bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoclonal antibody against a major latex allergen reacts with latex products and ammoniated natural latex
Authors: Lu L.‐J. , Kurup V. P. , Kelly K. J. , Fink J. N.
Published: May 2007

Spina bifida patients have been shown to be a high‐risk group for latex allergy. Of the several latex proteins identified from nonammoniated natural latex, a polypeptide with a molecular mass of about 23 kDa was shown to be one of the major allergens reacting with IgE in the sera from such patients. Using hybridoma technology, a monoclonal antibody (mAb) 1E2 against the 23‐kDa latex allergen was produced. The presence of the 23‐kDa or related allergens in finished latex products was evaluated using 1E2. Of the 16 extracts of finished latex products, 12 reacted with 1E2. The other four products are not used in health care. Since the majority of latex products used in health care are manufactured from ammoniated latex and ammoniation may alter latex proteins, we also investigated the effect of ammoniation on the 23‐kDa allergen. Although ammoniation degraded latex proteins, the 23‐kDa antigen could still be detected by using mAb 1E2 on immunoblot of ammoniated latex proteins. Furthermore, ammoniation resulted in the appearance of additional proteins in high molecular weight positions not present in nonammoniated natural latex, which retained the 23‐kDa epitope. The 23‐kDa allergen could also be detected on surgical gloves after extensive washing.
Topical nitroprusside may reduce histamine‐induced plasma exudation in human nasal airways
Authors: Greiff L. , Andersson M. , Svensson C. , Nilsson M. , Erjefält I. , Erjefält J. S. , Persson C. G. A.
Published: May 2007

Mucosal exudation of nonsieved bulk plasma is a key feature of airway defense and inflammation. We have previously observed in guinea pig tracheobronchial airways that endogenous nitric oxide (NO) of the mucosa may tonically suppress the permeability of the subepithelial microcirculation, and that topical administration of the NO donor nitroprusside may reduce plasma exudation responses. The present study examines whether nitroprusside affects histamine‐induced mucosal exudation of plasma in the human nasal airway. In a dose‐finding tolerability experiment, using changes in nasal patency as response, placebo and nitroprusside (1.2 and 3.6 mg per nasal cavity) were applied on the mucosal surface with a nasal‐spray device. Nasal peak expiratory flow (PEF) rates were measured before the application and thereafter every third minute for 15 min. Nitroprusside produced a dose‐dependent decrease in nasal PEF rates compared to placebo. Placebo or nitroprusside (7.2 mg) was then given to the right nasal cavity, followed 3 min later by challenge with saline or histamine (600 μg). The drug and the challenge were both applied with a nasal‐spray device. With a nasal pool‐device, the same large part of the nasal mucosal surface was lavaged before and after the treatment/challenge. The lavage fluid levels of a2‐macroglobulin were measured as an index of mucosal exudation of bulk plasma. The histamine‐induced lavage fluid level of aj‐macroglobulin was significantly higher after treatment with placebo than with nitroprusside. The present data indicate that nitroprusside may have antiexudative effects in human airways. Hence, unlike other microvascular permeability active agents, this pharmacologic principle may be active in both guinea pig and human airways.
Do inhaled steroids have similar efficacy? A case of bronchial asthma suggesting different efficacy of inhaled glucocorticosteroids
Authors: Larsen B. B. , Dahl R.
Published: May 2007

We report a 35‐year‐old woman who had had bronchial asthma for 17 years. Her asthma worsened and became unstable on treatment with beclomethasone dipropionate (BDP), budesonide (BUD), and oral glucocorticosteroids (GC). At the age of 31, she had participated in a clinical trial with fluticasone propionate (FP), and after 2 weeks' treatment her asthma was well controlled. Because of pregnancy, her participation was terminated and treatment continued with available inhaled GC; however, the disease deteriorated and treatment with FP was resumed 2 years ago. Lung function normalized after 3 weeks and she has remained clinically stable since.
Cross‐reacting IgE antibodies recognizing latex allergens, including Hev b 1, as well as papain
Authors: Baur X. , Chen Z. , Rozynek P. , Diiser M. , Raulf‐Heimsoth M.
Published: May 2007

The cross‐reactivity of IgE antibodies recognizing epitopes of latex allergens and papain was studied in sera of 36 latex‐exposed subjects and 22 papain workers. Eight out of 24 latex‐sensitized persons also showed positive reaction to papain in the CAP assay (mostly of low or moderate degree). On the other hand, six out of the 12 sensitized papain workers also revealed IgE binding to latex allergen(s). Reciprocal inhibition experiments confirmed that groups monosensitized to one of the two allergens can be separated from a group showing partial or nearly complete immunologic cross‐reactivity. Papain inhibited IgE binding by 20–33% in these subjects, whereas IgE binding to papain was strongly blocked in most cases. Comparison between the primary sequences of Hev b 1, a major latex allergen, and papain suggests that the cross‐reactivity may be due to several identical trimers and tetramers.
Prevalence of asthma and asthma symptoms in a general population sample from northern Italy
Authors: Marinoni Alessandra
Published: May 2007

