Sicco van der Heide

Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens.

BACKGROUND Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects. OBJECTIVE We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens. METHODS Twenty asthmatic children sensitized to pet allergens (cat/dog) and with an animal at home participated in a double-blind, placebo-controlled, cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners. Before and after each study period, lung function, airway hyperresponsiveness (adenosine monophosphate), and peak flow variation were recorded. Cat and dog allergen levels were assessed in the filters of the air cleaners. RESULTS After a 3-month intervention with active air cleaners, airway hyperresponsiveness decreased significantly, showing a 1.2 doubling dose increase of PC(20 )adenosine (P =.003). Peak flow amplitude also decreased (P =. 045). Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well. Allergen levels in floor dust were not changed. CONCLUSION In young asthmatic patients sensitized and exposed to pets in the home, application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude.

Seasonal variation in airway hyperresponsiveness and natural exposure to house dust mite allergens in patients with asthma

Nonspecific airway hyperresponsiveness is a fundamental characteristic of patients with asthma and can be influenced by several stimuli. In nine patients with asthma and an isolated allergy to house dust mite, the variation of natural exposure to the house dust mite allergen Der p I and the corresponding changes in nonspecific airway hyperresponsiveness were followed up for 1 year. The concentration of Der p I in floor dust from living rooms and bedrooms (as a measure of exposure) reached maximum levels in late summer and the beginning of autumn (August to October), whereas the lowest levels were found during the months of March to May (delta Der p I = +2.31 micrograms/gm and -1.33 micrograms/gm respectively, both compared with the year average). Airway hyperresponsiveness (as measured by the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second [PC20] threshold) also showed a seasonal variation, with most severe hyperresponsiveness during the months of August to November, almost the same period in which the exposure to house dust mite allergens reached maximal levels (delta PC20 histamine = -1.47 mg/ml in November vs +1.79 mg/ml in March, both compared with the year average). Our results support the view that seasonal changes of exposure to environmental allergens such as house dust mite allergens will have an effect on the level of airway hyperresponsiveness in patients with allergic asthma.

Preeclampsia is associated with lower percentages of regulatory T cells in maternal blood.

Objective: Immunological mechanisms are involved in the pathophysiology of preeclampsia. During pregnancy there is an increase in regulatory T (Treg) cells, which has an important role in regulating tolerance to the immunologically distinct fetus. We hypothesised that percentages of Treg cells are decreased in preeclamptic patients. Methods: Peripheral blood was obtained from 26 healthy pregnant controls and 18 preeclamptic patients. Treg cells were measured using flow-cytometry. Results: Women with pregnancies complicated by preeclampsia had significantly lower percentages of CD4+FOXP3+ Treg cells. Conclusion: We conclude that a deficiency of regulatory T cells may play a role in the pathophysiology of preeclampsia.

Lack of reproducibility of a single negative sting challenge response in the assessment of anaphylactic risk in patients with suspected yellow jacket hypersensitivity

To investigate the reproducibility of a single negative response to sting challenge with a living insect, we rechallenged a group of 61 patients who showed no clinical response to a first sting challenge. All patients had previously had symptoms suggestive of anaphylaxis after a yellow jacket field sting. Thirteen patients (21%) had anaphylactic responses after the second sting challenge, and six of these patients had severe reactions including symptomatic hypotension requiring administration of Adrenalin. This rate was significantly lower than the response rate of the original patient group to a first sting challenge (39%). Thus although fewer positive responses were observed in patients who had had a previous negative challenge response, the number of anaphylactic reactions was considerable and included patients with potentially life-threatening symptoms. Consequently, a single sting challenge may not be used to select patients for venom immunotherapy.

