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Biomedical subjects

F Horak

Publications and source records attributed to F Horak.

At least 19 recordsLinked to original sources
PubMed2006

Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis.

BACKGROUND: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the airway. Due to the importance of NO in cell homeostasis and innate immunity, any defect in the pathway associated with CF would be a potential target for treatment. METHODS: Cells were obtained by tracheobronchial brushing from 40 children with CF of mean (SD) age 2.1 (1.5) years and from 12 healthy non-atopic children aged 3.4 (1.2) years. Expression of iNOS mRNA was measured using quantitative PCR and iNOS protein by immunofluorescence and Western blot analysis. RESULTS: Inducible NOS mRNA expression was significantly lower in CF patients with and without bacterial infection than in healthy children (0.22 and 0.23 v 0.76; p=0.002 and p=0.01, respectively). Low levels of iNOS gene expression were accompanied by low levels of iNOS protein expression as detected by Western blot analysis. CONCLUSIONS: These results support the findings of previous studies in adult patients with advanced disease, cell lines, and animal models. Our findings reflect the situation in children with mild lung disease. They indicate that low iNOS expression may be an innate defect in CF with potential consequences for local antimicrobial defence and epithelial cell function and provide evidence for an approach to treatment based on increasing epithelial NO production or the sensitivity of NO dependent cellular processes.

Analysis of Variance↗
PubMed2006

Exhaled nitric oxide is not reduced in infants with cystic fibrosis.

Fractional exhaled nitric oxide (F(eNO)) has been reported to be reduced in cystic fibrosis (CF) patients. However, data from young children are conflicting and it is not clear whether this is a primary feature of the disease or a secondary response. The present study compared F(eNO) between CF and healthy infants using a validated single-breath technique. A total of 23 healthy infants (11 females; mean age 40.1 weeks) and 18 infants with CF (nine females; 64.9 weeks) underwent tests of lung function and F(eNO). Bronchoalveolar lavage (BAL) was collected from all CF infants 2-5 days after lung function testing. There was no significant difference in F(eNO) between the CF and healthy infants (geometric mean: 23.1 parts per billion (ppb) and 17.0 ppb, respectively). There was an inverse relationship between age and F(eNO) in the CF patients, but not in the healthy group. Within the CF group, there was no association between F(eNO) and any marker of airway inflammation measured in the BAL. Exhaled nitric oxide is not reduced in cystic fibrosis infants, but does decrease with age. The current data indicate that F(eNO) is not a good marker of airway inflammation in cystic fibrosis.

Age Factors↗
PubMed2005

Interaction of involuntary post-contraction activity with locomotor movements.

Involuntary post-contraction muscle activity may occur after performing a strong long-lasting (about 30 s) isometric muscle contraction (Kohnstamm phenomenon). Here we examined how this putative excitatory state may interact with a locomotor movement. The subjects stood upright and were asked to oppose a rotational force applied to the pelvis for about 30 s either in the clockwise or in the counterclockwise direction. After that, they were asked to perform various motor tasks with the eyes closed. During quiet standing, we observed an involuntary post-contraction torsion of the trunk. During walking, the post-contraction facilitatory effect of body torsion was not overridden by the voluntary activity, but instead significantly influenced the forward locomotor program such that subjects walked along a curved trajectory in the direction of the preceding torsion. In contrast, we did not observe any rotational component when subjects were asked to step in place. We conclude that the post-contraction rotational aftereffect does not transfer to just any motor task but apparently manifests itself in those movements that incorporate the activated axial muscle synergy or rotational component. We argue that central excitability changes following the voluntary effort may contribute to the phenomenon and highlight the role of tonic influences in fine-tuning of the spinal cord.

Adult↗
PubMed2005

Comparison of purified Dermatophagoides pteronyssinus allergens and extract by two-dimensional immunoblotting and quantitative immunoglobulin E inhibitions.

BACKGROUND: The allergens of the house dust mite (Dermatophagoides pteronyssinus, Der p), one of the most important indoor allergen sources, occur as isoallergens that differ in their amino acid sequence. These variations may influence allergenic activity and thus may have impact on diagnostic tests and specific immunotherapy. OBJECTIVE: We investigated whether single purified recombinant mite allergens contain the IgE epitopes of the natural Der p isoallergens. METHODS: A panel of purified recombinant (rDer p 2, 5, 7, 8, 10 and 14) and two natural (nDer p 1 and 4) mite allergens were used to establish IgE reactivity profiles of Der p allergic patients and to inhibit IgE reactivity to two-dimensionally separated Der p isoallergens. In addition, we determined the percentage of Der p extract-specific IgE which could be preadsorbed with a mixture of purified mite allergens (nDer p 1, rDer p 2, 5, 7, 8 and 10) from sera of mite-allergic patients (n=18) in a non-denaturing RAST-based inhibition. RESULTS: We demonstrate that single recombinant mite allergens inhibit IgE reactivity to the corresponding natural isoallergens. A mixture of purified mite allergens (nDer p 1, rDer p 2, 5, 7, 8 and 10) bound on an average 76% of Der p-specific IgE antibodies. CONCLUSION: The studied recombinant and natural mite allergens contain a large portion of Der p-specific IgE and may be used for diagnostic tests and therapy of Der p allergy.