The European Community Respiratory Health Survey is an international survey of the general population which aims to establish whether there are significant variations in the prevalence of asthma among European countries. The present paper reports the prevalence of asthma and asthma‐like symptoms in a sample of subjects living in three areas of northern Italy: Turin, Pavia, and Verona. Samples of residents 20–44 years old (3000 subjects in Turin and Verona and 1000 in Pavia) stratified by sex (M:E= 1/1) were randomly selected from local health authority lists in the three participating areas. To correct the observed prevalence estimate for nonresponse bias, a method proposed by Drane was applied. Of the sampled subjects, 86% (6031) participated in the survey. Two different definitions of asthma were adopted: 1) prevalence of asthma attack in the last 12 months; 2) prevalence of asthma attack or treatment with antiasthmatic drugs, or both wheezing apart from the common cold and wheezing with shortness of breath. This combination of symptoms has been called current asthma. According to these definitions, the prevalence of asthma attack was 3.47% (3.74%, in men and 3.14% in women), and the prevalence of current asthma was 5.01% (5.07% in men and 4.90% in women). The lowest prevalence was found in Pavia; the highest in Turin. Our findings support the hypothesis that the difference in prevalence reflects the difference in mortality.
A comparative study of eosinophil isolation by different procedures of CD 16‐negative depletion
Authors: Chihara J. , Kurachi D. , Yamamoto T. , Yamada H. , Wada T. , Yasukawa A. , Nakajima S.
Published: May 2007

Eosinophils were isolated by the three methods of CD16‐negative depletion: 1) magnetic beads, 2) fluorescence‐activated cell sorter (FACS), and 3) complement reaction. Their purity, yield, and viability were compared. The second procedure produced well purity and viability (94.65 ± 1.51% and 94.98 ± 1.40%, respectively) but low yield of eosinophils (65.47 ± 2.47%). The viability of cells obtained by the third procedure was not efficient (80.83 ± 2.85%), while the purity and the yield were efficient (96.23 ± 1.09% and 90.75 ± 1.72%, respectively). In conclusion, the magnetic beads method (purity: 98.02 ± 0.45%, yield: 91.05 ± 2.43%, viability: 97.57 ± 0.37%) was the most advantageous of these three procedures. Moreover, in the functional assay, radical oxygen products from eosinophils isolated by the procedure with complement reaction were less than with the magnetic beads or FACS procedures.
Methods to assess RAST results in patients exposed to chemical allergens
Authors: Karol M. H. , Kramarik J. A. , Ferguson J.
Published: May 2007

RAST is routinely used to assess the presence of IgE antibodies against environmental allergens in the sera of symptomatic patients. With exposure to low‐mol.‐mass (chemical) allergens, RAST is also done, but the interpretation of results is more difficult. A study was undertaken to assess methods which have been employed to determine the positivity of sera and to develop an objective, statistically based procedure for determination of RAST positivity to chemical allergens. Sera were obtained from 14 nonsensitized (control) subjects and examined for total IgE by radioimmunoassay, and for cyanuric chloride (CyCl)‐specific IgE by RAST. Linear regression analysis revealed the correlation between the tests to be 0.94. Equations for the 95% and 99% predicted intervals were obtained. Sera from 19 cyanuric chloride workers were tested for total and specific IgE. Positivity of RAST results was determined by three methods: RAST inhibition, RAST ratio (binding to CyCl‐human serum albumin (HSA) disks/HSA disks), and the regression equation where values outside the 99% predicted interval were considered to be positive and those ≥95%≤99%, were considered to be borderline values. Determination of CyCl RAST positivity by the regression method gave results comparable to those obtained from RAST inhibition, whereas the RAST ratio resulted in many more false positive conclusions. This statistical approach to RAST analysis was also used to assess sera from patients exposed to the unrelated chemical allergens, toluene diisocyanate and formaldehyde. Conclusions based on the regression method were in good agreement with those from RAST inhibition assay. Moreover, use of one standard curve may be sufficient for interpretation of RAST results for diverse haptenic allergens. These results indicate that the regression method provides a statistical basis from which to determine positivity of RAST analyses while eliminating the need for RAST inhibition assays.
Determinants of cord‐blood IgE concentrations in 6401 German neonates
Authors: Bergmann R. L , Schulz J. , Günther S. , Dudenhausen J. W. , Bergmann K. E. , Bauer C. P. , Dorsch W. , Schmidt E. , Luck W. , Lau S. , Graß Th. , Wahn U.
Published: May 2007

For screening atopy risk in 6401 (84%) of all infants born during the year 1990 in six obstetric departments of five German cities, cord‐blood IgE values were determined with CAP‐RAST‐FEIA. After cases with elevated IgA values had been excluded, 25 % of the values were above the detection limit of 0.35 kU/1, and 8.5% were above 0.9 kU/1. Boys had significantly higher values than girls (P≤0.001). The distribution of values was significantly different for different nationalities of mothers (P≤0.001). The percentage of elevated values (≥0.9kU/l) increased significantly with the number of close family members with atopic history (P≤0.001). Regarding the atopic history of the father, siblings, and mother separately, only the mother's history had a significant association with the cord‐blood IgE class (P≤0.001). The IgE values of 81 twin pairs correlated significantly with a coefficient of r = 0.4909 (P≤0.001). The smoking history of the parents during pregnancy showed an association with cord‐blood IgE values (P≤0.02). No significant association could be shown between cord‐blood IgE distribution and other variables, i.e., gestational age, birth size, birth modus, Apgar score, cord‐blood pH value, neonatal problems, parity, age of the mother, medication during pregnancy, educational level of mother or father, time of year, or obstetric department. It is hypothesized that, in addition to some postpartum contamination or placental transfer of maternal IgE, cord‐blood IgE values are also determined by the fetal immunologic reaction to intrauterine exposure to allergens and trigger factors, and by genetic influences.
Levels of soluble ICAM‐1 in atopic dermatitis A new marker for monitoring the clinical activity?
Authors: Wüthrich B. , Joller‐Jemelka H. , Kägi M.K.
Published: May 2007

Levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) were measured in sera from patients with an acute exacerbation of their atopic dermatitis (AD) (n= 16) on admission to and discharge from our department of dermatology. At admission, the sICAM‐1 levels in sera from patients with AD were slightly higher than those of the blood donors (n= 100) and dropped at discharge significantly (P= 0.014) after improvement of the skin conditions. Therefore, sICAM‐1 may be, together with soluble interleukin‐2 receptor (sIL‐2), eosinophilic cationic protein (ECP), and CD14, another marker for monitoring AD.
Basic isoforms of Par o 1, the major allergen of Parietaria officinalis pollen
Authors: Coscia M. R. , Ruffilli A. , Oreste U.
Published: May 2007

We describe a group of basic isoforms of Par o 1 (cumulatively referred to as Par o lb), purified by anion‐exchange chromatography. The allergenic activity of Par o lb was compared with that of the acidic isoform (Par o la) by RAST inhibition. Par o lb showed a cathodic mobility in crossed immunoelectrophoresis. It was found to be homogeneous in SDS‐PAGE and SE‐HPLC (14.5 kDa), and heterogeneous in PAG‐IEF, yielding five IgE‐binding bands with pi ranging between 7.9 and 9.6. PAG‐IEF individual components were isolated by cation‐exchange HPLC. The N‐terminal amino acid sequence of the main component (pI 8.8) was determined and found to be similar to that of Par o la.
An analysis of β‐lactam‐derived antigens on spleen cell and serum proteins by ELISA and Western blotting
Authors: Wairbrick E. V. , Thomas A. L. , Stejskal V. , Coleman J. W.
Published: May 2007

Penicillins and related β‐lactam antibiotics are known to conjugate to proteins to generate potentially antigenic (haptenic) determinants. In the present study, we used a rabbit polyclonal antibody raised against benzylpenicillin (BP) to investigate the capacity of six penicillins and one cephalosporin to generate haptenic groups in vitro on cultured mouse spleen cells and on serum proteins in the culture medium. All of the drugs tested, namely, BP, amoxicillin (AMX), ampicillin (AMP), cephalothin (CEP), cloxacillin (CLX), flucloxacillin (FLX), and phenoxymethylpenicillin (PMP) generated antigens in a concentration‐dependent manner on cell and serum proteins, which could be detected by ELISA, although antigens generated by BP, CEP, FLX, or PMP in either cell‐ or serum‐conjugated form were more readily detected than those generated by AMX, AMP, or CLX. Western blot analysis revealed that BP‐derived antigens were generated relatively slowly on cell proteins (maximum binding was not yet reached after 8 h), compared to serum proteins (maximum binding within 1 h). BP, CEP, and PMP all generated similar distinctive patterns of immunostaining of electrophoresed cell or serum proteins which did not reflect the relative abundance of different proteins as revealed by Coomassie brilliant blue staining. FLX, CLX, AMP, and AMX did not generate antigens that could be detected on Western blots. In conclusion, we have shown that various β‐lactam antibiotics generate antigens on cell and serum proteins that can be detected and characterized immunochemically with polyclonal antiserum. Further application of these methods may offer potential for further identification of immunologically relevant cellular and serum antigens generated by these drugs.
Double‐blind trial of house‐dust mite immunotherapy in asthmatic children resident at high altitude
Authors: Peroni D. G. , Piacentini G. L. , Martinati L. C. , Warner J. O. , Boner A. L.
Published: May 2007

Twenty‐three Dermatophagoides pteronyssinus (Dpt)‐sensitive asthmatic children aged 7–14 years entered a double‐blind, placebo‐controlled trial of standardized immunotherapy (IT) (Alpare) while resident at high altitude. Dpt sensitivity was evaluated by skin prick tests at different allergen concentrations at the enrollment and after 6 and 12 months of treatment. Bronchial hyperreactivity was evaluated at the same time points, and on each occasion, histamine challenge and, the following day, Dpt bronchial challenge were performed. All patients, irrespective of active treatment, improved clinically and in lung function with increased PC20 and Dpt‐PD20. Alpare‐treated patients had a significantly decreased sensitivity on Dpt skin testing (P ≤0.009) and felt that their asthma had improved (P ≤0.001) compared with placebo‐treated subjects, but there was no difference between the treatment groups in lung function or bronchial challenge response. IT neither increased nor decreased bronchial histamine sensitivity. Our results indicate that Dpt IT benefits asthmatic children, but improvement by allergen avoidance at high altitude is even greater.
The effect of sucrose on the quality of ryegrass (Lolium perenne) pollen extracts
Authors: Cadot P. , Lejoly M. , Stevens E. A. M.
Published: May 2007