Threshold dose distributions for 5 major allergenic foods in children

BACKGROUND For most allergenic foods, insufficient threshold dose information within the population restricts the advice on levels of unintended allergenic foods which should trigger precautionary labeling on prepackaged foods. OBJECTIVE We wanted to derive threshold dose distributions for major allergenic foods and to elaborate the protein doses at which a proportion of the allergic population is likely to respond. METHODS For 7 allergenic foods double-blind, placebo-controlled food challenges (DBPCFCs) with a positive outcome for allergic reactions were selected from the clinical database of children routinely tested to diagnose food allergy at the University Medical Center Groningen. For each allergen 2 population threshold distributions were determined with the individual minimal eliciting dose and the preceding dose of each DBPCFC for objective symptoms and any symptom (either subjective or objective). RESULTS Individual positive DBPCFCs were available for peanut (n = 135), cows milk (n = 93), hens egg (n = 53), hazelnut (n = 28), and cashew nut (n = 31). Fewer children were challenged with soy (n = 10) or walnut (n = 13). Threshold dose distributions showed a good statistical and visual fit. The protein dose at which 5% of the allergic population is likely to respond with objective reactions was 1.6 mg for peanut, 1.1 mg for cows milk, 1.5 mg for hens egg, 7.4 mg for cashew nut, and 0.29 mg for hazelnut. Thresholds for any symptom were on average 2 to 6 times lower than for objective symptoms. The 95% upper and lower confidence intervals of the threshold distributions were overlapping. The peanut threshold distribution on objective symptoms was similar to the distribution of another European center. CONCLUSIONS Threshold distribution curves and eliciting doses are a powerful tool to compare different allergenic foods and for informing policy on precautionary labeling.

Change in inflammation in out-patient COPD patients from stable phase to a subsequent exacerbation

Background Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes. Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes. Aim To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations. Methods In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV1 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation. Results Sputum total cell counts (9.0 versus 7.9 × 106/mL), eosinophils (0.3 versus 0.2 × 106/mL), neutrophils (6.1 versus 5.8 × 106/mL), and lymphocytes (0.07 versus 0.02 × 106/mL) increased significantly during an exacerbation compared to stable disease. A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation. These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-α (TNF-α) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection. Sputum TNF-α level during an exacerbation had the best test characteristics to predict a bacterial infection. Conclusion Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations. The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways. Sputum TNF-α is a candidate marker for predicting airway bacterial infection.

Comparison of antibody measurements against Aspergillus fumigatus by means of double-diffusion and enzyme-linked immunosorbent assay (ELISA)

IgG antibody titers against Aspergillus fumigatus from different sera were measured by means of a standardized ELISA and compared with precipitates measured by double diffusion (D.D.). There was a significant correlation between the number of precipitates and the ELISA IgG titers in the 758 sera examined. However, in several individual sera within this group, large deviations between these two immunologic parameters were found. Further analysis indicated that ELISA detects antibodies against nonprecipitating antigenic components in addition to the antibodies detected by D.D. Furthermore, not all precipitating antigenic components appear to play a role in the detection of antibodies against A. fumigatus by ELISA. Patients with aspergillosis largely show increased titers of IgG antibody by ELISA even when the results of D.D. are negative, except those of patients with Aspergillus-provoked asthma which fall within a normal range.

Higher mast cell load decreases the risk of Hymenoptera venom-induced anaphylaxis in patients with mastocytosis

BACKGROUND Increased basal serum tryptase (bsT) levels are a well-described risk factor for Hymenoptera venom-induced anaphylaxis (HVAn) in patients allergic to Hymenoptera venom. Increased bsT levels might also indicate the presence of mastocytosis. In this study we evaluated whether the risk of HVAn increases with increasing mast cell load in patients with mastocytosis. METHODS Consecutive patients with different subtypes of mastocytosis (n = 329) admitted to the University Medical Center Groningen were retrospectively assessed. As markers for mast cell load, levels of both bsT and the urinary histamine metabolites methylhistamine and methylimidazole acetic acid (MIMA) were used. RESULTS In the entire patient group, irrespective of disease subtype and Hymenoptera venom exposure, HVAn prevalence gradually increased with increasing marker levels to a maximum of 36% to 47% at a bsT level of 28.0 μg/L, a methylhistamine level of 231.0 μmol/mol creatinine, and a MIMA level of 2.7 mmol/mol creatinine but decreased thereafter with a further increase in these levels. In patients with indolent systemic mastocytosis with a history of Hymenoptera venom exposure after age 15 years or greater (n = 152), MIMA and age at the most recent Hymenoptera sting were independent predictors for HVAn (odds ratios of 0.723 [P = .001] and 1.062 [P < .001], respectively). CONCLUSIONS In patients with mastocytosis, HVAn prevalence does not increase constantly with increasing levels of mast cell load parameters: after a gradual increase to a maximum of near 50%, it decreases with a further increase in these levels. In the indolent systemic mastocytosis population, all mast cell load markers were independent negative predictors of HVAn. These findings suggest a complex pathophysiologic association between mast cell load and HVAn risk in patients with mastocytosis.

