bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene polymorphisms of endothelial nitric oxide synthase and angiotensin‐converting enzyme in patients with asthma
Authors: Lee Y. C. , Cheon K. T. , Lee H. B. , Kim W. , Rhee Y. K. , Kim D. S.
Published: March 2003

Background: Nitric oxide, including that produced by endothelial constitutive nitric oxide synthase (ecNOS), may regulate vascular and airway tone in the lungs and may influence various aspects of airway homeostasis. Angiotensin‐converting enzyme (ACE) is expressed at high levels in the lungs and plays a role in the metabolism of angiotensin II, bradykinin, and substance P, all of which are potentially involved in the pathogenesis of asthma. An insertion‐deletion polymorphism of the ACE gene has been shown to be associated with enzyme activity levels of ACE. To examine the possible involvement of the ecNOS and/or ACE genes as the genetic basis of bronchial asthma, we investigated whether there was any association between bronchial asthma and polymorphisms of the ecNOS and/or ACE genes.

Methods: A total of 310 patients with bronchial asthma and 121 healthy subjects took part in this study. The ecNOS and ACE genotypes were determined in all subjects by polymerase chain reaction.

Results:

The distribution of one genotype (bb) of ecNOS was significantly higher in the asthma group than in the control population.

The ACE genotype distribution was not significantly different between the control and the asthma groups.

In asthmatic patients, the ACE and ecNOS genotype distribution did not differ significantly among groups of patients with different severities of asthma.

Conclusions: These results suggest that polymorphisms of the ecNOS gene, but not the ACE gene, may be associated with the development of asthma. However, the severity of asthma may not be influenced by polymorphisms of the ecNOS and ACE genes.
Cetirizine inhibits bradykinin‐induced cutaneous wheal and flare in atopic and healthy subjects
Authors: Fadel R. , Ramboer I. , Chatterjee N. , Rihoux J.‐P. , Derde M.‐P.
Published: March 2003

Background: Kinins are vasoactive mediators involved in allergic reactions. When applied on the skin or in the nose, bradykinin (BK) elicits inflammation that is poorly affected by previous H1‐blockade. The aim of this study was to compare the possible effect of cetirizine (an H1‐antagonist) on wheal and flare responses to BK, histamine, and compound 48/80 in atopic and healthy subjects.

Methods: In a randomized, double‐blind, crossover study, eight atopic and eight healthy subjects received cetirizine (10 mg/day) or placebo for 3 days before cutaneous tests. Intradermal tests (IDT) and prick tests (PT) were performed with BK (20 nmol/ml for IDT and 20 μmol/ml for PT), histamine (100 μg/ml IDT and 100 mg/ml PT), and compound 48/80 (100 μg/ml IDT and 100 mg/ml PT) as positive controls and saline as negative control. The skin responses were monitored by measurement of wheal and flare areas.

Results: BK, histamine, and 48/80 induced wheal and flare reactions in all placebo‐treated subjects. Histamine elicited larger wheal and flare reactions than BK and 48/80. IDT with BK induced four‐ to sixfold larger wheal and flare reaction than PT. No differences in BK‐induced wheal and flare were observed between atopic and healthy subjects. In atopic subjects, cetirizine induced a significant reduction of flare reactions after the BK test (80% for IDT, and 94% for PT [P<0.01]). Moreover, cetirizine reduced significantly BK‐induced wheals by 70% for IDT (P<0.01) and 65% for PT (P<0.01). A similar inhibiting effect of cetirizine was also observed in healthy subjects.

