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.

Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings.

Asthma is a disease characterized by chronic inflammation and reversible obstruction of the small airways resulting in impaired pulmonary ventilation. Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had ventilation defects distributed throughout the lungs compared with none of the normal subjects. These ventilation defects were more numerous and larger in the two symptomatic asthmatics who had abnormal spirometry. Ventilation defects studied over time demonstrated no change in appearance over 30-60 minutes. One asthmatic subject was studied twice in a three-week period and had ventilation defects which resolved and appeared in that time. This same subject was studied before and after bronchodilator therapy, and all ventilation defects resolved after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible ventilation defects that characterize asthma. The ability to visualize lung ventilation offers a direct method of assessing asthmatics and their response to therapy.

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.

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.

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.

Mite, cat, and cockroach exposure, allergen sensitisation, and asthma in children: a case-control study of three schools.

BACKGROUND: The amount of allergen necessary to sensitise genetically "at risk" children is unclear. The relation between allergen exposure and asthma is also uncertain. METHODS: To ensure a wide range of allergen exposures the data from case-control studies of asthma in children aged 12-14 years attending three schools in Los Alamos, New Mexico and Central Virginia were combined. Skin prick tests to indoor and outdoor allergens and bronchial hyperreactivity to histamine were assessed in children with and without symptoms of asthma. The concentration of mite, cat, and cockroach allergens in dust from the children's homes was used as a marker of exposure. RESULTS: Three hundred and thirty two children (157 with asthmatic symptoms and 175 controls) were investigated. One hundred and eighty three were classified as atopic on the basis of allergen skin prick tests and 68 as asthmatic (symptoms plus bronchial responsiveness). The prevalence and degree of sensitisation to mite and cockroach, but not cat, was strongly associated in atopic children with increasing domestic concentrations of these allergens. Asthma was strongly associated with sensitisation to indoor allergens (p<10(-6)) and weakly to outdoor allergens (p = 0.026). There was an association between current asthma and the concentration of mite allergen amongst atopic children (p = 0.008) but not amongst those who were specifically mite sensitised (p = 0.16). CONCLUSIONS: The domestic reservoir concentration of mite and cockroach, but not cat, allergen was closely related to the prevalence of sensitisation in atopic children. However, the prevalence of current asthma had a limited relationship to these allergen measurements, suggesting that other factors play a major part in determining which allergic individuals develop asthma.

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.

Sensitization to dust mites as a dominant risk factor for asthma among adolescents living in central Virginia. Multiple regression analysis of a population-based study.

Factors influencing asthma were investigated in a population of school children in central Virginia. A survey of 1,054 children in two middle schools (one urban and one suburban) identified 135 students with symptoms suggestive of asthma. Eighty-eight symptomatic children and 123 control subjects were randomly selected for further evaluation by skin testing using common indoor and outdoor allergens; serum assays for total IgE and specific IgE; dust samples assayed for mite (Der p 1 Der f 1), cat (Fel d 1), and cockroach (Bla g 2) allergens; and provocation with histamine to test for bronchial hyperreactivity. Forty-eight of the children with symptoms responded to < or = 3.9 mumol of histamine and were considered to have asthma. Marginal analysis identified elevated total IgE and dust mite, cat, and cockroach sensitization as significant risk factors for asthma. Using multiple regression, only dust mite sensitization was independently associated with asthma (odds ratio = 6.6; p < 0.0001). Dust from 81% of the houses contained high levels of mite allergen (> 2 micrograms/g), while approximately 40% of the children were exposed to cat and 17% were exposed to cockroach allergen. In this population, there was no significant association between asthma and race, socioeconomic status, home smoking, sensitization to outdoor allergens, or allergen concentration in the child's home. In an area where there is a high prevalence of asthma and most houses contain high concentrations of dust mite allergen, sensitization to this allergen is the dominant risk factor for asthma defined as symptomatic bronchial hyperreactivity

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.

Risk management, safety management, and quality assurance.

The changes that have taken place in health care during the past few years have also created changes in our hospital safety programs. We can no longer address the safety issue as a dual function of a department manager. The safety management program plays an important role in the overall success of the quality of the facility. Safety is no longer a program that stands alone and oversees the fire safety program. To have a successful risk management and quality assurance program, safety management has to be included as an integral part.

Pulpal necrosis of an unknown etiology in a newly erupted premolar: report of case.

A case of pulpal necrosis of unknown etiology in a newly erupted premolar is presented. The cause of the lesion and the pulpal involvement are open to conjecture.