The eliciting dose of peanut in double-blind, placebo-controlled food challenges decreases with increasing age and specific IgE level in children and young adults.

BACKGROUND Several risk factors for severe anaphylactic reactions to food in daily life are known. However, to date, it is not possible to predict the severity of allergic reactions to food in the individual patient with accuracy. Some studies show that a history of severe reactions is associated with a lower eliciting dose in double-blind, placebo-controlled food challenges (DBPCFCs). Therefore, in this study, the eliciting dose was used as a measure of clinical sensitivity. OBJECTIVES To study whether risk factors for severe allergic reactions to food in daily life such as age, degree of sensitization, and coexistent atopic disease influence the eliciting dose in DBPCFCs in children allergic to peanut. METHODS Data from children who had clinical reactions to peanut during DBPCFCs at the University Medical Center Groningen (2001-2009) were analyzed. A Cox regression model was used to analyze the association of the determinants with the eliciting dose. RESULTS One hundred twenty-six positive DBPCFCs with peanut were analyzed. Age older than 10 years, a specific IgE level above the lowest tertile (≥ 5.6 kU/L), and the absence of atopic dermatitis were associated with reactions to lower doses: respective hazard ratios 1.89 (95% CI, 1.28-2.81; P = .001), 2.03 (95% CI, 1.37-3.00; P < .0001), and 0.45 (95% CI, 0.29-0.71; P = .001) present versus absent. No significant associations with the eliciting dose were found for sex, the presence of asthma and rhinitis, and the severity of food reactions by history. CONCLUSIONS Using the eliciting dose as a measure of clinical sensitivity, greater clinical sensitivity in DBPCFCs to peanut was found to be associated with increasing age, higher specific IgE level, and the absence of atopic dermatitis. This finding may explain why adolescents experience severe allergic reactions in daily life to peanut more often than do younger children.

In vitro and in vivo anti-allergic effects of Arctium lappa L.

The discovery of drugs that can be used for the treatment of allergic disease is important in human health. Arctium lappa Linne (Compositae) (AL) has been used as a traditional medicine in Brazil and throughout Asia and is known to have an anti-inflammatory effect. In this study, the inhibitory effects of AL on degranulation and the release of mediators as well as on inhibition of cys-leukotriene biosynthesis by basophils were investigated. AL was selected out of 10,000 herbal extracts in a set-up for high throughput screening in which the degree of degranulation was monitored by the release of β-hexosaminidase from rat basophil leukemia (RBL-2H3) cells. The AL extract significantly reduced degranulation and biosynthesis of cys-leukotrienes of human basophils in peripheral blood mono-nuclear cells (PBMCs) (50% inhibitory concentration [IC50] = 8.3 and 11.4 μg/ml, respectively). Viability and metabolic activity of the PBMCs were not affected. Although arctiin, the active component of AL that has been described in the literature, was not able to reduce degranulation in RBL-2H3 cells, a single high-performance liquid chromatography (HPLC) fraction from the AL extract inhibited β-hexosaminidase release (IC50 = 22.2 μg/ml). Topical administration of an aqueous extract of AL (5 mg/ear) on the ear of whey-sensitized mice 4 hrs before challenge with whey in the ear inhibited acute ear swelling by 50% in an in vivo cow’s milk allergic model. The extract had no effect in this model when administered orally. In conclusion, the active component present in the active HPLC fraction of the AL extract was able to significantly reduce the release of inflammatory mediators through inhibition of degranulation and cys-leukotriene release in vitro. In addition, this active component was able to inhibit acute skin response in mice in vivo, indicating that AL is a very promising natural component for use in anti-allergic treatment.