Conclusions: These findings showed that the wheal and flare reactions induced by BK challenge were markedly inhibited by previous intake of cetirizine. The mechanism by which this effect is mediated cannot be established at present.
A comparison of the clinical efficacy and safety of intranasal fluticasone propionate and antihistamines in the treatment of rhinitis
Authors: Foresi A.
Published: March 2003

Adequate management of allergic rhinitis is needed to avoid its considerable adverse social, clinical, and economic impact. Both topical intranasal steroids and oral or topical antihistamines are recognised as effective treatments for this condition. In comparative studies, however, intranasal steroids and, in particular, fluticasone propionate aqueous nasal spray (FPANS), have afforded consistently better symptomatic relief, and have a greater beneficial effect on quality of life. Furthermore, the addition of an antihistamine to FPANS therapy has generally produced little further benefit. Intranasal administration is associated with a low systemic absorption of fluticasone propionate and, following regular use of FPANS, placebo, or an oral antihistamine, no significant differences were seen between treatment groups in plasma or urinary cortisol. Overall, therefore, the data indicate that FPANS is superior to second‐generation antihistamines in the management of allergic rhinitis.
Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing
Authors: Torres J. , Romano A. , Mayorga C. , Carmen M. , Guzman A. E. , Reche M. , Juarez C. , Blanca M.
Published: March 2003

Background: Penicillin is no longer the most commonly prescribed β‐lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin‐allergic subjects from a population where benzylpenicillin is not now the most frequently used β‐lactam.

Methods: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake.

Results: After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders.

Conclusions: Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.
The potential role of orbicules as a vector of allergens
Authors: Vinckier S. , Smets E.
Published: March 2003

Background:In the locules of anthers of flowering plants, tiny (1.5‐2 µm) granules of sporopollenin may occur next to the pollen grains. Those granules, called orbicules, mostly occur on the radial and innermost tangential wall of secretory tapetum cells.

Methods:We have investigated the presence of orbicules in 15 important European allergenic species with scanning electron microscopy (SEM).

Results:Orbicules were present in all species investigated of the families Betulaceae, Chenopodiaceae, Fagaceae, Poaceae, Polygonaceae, and Urticaceae. However, in the Asteraceae and Oleaceae species studied, orbicules were lacking. In all Chenopodiaceae, Poaceae, and Urticaceae species, orbicules were attached to the pollen exine. These observations indicate the possibility of the dispersal of orbicules into the atmosphere during anthesis.

Conclusions:The hypothesis of the potential role of orbicules as possible important vectors of allergens is put forward, based on the comparison of our results with recent literature about the evidence of allergenic activity in the smaller micronic atmospheric aerosol fraction. Our results provide evidence that an in‐depth investigation of the sites of allergens across the whole anther is required. We suggest that allergen researchers apply immunoelectron microscopy on whole anthers to determine whether orbicules possess allergens.
Safety of sublingual immunotherapy with monomeric all_ergoid in adults: multicenter post‐marketing surveillance study
Authors: Lombardi C. , Gargioni S. , Melchiorre A. , Tiri A. , Falagiani P. , Walter Canonica G. , Passalacqua G.
Published: March 2003

Background: Sublingual immunotherapy (SLIT) appears to be acceptably safe in clinical trials, but post‐marketing data are needed to provide essential information. This study specificall_y evaluated the safety of commercial SLIT in adult patients in a post‐marketing phase.

Methods: A total of 198 patients (83 male, 115 female, mean age 24.4 years) receiving SLIT for respiratory all_ergy were followed up for 3 years by a specific questionnaire for side‐effects. SLIT (LAIS, Lofarma SpA, Milan, Italy), a monomeric all_ergoid in tablets, was administered, in association with drug therapy, pre‐ or pre‐coseasonall_y for pollen and continuously for mites. The average duration was 12–36 months, and the total of doses was about 32 800. Side‐effects were grouped as ocular, gastrointestinal, rhinitis, asthma, urticaria, edema of tongue/lips, and anaphylaxis. The severity was graded as low (no need for treatment or dose adjusting, no interference with activities), moderate (interference with activities/need for drugs/SLIT discontinuation), and severe (life‐threatening/hospitalization/emergency care).

Results: Seventeen events corresponding to 7.5% of patients and 0.52 per 1000 doses were reported. Seven episodes of rhinitis (two in two patients), three of oral itching, and one of abdominal pain were self‐limiting. Two cases of urticaria and two of abdominal pain/nausea were controlled by a temporary dose‐adjustment, and one case of urticaria and conjunctivitis required oral antihistamines. Medical intervention was needed in six patients only during a 3‐year period.

