IgE receptors on human basophils. Relationship to serum IgE concentration.

As reported previously, and confirmed here in 26 donors, the serum IgE level (2.6-5,500 ng/ml) correlates well (rs = 0.95, P less than 0.001) with the in vivo number of IgE molecules/basophil (6,000-600,000). The total number of IgE receptors/basophil was monitored by incubating them with an IgE-rich serum (15 microgram/ml), quantitatively stripping IgE from the cells at pH 3.7, and measuring eluted IgE by a direct radioimmunosorbent test. Saturation of receptors for each donor was achieved with 15 nM IgE (3 microgram/ml). The proportion of receptors occupied in vivo correlated with the serum IgE (rs = 0.84, P less than 0.001) whereas the average association constant of the receptors was independent of serum IgE and ranged from 7.1 X 10(8)/M to 2.8 X 10(10)/M, averaging 7.7 X 10(9)/M. Unexpectedly, the total number of IgE receptors/basophil was closely related to the serum IgE level. (rs = 0.92, P less than 0.001). Thus, either there is genetic association between serum IgE and the number of basophil IgE receptors, or, more likely, the receptor number is modulated by the serum IgE concentration.

The role of basophils in inflammatory reactions.

This review demonstrates that basophils reflect skin and lung mast cell reactivity and show characteristic changes in mediator release associated with clinical disease. Although the numbers of IgE molecules and IgE receptors on basophils have been enumerated, these have, in most instances, little influence on the release of histamine after challenge. There is, rather, a parameter of "releasability" that may be a major variable in allergic disease states. Basophils contain and release histamine, the eosinophil chemotactic factor of anaphylaxis (ECFA), a slow reacting substance of anaphylaxis (SRS-A), and a kallikrein. The release process is controlled by hormone-basophil receptor interactions that determine the cyclic AMP level; plasma and tissue adenosine levels appear prominent in this control. Histamine feeds back to negatively modulate basophil and mast cell release through a specific histamine 2-receptor; it also inhibits lymphocyte and neutrophil function. Like neutrophils, basophils contain beta-glucuronidase while neutrophils contain SRS-A and a low-molecular-weight ECF. The stimuli for primary basophil and neutrophil release are, however, quite different, although phagocytic stimuli, which fail to cause basophil mediator release, potentiate the IgE response. It is concluded that basophols play a significant in vivo role in inflammation by acting as an interface between foreign antigens, the serum cascade systems, and other inflammatory cells.

Verofylline, a methylxanthine bronchodilator, in asthma.

Verofylline, a long-acting polysubstituted methylxanthine bronchodilator, was taken orally by eight adult patients with asthma in a double-blind, crossover tolerance study. Peak expiratory flow, forced vital capacity, and its subdivisions were measured weekly 2, 4, and 6 hr after oral dosing with drug or placebo. Peak drug activity developed between 4 and 6 hr after dosing. Subject tolerance was good at the doses used. Dose-response curves for mean forced expiratory volume in one second, peak expiratory flow rate, and forced expiratory flow at the end of 4 hr were greater after 0.05 mg/kg verofylline than after placebo or higher doses of verofylline. Mean percent change in forced vital capacity remained increased as long as 6 hr after 0.15 mg/kg active drug. Verofylline was not very effective as a bronchodilator at the doses used.

Medications used by children with asthma living in the inner city.

OBJECTIVE: The purpose of the study was to examine medication use reported by families participating in an urban school-based community intervention program and to relate this use to other social and medical variables. DESIGN: The design of the study was a cross-sectional questionnaire survey. SETTING: Patients and their families recruited from elementary schools in a community setting were interviewed between December 1991 and January 1992. PARTICIPANTS: A total of 508 children with asthma were identified by school health records and teacher surveys. Their families confirmed the diagnosis and agreed to enter the study. Questionnaires were completed by 392 families. INTERVENTION: The 392 families participated in a controlled trial of asthma education after providing the data that are the basis of this report. RESULTS: More than half of the children took two or more medications for asthma. Thirty-one percent took theophylline alone or in combination with an adrenergic agent; 11% took some form of daily antiinflammatory medication, either cromolyn (8%) or inhaled steroids (3%). The pattern of medication use related to measures of severity and to regular visits to physicians or nurses. In general, however, children were undermedicated. A total of 78 children (20%) reported no medication or over-the-counter medication use, although 37% reported asthma severe enough to be associated with >/=20 days of school missed per month, and 37% had had an emergency room visit for asthma in the past 6 months. More than half of children >/=9 years old supervised their own medication. CONCLUSIONS: We concluded that undermedication is common in poor children with asthma living in urban areas. Antiinflammatory medications are used less commonly than in the general population, and theophylline is used more often. School children may be likely to supervise their own medication.