We studied the protein‐stabilizing properties of sucrose, in the extraction medium, on the composition and stability of ryegrass (Lolium perenne) pollen extracts. The effect of 0.5 M and 1 M sucrose was assessed in the presence and absence of 0.5% phenol, which is commonly used as a disinfectant in industrially prepared allergenic extracts. In the absence of phenol, sucrose improves the stability of extracts during storage, but it has little influence on the extraction process. In the presence of 0.5% phenol, however, both the quality of fresh extracts and the stability are greatly improved by 0.5 M and by 1 M sucrose, as shown by electrophoresis, immunoblotting, and RAST‐inhibition experiments. The protection afforded by sucrose against the degrading effect of phenol is particularly evident for the major allergen Lol p 1 and for a set of basic allergens. In this respect, sucrose has been found to be superior to glycerol, on an equimolar basis. One may envisage the use of 0.5 M sucrose in allergenic extracts for intradermal testing and immunotherapy.
Role of two‐dimensional electrophoretic analysis in the diagnosis and characterization of IgD monoclonal gammopathy
Authors: Spertini F. , Tissot J. D. , Dufour N. , Francillon C. , Frei P. C.
Published: May 2007

Over a period of 5 years, an isolated light chain ‘K = 9, λ= 12) was detected in 21 sera by immunofixation electrophoresis. Further analysis with anti‐δ‐ and anti‐ɛ‐specific antisera identified four δ heavy chains, all associated with a λ light chain, and no ɛ heavy chains. For evaluation of the role of two‐dimensional polyacrylamide gel electrophoresis ‘2D‐PAGE) in the diagnosis of IgD paraproteins, as a possible alternative or complement to immunofixation, IgD paraproteins were retrospectively analyzed by 2D‐PAGE. δ Heavy chains migrated to gel areas clearly distinguishable from other heavy chains α, γ, or μ, and in a wide range of isoelectric points ‘pl: 5.4‐8). In one serum, the monoclonal δ chain had a pi range comparable to that of albumin and was undetectable. However, all four δ chains were easily identified when analyzed from affinity‐purified immunoglobulin fractions. These observations showed the following:

1) IgD paraproteins are not rare among apparently isolated monoclonal light chains detected by routine immunofixation, Ostrongly confirming the need for further analysis with anti‐δ antisera, before assumption of a light‐chain disease.

2) 2D‐PAGE analysis of affinity‐purified immunoglobulin fractions allowed correct identification of IgD monoclonal gammopathies in all cases.

3) However, although 2D‐PAGE analysis is now easy to perform, well standardized, and highly sensitive, this technique remains time‐consuming and expensive, and does not appear suitable for routine practice as a first‐line diagnostic procedure.

2D‐PAGE should find its place as a complement to immunofixation and in the definitive demonstration, in selected ambiguous cases, of the clonal pattern of a suspected gammopathy at immunofixation.
An enzyme‐linked immunosorbent assay specific for transient ‘29‐37‐kDa) fragments of soluble CD23/IgE‐binding factors
Authors: Katira A. , Gordon J.
Published: May 2007

The low‐affinity IgE receptor ‘FcɛRII) of B cells and monocytes ‐ also known as CD23 ‐ is released from the cell surface by proteolytic cleavage to yield a series of soluble fragments which can accumulate in cell culture supernatants and body fluids. Of these, the most stable is a 25‐kDa molecule which is generated from transient intermediates ranging in size from 29 to 37 kDa. It has been claimed that these latter species act as IgE‐promoting factors while the 25‐kDa molecule is endowed with various cytokine‐like activities which are independent of IgE binding. We describe here a novel enzyme‐linked immunosorbent assay ‘ELISA) which allows for the distinction between these two classes of soluble CD23. It is based on the observation that the CD23 antibody EBVCS1 can capture recombinant 29‐kDa and 37‐kDa fragments of CD23 but does not bind to the 25‐kDa species: when EBVCS5 is used as the capture antibody, all three fragments are bound. The availability of these differential ELISA should facilitate investigations on the biological properties of CD23 fragments in health and disease.
Circulating leukocyte adhesion molecules in stable asthma and nonobstructive chronic bronchitis
Authors: Riise G. C. , Larsson S. , Löwhagen O. , Andersson B. A.
Published: May 2007

Leukocyte adhesion molecules have been associated with airway inflammatory diseases such as asthma and obstructive chronic bronchitis. Lately, it has become possible to measure circulating forms of cell adhesion molecules ‘cCAMs) in body fluids. Elevated serum levels have been found in acute asthma and in obstructive chronic bronchitis. We investigated whether the patterns of cICAM‐1, cVCAM‐1, and cE‐selectin could serve as markers for airway inflammation in stable asthma and stable nonobstructive chronic bronchitis. Small‐volume bronchial lavage ‘BL) and serum from 15 controls, 13 asthmatics without steroid inhalation therapy, 11 asthmatics with regular steroid inhalation therapy, and 10 smokers with chronic bronchitis were analyzed. We found cICAM‐1, cVCAM‐1, and cE‐selectin to be present in serum from patients with stable asthma and stable nonobstructive chronic bronchitis. Only cICAM‐1 was found in BL fluid. No differences were seen between the subject groups for either cCAM, but levels of ECP were increased in the non‐steroid‐treated asthmatic group. Subject atopy or smoking did not increase the cCAM levels. In conclusion, the degree of airway inflammation in stable nonobstructive chronic bronchitis and stable asthma does not appear to be well associated with circulating ICAM‐1, cVCAM‐1, and cE‐selectin.
The airway inflammatory response in allergic asthma and its relationship to clinical disease
Authors: Howarth Peter H.
Published: May 2007

