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Biomedical subjects

P W Heymann

Publications and source records attributed to P W Heymann.

At least 19 recordsLinked to original sources
PubMed2001

Detection of IgA and IgG but not IgE antibody to respiratory syncytial virus in nasal washes and sera from infants with wheezing.

BACKGROUND AND OBJECTIVE: The capacity of respiratory syncytial virus (RSV) to stimulate an IgE antibody response and enhance the development of atopy and asthma remains controversial. Nasal washes and sera from 40 infants (20 with wheezing, 9 with rhinitis, and 11 without respiratory tract symptoms) were obtained to measure IgE, IgA, and IgG antibody to the immunodominant, F and G, virion proteins from RSV. STUDY DESIGN: Children (aged 6 weeks to 2 years) were enrolled in the emergency department during the mid-winter months and seen at follow-up when they were asymptomatic. All nasal washes were tested for RSV antigen. Determinations of antibody isotypes (IgE, IgA, and IgG) to RSV antigens were done in nasal washes and sera by using an enzyme-linked immunosorbent assay. In a subset of nasal washes, IgE to RSV was also evaluated by using a monoclonal anti-F(c)E antibody-based assay. RESULTS: Fifteen patients with wheezing, two with rhinitis, and one control subject tested positive for RSV antigen at enrollment. Thirteen patients with wheezing were <6 months old, and most (77%) were experiencing their first attack. Among the children with positive test results for RSV antigen, an increase in both nasal wash and serum IgA antibody to RSV-F(a) and G(a) was observed at the follow-up visit. However, there was no evidence for an IgE antibody response to either antigen. CONCLUSION: Both IgA and IgG antibodies to the immunodominant RSV-F(a) and G(a) antigens were readily detected in the nasal washes and sera from patients in this study. We were unable to demonstrate specific IgE antibody to these antigens and conclude that the production of IgE as a manifestation of a T(H)2 lymphocyte response to RSV is unlikely.

Antigens, Viral↗
PubMed2000

Salivary cotinine levels in children presenting with wheezing to an emergency department.

We set out to evaluate salivary cotinine concentrations to judge tobacco smoke exposure among infants and children, and to examine the results in relation to age and wheezing. This was a case-control study of wheezing children (n = 165) and children without respiratory tract symptoms (n = 106) who were enrolled in the Pediatric Emergency Department at the University of Virginia. The age range of both wheezing and control patients was 2 months to 16 years. Questionnaires were combined with cotinine assays in saliva to evaluate exposure to environmental tobacco smoke (ETS) for each child. The prevalence of exposure to one or more smokers at home was high (68%); and 43% of the children enrolled were exposed to ETS from their mothers. According to the questionnaires, and after adjusting for age and race, a wheezing child in this study was more likely than a control to be exposed to at least one smoker at home (odds ratio = 1.9; 95% CI = 1.1-3.4). However, the odds of exposure to ETS from smoking mothers did not differ significantly between wheezing and control patients, and no significant association was found between the presence of wheezing and salivary cotinine levels. Among children exposed to ETS at home, cotinine levels were significantly higher in saliva from those under the age of two years, and from toddlers aged 2 and 3 years, compared to values from children over age 4 years. Moreover, the number of smokers in the home strongly influenced cotinine levels from children under age 4 years. In addition, higher cotinine levels were observed in saliva from children under age 2 years who were exposed to ETS from their mothers. Cotinine levels were similar and significantly correlated in paired samples of saliva and serum from children under 4 years of age (n = 54), (r = 0.92, P < 0.001). Based on information gathered from questionnaires, the results indicate that wheezing children were more likely than controls to be exposed to ETS at home. However, significant differences in ETS exposure between wheezing and control groups with respect to maternal smoke exposure or comparisons of salivary cotinine levels were not apparent. It was clear that determinations of salivary cotinine for monitoring the prevalence and intensity of household smoke exposure in this study were most valuable during the first 4 years of life.

Adolescent↗
PubMed2000

The relevance of allergen exposure to the development of asthma in childhood.