Adolescent↗
PubMed2005

Correlation of forced oscillation technique in preschool children with cystic fibrosis with pulmonary inflammation.

BACKGROUND: Lung disease in cystic fibrosis (CF) is established in early childhood with recurrent bacterial infections and inflammation. Using spirometry, the effect of this early lung damage cannot be measured until a child is 6 years of age when some irreversible lung damage may already have occurred. Techniques for measurement of lung function in infants and young children include raised volume rapid thoracic compression (RVRTC) and low frequency forced oscillation (LFFOT). The aim of this study was to investigate the role of inflammation and infection on a population of infants and young children with CF and to determine whether lung function in this population (measured by LFFOT) is affected by early lung disease. METHODS: Lung function was measured by LFFOT in 24 children undergoing bronchoalveolar lavage (BAL) on 27 occasions as part of an annual programme while still under general anaesthesia. Following lung function testing, three aliquots of saline were instilled into the right middle or lower lobe. The first aliquot retrieved was processed for the detection of microbes, and the remaining aliquots were pooled to assess inflammatory markers (cytology, IL-8, NE, LTB(4)). RESULTS: Inflammation (percentage and number of neutrophils) was significantly higher in children with infections (p<0.001, p = 0.04, respectively), but not in those with symptoms. Several markers of inflammation significantly correlated with LFFOT parameters (R, G, and eta). CONCLUSION: Infections and inflammation are established before symptoms are apparent. Inflammation is correlated with measures of parenchymal changes in lung function measured by LFFOT.

Airway Resistance↗
PubMed2004

Vaccination with genetically engineered allergens prevents progression of allergic disease.

IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.

Allergens↗
PubMed2004

Effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a multinational randomized, controlled birth-cohort study -- 24 months results of the Study of Prevention of Allergy in Children in Europe.

BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.

Allergens↗
PubMed2004

Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens.

BACKGROUND: Mites belong to the most frequent and potent allergen sources. Immunotherapy with mite allergen extracts is frequently performed if allergen avoidance is not possible or successful. However, highly controversial results have been reported for mite-specific immunotherapy. OBJECTIVE: The aim of this study was to develop diagnostic concepts that may contribute to an improved selection of patients for immunotherapy with Der p allergen extracts and that may be used for immunological monitoring of patients undergoing this treatment. METHODS: The IgE reactivity profiles to Der p extract were determined in a Middle European mite-allergic population by IgE immunoblotting and by using a panel of seven purified natural or recombinant Der p allergens (nDer p 1, nDer p 4, rDer p 2, rDer p 5, rDer p 7, rDer p 8, rDer p 10). Furthermore, we investigated the sensitization and cross-reactivity to house-dust- and storage-mite allergen extracts by CAP FEIA measurements and by IgE competition studies. RESULTS: More than 95% of the patients could be diagnosed with a combination of nDer p 1 and rDer p 2. With the methods used, we could discriminate mite-allergic patients who were mainly sensitized to the major Der p allergens (Der p 1, Der p 2) from patients with a broad sensitization profile, including highly cross-reactive allergens (e.g. Der p 10: tropomyosin) as well as reactivity to storage mites. CONCLUSIONS: Diagnostic tests containing the major mite allergens (i.e. Der p 1, Der p 2) and highly cross-reactive mite allergens (e.g. Der p 10) may improve the diagnostic selection of patients for immunotherapy with Der p extracts. These tests may also be used for the immunological monitoring of patients undergoing immunotherapy.

Adolescent↗
PubMed2004

Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath.