Endobronchial biopsy and lavage studies have revealed the presence of mast cell, eosinophil, T‐lymphocyte and epithelial cell activation in asthma, along with the structural changes of tissue eosinophil infiltration, loss of superficial columnar ciliated epithelial cells and enhanced collagen deposition in the laminar reticularis. As these cellular and structural changes underlie the clinical features of asthma, i.e., symptom expression, variable airflow obstruction and bronchial hyperresponsiveness, an understanding of their induction and regulation is essential to the understanding of the asthmatic process. The acute airway response to allergen has been studied by the technique of local endobronchial allergen challenge with direct airway sampling in asthma. These studies identify allergen‐mast cell interaction as the initial airway event, with mediator release inducing bronchoconstriction and enhancing vascular permeability. As preformed cytokines are present in mast cells, cytokine release from this cell population is likely to initiate the process of endothelial cell activation, with upregulation of cell adhesion molecules, and tissue cell recruitment. Subsequent cytokine elaboration from airway macrophages and T‐lymphocytes will perpetuate this response while in chronic clinical disease T‐lymphocytes, mast cells, matrix tissue, epithelial cells and eosinophils themselves are all likely to contribute to the cytokine pool within the airways and thus to the regulation of inflammatory cell migration and activation.
A new classification of H1‐receptor antagonists
Authors: Simons F. E. R.
Published: May 2007

Simons FER. A new classification of H1‐receptor antagonists — introduction.
Psychometric aspects of antihistamines
Authors: Hindmarch I.
Published: May 2007

Hindmarch I. Psychometric aspects of antihistamines.
The role of CD8+ T cells in immunoglobulin E regulation
Authors: Kemeny D. M. , Noble A. , Holmes B. J. , Diaz‐Sanchez D. , Lee T.H.
Published: May 2007

The link between immunoglobulin E (IgE) antibodies and environmental allergens, allergic sensitization and atopic diseases such as asthma, rhinitis and eczema is well established, yet treatment of these diseases is largely symptomatic and fails to correct the underlying immune disorder. B‐cell production of IgE depends on interleukin 4 (IL‐4) and is inhibited by interferon (IFN‐γ). These cytokines are produced by T‐helper 2 (Th2) and T‐helper 1 (Th1) CD4+ T cells respectively. In atopic dermatitis skin and asthmatic lung, Th2 cells predominate but antigen‐specific CD4+ T‐cell clones derived from peripheral blood are a mixture of Th1, Th2, and Th0. Circulating allergen‐specific CD4+ T cells differentiate into Th1‐ and Th2‐like clones in the presence of IL‐12 and IL‐4 respectively. In rats, CD8+ T cells are potent regulators of IgE responses in vivo, although the mechanism for this is still unclear. CD8+ T‐cell depletion in immunized animals prolonged the IgE response but prior depletion did not. Indeed, prior depletion of CD8+ T cells actually inhibited IgE production, suggesting that there may be more than one type of IgE regulatory CD8+ T cell. This was supported by the observation that CD8+ T cells inhibited the differentiation of both Th1 and Th2 CD4+ T cells in vitro as well as IL‐4‐but not IL‐2‐induced Th2 CD4+ T‐cell growth. The existence of distinct CD8+ T‐cell subsets is supported by the observation that IL‐4 and IFN‐γ regulate the growth and differentiation of CD8+ T cells. IL‐4 inhibits the development of CD8+ T cells that produce IL‐2 and IL‐6 and enhances the generation of cells that make IL‐4 and IL‐5. A combination of IL‐4 and anti‐IFN‐γ enhanced IFN‐γ and IL‐10 production. Studies are continuing to characterize different CD8+ T‐cell subsets at a clonal level and to determine their role in IgE regulation.
Monitoring allergen exposure in asthma: new treatment strategies
Authors: Chapman M. D. , Heymann P. W. , Sporik R. B. , Plans‐Mills T. A. E.
Published: May 2007

The development of monoclonal antibody‐based enzyme‐linked immunosorbent assay technology for measuring environmental allergen exposure has provided a benchmark for assessing the role of indoor allergens in causing asthma and other allergic diseases. Epidemiological studies from several parts of the world have shown that immunoglobulin E (IgE)‐mediated sensitization to indoor allergens (mite, cat, dog and cockroach) is a risk factor for asthma attacks. A dose‐response relationship between allergen exposure and sensitization has been demonstrated for mite allergens, and threshold values for exposure levels leading to sensitization or to exacerbations of symptoms have been defined. Comparative studies on airborne allergen levels have made it possible to determine the properties of aeroallergen particles, their concentration in indoor air, and the relationship to clinical symptoms. Together, these studies provide strong evidence that allergen exposure plays a causal role in the development of bronchial hyperreactivity and of the chronic inflammatory responses seen in patients with asthma. Logically, the primary preventive treatment should be allergen avoidance. Through knowledge of indoor allergen levels, both in dust and in the air, different avoidance strategies have been applied to the various indoor allergens, and there is increasing evidence of their clinical efficacy. Monitoring allergen levels in patients' houses should improve their understanding of the role of allergens in asthma and improve compliance with avoidance measures.
In pursuit of the “holy grail”: recombinant allergens and peptides as catalysts for the allergen‐specific immunotherapy
Authors: Mohapatra S. , Cao Y. , Ni H. , Salo D.
Published: May 2007