Conclusions: The results of this study, performed in a real situation of clinical practice, confirm the satisfactory safety profile of SLIT.
Specific immunotherapy prevents increased levels of allergen‐specific IL‐4‐ and IL‐13‐producing cells during pollen season
Authors: Gabrielsson S. , Söderlund A. , Paulie S. , Van Der Pouw Kraan T.C.T.M. , Troye‐Blomberg M. , Rak S.
Published: March 2003

Background: Specific allergen immunotherapy (SIT) is effective for treatment of IgE‐mediated diseases; however, the mechanisms of action still remain unclear. Earlier, we showed that IL‐4 and IL‐13 are produced in response to specific allergens. The aim of this study was to investigate whether these cytokine responses were affected by allergen SIT, and, furthermore, to evaluate the effect of SIT on allergen‐specific IgE and IgG4 levels.

Methods: Blood samples from pollen‐sensitized individuals were collected before the pollen season (before treatment) and during the pollen season (after SIT or placebo treatment). Peripheral blood mononuclear cells were activated in vitro with allergens and the numbers of IL‐4‐, IL‐13‐, IL‐10‐, and IFN‐γ‐producing cells were determined by ELISPOT. Serum levels of allergen‐specific IgE and IgG4 were measured by RAST and ELISA, respectively.

Results: The numbers of IL‐4‐ and IL‐13‐producing cells were shown to be increased in the placebo group during the pollen season, an increment which was absent in patients receiving allergen SIT. We found an increase in allergen‐specific IgG4 in the SIT‐treated individuals, but not in the placebo group. Both groups displayed elevated specific IgE levels during the pollen season.

Conclusions: Taken together, our data show a downregulation of IL‐4‐ and IL‐13‐producing cells in peripheral blood after SIT, suggesting induction of nonresponsiveness/tolerance or a redistribution of these cells. Furthermore, we demonstrate that SIT acts on antibody production by increasing the specific IgG4 levels.
Retrospective study on fluticasone propionate aqueous nasal spray efficacy in patients with allergic rhinitis: evaluation of clinical and laboratory parameters
Authors: Ventura M. , Piccinni T. , Matino M. G. , Giuliano G. , Di Corato R. , Di Napoli P. , Tursi A.
Published: March 2003

Background: In allergic rhinitis, allergenic stimulation causes the release of various mediators that induce symptoms and the development of chronic inflammation, which, in turn, is caused by cells involved in the late phase of inflammation, such as eosinophils. The eosinophils also cause damage at the mucosal level through the secretion of eosinophil cationic protein and other preformed factors contained in their granules. The objective was to verify the efficacy of fluticasone propionate aqueous nasal spray in patients with allergic rhinitis; in a retrospective study, we have evaluated mediators of inflammation, making correlations with the clinical symptoms score during and outside the pollen season.

Methods: Forty patients with allergic rhinitis and 15 normal controls were included in our study. Eosinophil cationic protein, eosinophil chemotactic activity, and blood and nasal lavage eosinophil count were evaluated as laboratory parameters.

Results: We found a significant increase in nasal lavage levels of eosinophil cationic protein in allergic patients, and this was strictly correlated with the clinical symptoms score. No differences were found in the eosinophil count of allergic patients and in the serum eosinophil cationic protein of patients sensitized to seasonal allergens in comparison with normal subjects. By contrast, an increase in serum eosinophil cationic protein level was found in patients sensitized to perennial allergens. After topical administration of fluticasone propionate aqueous nasal spray, a reduction in nasal lavage eosinophil cationic protein secretion was obtained with a reduction of eosinophil chemotactic activity at the local level. This reduction correlated with an improvement of clinical symptoms.