Environmental risk factors of childhood asthma in urban centers.

Asthma morbidity and mortality are disproportionately high in urban centers, and minority children are especially vulnerable. Factors that contribute to this dilemma include inadequate preventive medical care for asthma management, inadequate asthma knowledge and management skills among children and their families, psychosocial factors, and environmental exposure to allergens or irritants. Living in substandard housing often constitutes excess exposure to indoor allergens and pollutants. Allergens associated with dust mites (DM) and cockroaches (CR) are probably important in both onset and worsening of asthma symptoms for children who are chronically exposed to these agents. Young children spend a great deal of time on or near the floor where these allergens are concentrated in dust. Of children (2 to 10 years of age) living in metropolitan Washington, DC, 60% were found to be sensitive to CR and 72% were allergic to DM. Exposure to tobacco smoke contributes to onset of asthma earlier in life and is a risk factor for asthma morbidity. Since disparity of asthma mortality and morbidity among minority children in urban centers is closely linked to socioeconomic status and poverty, measures to reduce exposure to environmental allergens and irritants and to eliminate barriers to access to health care are likely to have a major positive impact. Interventions for children in urban centers must focus on prevention of asthma symptoms and promotion of wellness.

Maternal depressive symptoms and emergency department use among inner-city children with asthma.

CONTEXT: Inner-city minority children with asthma use emergency departments (ED) frequently. OBJECTIVE: To examine whether maternal depressive symptoms are associated with ED use. DESIGN, SETTING, AND PATIENTS: Baseline and 6-month surveys were administered to mothers of children with asthma in inner-city Baltimore, Md, and Washington, DC. MAIN OUTCOME MEASURES: Use of the ED at 6-month follow-up was examined. Independent variables included asthma morbidity, age, depressive symptoms, and other psychosocial data. RESULTS: Among mothers, nearly half reported significant levels of depressive symptoms. There were no demographic or asthma-related differences between the children of mothers with high and low depressive symptoms. However, in bivariate analyses, mothers with high depressive symptoms were 40% (prevalence ratio [PR], 1.4; 95% confidence interval [CI], 1.0-3.6; P =.04) more likely to report taking their child to the ED. Mothers aged 30 to 35 years were more than twice as likely (PR, 2.2; 95% CI, 1.9-9.3; P =.001) to report ED use, as were children with high morbidity (PR, 1.9; 95% CI, 1.4-7.1; P =.006). Child age and family income were not predictive of ED use. After controlling for asthma symptoms and mother's age, mothers with depressive symptoms were still 30% more likely to report ED use. CONCLUSIONS: Depression is common among inner-city mothers of children with asthma. Beyond asthma morbidity, maternal age and depressive symptoms are strong predictors of reports of ED visits. Identifying and addressing poor psychological adjustment in mothers may reduce unnecessary ED visits and optimize asthma management among inner-city children.

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.

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.

Distinguishing between activated and nonactivated eosinophils by AC impedance measurements.

A cellular electrical impedance device which can detect the activated state of eosinophils has been developed and tested. This impedance device consists of a small gold electrode (50 microns x 50 microns) and a large gold electrode (1.5 cm x 0.5 cm) on a glass substrate, and it was fabricated by standard photolithographic techniques. Eosinophils, which belong to the granulocytic class of white blood cells, exhibit different physical properties when they change from the nonactivated state to the activated state. Hypothetically, these changes should correspond to a change in the measured electrical impedance. In this paper, data from the measured electrical impedance of eosinophils is presented. The measurements show that the average impedance of the activated eosinophils is 26% lower than the average impedance of the nonactivated eosinophils. Statistical analysis of the measured data shows that there is a significant difference between the measured impedances of activated and nonactivated eosinophils.

Influence of dietary cyanide on immunoglobulin and thiocyanate levels in the serum of Liberian adults.