This presentation reviews recent progress in knowledge of (i) molecular biology and immunology of allergens and (ii) the methods for the modulation of allergen‐specific immune response, with special emphasis on our grass pollen allergens, particularly Pao p IX AL, used as a model. The last few years have seen tremendous progress in molecular characterization of allergens, leading to synthesis of a number of recombinant allergens. Furthermore, studies of the structure‐activity relationship of allergens have led to the delineation of the epitopes of these allergens and of widespread cross‐reactivities among diverse allergens. In view of the requirement for extensive pre‐clinical studies, the application of the recombinant allergens and epitopes in the clinical realm has just begun. Studies in murine systems suggest that these allergens and/or their epitopic peptides downregulate allergen‐specific immune responses de novo. The potential and drawbacks of the recombinant allergens and peptides for improving the existing immunotherapeutic approaches and for developing new approaches to specific immunotherapy are discussed.
Mediator release is altered in immunotherapy‐treated patients: a 4‐ear study
Authors: Dokic D. , Nethe A. , Kleine‐Tebbe J. , Kunkel G. , Baumgarten C. R.
Published: May 2007

In recent years, it has been possible to demonstrate mediator release into the nasal secretion after nasal allergen challenge in patients with allergic rhinitis. Using the nasal provocation model, we determined whether the mediator release was altered in immunotherapy‐treated patients. Seventeen grass‐pollen‐allergic patients were examined under controlled, reproducible conditions. Serial challenges with increasing doses of grass pollen produced increasing numbers of clinical symptoms and release of mediators such as kinins, TAME‐esterase activity, and histamine. Ten patients received a semidepot perennial grass‐pollen extract for 4 years. Seven patients served as controls and did not receive immunotherapy during the observation period. Data from the group of patients receiving immunotherapy over the first year already showed a partially significant decline in the maximal mediator release after nasal allergen challenges compared to the results of pretreated challenges, whereas controls did not show any significant changes. Nasal allergen challenges after termination of 4 years' immunotherapy significantly modified the mediator release compared to pretreatment values (TAME‐esterase activity P<0.05, kinins P<0.01, and histamine P<0.01). Decrease of mediator release paralleled the symptom‐medication scores and quantitative skin prick test. Finally, we could demonstrate a significant correlation between specific IgG increase and mediator decrease in the treated group.
Formaldehvde and Dhenol exposure during an anatom; dissecdon course: a Dossible source of IgE‐mediated sensitizkion?
Authors: Wantke F. , Focke M. , Hemmer W. , Tschabitschel. M. , Gann M. , Tappler P. , Götz M. , Jarisch R.
Published: May 2007

The sensitizing potency of formaldehyde and phenol exposure during 4 weeks of an anatomy dissection course was assessed in 45 medical students. Specific IgE against formaldehyde by RAST and by ELISA and specific IgE against phenol by ELISA were assessed before and after the course. At the start of the course. symptoms, type I allergy, respiratory diseases, and smoking habits were noted. At the end of the course, only symptoms experienced during the dissection lessons were assessed. Indoor formaldehyde levels were measured continuously. The mean indoor formaldehyde level was 0.124±0.05 ppm, with a minimum of 0.059 ppm and a maximum of 0.219 ppm. Specific IgE against formaldehyde or phenol was found in none of the subjects at the beginning of the course, and no student showed specific IgE against formaldehyde or phenol after the course. Assessment of primarily irritant symptoms during the lessons revealed itch and paraesthesia of hands in 33/45 students (P<0.00005), headache in 15/45 students, burning eyes in 13/45 students (P<0.02), dizziness in 8/45 students (P<0.008), sneezing in 4/45 students, epistaxis in 2/45 students, and shortness of breath in 1/45 students. According to our data, l‐month exposure to formaldehyde and phenol during an anatomy dissection course does not induce specific IgE against formaldehyde or phenol.
Allergen sensitization and exposure to irritants in infancy
Authors: Søyseth V. , Kongerud J. , Boe J.
Published: May 2007

We investigated the relationship between residence in the neighbourhood of an aluminium smelter and the prevalence of atopy in schoolchildren (7–13 years of age). Atopy was assessed in 556 of the 620 participants by a skin prick test with eight common aeroallergens. The median exposures to sulphur dioxide and fluoride during the pollen season in the age interval 19–36 months were 24 and 3.1 μg/m3 in the spring and 20 and 3.3 μg/m3 in the summer, respectively. The odds ratio (OR) of having atopy was 2.0 (95% CI: 1.2–3.3) in those children who had lived in the index area for 7 years or more compared with those who had lived there less than 7 years (cumulative effect). The OR of atopy was 2.5 (1.44.4) in those who had lived in the index area during the age interval of 19–36 months compared with rural residence during this age‐interval (age‐specific effect). When the age‐specific effect and the cumulative effect were compared in the same logistic model, the former decreased to 1.1 (0.43.0), whereas the latter was 2.2 (0.7–6.6). The results indicate that exposure to these low levels of irritants during early childhood increases allergen sensitization in children.
Formoterol inhaled as dry powder or via pressurized metered‐dose inhaler in a cumulative dose‐response study
Authors: Ullman A. , Löfdah1 C.‐G. , Melander B. , Svedmyr N.
Published: May 2007