Sensitization to 1 or more of the common indoor allergens has been consistently associated with asthma among children and young adults (odds ratios for asthma, 3-18). For dust mite and cockroach allergens, there is a dose response relationship between domestic exposure and sensitization. Given that allergen provocation can induce many of the features of asthma, the findings strongly suggest that there is a causal relationship between allergen exposure in the home and asthma. However, it remains unclear at what time the critical exposure occurs (ie, in infancy or later) and what role allergen exposure has played in the increasing prevalence and severity of asthma. Objective evidence of an immune response to allergens is generally not present until after 2 years of age. Viral infections play several different roles in asthma in childhood. In infancy, respiratory syncytial virus infection can induce bronchiolitis and set up recurrent wheezing over the next few years. However, the risk factors for this are maternal smoking and small lungs at birth, rather than allergy. By contrast, the role of rhinovirus in precipitating attacks in children and young adults is strongly associated with allergy. Thus the likely scenario is that allergen exposure over the first few years of life induces sensitization (ie, T(H2) cells and IgE antibodies). Continuing exposure can maintain inflammation in the nose and lungs. However, many other factors contribute to wheezing such that there is no simple relationship between allergen exposure and asthma. Nonetheless, it is clear that the changes that have increased asthma have acted on allergic children.

Allergens↗
PubMed2000

Lactoferrin and eosinophilic cationic protein in nasal secretions of patients with experimental rhinovirus colds, natural colds, and presumed acute community-acquired bacterial sinusitis.

To distinguish sinusitis from uncomplicated "colds," we examined lactoferrin and eosinophilic cationic protein (ECP) in nasal secretions. Lactoferrin titers were >/=1:400 in 4% of persons with uncomplicated colds and controls but in 79% of persons with sinusitis or purulent sputa. ECP levels were >200 ng/ml in 61% of persons with colds and >3,000 ng/ml in 62% of persons with sinusitis. Nasal lactoferrin helps distinguish sinusitis from colds.

Bacterial Infections↗
PubMed2000

Specific and nonspecific obstructive lung disease in childhood: causes of changes in the prevalence of asthma.

Reversible airway obstruction in childhood includes two major groups of patients: those with recurrent wheezing following bronchiolitis in early childhood, and those with allergic asthma, which represents an increasingly large proportion of cases through the school years. Over the last 40 years of the 20th century, allergic asthma has increased in many countries and in relation to several different allergens. Although this increase has differed in magnitude in different countries and also in the social groups most affected, it has had several features in common. The increase generally started between 1960 and 1970, has been progressive since then, and has continued into the 1990s without a defined peak. Among children 5-18 years of age, the increase has predominantly been among allergic individuals. Theories about the causes of the increase in asthma have focused on two scenarios: a) that changes in houses combined with increased time spent indoors have increased exposure to relevant allergens, or b) that changes in diet, antibiotic use, immunizations, and the pattern of infections in childhood have led to a change in immune responsiveness such that a larger section of the population makes T(H)2, rather than T(H)1 responses including IgE antibodies to inhalant allergens. There are, however, problems with each of these theories and, in particular, none of the proposed changes can explain the progressive nature of the increase over 40 years. The fact that the change in asthma has much in common with epidemic increase in diseases such as Type II diabetes or obesity suggests that similar factors could be involved. Several lines of evidence are reviewed that suggest that the decline in physical activity of children, particularly those living in poverty in the United States, could have contributed to the rise in asthma. The hypothesis would be that the progressive loss of a lung-specific protective effect against wheezing has allowed allergic children to develop symptomatic asthma. What is clear is that current theories do not provide either an adequate explanation of the increase or a practical approach to reversing the current trend.

Allergens↗
PubMed1999

Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses.

This cross-sectional emergency department study of 70 wheezing children and 59 control subjects (2 mo to 16 yr of age) examined the prevalence of respiratory viruses and their relationship to age, atopic status, and eosinophil markers. Nasal washes were cultured for respiratory viruses, assayed for respiratory syncytial virus (RSV) antigen, and tested for coronavirus and rhinovirus RNA using reverse transcription-PCR (RT-PCR). Also evaluated were eosinophil numbers and eosinophil cationic protein (ECP) in both nasal washes and serum, along with total IgE and specific IgE antibody in serum. Respiratory viruses were detected in 82% (18 of 22) of wheezing infants younger than 2 yr of age and in 83% (40 of 48) of older wheezing children. The predominant pathogens were RSV in infants (detected in 68% of wheezing subjects) and rhinovirus in older wheezing children (71%), and both were strongly associated with wheezing (p < 0.005). RSV was largely limited to wheezing children younger than 24 mo of age, but rhinovirus was detected by RT-PCR in 41% of all infants and in 35% of nonwheezing control subjects older than 2 yr of age. After 2 yr of age the strongest odds for wheezing were observed among those who had a positive RT-PCR test for rhinovirus together with a positive serum radioallergosorbent testing (RAST), nasal eosinophilia, or elevated nasal ECP (odds ratios = 17, 21, and 25, respectively). Results from this study demonstrate that a large majority of emergent wheezing illnesses during childhood (2 to 16 yr of age) can be linked to infection with rhinovirus, and that these wheezing attacks are most likely in those who have rhinovirus together with evidence of atopy or eosinophilic airway inflammation.