Serum thiocyanate, antibody titers to thiocyanates, and serum immunoglobulins (IgM, IgG, IgA) were measured in 73 Liberian adults normally consuming diets of low, moderate, high, or no (control) cassava-derived cyanide (CN(-)). When control and low groups (n = 40; daily intake less than 0.60 mg CN(-) per kg body weight) were contrasted with moderate and high groups (n = 33; daily intake greater than or equal to 0.60 mg CN(-) per kg body weight), the authors observed that (1) one-time serum thiocyanate measurements were not sensitive to long-term cyanide intake; however, (2) antibody titers to thiocyanates were positively correlated with cassava-based cyanide intakes (r = .22, P = 0.05); and (3) serum IgM, IgG, and IgA levels were elevated in individuals regularly consuming moderate and high levels of dietary cyanide. Possible responsible mechanisms and health implications are discussed.

Social factors associated with behavioral problems in children with asthma.

The objective of this study was to describe the proportion of children with a behavior problem and examine which independent variables are associated with the presence of a behavior problem in a group of 392 inner-city children with asthma. Data on child asthma symptoms, medication use, health-care utilization, and school absences were obtained from the parent during a structured telephone interview. Included in the interview was a measure of behavior problems and social support questions. Children classified with a high level of asthma symptoms were more than twice as likely to experience a behavior problem than children classified with a low level of asthma symptoms (P = 0.002). Use of theophylline medication was not correlated with behavior problems (P = 0.45). Significant variables were low level of social support and high or moderate level of asthma symptoms. We have identified a group of children at risk for behavior problems, specifically in families that lack adequate social and financial resources.

Use of community health workers with inner-city children who have asthma.

Use of community health workers (CHWs) to obtain health, social, and environmental information from African-American inner-city children with asthma was one component of a larger intervention study designed to reduce morbidity in African-American children with asthma. A subset of 140 school-aged children with asthma was recruited and enrolled in a program to receive home visits by CHWs for the purposes of obtaining medical information and teaching basic asthma education to the families. Data obtained by the CHWs revealed low inhaled steroid use, high beta 2 agonist use, frequent emergency-room visits, decreased primary-care visits, and increased allergen and irritant exposure. Appropriately recruited and trained CHWs are effective in obtaining useful medical information from inner-city families with children with asthma and providing basic asthma education in the home.

Moving health care education into the community.

The A+ Asthma Club, an educational program developed for elementary school children in inner-city schools, is offered through a series of six sessions during school hours with an additional three booster sessions. This article describes how the program was designed, its theoretical basis, the curriculum and its staffing.

Staphylococcal acid phosphatase: preliminary physical and chemical characterization of the loosely bound enzyme.

At temperatures between 45 and 50 C, staphylococcal acid phosphatase purified 44-fold had maximal activity at pH 5.2 to 5.3. However, the enzyme was most stable in the alkaline range (pH 8.5 to 9.5) at temperatures below 50 C. Iodoacetate and ethylenediamine-tetraacetic acid were effective inhibitors, whereas mercaptoethanol and Cu(2+) acted as stimulators. The energy of activation for hydrolytic cleavage of the synthetic substrate, p-nitrophenyl phosphate, was 19.5 Kcal/mole. K(m) for the same substrate was 4.5 x 10(-4)m. The purified enzyme was most active against the substrates p-nitrophenyl phosphate and glyceraldehyde 3-phosphate.

Staphylococcal acid phosphatase: extensive purification and characterization of the loosely bound enzyme.

Acid phosphatase of Staphylococcus aureus PS55 was eluted from the surface of these cells with 1.0 m KCl at pH 8.5 by gentle agitation at 25 C and was purified 44-fold (51% recovery) by two cycles of dialysis and gel filtration. The eluted enzyme which had a 280/260 (nm) absorbancy ratio of 0.71 required at least 0.5 m salt solution for solubilization; however, most of the purified product which had a 280/260 (nm) absorbancy ratio of 1.72 was soluble in dilute buffer solution [0.01 m tris(hydroxymethyl)aminomethane chloride, pH 8.5]. Purified acid phosphatase appeared homogeneous according to the criteria of gel filtration, starch-block electrophoresis, and analytical ultracentrifugation. In a starch block, migration was toward the cathode at pH 8.0. Maximal activity occurred at pH 5.2 to 5.3 and salt concentration had little effect on phosphatase activity up to 1.0 m KCl or NaCl. Progressive loss of enzymatic acitivity occurred at higher salt concentrations. Molecular weight of purified acid phosphatase was estimated to be 58,000.