Formoterol administered by a dry‐powder (DP) capsule inhaler was compared with a pressurized metered‐dose inhaler (pMDI) with regard to bronchodilating and systemic effects. The study used a double‐blind, crossover, double‐dummy technique. Twelve patients with moderate reversible asthma in a stable phase were examined on two separate study days, and the inhalers were given in randomized order. After baseline measurements, increasing doses of formoterol were given at intervals of 75 min. FEV1 and heart rate and tremor measurements were repeated after each dose, and the doses were 12 + 12 + 24 + 48 μg, giving a total dose of 96 μg. The peak expiratory flow rate (PEFR) was recorded in the morning before the first dose, after the last dose, and then repeatedly at home until 19 h after the last dose. There was an equal increase in ventilatory capacity at each dose level, independent of inhaler device. Repeated PEFR measurements after the last dose did not reveal any differences in duration of effect. There was a slight but statistically significant increase in heart rate and tremor after the highest doses of the DP formulation compared to the pMDI. These systemic effects can probably be explained by the reduced oral deposition of the aerosol caused by using a spacer. This study indicates that the DP and pMDI formulations of formoterol are equipotent in bronchodilation.
Immunotherapy with standardized extract of Dermatophagoides pteronyssinus in bronchial asthma: a dose‐titration study
Authors: Olaguibel J. M. , Tabar A. I. , García Figueroa B. E. , Cortés C.
Published: May 2007

According to the maximum tolerated dose (MTD) achieved, we assessed the changes in clinical and laboratory parameters, induced by specific immunotherapy (SIT), in a group of 43 asthmatic patients sensitized to Dermatophagoides pteronyssinus, over a period of 18 months. A standardized extract (100 Bu/ml; 40 μg/ml of Der p 1; 20 μg/ml of Der p 2) was used. The patients were divided into two groups: the high‐dose immunotherapy (HDI) group (MTD ≥ 4 μg Der p 1) and the conventional immunotherapy (CI) group (MTD <4 μg Der p 1). Changes in clinical severity index, medication, and symptom scores; in cutaneous and conjunctival reactivity; and in the levels of specific IgE, IgG, IgGl, and IgG4 to D. pteronyssinus (Der p 1 and Der p 2) were measured (ELISA monoclonal antibodies). Safety was monitored according to the EAACI guidelines. The range of the MTD was 0.8‐16 μg of Der p 1. Ninety percent of the patients tolerated a dose of 3.2 μg, but only 18% of the patients reached a maintenance dose of 16 μg. The medians of the accumulated dose were 197 μg of Der p 1 for the HDI group, and 50 μg for the CI group. Conjunctival and cutaneous reactivity was significantly lowered (P<0.001) after SIT, as were the clinical severity score and medication score in both groups, without significant differences between the groups, except for cutaneous reactivity. Levels of specific IgE decreased significantly (P<0.01) in both groups, again without significant differences between the groups. The range of the increase in medians of specific IgG, IgGl, and IgG4 was 4.4‐120‐fold for the HDI group and 3‐24‐fold for the CI group (P<0.01). The increase in the levels of Der p 1 and Der p 2 IgG4 were correlated to the changes in cutaneous and conjunctival reactivity (P<0.01). These results show that a maintenance dose of 3.2 μg Der p 1 (8 BU) can induce pronounced clinical and immunologic changes with an excellent safety profile.
Possible mechanisms of the concentration‐dependent action of substance P to induce histamine release from rat peritoneal mast cells and the effect of extracellular calcium on mast‐cell activation
Authors: Amano H. , Kurosawa M. , Miyachi Y.
Published: May 2007

Rat peritoneal mast cells purified on a Percoll gradient were loaded with the fluorescent Ca2+ indicator fura‐2 and were challenged with different concentrations of substance P (SP), and intracellular calcium concentrations ([Ca2+]i) were measured by a spectrofluorometric assay. SP at 5 × 10−6 mol/1 and 10−5 mol/1 caused a significant histamine release with a significant increase in [Ca2+]i in a dose‐dependent manner. However, SP at 10−8‐10−6 mol/1 did not induce either histamine release or increase in [Ca2+]i. Extracellular calcium at 0.9 mM inhibited the histamine release with a significant reduction of [Ca2+]i compared with that of the cells in a nominally calcium‐free condition. These results indicate that the action of SP on rat mast cells relies upon [Ca2+]i to induce histamine release.
Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity
Authors: Pichler C. E. , Marquardsen A. , Sparholt S. , Løwenstein H. , Bircher A. , Bischof M. , Pichler W. J.
Published: May 2007

To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double‐blind, placebo‐controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo‐treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo‐ and verum‐treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum‐treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite‐allergen‐induced asthma may reduce not only immediate, IgE‐mediated symptoms but, after a rather long time period of 12–18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.
Latex allergen elimination in natural latex sap and latex gloves by treatment with alkaline potassium hydroxide solution
Authors: Baur X. , Rennert J. , Chen Z.
Published: May 2007

Antigenic proteins in latex products can cause type I allergy. We investigated the effects of potassium hydroxide (KOH) solution on the allergenicity of proteins in natural latex sap and latex gloves by using an EAST competitive inhibition immunoassay and skin prick test. Latex sap was mixed with KOH solution at different concentrations and incubated over various periods of time at room temperature. Latex gloves were washed in KOH solution for different times at 30°C and 90°C. Our immunoassay results for the subsequently extracted latex proteins demonstrated a KOH concentration‐, temperature‐, and lime‐dependent decrease in allergenicily, finally resulting in complete loss of IgE‐binding activity. In the skin prick test, we found only four weakly positive reactions to proteins extracted from KOH‐washed gloves in 30 latex‐sensitized patients. In addition, up to 97% of the aqueous extractable protein content could be removed from latex gloves by washing in KOH solution under certain conditions. These results suggest that antigenic proteins in natural latex sap and latex gloves can be changed by treatment with KOH solution, which is followed by a loss of their capability to bind specific IgE antibodies from most latex‐sensitized patients.
Serum eosinophil peroxidase (EPO) levels in asthmatic patients
Authors: Sanz M. L. , Parra A. , Prieto I. , Diéguez I. , Oehling A. K.
Published: May 2007