Conclusions: The clinical improvement and reduction in nasal lavage eosinophil cationic protein and eosinophil chemotactic activity after administration of fluticasone propionate aqueous nasal spray further confirms the role of this treatment in allergic rhinitis.
Interleukin‐4‐positive mast cells are highly associated with the extent of immediate allergic wheal reaction in the skin
Authors: Saarinen J. V. , Harvima R. J. , Horsmanheimo M. , Harvima I. T. , Naukkarinen A.
Published: March 2003

Background: In addition to histamine, mast cells contain other potent mediators which can contribute to the allergic wheal reaction in the skin.

Methods: To study the association of tryptase‐, chymase‐, and interleukin‐4 (IL‐4)‐positive mast cells with the size of the prick‐test wheal reaction, 50 sensitive atopic subjects were prick‐tested with the cow‐dander allergen on the forearm skin, and the wheal area was measured. A corresponding site of intact healthy‐looking skin was biopsied and examined enzyme‐histochemically for tryptase and chymase. A double‐staining method was used to demonstrate the immunoreactivity of IL‐4 and chymase inhibitors (α1‐proteinase inhibitor and α1‐antichymotrypsin) in mast cells. The levels of total and cow‐specific immunoglobulin E (IgE) were measured in serum.

Results: The number of tryptase‐ and chymase‐positive mast cells or those containing chymase inhibitors revealed no correlation with the wheal reaction. In contrast, both the percentage and the number of IL‐4‐positive mast cells showed significant positive correlation with the wheal size per se (P<0.0001), as well as with the ratio of the wheal size by cow allergen to that by histamine control (P<0.003). In addition, tryptase‐, chymase‐, and IL‐4‐positive mast cells correlated with total IgE, but not with specific IgE, levels, and they showed no relation to the clinical manifestation of atopic disease, asthma or atopic dermatitis.

Conclusions: The novel finding was that IL‐4‐positive, but not tryptase‐ and chymase‐positive, mast cells are intimately associated with the extent of the prick‐test wheal.
The mechanisms of serum‐treated zymosan (STZ)‐induced oxidative metabolism by human eosinophils and the effects of IL‐5 priming
Authors: Woschnagg C. , Garcia R. C. , Venge P.
Published: March 2003

Background: The aim of this work was to study the mechanisms of action of IL‐5 on the subsequent stimulation of the oxidative metabolism of blood eosinophils by serum‐treated zymosan (STZ), in terms of signal transduction characteristics, and by comparing the response of cells from healthy and allergic subjects during environmental exposure to birch pollen.

Methods: Eosinophils from healthy controls and allergic patients were purified to over 95% by Percoll gradients and the MACS system. Oxidative metabolism was measured by a lucigenin‐enhanced chemiluminescence (CL) assay. Eosinophils were primed with IL‐5 and subsequently stimulated with STZ. The signal transduction mechanisms of IL‐5 priming were studied with the MEK inhibitor PD 98059,the PkC inhibitors staurosporine and Ro 318220, and the PI3 kinase inhibitor wortmannin.

Results: IL‐5 increased the maximum radical production (P=0.0079) and reduced the t½ rise (0.000018) of the CL reactions. The t½ rise was PkC dependent and MEK independent, while the maximum radical production was PkC, MEK, and PI3 kinase dependent. During the pollen season, IL‐5 reduced the total STZ‐induced CL response in the patients' cells (P=0.016), but not in the control cells, whereas it primed the response to STZ of both cell populations in terms of the t½ rise (P=0.012 and 0.00066, respectively).

Conclusions: STZ‐induced oxidative metabolism consists of different stages. The initial stage (t½ rises of the curves) is PkC dependent and MEK independent, while the end stage (maximum radical production) is PkC, MEK, and PI3 kinase dependent. IL‐5 shortened the initial stage, and increased the end stage. During allergen exposure, however, the end stage was reduced by IL‐5. This could be due to increased amounts of hypodense eosinophils and/or some abnormality in cell responses.
Matrix metalloproteinases and TIMP‐1 production by peripheral blood granulocytes from COPD patients and asthmatics
Authors: Cataldo D. , Munaut C. , Noël A. , Frankenne F. , Bartsch P. , Foidart J. M. , Louis R.
Published: March 2003