Adolescent↗
PubMed1997

The role of domestic allergens.

The documented increase in asthma has been almost entirely in perennial asthma and a large proportion of the cases are allergic to one of the common allergens found all year round in houses, i.e. house dust mites, cats, dogs or cockroaches. In population and case-control studies sensitization to one of these allergens is the strongest risk factor for asthma (adjusted odds ratios > or = 4). Using monoclonal antibody-based assays for the major indoor allergens it has been shown that sensitization to house dust mites is directly related to the concentration of Group 1 mite allergen in dust. This led to the hypothesis that increases in mite allergen secondary to changes in houses were responsible for increases in asthma. However, asthma has also increased in areas of the world where mites do not flourish. In these dry areas sensitization to one of the other indoor allergens is the major risk factor for asthma. Although sensitization of asthmatics reflects the concentration of allergens in their houses, these measurements of exposure do not accurately predict severity of symptoms. Other factors that can contribute to the symptoms of asthma may also have increased. In particular, diesel particulates, ozone, beta 2-agonists, endotoxin and rhinovirus infection have each been shown to enhance the inflammatory response to inhaled allergens. Increases in asthma must relate to some aspect of our predominantly sedentary indoor lifestyle; this could be either increased exposure to allergens or an increase in factors that enhance the response of the lungs to foreign proteins.

Allergens↗
PubMed1996

Changing concepts of allergic disease: the attempt to keep up with real changes in lifestyles.

In the past 100 years, changes have occurred in the outdoor environment and in houses that have contributed to the increased prevalence of hay fever and asthma. Much evidence indicates that exposure to indoor allergens is an important cause of asthma. Changes in housing that have contributed to the increased prevalence and severity of asthma include increased temperature, decreased ventilation, and permanent carpeting. In addition to these changes, geographic differences in allergens, deficiencies in cleanliness, poor health care, passive smoke, and lack of exercise also contribute to the increase in severity of asthma that has occurred. The management of asthma includes controlling exposure to indoor allergens and seeking additional treatable causes of asthma (e.g., fungal allergens). Changes will continue to occur, and physicians who treat allergic diseases should become involved in the design of houses to limit exposure. Many questions regarding allergen measurement and control remain.

Allergy and Immunology↗
PubMed1995

Eosinophil cationic protein in serum and nasal washes from wheezing infants and children.

OBJECTIVE: To compare eosinophil counts and concentrations of eosinophil cationic protein (ECP) in serum and nasal wash fluid from wheezing infants and children with those from age-matched children without respiratory tract symptoms. DESIGN: A case-control study of 71 children treated for wheezing and 59 control subjects in the University of Virginia Pediatric Emergency Department. The patients ranged from 2 months to 16 years of age. Eosinophil numbers and ECP concentrations were assessed in serum and nasal washes. Total serum IgE was measured and the radioallergosorbent test was used to measure IgE antibody to common inhalant allergens. RESULTS: Among children less than the age of 2 years, markedly elevated levels of ECP (> 200 ng/ml) were measured in nasal washes from 9 (41%) of 22 wheezing patients and 1 (6%) of 17 control subjects (p < 0.03). None of these children had a positive radioallergosorbent test result for IgE antibody to common aeroallergens or a nasal smear containing 10% eosinophils. Few of the wheezing children under 2 years of age had either increased concentrations of total IgE or ECP in their serum or an elevated total blood eosinophil count. After the age of 2 years, the percentage of patients with nasal ECP levels greater than 200 ng/ml was also significantly higher in wheezing children than in control subjects (p < 0.001), and a positive correlation was observed between ECP concentrations in their nasal washes and other eosinophil responses (total blood eosinophil counts, serum ECP levels, and nasal eosinophil counts). CONCLUSION: Increased concentrations of ECP were detected in nasal washes from wheezing infants and children, indicating that eosinophils may contribute to the pathogenesis of airway inflammation in some children who wheeze early in life.

