness and partnership. Patient-centered style with children was associated with five times the amount of talk from children and with higher parent ratings for "good care," but not for informativeness or partnership. CONCLUSIONS: Communication during emergency asthma care was overwhelmingly biomedical. Children took little part in discussions. A patient-centered style correlated with increased parent and child participation, but required directing conversation toward both parents and children.

A cost-saving algorithm for children hospitalized for status asthmaticus.

OBJECTIVE: To test the ability of an assessment-driven algorithm for treatment of pediatric status asthmaticus to reduce length and cost of hospitalization. DESIGN: Nonrandomized, prospective, controlled trial. SETTING: Tertiary care children's hospital. PATIENTS: Children aged 1 to 18 years hospitalized for status asthmaticus; 104 were treated using the asthma care algorithm (intervention) and 97 using unstructured standard treatment (control). INTERVENTION: Patients were treated using either an assessment-based algorithm or standard care practices. The algorithm group was treated with standard medications (aerosolized albuterol, systemic corticosteroids, epinephrine, ipratropium) administered at a frequency driven by the patient's clinical condition. Specific criteria were outlined for decreasing or augmenting therapy, transferring to intensive care, and discharging to home. A unique patient record containing assessments, algorithm cues, and a treatment record was used. Intervention group patients were interviewed by telephone 1 week after discharge. MAIN OUTCOME MEASURES: Hospital length of stay, cost per hospitalization, relapse rate, protocol adherence. RESULTS: Average hospital stay for intervention patients was significantly shorter than for control patients (2.0 vs 2.9 days, P<.001). Although intervention patients received fewer aerosolized albuterol doses than controls, there was no difference in short-term relapse rate between groups. The intervention saved more than $700 per patient in hospital charges. Adherence to the protocol was excellent, with only 8 variances per patient stay out of more than 150 opportunities. CONCLUSION: An intensive, assessment-driven algorithm for pediatric status asthmaticus significantly reduces hospital length of stay and costs without increasing morbidity.

Reported difficulties in access to quality care for children with asthma in the inner city.

OBJECTIVE: To characterize perceived access and barriers to quality health care for asthma among the caregivers of children in the inner city. DESIGN: Multicenter, cross-sectional survey. SETTING: Eight sites in 7 major metropolitan US inner cities. PARTICIPANTS: A systematic sample of children with asthma, aged 4 to 9 years, and their caregivers who resided in census tracts in which at least 30% of the households were below the 1990 federal poverty guidelines, recruited from 25 primary care clinics and 13 emergency departments (EDs) from November 1, 1992, through October 31, 1993. RESULTS: Of the 1528 children enrolled, 1376 had physician-diagnosed asthma and form the basis of this report. This group was further divided into 284 children (20.6%) who met all recruitment criteria for severe asthma and 207 (15.0%) with mild asthma who met none. Of parents in the total sample, 95.6% reported a usual place for short-term asthma care for their child; 75.4% used the ED. Children with severe asthma were significantly more likely to use the ED than those with mild asthma (84.3% vs 63.0%; P<.01). A usual place for follow-up asthma care was reported by 96.7% of subjects. There were no differences in access or type of facility used by asthma severity. More than half the study group reported difficulty in accessing care for acute asthma attacks and for follow-up care with no differences by asthma severity. Among those with severe asthma, 47.5% used inhaled steroids or cromolyn, 52.8% used a spacer device if they had been prescribed a metered dose inhaler, and 21.2% of children older than 6 years were prescribed a peak flowmeter. Patients with mild asthma were significantly less likely to report use of all 3 items (steroids or cromolyn, 1.4%; spacer device, 15.4%; and peak flowmeter, 3.1%, respectively; P<.01). CONCLUSION: Although access to asthma care among children in US inner cities appears adequate as determined by the traditional measure of reporting a regular source of care, barriers are frequently reported, as are deficiencies in the quality of medical care.

Design and methods of the National Cooperative Inner-City Asthma Study.

