J. S. Van Der Zee

Influx of neutrophils into the airway lumen at 4 h after segmental allergen challenge in asthma.

Background: Segmental allergen challenge is a powerful tool to study inflammatory reactions in asthmatic airways. There is little information on the early events at 5 min and 4 h after allergen challenge with respect to the cell influx and the chemokine interleukin–8 (IL–8). Methods: Seven mild to moderate allergic asthmatics (AA group), 5 allergic nonasthmatics (ANA group) and 5 nonallergic controls underwent segmental allergen challenge, with allergen doses based upon skin reactivity. Bronchoalveolar lavage (BAL) samples were obtained before, 5 min and 4 h postchallenge, and were analyzed for cell numbers and differential counts, eosinophil and neutrophil chemotactic activity, and levels of IL–8. Results: At 5 min postchallenge, no changes were observed compared to baseline. At 4 h postchallenge, an increase was found in the number of neutrophils and the levels of IL–8, which was dependent on the dose of allergen in the AA and ANA group. At the same allergen dose, the increases in neutrophils and levels of IL–8 were calculated to be 91 and 67 times higher, respectively, in AA than in ANA. Levels of IL–8 correlated with the number of neutrophils and with the in vitro neutrophil chemotactic activities in BAL fluid. Conclusions: Neutrophil chemotactic activity is increased in BAL fluid at 4 h after segmental allergen challenge. We suggest that apart from IgE–mediated mast cell degranulation, additional local factors in the airways determine the degree of IL–8 increase and neutrophil influx.

Synbiotics reduce allergen-induced T-helper 2 response and improve peak expiratory flow in allergic asthmatics

To cite this article: van de Pol MA, Lutter R, Smids BS, Weersink EJM, van der Zee JS. Synbiotics reduce allergen‐induced T‐helper 2 response and improve peak expiratory flow in allergic asthmatics. Allergy 2011; 66: 39–47.

Toll-like receptor mRNA levels in alveolar macrophages after inhalation of endotoxin

Toll-like receptors (TLRs) are pattern-recognition receptors that have been implicated in the initiation of innate immune responses upon the first encounter with invading pathogens. The airways are frequently exposed to various types of lipopolysaccharide (LPS) from the environment or from pathogens. The current study was designed to determine the effect of LPS on TLR gene expression in human alveolar macrophages in vivo. In total, 16 healthy subjects were enrolled in a single-blinded, placebo-controlled study. Subjects inhaled 100 μg LPS or normal saline (n = 8 per group). Measurements were performed in alveolar macrophages purified from bronchoalveolar lavage fluid obtained 6 h post-challenge. Inhalation of LPS by healthy human volunteers resulted in enhanced alveolar macrophage expression of mRNAs encoding TLRs 1, 2, 7, 8 and CD14, and reduced expression of mRNAs encoding TLR4 and lymphocyte antigen 96. In conclusion, lipopolysaccharide differentially influences the toll-like receptor mRNA expression profile in human alveolar macrophages in vivo.

Serum surfactant protein D is elevated in allergic patients

Background There is evidence that surfactant protein (SP)‐D is important in the innate, as well as in the adaptive pulmonary immune response. Serum concentrations of SP‐D have been proposed as parameter of the integrity of the blood–airspace barrier in interstitial lung diseases. We hypothesized that serum SP‐D concentrations are affected in allergic patients and correlate with changes in allergic airway inflammation.

IgE Antibodies Reactive with Silverfish, Cockroach and Chironomid Are Frequently Found in Mite-Positive Allergic Patients

Approximately 30% of the house dust mite allergic patients in The Netherlands have IgE antibodies reactive with silverfish, cockroach and/or chironomid. In allergic patients without IgE antibodies against Dermatophagoides pteronyssinus less than 5% have IgE antibodies reactive with these insects. By means of RAST inhibition studies it is shown that cross-reactivity exists between D. pteronyssinus and silverfish, cockroach or chironomid. This means that a positive RAST for silverfish, cockroach, chironomid or D. pteronyssinus cannot be taken as evidence for exposure.