Adolescent↗
PubMed1995

Monitoring allergen exposure in asthma: new treatment strategies.

The development of monoclonal antibody-based enzyme-linked immunosorbent assay technology for measuring environmental allergen exposure has provided a benchmark for assessing the role of indoor allergens in causing asthma and other allergic diseases. Epidemiological studies from several parts of the world have shown that immunoglobulin E (IgE)-mediated sensitization to indoor allergens (mite, cat, dog and cockroach) is a risk factor for asthma attacks. A dose-response relationship between allergen exposure and sensitization has been demonstrated for mite allergens, and threshold values for exposure levels leading to sensitization or to exacerbations of symptoms have been defined. Comparative studies on airborne allergen levels have made it possible to determine the properties of aeroallergen particles, their concentration in indoor air, and the relationship to clinical symptoms. Together, these studies provide strong evidence that allergen exposure plays a causal role in the development of bronchial hyperreactivity and of the chronic inflammatory responses seen in patients with asthma. Logically, the primary preventive treatment should be allergen avoidance. Through knowledge of indoor allergen levels, both in dust and in the air, different avoidance strategies have been applied to the various indoor allergens, and there is increasing evidence of their clinical efficacy. Monitoring allergen levels in patients' houses should improve their understanding of the role of allergens in asthma and improve compliance with avoidance measures.

Allergens↗
PubMed1994

Monoclonal antibodies to group II Dermatophagoides spp. allergens: murine immune response, epitope analysis, and development of a two-site ELISA.

BACKGROUND: Group II allergens are a major cause of sensitization in patients allergic to mites. To facilitate the antigenic analysis of group II allergens and to develop improved methods of allergen detection, we compared IgG anti-group II antibody responses in inbred mouse strains and raised a panel of monoclonal antibodies (mAbs). METHODS: IgE antibody responses were compared by antigen-binding radioimmunoassay. Epitope specificity of the mAbs was analyzed by two-site binding assays and by cross-inhibition radioimmunoassays. RESULTS: Comparison of polyclonal IgG antibody responses in five BALB congenic strains showed that H-2d mice had poor responses, whereas H-2b and H-2k mice had strong, cross-reactive, IgG anti-group II responses. The specificities of nine anti-Der p II IgE mAbs raised in A/J mice were compared with specificities of seven mAbs produced previously. Most mAbs (11 of 16) recognized common epitopes on Der p II and Der f II: three were specific to Der p II, and two showed high binding to Der f II. Epitope analysis showed that the mAbs defined four cross-reactive, nonoverlapping sites on the group II allergens. Binding of several combinations of mAbs was compared, and a two-site ELISA for group II antigens was developed. Linear regression analysis showed an excellent correlation between results of this assay and group II radioimmunoassay of house dust samples (n = 40, r = 0.85, p < 0.001). CONCLUSIONS: There are multiple cross-reactive B-cell epitopes on group II allergens. The group II ELISA has several important applications, including assessment of environmental allergen exposure, monitoring of the efficacy of avoidance procedures, and standardization of commercial mite allergen extracts.

Allergens↗
PubMed1994

Development of immune responses to Aspergillus at an early age in children with cystic fibrosis.

Although the ability of Aspergillus organisms to colonize the respiratory tract in patients with cystic fibrosis (CF) is well recognized, the contribution of Aspergillus to the disease process is poorly understood. Using sera from 147 CF patients (age 5 to 43 yr), we measured IgE antibody (ab) to Aspergillus fumigatus and five common inhalant allergens with a radioallergosorbent test (RAST). Total IgE levels and IgG ab to radio-labeled Asp f I, an allergen purified from A. fumigatus and a potent inhibitor of protein synthesis, were also measured. Thirty (20%) of the patients had IgE ab to A. fumigatus, and 22 (15%) of these patients had developed total IgE levels > or = 400 IU/ml, raising the consideration of a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). Five of the 22 patients developed these IgE responses by age 5 yr and 14 by age 10 yr. The proportion of patients with IgE ab to one or more of the other allergens tested was not significantly different from that of control subjects without respiratory symptoms. A striking proportion (84%) of CF sera contained IgG ab to Asp f I, compared with 6% of sera from control patients and 20% of sera from allergic children with asthma (n = 25), only one of whom had IgE ab to A. fumigatus. In an examination of additional sera from young CF patients, IgG anti-Asp f I ab was detected in 41% of these sera from patients 5 yr of age or older, increasing to 98% of 89 sera from patients older than age 10.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Risk factors for acute wheezing in infants and children: viruses, passive smoke, and IgE antibodies to inhalant allergens.