BACKGROUND: The fractional concentration of nitric oxide (NO) in exhaled breath (FeNO) is increased in asthma. There is a general assumption that NO synthase (NOS) 2 in epithelium is the main source of NO in exhaled breath. However, there is no direct evidence to support the assumption and data from animal models suggest that non-inducible NOS systems have important roles in determining airway reactivity, regulating inflammation, and might contribute significantly to NO measured in exhaled breath. METHODS: Bronchial epithelial cells were obtained from healthy, atopic, and asthmatic children by non-bronchoscopic brushing. Exhaled NO (FeNO) was measured directly using a fast response chemiluminescence NO analyser. RNA was extracted from the epithelial cells and real time polymerase chain reaction was used to determine the expression of NOS isoenzymes. NOS2 was examined in macrophages and epithelial cells by immunohistochemistry. RESULTS: NOS1 mRNA was not detectable. NOS3 mRNA was detected in 36 of 43 samples at lower levels than NOS2 mRNA which was detectable in all samples. The median FeNO was 15.5 ppb (95% CI 10 to 18.1). There was a significant correlation between FeNO and NOS2 expression (R = 0.672, p<0.001). All epithelial cells exhibited NOS2 staining, whereas staining in the macrophages was variable and not related to phenotype. CONCLUSIONS: Only NOS2 expression was associated with FeNO in respiratory epithelial cells obtained from children (R = 0.672; p<0.001). This suggests that FeNO variability is largely determined by epithelial NOS2 expression with little contribution from other isoforms.

Adolescent↗
PubMed2004

Long- and medium-term ozone effects on lung growth including a broad spectrum of exposure.

The effects of semi-annual and 3.5 yr mean ozone (O3) concentrations on children's forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were assessed over a study period of 3.5 yrs in 2,153 schoolchildren from 15 study sites in South Western Germany and Lower Austria. Spirometric parameters were assessed twice a year, and differences between consecutive measurements divided by days were considered as a measure of lung growth. Exposure was analysed in four classes, separately for winter and summer (semi-annual mean O3 concentrations 22-30, 30-38, 38-46, 46-54 parts per billion (ppb) in summer and 4-12, 12-20, 20-28, 28-36 ppb in winter). Regression methods for repeated measurements were used, and these revealed a significantly lower FVC (FEV1) increase estimated at -19.2 (-18.5) mL x 100 days(-1) for semi-annual mean O3 exposure in summer between 46 and 54 ppb compared to exposure between 22 and 30 ppb. However, in winter, the estimated difference in FVC (FEV1) was 16.4 (10.9) mL x 100 days(-1) between the semi-annual O3 class 28-36 ppb and the 4-12 ppb class. By means of linear regression the study found that there was no association between growth rates and mean summer O3 for FVC and FEV1 over a 3.5 yr period. The authors conclude that medium-term effects on schoolchildren's lung growth are possibly present, but are in the long-term not detectable for forced vital capacity and forced expiratory volume in one second over a 3.5 yr period due to partial reversibility.

Air Pollutants↗
PubMed2004

A direct comparison of the efficacy of antihistamines in SAR and PAR: randomised, placebo-controlled studies with levocetirizine and loratadine using an environmental exposure unit - the Vienna Challenge Chamber (VCC).

OBJECTIVE: The Vienna Challenge Chamber (VCC) is an established method for the controlled exposure of patients to specific allergens, used to make valid comparisons between antihistamines. The aim of the significantly more than loratadine at all time two placebo-controlled, randomised studies reported here was to compare the efficacy and safety of levocetirizine 5 mg od and loratadine 10 mg od in subjects suffering from seasonal allergic rhinitis (SAR) or perennial allergic rhinitis (PAR). SUBJECTS AND METHODS: During each study period, SAR and PAR subjects were exposed to grass pollen or house-dust mite allergens, respectively for 6 h on 2 consecutive days in the VCC. Each day, medications were administered 2 h after the start of the challenge; with a washout of at least 5 days between each period. The main criterion for evaluation of efficacy was the major symptom complex (MSC) for SAR and the complex symptom score (CSS) for PAR. RESULTS: The pattern of patients' response was similar in SAR and PAR. Both levocetirizine and loratadine were superior to placebo in alleviating SAR and PAR symptoms at all time intervals evaluated during the two study days. Levocetirizine decreased the mean MSC score intervals in SAR subjects, with the most marked difference observed on day 2 (p = 0.002). In PAR patients, although with borderline significance (p = 0.08), levocetirizine decreased the mean CSS more than loratadine. Levocetirizine appeared to have a faster onset of action than loratadine in SAR (45 min versus 1 h 15 min) and PAR (1 h versus 1 h 30 min). However, these apparent differences were not tested for statistical significance. Both medications were well tolerated and no treatment-related adverse events were reported. This level of antihistamine efficacy was maintained regardless of whether the subjects' rhinitis was seasonal or perennial. CONCLUSION: This study demonstrated that levocetirizine is superior to loratadine in improving symptoms in SAR and that there is a similar trend in PAR.

Cetirizine↗
PubMed2003

Comparison of the effects of desloratadine 5-mg daily and placebo on nasal airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure.