Both asthmatic and COPD patients were found to have increased amounts of granulocytes and matrix metalloproteinase‐9 (MMP‐9) in their sputum. The present study was conducted to investigate whether the elevated amounts of MMP‐9 and TIMP‐1 found in such patients' airways may be linked to an enhanced secretion by granulocytes. Blood granulocytes from asthmatics (n=10), COPD patients (n=11), and healthy controls (n=11) were isolated and cultured under basal conditions or after stimulation by phorbol 12‐myristate 13‐acetate (PMA) or N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine (fMLP). MMP‐9 activity was detected by zymography while MMP‐8 and TIMP‐1 levels were measured by ELISA. In zymography, pro‐ and activated forms of MMP‐9 were present in each group (healthy subjects, asthmatics, and COPD patients). Spontaneous release was not different between the three groups. Stimulation by fMLP and PMA increased to a similar extent the release of MMP‐9 by granulocytes in all the three groups. TIMP‐1 levels were also increased after stimulation by PMA and fMLP only in healthy subjects and COPD patients. MMP‐8 levels were barely detectable. We conclude that circulating granulocytes from COPD patients and asthmatics do not display an abnormal secretion of MMP‐9, and that granulocytes from asthmatics have an impaired ability to release TIMP‐1 upon stimulation.
Increased prevalence of atopy among children exposed to mold in a school building
Authors: Savilahti R. , Uitti J. , Roto P. , Laippala P. , Husman T.
Published: March 2003

Background: The purpose of this study was to assess the occurrence of immunoglobulin E sensitization to common environmental allergens (atopy) and new allergic diseases among schoolchildren after starting school in a water‐damaged school building. The staff and pupils of a Finnish elementary school with visible water damage and mold complained of respiratory and skin symptoms. The school building was examined and widespread moisture damage was found. A control school with no visible water damage was also examined. No indication of exceptional microbial growth was found in the samples taken from this school.

Methods: History of allergic diseases and the year of diagnosis were established by a questionnaire. IgE antibodies to the common environmental allergens were determined from randomly selcted groups from both schools.

Results: Elevated IgE values were significantly more common among the exposed children, as was the occurrence of new allergic diseases after the children started at the school.

Conclusions: The odds ratios for the IgE values of the study groups indicated a possible relationship between exposure to microorganisms and IgE sensitization. Exposure to spores, toxins, and other metabolites of molds may have complex results with unknown immunogenic effects that may act as a nonspecific trigger for allergic sensitization leading to the development of atopy.
An Internet‐based survey of anaphylactic reactions to foods
Authors: Eigenmann P. A. , Pastore F. D. , Zamora S. A.
Published: March 2003

Background: A favorable outcome of anaphylaxis depends on the rapidity of adequate initial management and epinephrine injection. However, few data on the management of anaphylactic reactions are available. The aim of this study was to investigate the management and awareness of anaphylaxis to foods by mean of an Internet‐based survey.

Methods: Visitors to a website with information on food allergy were invited to join the survey. Items in the survey included the management of anaphylactic reactions, investigations done by the diagnosing physician, and information given to the responder in anticipation of a new anaphylactic reaction.

Results: Almost all of the 264 responders were from North America, Europe, Australia, or New Zealand (263/264). The most recent reaction was treated by epinephrine injection in 68.7% (180/262) of cases, or by antihistamines in 14.1% (37/262). Epinephrine was the first treatment for the most severe reaction in only 43.9% (101/230), while antihistamines were given first in 43.5% (100/230). One‐third (62/210=29.5%) of the responders diagnosed by a physician received neither a diagnostic blood test nor a skin test. Responders diagnosed by an allergist were more often investigated (91/105=86.7%) than those diagnosed by a pediatrician or an internist (29/44=65.9%), a general practitioner (22/45=48.9%), or another physician (6/16=37.5%) (P<0.001). Most responders had received instructions on how to deal with a new episode of anaphylaxis (244/263=92.8%). Responders instructed by an allergist were most frequently satisfied with the instructions (115/131=87.8%).

