IgE expression pattern in lung: relation to systemic IgE and asthma phenotypes

BACKGROUND: IgE-mediated responses contribute to allergy and asthma. Little is understood regarding the relationship of tissue IgE to systemic IgE, inflammation or clinical outcomes. OBJECTIVES: To evaluate local IgE expression and cellular inflammation in the proximal and distal lung of normal subjects and subjects with asthma of varying severity and relate those tissue parameters to systemic IgE levels, atopy, lung function, and history of severe exacerbations of asthma. METHODS: Tissue from more than 90 subjects with eosinophilic (SAeo(+)) and noneosinophilic (SAeo(-)) severe asthma, mild asthma and normal subjects were immunostained for IgE, signal-amplifying isoform of IgE receptor (FcepsilonRIbeta) and markers of mast cells, eosinophils, and lymphocytes. Tissue expression of IgE, FcepsilonRIbeta, cellular inflammation, serum IgE, and atopy were compared. Regression models were used to determine the relationship of local and systemic IgE to lung function and severe exacerbations of asthma. RESULTS: Mast cell-bound IgE was present along airways but absent in lung parenchyma. Although the groups were similar in systemic/serum IgE and atopy, local/tissue IgE was highest in SAeo(+) and correlated with eosinophils and lymphocytes (r(s) = 0.52, P < .0001; and r(s) = 0.23, P = .03, respectively). Higher local IgE was associated with better lung function, but also with more severe exacerbations of asthma. CONCLUSION: Local IgE appears to be primarily a component of responses within the mucosal immune compartment and is related to cellular inflammation, lung function, and clinical outcomes in asthma. CLINICAL IMPLICATIONS: Local/airway IgE-related processes rather than systemic markers of atopy may be relevant in determining clinical outcomes in asthma.     

Clinical correlates of rhinovirus infection in preschool asthma

Background

Investigation of preschool asthma is important since not all children outgrow their illness during this age. Data are scarce on the role of rhinovirus (RV) infections in this patient group.

Objectives

To investigate the role of RV infections in preschool asthma: (i) susceptibility factors, (ii) clinical course, and (iii) medium-term outcome.

Methods

A total of 130 asthmatic children aged 4-6 years from the multinational PreDicta cohort were prospectively followed for a 12-month period. Allergy tests and a standard health questionnaire were carried out at study entry. Respiratory virus presence in nasopharyngeal washes was studied at illness visits and at 3 scheduled visits.

Results

At study entry, mean age of the children was 5.3 years. Of 571 visits, 54% were positive for any virus and 39% for RV. Patient characteristics were only assessed with RV infection due to low number of other viruses. The use of supplementary vitamin D was inversely associated with RV infection (P < .05). RV infection was associated with more severe course of acute illness in terms of more severe nighttime coughing, more sleep disturbances, and more days with runny nose (all P < .05). RV infection was also associated with more severe disease course during the 12-month follow-up in terms of more nights with awakenings and more days of exercise-related symptoms (both P < .05).

Conclusions

Vitamin D supplementation may have an anti-rhinovirus effect. Both short- and medium-term outcomes suggest RV infection to be an important clinical marker of instable preschool asthma.

     

Ascaris reinfection of slum children: relation with the IgE response.

Total and Ascaris-specific serum IgE levels were measured in a group of 98 Ascaris-infected children from a slum area of Caracas, Venezuela, in whom the infections were eliminated by regular treatment for 22 months with the anthelmint Oxantel/Pyrantel ('Quantrel'). The children were re-evaluated at the end of the treatment programme, and then 8 months later, at which time reinfection was assessed. Total IgE levels at the beginning of the study were significantly higher in the children who became reinfected after treatment, compared with those who did not. The anthelmint treatment caused a significant decrease in the total IgE levels in most of the children, and after a period of 8 months without treatment these continued to decrease in the non-reinfected group, but increased again in the reinfected children. The reverse pattern was found for Ascaris-specific IgE antibody levels, and in fact an inverse correlation was found between total and anti-Ascaris IgE levels. Striking associations were found between reinfection and high pretreatment values of total IgE, but low levels of specific IgE antibody. These data support the concept that specific IgE antibody may participate in the protection against helminthic infection, and suggest that the polyclonal stimulation of IgE synthesis caused by these parasites may reduce the effectiveness of such responses. The results also indicate that different individuals have varying propensities to respond polyclonally to the helminths, and this influences their resistance to infection.     

Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy

BACKGROUND: Annual influenza vaccination is currently recommended as a preventative measure for all patients with asthma. However, the effect of maintenance corticosteroid therapy on the immune response to influenza vaccine has received limited evaluation. OBJECTIVE: In this study, we evaluated the effect of corticosteroid therapy on the immune response to influenza vaccine in children and adults with asthma. METHODS: This was a substudy of a larger multicenter, randomized, double-masked, placebo-controlled, crossover study investigating the safety of trivalent influenza vaccine in patients with asthma. At baseline, 294 subjects were randomized to receive either placebo first (n=139) or inactivated trivalent split-virus influenza vaccine first (n=155). Study subjects were categorized into 2 groups: subjects in group 1 (n=148) were receiving medium-dose or high-dose inhaled corticosteroids (ICSs) or oral corticosteroids, whereas subjects in group 2 (n=146) were not receiving corticosteroids or were receiving low-dose ICSs. Serum hemagglutination inhibition antibody titers for the vaccine antigens were measured before and 4 weeks after the administration of placebo or vaccine. RESULTS: Serologic responses to each influenza vaccine antigen were significantly higher in vaccine than in placebo recipients and were similar among influenza vaccine recipients in groups 1 and 2 for the following endpoints: rise in antibody titer, percent of participants who developed a serological response, and percent of subjects who developed a serum hemagglutination inhibition antibody titer > or =1:32. Post hoc subgroup analyses demonstrated an attenuated response to influenza B antigen in subjects receiving high-dose ICS compared with subjects who were steroid-na?ve (P<.05). CONCLUSION: The immune response to the A antigens of the inactivated influenza vaccine in subjects with asthma is not adversely affected by ICS therapy. High-dose ICS therapy may diminish the response to the B antigen of the vaccine, an observation that needs further investigation.     

Epidemiological analysis and follow‐up of human rhinovirus infection in children with asthma exacerbation

To determine the prevalence of human rhinovirus (HRV) infection in children with acute asthma exacerbations, investigation of HRV viral load and severity of asthma exacerbations is also required. Nasopharyngeal aspirates and swabs were collected and assessed for respiratory viruses. HRV‐positive samples were sequenced to identify types and determine viral load. Outpatients with asthma exacerbations underwent follow‐up evaluations, their swabs were collected and clinical outcomes were recorded at their next clinic visit 4 weeks later. One hundred forty‐three inpatients and 131 outpatients, including 88 patients with asthma exacerbations and 43 controls with stable asthma were recruited. HRV‐A was mainly detected in September and February (45.5% and 33.3%, respectively), while HRV‐C was mainly detected in November and April (70.0% and 55.6%, respectively). HRV‐C was the primary type and was primarily found in inpatients with severe asthma exacerbations. HRV‐A viral load in the group of inpatients with severe exacerbations was higher than in the mild and moderate groups (P < 0.001 and P = 0.022). The HRV‐A viral load of both inpatients and outpatients was higher than that of HRV‐C (P < 0.001 and P = 0.036). The main genotypes were HRV‐C53 and HRV‐A20 among inpatients, and this genotype caused more severe clinical manifestations. HRV persisted for no more than 4 weeks, and their symptoms or signs of disease were well‐controlled well. HRV‐C was most frequently detected in asthma exacerbations. HRV‐A with high viral load led to severe asthma exacerbations.

     

Autoantibodies to the high-affinity IgE receptor in patients with asthma

Autoimmune diseases have been implicated as a cause of intrinsic asthma; however, there is little data on the role of autoimmunity in the pathogenesis of asthma. The purpose of this study was to investigate circulating autoantibodies against the high-affinity IgE receptor Fc(epsilon)RI in patients with asthma. Seventy-eight patients with asthma and 32 healthy individuals as control subjects were included. All subjects were tested with basophil histamine releasing assay and immunoblotting to assess for the potential presence of receptor Fc(epsilon)RI autoantibodies. Of the 78 asthma patients total subjects, 25 (32.1%) had a positive by basophil histamine releasing assay and 23 (29.5%) by immunoblotting. Both of them were significant higher than the positive rate, 9.4% (p < 0.05) and 9.4% (p < 0.05), respectively. Our data demonstrated that aberrant autoantibodies against the high-affinity IgE receptor Fc(epsilon)RI were found in some patients with asthma implies that the autoimmunity may be one factor in intrinsic asthma pathogenesis.     

Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes

BACKGROUND: Viral respiratory tract infections represent the most frequent cause of asthma exacerbation in both children and adults, but the precise mechanism of such exacerbation remains unknown. OBJECTIVES: To determine the critical mediator of naturally occurring parainfluenza virus (PIV) 3-induced mild asthma exacerbations in adults. METHODS: The study subjects were 19 adult asthmatics with mild asthma exacerbation (peak expiratory flow = 60-80% of predicted before bronchodilator use and >80% of predicted after initial bronchodilator treatment). Differential cell counts and concentrations of inflammatory markers including eosinophil cationic protein (ECP), cysteinyl leukotrienes (cysLTs), interleukin (IL)-5, IL-10 and IL-12 were measured in the induced sputum obtained from adults with PIV3- (n = 9) and non-cold-induced (n = 10) exacerbation of asthma during both acute and convalescent phases. RESULTS: PIV3 infection was confirmed by the presence of viral RNA in nasopharyngeal aspirates. Mild exacerbation of asthma was not associated with significant changes in sputum differential cell counts. Concentrations of sputum ECP and cytokines were comparable between PIV3 and non-cold-induced patients. In contrast, PIV3 infection was associated with a significant increase in sputum cysLTs during the acute phase of mild asthma exacerbation. CONCLUSIONS: Our results identified cysLTs as a critical mediator of PIV3-induced acute asthma exacerbation.