BACKGROUND: Nasal congestion is a chronic symptom of seasonal allergic rhinitis (SAR) that is often difficult to treat with antihistamines. Desloratadine, a new, potent, H1-receptor antagonist has been shown to decrease nasal congestion in clinical trials and to maintain nasal airflow in response to grass pollen exposure. We compared the effects of desloratadine 5 mg and placebo on nasal airflow, nasal secretion weights and SAR symptoms, including nasal congestion, in patients exposed to grass pollen in an environmental exposure unit. METHODS: Forty-six grass pollen allergic SAR patients received desloratadine or placebo for 7 days, followed by a 10-day washout, and then crossed over to the other treatment for 7 days. A 6-h allergen exposure was performed at the end of each treatment period. RESULTS: Desloratadine was significantly superior to placebo in maintaining nasal airflow (P <or= 0.014) and lessening the increase in nasal secretion weights (P < 0.001) throughout allergen exposure. SAR symptom scores, including nasal congestion, were significantly less with desloratadine than placebo (P <or= 0.001). Desloratadine was well tolerated. CONCLUSIONS: This study confirms that, compared with placebo, desloratadine can maintain nasal airflow and reduce nasal secretion weights and the severity of SAR symptoms, including nasal congestion, in SAR patients exposed to grass pollen allergen.

Adult↗
PubMed2002

Impact and modulation of nasal obstruction.

Nasal obstruction, the leading symptom of allergic rhinitis, results from the combined activity of early- and late-phase allergic reactions. Desloratadine inhibits both early- and late-phase inflammatory mediators in vitro. Thus, double-blind, placebo-controlled, randomized, crossover trials were conducted to assess the efficacy of desloratadine against nasal obstruction, measured objectively and subjectively, during controlled exposure of patients with seasonal allergic rhinitis to allergen. Positive results were obtained in three single-dose studies; desloratadine 5 mg resulted in a greater improvement from baseline than did placebo in the total symptom score and the nasal obstruction symptom score (P </= 0.02). Desloratadine was more effective than placebo in a multiple-dose study; desloratadine 5 mg was given once daily for 7 days, and a 6-h allergen challenge was administered at the end of treatment compared with placebo. Desloratadine treatment was associated with less deterioration from baseline in the mean nasal airflow (P < 0.05) and in the mean severity score for the symptom of nasal obstruction (P < 0.03). Desloratadine significantly reduces the severity of nasal obstruction in patients with seasonal allergic rhinitis.

Histamine H1 Antagonists↗
PubMed2002

Parental farming protects children against atopy: longitudinal evidence involving skin prick tests.

BACKGROUND: There is growing evidence that the development of allergic sensitization can be influenced by environmental co-factors. Studies showed that growing up on a farm can protect children against allergic sensitization. However, little is known whether this 'farming effect' can only be observed in early lifetime or whether it also plays a role in later childhood. OBJECTIVE: The aim of our study was to test whether a farming environment is negatively associated with a new occurrence of skin prick test (SPT) positivity in school children. As a secondary outcome we investigated whether children living on a farm lose their allergic sensitization more frequently than other children. METHODS: In a longitudinal design, 1150 elementary school children (mean age 7.8 years, SD 0.7) were recruited from nine different areas of Austria in 1994. A questionnaire and an SPT involving seven common aero-allergens were performed at study entry and at follow-up 3 years later. RESULTS: A total of 844 children, who underwent two SPTs, were included in the analyses; 15.1% of their families reported working on a farm. Adjusting for potential confounders (parental education, number of siblings, sex, family history of allergy), parental farming was inversely related to the prevalence and new occurrence of SPT positivity [no farming 12.2%, part-time farming 6%, full-time farming 2.2% incidence; odds ratio (OR) farming vs. non-farming 0.34, 95% confidence interval (CI) 0.12-0.98]. Furthermore, children living in a farming environment were more likely to lose their SPT positivity during follow-up (no farming 14.6%, part-time farming 50%, full-time farming 60% loss of sensitization; OR farming vs. non-farming 8.06; 95% CI 2.05-31.75). No difference in the pattern of sensitization to specific allergens could be observed between farming and non-farming children. CONCLUSION: A farming environment has a strong negative effect on the development of allergic sensitization. Furthermore, the study provides evidence that atopic children living on a farm lose their SPT positivity more frequently than children from non-farming environments.

Agriculture↗
PubMed2002

Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren.