Conclusions: A large number of responders did not receive epinephrine for treatment of their most severe, or most recent anaphylactic reaction, and did not undergo allergy tests. The conventional management of anaphylaxis might still be improved.
Allergenic diversity of the olive pollen
Authors: Rodríguez R. , Villalba M. , Batanero E. , González E. M. , Monsalve R. I. , Huecas S. , Tejera M. L. , Ledesma A.
Published: March 2003

A great number of allergenic proteins have been detected in olive pollen extracts. To date, nine allergens have been isolated and characterized, which have been called Ole e 1 to Ole e 9. The most prevalent olive allergen is Ole e 1, which affects more than 70% of patients hypersensitive to olive pollen, but others, such as Ole e 2, Ole e 8, and Ole e 9, have been demonstrated to be major allergens, and Ole e 6 or Ole e 7 reach high values of clinical incidence. Many of these allergens, such as Ole e 2 (profilin) and Ole e 3 (polcalcin), are involved in cross‐reactivities, which agrees with their adscription to panallergenic families. Among the many olive allergens of high molecular mass, only Ole e 9 (46 kDa) has been characterized. The allergen is a polymorphic and glycosylated β‐1,3‐glucanase, which belongs to a pathogenesis‐related (PR‐2) protein family. In addition to the polypeptide epitopes, Ole e 1 also exhibits IgE‐binding determinants in the carbohydrate, which are recognized by more than 60% of the sera from patients sensitive to the whole allergen, although the level of such glycan‐specific IgE seems not to be clinically relevant in the overall content of the sera. Recent advances in the elucidation of the structure of the Ole e 1‐oligosaccharide component allows us to explain the antigenicity of the molecule. Finally, the recombinant production of several allergens from olive pollen in both bacterial and eukaryotic cells has allowed us to resolve problems derived from the polymorphism and scarcity of the natural forms of these allergens. The biological equivalence between the natural and recombinant forms lets us initiate studies on the design of mixtures for clinical purposes, in which hypoallergenic derivatives of these allergens could play a definitive role.
Characterization of specific IgE response in vitro against protein and drug allergens using atopic and normal donors
Authors: Åkesson A. , Ingvarsson S. , Karlsson F. , Leyva L. , Blanca M. , Cuerden S. A. , Smith J. A. , Coleman J. W. , Borrebaeck C. A. K.
Published: March 2003

Background: As the incidence of allergy to different compounds increases in society, the need to understand and characterize specific IgE responses becomes obvious. Different cell culture systems have been evaluated for their ability to support such IgE secretion.

Methods: One system employed human peripheral lymphocytes (PBL) from normal donors stimulated with anti‐CD3 activated T cells with or without the presence of allergens like benzylpenicillin (BP) and Phlenum pratense (PP). Secretion of IgE was analyzed in ELISA and compared to the IgG response to the nonallergenic antigen tetanus toxoid (TT). Another system employed stimulation of T and B cells with a heterotope, consisting of a T helper cell epitope derived from TT, and a B cell allergen epitope derived from BP. The specific IgE secretion was compared, using lymphocytes from normal as well as BP‐allergic donors.

Results: Anti‐CD3 stimulated T cells supported BP‐specific IgE secretion in six of 11 normal donors. This response was inhibited in four donors and enhanced in two donors by the addition of the BP‐allergen to the culture. In contrast, addition of the protein allergen (PP) or antigen (TT) to the same culture system inhibited both IgE and IgG synthesis in all experiments. Cells from the majority (10/16) of the BP‐allergic donors failed to produce BP‐specific IgE in vitro, when cultured in the presence of allergen.

Conclusions: An allergen specific immune response is readily generated in vitro. The differential response against benzylpenicillin between different donor categories most probably reflects the level of pre‐exposure to this allergen in vivo.
Cellular immune responses to ovalbumin and house dust mite in egg‐allergic children
Authors: Ng T.‐W. , Holt P. G. , Prescott S. L.
Published: March 2003

Background: Although IgE‐mediated food (egg) allergy is typically lost with age the underlying immune mechanisms are not understood, particularly in relation to the development of persistent IgE‐mediated aeroallergen sensitivity.