Eosinophil granular proteins are a useful eosinophilic activation marker in asthmatic patients. In this study, the eosinophil peroxidase (EPO) levels were assessed in different stages of bronchial asthma, in 123 patients suffering from asthma, classified as mild (n=49), moderate (n=49), and severe (n=25), according to the International Consensus Report on Diagnosis and Treatment of Asthma, as well as in 27 healthy controls, with the aim of evaluating the importance of this protein as a severity marker in bronchial asthma, and its possible correlation with parameters such as anamnesis, respiratory function tests, and peripheral blood eosinophil count, and also with some allergologic diagnostic tests, both in vivo and in vitro. The geometric mean serum level of EPO was 9.3±11.3 ng/ml (median±SD) in controls, and 28±37.8 ng/ml in the asthmatic patients. Depending on the asthma severity, the EPO levels were 25±30.5; 29±37.1, and 41 ±47.3 ng/ml in mild, moderate, and severe asthmatics, respectively, being the significant differences between the group of patients with mild and severe asthma (P<0.001). The number of eosinophils (eos) in peripheral blood was 157±20 eos/mm3 in the controls, 334+35 eos/mm3 in mild asthmatics, 510 ±87 eos/mm3 in moderate asthmatics, and 658±72 eos/mm3 in severe asthmatics, with significant differences between all the groups (from P<0.05 to P<0.001). Both the serum levels of EPO and the number of eosinophils were greater in patients with active asthma than in patients with inactive asthma (P<0.001). Significant negative correlations (P < 0.001) were found between serum levels of EPO and FEY, (rs= 0.30), MEF25‐75 (rs= ‐0.33), and MEF50 (rs= ‐0.34), and a good positive correlation (rs= 0.80, P<0.001) was found between EPO levels and the number of eosinophils in peripheral blood. We also found a significant positive correlation between eosinophil number and clinical score (rs= 0.54, P<0.001) and between EPO levels and the mentioned score (rs= 0.46, P<0.001).
Systemic effects of two nasally administered glucocorticosteroids
Authors: Wihl J.‐Å. , Andersson K.‐E. , Johansson S.‐Å.
Published: May 2007

Two topical corticosteroids, budesonide (BUD) and beclomethasone dipropionate (BDP), both administered as suspensions in water, were investigated in healthy volunteers regarding influence on cortisol in plasma and urine (U‐cortisol) after nasal application. In the first study, single doses of 200, 400, and 800 μg of BDP and BUD were given at 10:00 pm. In the second study, 100, 200, and 400 μg were given mornings and evenings for 4 days. In the single‐dose study, none of the drugs or doses showed any significant influence on cortisol in plasma. However, U‐cortisol decreased significantly after BUD 400 and 800 μg. In the multidose study, U‐cortisol values were significantly reduced after all doses of BUD and the highest dose of BDP. The compounds tested showed different ability to cause measurable systemic effects after nasal application. The clinical implication is that the prescriber, when choosing a compound, should take the application site into consideration and should also be encouraged to find the lowest effective dose.
Occupational type I allergy to Christmas cactus (Schlumbergera)
Authors: Paulsen E. , Skov P. Stahl , Bindslev‐Jensen C. , Voitenko V. , Poulsen L. K.
Published: May 2007

The study aimed to determine whether occupational contact urticaria and symptoms of mucous membranes, reported by five workers in a cactus nursery, were due to IgE‐mediated allergy to Schlumbergera cacti. The five persons had positive skin prick tests to the plants as is and positive histamine‐release tests, and in three of them specific IgE to the cacti could be demonstrated by Maxisorp RAST and immunoblotting. Four of the patients were atopic, and the fifth had a positive skin prick test to cat dander, indicating latent atopy. Skin prick tests with cacti were negative in most atopic volunteers, and all had negative histamine‐release tests. The results suggest a true IgE‐mediated allergy to the cacti, and both genetic predisposition and close contact with the plants at work seem to be important factors in the emergence of this new occupational allergy.
IgE‐mediated hypersensitivity to latex in childhood
Authors: Theissen U. , Theissen J. L. , Mertes N. , Brehler R.
Published: May 2007

A total of 267 children scheduled to receive anesthesia during a surgical, neurosurgical, or orthopedic intervention were investigated. IgE antibodies against latex were detected in serum samples of 6.4% (17/267 children) of the patients. The most important difference between sensitized and nonsensitized children was the number of surgical interventions in the past. The median of surgical interventions was 1.0 in the nonsensitized group of children and 3.0 in the sensitized group. Only 0.9% of the children with up to two surgical interventions and 34.1% with three or more procedures were sensitized to latex. Only one of the sensitized children developed intraoperative anaphylaxis during intervention after our investigation. We conclude that children with a history of three or more surgical interventions have a high risk of sensitization to latex proteins. Nevertheless, the predictive value of IgE antibodies against latex for development of anaphylaxis during anesthesia seems to be low.