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Notes: Christopher Robin had wheezles and sneezles, they bundled him into his bed.They gave him what goes with a cold in the nose, and some more for a cold in the head.They wondered if wheezles could turn into measles, if measles would turn into mumps;They examined his chest for a rash, and the rest of his body for swellings and lumps.They sent for some doctors in sneezles and wheezles, to tell them what ought to be done.All sorts and conditions of famous physicians came hurrying round at a run.They all made a note of the state of his throat, they asked if he suffered from thirst;They asked if the sneezles came after the wheezles, or if the first sneezle came first.They said, ‘If you teazle a sneezle or wheezle, a measle may easily grow.But humour or pleazle the wheezle or sneezle, the measle will certainly go.’They expounded the reazles for sneezles and wheezles, the manner of measles when new.They said ‘If he freezles in draughts and in breezles, then PHTHEEZLES may even ensue.’Christopher Robin got up in the morning, the sneezles had vanished away.And the look in his eye seemed to say to the sky, ‘Now, how to amuse them today?’A. A. Milne, Now We Are Six, 1927.

Notes: Background Increased production of IL-4 and IL-5 and decreased production of IFN-γ by CD4+ T cells has been implicated in asthma pathogenesis. However, CD8+ T cells also produce type 1 and type 2 cytokines and the relative roles of CD4+ and CD8+ T cell cytokine production in asthma have not been previously studied.Objective To determine the production of the type 1 and type 2 cytokines by CD4+ and CD8+ T cell subsets in asthmatic and normal subjects.Methods Intracellular cytokine staining for IL-4, -5, -10, -13 and IFN-γ was analysed in peripheral blood CD4+ and CD8+ T cells from 24 atopic asthmatic and 20 normal subjects.Results Both subsets of T cells produced all cytokines studied and there were no significant differences between CD4+ and CD8+ T cells in their capacity to produce either type 1 or type 2 cytokines. There were significantly increased frequencies of IFN-γ-positive CD4+ (13.1 ± 2.4%, vs. 7.3 ± 1.4%) and CD8+ (20.0 ± 2.9%, vs. 9.6 ± 2.1%) T cells in asthmatic subjects compared with normal subjects (P 〈 0.05), but not in frequencies of CD4+ or CD8+ T cells staining positively for IL-4, -5, -10 or -13.Conclusion The frequencies of peripheral blood CD8+ T cells producing type 1 and type 2 cytokines are comparable with the frequencies of CD4+ T cells. There was an increased frequency of IFN-γ producing CD4+ and CD8+ T cells in asthmatic compared with normal subjects. Further studies investigating T cells derived from the airways and investigating various stages within the disease process are required to further elucidate the importance of type 2 and type 1 T cell cytokine production in the pathogenesis of human allergic disease.

Notes: Background Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention.Objective To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in-vitro.Methods BEAS-2B cells were infected with major and minor RVs and the mRNA expression of IL-8, RANTES, MIP-1α, eotaxin, eotaxin-2, MCP-2, MCP-3 and MCP-4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus-specificity of the observed reactions, cells were also exposed to inactivated RVs.Results RV infection was able to up-regulate mRNA expression of IL-8, RANTES, MIP-1α, eotaxin and eotaxin-2, did not affect MCP-4, while MCP-2 and MCP-3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL-8, RANTES and eotaxin, but not for MIP-1α. When RVs were inactivated cytokine up-regulation was almost completely lost.Conclusion Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil-specific molecules eotaxin and eotaxin-2, in addition to IL-8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus-induced asthma exacerbations.

Notes: Abstract. Evidence suggests that atopic individuals may be predisposed to more severe rhinoviral colds coupled to a worsening of existing airway disease than those with asthma. The role of atopy and IgE levels, as well as their relationship to clinical disease expression have not been defined. We hypothesized that an allergic diathesis modulates rhinoviral colds and have initiated studies of normal, atopic and asthmatic subjects employing experimental rhinoviral infection, with measurements of symptom scores, viral shedding and cultures, albumin in nasal washes and serological responses. Twenty-two subjects (11 normal, 5 atopic, 6 atopic and asthmatic) participated and were inoculated with human rhinovirus serotype 16 (HRV 16). Measurements of neutralizing antibody and viral culture were performed at screening, pre-inoculation, during the cold and at 8–10 weeks convalescence. Daily symptoms were noted, nasal washes done, IgE measured and atopy was diagnosed by skin tests. Seventeen volunteers developed clinical colds as assessed by symptom scores, virus shedding was demonstrated (with positive culture) in all subjects and a fourfold or higher seroconversion occurred in 11/22. Neutralizing HRV antibody developed unexpectedly in 10 subjects between screening and inoculation and the presence or absence of this pre-inoculation antibody determined subsequent severity of colds in normal but not in atopic subjects. Atopic antibody positive individuals developed severe clinical colds that were independent of preinoculation antibody in contrast to normal subjects who developed mild colds in the presence of a neutralizing antibody (.P= 0.01). Both atopic and normal antibody negative subjects developed severe colds. This differential response was matched by nasal wash albumin levels which were significantly increased (P= 0–01) during the cold in atopic (but not in normal) volunteers with pre-inoculation antibody. Levels of IgE were not correlated with severity of clinical disease or viral shedding. Our studies of HRV disease in atopic subjects suggest heightened susceptibility to the detrimental effects of colds; additional studies are needed to clarify the relevant mechanisms.

Notes: As part of a larger epidemiological study, 114 children with respiratory symptoms, born between 1978 and 1980, were skin-prick tested to Dermatophagoides pteronyssinus (DP), mixed grass pollens (G) and cat dander (C), and to histamine and saline controls (Bencard, U.K.) using 1 mm prick-lancets (Dome/Hollister-Stier), between July and September 1987 and again in October 1989. A weal ≥ 2 mm to one or more allergens was regarded as a positive result. Each child was tested by the same investigator on each occasion, using similar techniques. Three children were excluded from analysis as they had failed to respond to histamine testing on one of the two occasions. In 1987, of the 111 children analysed, 58 (52%) children were skin-test positive, and 53 (48%) skin-test negative, while in 1989 62 (56%) were positive and 49 (44%) negative. Twelve children (11%) changed status from negative to positive, while eight (7%) changed from positive to negative. For the group as a whole the percentage agreement between the results obtained 2 years apart was 82%. In comparison to previous studies a greater number of subjects in this population than expected changed atopic status. We therefore further examined the data from those who had changed status and classified as borderline those subjects with no difference in weal size of greater than 2 mm for any allergen between 1987 and 1989. Only five children then changed status from negative to positive, none from positive to negative and 15 demonstrated only borderline changes. The coefficients of repeatability for the 106 children who did not change status were 3.37 mm, 2.80 mm and 2.33 mm for D. pteronyssinus, mixed grass pollens and cat dander respectively. The good short-term repeatability of the testing method was demonstrated in a group of 29 similar children; the coefficients of repeatability were 0.38 mm for DP and G, and 0.72 mm for C. These data demonstrate that, in a population of children with respiratory symptoms, skin-prick testing within individuals is highly repeatable over the short term, but poorly repeatable over a 2 year period. However, the percentage agreement in skin-prick test status for the group as a whole was high (82%). While no child became unequivocally skin-test negative having been previously positive, a small number of children changed status from negative to unequivocally positive, suggesting a genuine but small (4%) increase in the prevalence of skin-test positivity in this population.