The National Cooperative Inner-City Asthma Study (NCICAS) was established to identify and then intervene on those factors which are related to asthma morbidity among children in the inner-city. This paper describes the design and methods of the broad-based initial Phase I epidemiologic investigation. Eight research centers enrolled 1,528 children, 4 to 9 years of age, from English- or Spanish-speaking families, all of whom resided in major metropolitan inner-city areas. The protocol included an eligibility assessment and an extensive baseline visit, during which symptom data, such as wheezing, lost sleep, changes in activities of daily living, inpatient admissions, and emergency department and clinic visits were collected. A comprehensive medical history for each child was taken and adherence to the medical regimen was assessed. Access, as well as barriers, to the medical system were addressed by a series of questions including the location, availability, and consistency of treatment for asthma attacks, follow-up care, and primary care. The psychological health of the caretaker and of the child was also measured. Asthma knowledge of the child and caretaker was determined. Sensitization to allergens was assessed by skin-prick allergen testing and exposure to cigarette smoke and the home environment were assessed by questionnaire. For more than a third of the families, in-home visits were conducted with dust sample allergen collection and documentation of the home environment, such as the presence of pets and evidence of smoking, mildew, and roaches. Urine specimens were collected to measure passive smoke exposure by cotinine assays, blood samples were drawn for banking, and children age 6 to 9 years were given spirometric lung function assessment. At 3, 6 and 9 months following the baseline assessment, telephone interviews were conducted to ask about the child's symptoms, unscheduled emergency department or clinic visits, and hospitalizations. At this time, peak flow measurements with 2-week diary symptom records were collected.

Characteristics of inner-city children with asthma: the National Cooperative Inner-City Asthma Study.

Asthma morbidity has increased dramatically in the past decade, especially among poor and minority children in the inner cities. The National Cooperative Inner-City Asthma Study (NCICAS) is a multicenter study designed to determine factors that contribute to asthma morbidity in children in the inner cities. A total of 1,528 children with asthma, ages 4 to 9 years old, were enrolled in a broad-based epidemiologic investigation of factors which were thought to be related to asthma morbidity. Baseline assessment included morbidity, allergy evaluation, adherence and access to care, home visits, and pulmonary function. Interval assessments were conducted at 3, 6, and 9 months after the baseline evaluations. Over the one-year period, 83% of the children had no hospitalizations and 3.6% had two or more. The children averaged 3 to 3.5 days of wheeze for each of the four two-week recall periods. The pattern of skin test sensitivity differed from other populations in that positive reactions to cockroach were higher (35%) and positive reactions to house dust mite were lower (31%). Caretakers reported smoking in 39% of households of children with asthma, and cotinine/creatinine ratios exceeded 30 ng/mg in 48% of the sample. High exposure (> 40 ppb) to nitrogen dioxide was found in 24% of homes. Although the majority of children had insurance coverage, 53% of study participants found it difficult to get follow-up asthma care. The data demonstrate that symptoms are frequent but do not result in hospitalization in the majority of children. These data indicate a number of areas which are potential contributors to the asthma morbidity in this population, such as environmental factors, lack of access to care, and adherence to treatment. Interventions to reduce asthma morbidity are more likely to be successful if they address the many different asthma risks found in the inner cities.

Psychosocial characteristics of inner-city children with asthma: a description of the NCICAS psychosocial protocol. National Cooperative Inner-City Asthma Study.

Previous research has demonstrated a significant reciprocal relationship between psychosocial factors and asthma morbidity in children. The National Cooperative Inner-City Asthma Study investigated both asthma-specific and non-specific psychosocial variables, including asthma knowledge beliefs and management behavior, caregiver and child adjustment, life stress, and social support. This article presents these psychosocial characteristics in 1,528 4-9-year-old asthmatic urban children and their caretakers. Caretakers demonstrated considerable asthma knowledge, averaging 84% correct responses on the Asthma Information Quiz. However, respondents provided less than one helpful response for each hypothetical problem situation involving asthma care, and most respondents had more than one undesirable response, indicating a potentially dangerous or maladaptive action. Both adults and children reported multiple caretakers responsible for asthma management (adult report: average 3.4, including the child); in addition, children rated their responsibility for self-care significantly higher than did adults. Scores on the Child Behavior Checklist indicated increased problems compared to normative samples (57.3 vs. 50, respectively), and 35% of children met the criteria for problems of clinical severity. On the Brief Symptom Inventory, adults reported elevated levels of psychological distress (56.02 vs norm of 50); 50% of caretakers had symptoms of clinical severity. Caretakers also experienced an average of 8.13 undesirable life events in the 12 months preceding the baseline interview. These findings suggest that limited asthma problem-solving skills, multiple asthma managers, child and adult adjustment problems, and high levels of life stress are significant concerns for this group and may place the inner-city children in this study population at increased risk for problems related to adherence to asthma management regimens and for asthma morbidity.