OBJECTIVE: To examine the prevalence of viral infection, passive smoke exposure, and IgE antibody to inhaled allergens in infants and children treated for acute wheezing. DESIGN: Case-control study of actively wheezing children who were compared with children without respiratory tract symptoms. SETTING: University of Virginia Pediatric Emergency Room. PATIENTS: Convenience sample of 99 wheezing patients (2 months to 16 years of age) and 57 control patients (6 months to 16 years of age). MEASUREMENTS AND RESULTS: Serum IgE antibody to inhalant allergens, measured by radioallergosorbent test (RAST), was uncommon in wheezing and control patients under age 2. After 2 years of age, the percentage of RAST-positive patients increased markedly and was significantly higher in wheezing patients than controls after age 4 (72%, n = 54, and 30%, n = 40, respectively, P < .001). Total IgE levels and nasal eosinophilia were strongly correlated with a positive RAST after age 2. Viral pathogens, predominantly respiratory syncytial virus, were identified in nasal washes from 70% (n = 20) of wheezing patients younger than 2 years of age compared with 20% of controls (n = 10), P < .05. After age 2, viruses, particularly rhinovirus, were isolated in washes from 31% (n = 70) of wheezing patients, 64% of whom were also RAST-positive. Levels of cotinine, a nicotine metabolite, were elevated (> or = 10 ng/mL) in saliva from a large percentage of smoke-exposed, wheezing patients under 2 (74%, n = 19) compared with those over 2 (14%, n = 51), P < .001. Odds ratios for wheezing were significant for virus (8.2, confidence interval [CI] = 1.3 to 5.0), and cotinine (4.7, CI = 1.0 to 21.3) in children under 2, and IgE antibody by RAST (4.5, CI = 2.0 to 10.2), virus (3.7, CI = 1.3 to 10.6), and the combination of IgE antibody and virus (10.8, CI = 1.9 to 59.0) were significant risk factors after age 2. CONCLUSION: Wheezing children younger than 2 years of age had a high rate of viral infection and a low rate of IgE antibody to inhalant allergens. When these children were exposed to passive smoke, salivary cotinine levels were elevated suggesting heavy exposure. After 2 years of age, sensitization to inhaled allergens became increasingly important and viruses remained a significant risk factor for wheezing. These data support recommendations to reduce tobacco smoke exposure at home, especially for young patients, and to consider sensitization to inhaled allergens and allergen avoidance in wheezing children at an early age, particularly after age 2 years.

Adolescent↗
PubMed1992

Benzyl benzoate moist powder: investigation of acaricidal [correction of acarical] activity in cultures and reduction of dust mite allergens in carpets.

Despite advances in the understanding of dust mites, it remains difficult to control exposure to mite allergens, and it is particularly difficult to reduce mites in fitted carpets or sofas. Several chemicals have been demonstrated to kill mites or denature mite allergens, and some of these chemicals have been investigated in carpets. Benzyl benzoate (BB), which has been widely used to kill scabies mites and is known to kill mites of the genus Dermatophagoides, has been used as a method of treating carpets. The present article describes experiments in the laboratory and in houses in testing two preparations of BB, a moist powder and a foam. The moist powder is composed of two ingredients, a wetted "inert" cellulose, which is designed to act as a cleaning agent, and the active BB adsorbed onto silicates. The active powder kills 90% of mites in culture within 12 hours and 100% in 24 hours, whereas the cellulose is not acaricidal. The moist-powder preparation was highly effective at killing D. farinae and D. pteronyssinus mites in the laboratory. In carpets the moist powder, applied for 12 hours with repeated brushing, was demonstrated to reduce the concentrations of group I and group II dust mite allergens in dust recovered at 1 month. This decrease in concentration could, in part, be explained by a persistent increased recovery of dust caused by residual white powder. However, when the recovery of group II allergens was calculated as the total allergen recovered, the decrease was highly significant at 2 weeks and 4 weeks after treatment (p less than 0.001). Application of the powder to carpets for 4 hours or of the foam to sofas was less effective. After 2 months the effect on mite antigen in carpets was still present, but some increase was apparent, suggesting that repeat application after 2 or 3 months would be necessary to control mite-allergen levels.

Allergens↗