The effects of particulate matter <10 microm in diameter (PM10) and other air pollutants on lung function were assessed in 975 schoolchildren, from eight communities in Lower Austria between 1994-1997. In each community, air pollution data were collected. Spirometry was performed twice a year. PM10 concentration (mean concentration between two subsequent lung-function measures in spring and autumn (summer interval) or between autumn and spring (winter interval)) showed a mean value of 17.36 microg x m(-3) in the summer interval and 21.03 microg m(-3) in the winter interval. A slower increase in the forced expiratory volume in one second (FEV1) and midexpiratory flow between 25 and 75% of the forced vital capacity (MEF25-75) with age in children exposed to higher summer PM10 was observed in the 3-yr study period. After adjusting for potential confounders (sex, atopy, passive smoking, initial height, height difference, site, initial lung function) an increase of summer PM10 by 10 microg x m(-3) was associated with a decrease in FEV1 growth of 84 mL x yr(-1) and 329 mL x s(-1) x yr(-1) for MEF25-75. Nitrogen dioxide and ozone also showed a negative effect on lung-function growth, confirming previous work. The authors concluded that long-term exposure to particulate matter <10 microm in diameter had a significant negative effect on lung-function proxy for the development of large (forced expiratory volume in one second) and small (midexpiratory flow between 25 and 75% of the forced vital capacity) airways, respectively, with strong evidence for a further effect of ozone and nitrogen dioxide on the development of forced vital capacity and forced expiratory volume in one second.

Air Pollutants↗
PubMed2001

Assessment of deaths attributable to air pollution: should we use risk estimates based on time series or on cohort studies?

Epidemiologic studies are crucial to the estimation of numbers of deaths attributable to air pollution. In this paper, the authors present a framework for distinguishing estimates of attributable cases based on time-series studies from those based on cohort studies, the latter being 5-10 times larger. The authors distinguish four categories of death associated with air pollution: A) air pollution increases both the risk of underlying diseases leading to frailty and the short term risk of death among the frail; B) air pollution increases the risk of chronic diseases leading to frailty but is unrelated to timing of death; C) air pollution is unrelated to risk of chronic diseases but short term exposure increases mortality among persons who are frail; and D) neither underlying chronic disease nor the event of death is related to air pollution exposure. Time-series approaches capture deaths from categories A and C, whereas cohort studies assess cases from categories A, B, and C. In addition, years of life lost can only be derived from cohort studies, where time to death is the outcome, while in time-series studies, death is a once-only event (no dimension in time). The authors conclude that time-series analyses underestimate cases of death attributable to air pollution and that assessment of the impact of air pollution on mortality should be based on cohort studies.

Air Pollutants↗
PubMed2001

A well-tolerated grass pollen-specific allergy vaccine containing a novel adjuvant, monophosphoryl lipid A, reduces allergic symptoms after only four preseasonal injections.

BACKGROUND: We present data showing that a Th1-inducing adjuvant can reduce the number of injections required for allergy vaccination. Allergy vaccination is the only treatment for type 1 hypersensitivity that can alter the underlying disease process. A switch of specific T-cell activity from Th2 >Th1 to Th1 >Th2 is believed to be an important change seen after long-term vaccination therapy. An immunologic adjuvant that enhances such a switch could be used to reduce the number of injections required. This would improve compliance with the treatment and provide pharmacoeconomic advantages. Such an adjuvant is 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa). METHODS: A multicentre, placebo-controlled, randomized, double-blind clinical study was performed with a new standardized allergy vaccine comprising a tyrosine-adsorbed glutaraldehyde-modified grass pollen extract containing MPL adjuvant. Four subcutaneous injections of the active product were given preseasonally to 81 grass pollen-sensitive subjects, and 60 received placebo injections (tyrosine alone). Diary cards were used to record symptoms and medication taken during approximately 30 days of the grass pollen season. RESULTS: There was a statistical advantage in favour of the active treatment for nasal (P = 0.016) and ocular (P = 0.003) symptoms and combined symptom and medication scores (P=0.013). Titrated skin prick testing revealed a significant reduction of skin sensitivity in the active group compared to placebo (P = 0.04). Grass-pollen-specific IgG antibody was raised by active treatment (P < 0.01). A rise in IgE antibody was seen in the placebo group during the season (P < 0.01). The first year's treatment rise of IgE was not seen in the active group, and no rise occurred during the pollen season. More local adverse events were seen in the active group. There was no difference in generalized adverse events. CONCLUSION: A new, well-tolerated allergy vaccine, incorporating a Th1-inducing adjuvant, MPL, was efficacious and after only four preseasonal injections produced antibody changes normally associated with long injection schedules. This may encourage wider application of allergy vaccination. The vaccine is now available in a number of countries as Pollinex Quattro.

Adjuvants, Immunologic↗