Gary P. Rakes

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. J. Magn. Reson. Imaging 2001;13:378–384.

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.

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

Abstract 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, TH2 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. (J Allergy Clin Immunol 2000;105:S503-8.)

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.

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.

VIRUS-INDUCED WHEEZING IN CHILDREN: Respiratory Syncytial Virus (RSV) and Rhinovirus

The strong association between infantile wheezing and respiratory tract infections caused by the respiratory syncytial virus (RSV) has been well established. In studies of older children, rhinovirus becomes the major virus associated with asthma. These relationships are outlined in the box on page 36. In the past, this relationship was more difficult to appreciate, because rhinovirus does not always grow well in culture. In addition, the linkage between asthma and atopy during childhood has raised the question whether viral infections alone can precipitate exacerbations of asthma. Use of the polymerase chain reaction (PCR) to measure viral nucleic acid material has provided the opportunity to study virus-induced wheezing among children in greater detail, and investigations of experimental rhinovirus infections in adults have demonstrated how this virus can augment both the early and late phase manifestations of airway hyperreactivity. This article reviews recent advances that have enhanced our understanding of virus-induced wheezing, along with new information indicating that interactions between viral infections and allergic inflammation may be critical to the pathogenesis of acute symptoms.

Role of viral infections in exacerbations of asthma. Allergy must also be a factor.

EDITOR,--Sebastian L Johnston and colleagues from Southampton report impressive data supporting an association between viral infections (predominantly rhinoviruses) and exacerbations of asthma among children of school age.1 The association they observed was so strong that it is not surprising that they imply that there could be a causal relation between viral infection and exacerbations of asthma. They recognise that the argument that rhinoviruses could cause exacerbations of asthma is not new. They do not, however, mention that there have been …