Short-term compliance with peak flow monitoring: results from a study of inner city children with asthma.

The objective of the study was to assess the feasibility of initiating daily peak flow monitoring in a research study of asthma in inner city children. We performed a descriptive study of patterns of peak flow monitoring in children randomized to receive a simple mini-Wright (SM) or an electronic recording meter (ERM). The ERM served as a "covert" meter, providing objective documentation of actual peak flow use. Sixty-five Hispanic or African-American children, ages 5-9 years, with a history of physician-diagnosed asthma participated in the study. All children resided in census tracts with 40% or more of the population living at or below the poverty level. Subjects were instructed to use a peak flow meter (the SM or ERM) at least twice daily over a 3 week period, and to record peak flow values in a paper diary. Subjects who received the ERM were not made aware that measurements were also recorded electronically. Differences in patterns of use of the SM and ERM were assessed with the Wilcoxon signed rank test and Wilcoxon sum rank test. Adherence to peak flow monitoring was evaluated by comparing the percent days with missing values in the manually completed diary with those obtained by computer record. The Friedman statistic was used to compare changes in compliance (percent of days with missing peak flow entries) over time. Accuracy of peak flow readings was assessed by comparing the manual and electronic recordings with paired and unpaired t-tests and with Pearson product moment correlations. The percent of days with missing peak flow entries on diaries increased from 1.4% to 10.6% from the first to third week of monitoring (P < 0.004). The ERMs indicated a significantly greater percent of missing data than did the manual records (P < 0.0002). The difference in the percent of missing data for the electronic and manual records was most notable during the third study week, when the ERM and the manually completed records indicated that 52% and 15% of days, respectively, were without peak flow measures. Large inter-subject variations in the relationship between manually and electronically recorded peak flow measurements were observed, suggesting that errors in reading and transcribing peak flow rates occur in a subset of asthmatics. We conclude that children and caretakers in the inner city may have considerable difficulty initiating and maintaining peak flow recordings. Data obtained by manual records may considerably overestimate actual use. Compliance with monitoring decreases markedly between the first and third week of monitoring.

Pre- and perinatal risk factors for asthma in inner city African-American children.

The relations between pre- and perinatal risk factors and asthma were investigated using a case-control study of 262 African-American children aged 4-9 years, both asthmatic and nonasthmatic, all of whom resided in a poor urban area and received health care at a local hospital-based clinic. Risk factors were ascertained through review of obstetric, perinatal, and pediatric records. Asthmatic children had significantly lower birth weights and gestational ages than nonasthmatic children and were more likely to have required oxygen supplementation and positive pressure ventilation after birth than nonasthmatics (p < 0.05). The mothers of asthmatic children were more likely to have smoked during pregnancy (50% vs. 27%), to have gained less weight during pregnancy (26.3 pounds (11.9 kg) vs. 34.5 pounds (15.7 kg)), and to have had no prenatal care (12% vs. 2% ) than mothers of nonasthmatic children. Multiple logistic regression demonstrated that the strongest independent predictors of asthma were maternal history of asthma (adjusted odds ratio (OR) = 9,7), lack of prenatal care (OR = 4.7), history of bronchiolitis (OR = 4.7), positive pressure ventilation at birth (OR = 3.3), low maternal weight gain (<20 pounds (<9 kg)) (OR = 3.4), and maternal smoking during pregnancy (OR = 2.8). These data suggest that pre- and perinatal exposures may increase susceptibility to asthma in inner city children.