Fel d 1-Specific IgG Antibodies Induced by Natural Exposure Have Blocking Activity in Skin Tests

Cat-allergic patients frequently have IgG antibodies directed against Fel d 1. The aim of this study was to investigate whether these IgG antibodies influence the results of the skin test. Titrated skin tests were performed with Fel d 1 and IgE and IgG antibody levels were measured in 59 patients with cat allergy. Levels of specific IgG against Fel d 1 ranged from less than 0.25 to 3.5 microgram/ml. By means of a multiple regression analysis it was shown that the amount of specific IgG antibodies contributes significantly to the results of the skin test. Presence of specific IgG against Fel d 1 was accompanied by higher skin thresholds for Fel d 1. In conclusion, this study indicates that even low levels of specific IgG, induced by natural exposure to cat allergens, have a blocking effect on the early phase skin reaction.

Allergen-induced bronchial inflammation in house dust mite-allergic patients with or without asthma

Background It is presently unknown which factors determine the occurrence and persistence of asthma in house dust mite‐allergic individuals. The level of allergen‐specific IgE antibodies does not seem to be decisive for asthmatic symptoms. Moreover, levels of exposure to mite allergens do not seem to differ significantly between asthmatic and non‐asthmatics individuals.

Early activation of coagulation after allergen challenge in patients with allergic asthma

Asthma is characterized by allergic airway inflammation which is associated with bronchial hyperreponsiveness and airway obstruction [1]. Recent evidence indicates that activation of coagulation within the airways in asthma may aggravete inflammation [2]. Asthma patients were found to have elevated concentrations of thrombin, thrombin-antithrombin complexes (TATc) and soluble tissue factor and reduced activated protein C (APC)/thrombin ratios in induced sputum [3,4]. However, knowledge on coagulation activation in the lower airways in asthma in humans is limited, especially with regard to the acute impact of an allergen challenge. We therefore determined activation of coagulation in the bronchoalveolar space and the acute effect of a segmental allergen challenge hereon in asthma patients as compared to healthy controls. Our study population has been described previously [5]. In short, thirteen allergic asthmatic subjects and nine healthy volunteers were included. Patients had a positive skin prick test for house dust mite allergens, grass pollen or both. Patients had not experienced an exacerbation of asthma during at least 2 months and had not used bronchodilators for at least 8 h before the investigations. None of the subjects had experienced recent airway infection or used anti-inflammatory or anticoagulant drugs. The study was approved by the Internal Review Board of the Academic Medical Center Amsterdam and written informed consent was obtained from all participants. Intracutaneous dose-response series with house dust mite or grass pollen (ALK Abello, Nieuwegein, The Netherlands) were performed to determine the concentration that produced a 10 mm wheal response 15 min after injection. Asthmatic subjects underwent an intrabronchial challenge with 1 mL of this allergen concentration – brought to a final volume of 5 mL with saline – whereas controls were challenged with the highest concentration applied in the patient group. Levels of lipopolysaccharide in the allergen solution were < 1.3 pg mL )1 in all

Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma

Background: Addition of the long acting β2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma. Methods: After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 μg with or without salmeterol 50 μg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 μg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period. Results: Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p<0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p>0.05). However, adding salmeterol significantly reduced sputum ratios of α2-macroglobulin and albumin during the treatment period (p = 0.001). Conclusions: The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting β2 agonist is combined with inhaled corticosteroids.

Reactivity to IgE‐dependent histamine‐releasing factor is due to monomeric IgE

Background: IgE‐dependent histamine‐releasing factor (HRF) can distinguish between IgE+ and IgE−. In contrast to IgE−, IgE+ sensitizes basophils to release histamine in response to HRF. But we do not know what particular feature distinguishes IgE+ from IgE−. The objective was to investigate the hypothesis that IgE+ is polymeric IgE.