Methods: Lymphoproliferation and cytokine responses (IL‐5, IL‐10, IL‐13 and IFN‐γ) to house dust mite (HDM) allergen and egg ovalbumin (OVA) were assessed using peripheral blood mononuclear cells (PBMC) from children aged 6 months to 5 years (n = 59) with acute IgE‐mediated egg allergy (urticaria and angiedema or anaphylaxis), as confirmed by positive skin prick testing (SPT). Of these 46 had positive SPT on the day of blood collection and 13 had outgrown egg allergy (negative SPT and successful egg challenge). Where possible, responses were compared with previous data from nonallergic children of similar ages (n = 107).

Results: Transient lymphoproliferative responses to OVA were seen in both egg‐allergic and nonallergic children, but were more marked and more prolonged in egg‐allergic children. Younger egg‐allergic children (< 18 months) showed a mixed Th0 cytokine response to OVA, with readily detectable IFN‐γ, IL‐5, IL‐13 IL‐10. Although IL‐13 and IL‐5 responses (OVA) correlated in younger egg‐allergic children, there was a dissociation of these Th2 responses with age. Loss of clinical reactivity to egg was associated with almost complete loss of IL‐5 responses and OVA‐specific lymphoproliferation. Although IL‐13 levels tended to be lower with age, this was not significant. Strong IFN‐γ and IL‐10 responses to OVA persisted in older children after loss of OVA‐specific lymphoproliferation. Lymphoproliferative responses to HDM also developed earlier in egg‐allergic children compared with nonallergic children. Th1 (IFN‐γ) responses to HDM were largely below detection prior to 18 months of age, but increased significantly with age. In egg‐allergic children Th2 (IL‐5, IL‐13) HDM responses also progressively increased with age. At 3 years of age almost all egg‐allergic children had positive SPT to HDM and positive lymphoproliferative responses to HDM, with strong Th1 and Th2 (Th0) cytokine production.

Conclusions: IL‐5 responses (rather than IL‐13) responses most closely reflected clinical food allergy, with dissociation of IL‐5 and IL‐13 responses in older and egg‐tolerant children. In this population, food and aeroallergen sensitivity was not associated with inability to produce IFN‐γ, but rather with mixed Th2 and Th1 (Th0) responses. Strong IL‐10 and IFN‐γ responses where associated with the development of tolerance, suggesting persistent ‘regulatory’ populations of OVA‐specific T cells, rather than clonal deletion of OVA responsive T‐cells.
Cockroach allergy and exposure to cockroach allergen in Polish children with asthma
Authors: Stelmach I. , Jerzynska J. , Stelmach W. , Majak P. , Chew G. , Gorski P. , Kuna P.
Published: March 2003

Background:  Asthma morbidity increases every year, especially among children, and exposure to high levels of indoor allergens is a very important factor. We evaluated the prevalence and exposure to cockroach (CR) allergen in asthmatic children in Poland, and also tested the hypothesis that asthma with allergy to CR is more severe than with allergy to other antigens.

Methods:  One hundred and sixty children with asthma were examined, had skin prick tests (SPT) with common and CR allergens, underwent spirometry, and provocation tests to histamine. Children with positive SPT to CR had measured specific IgE levels to this antigen and Bla g 2 concentrations were measured in their homes.

Results: 
The most common allergen, was dust mite 51.3%, followed by pollen 48.8% and CR allergen 24.3%. In children with CR sensitivity, 13% had mild asthma, 26% moderate and 61% had severe asthma. Their levels for forced expiratory volume in one second (FEV
1
), and the provocative concentration of histamine that caused a 20% fall in FEV
1
(PC
20 ), were statistically lower than in the group of children with other than CR allergies. Bla g 2 antigen was detected in 55.13% samples. The highest levels of Bla g 2 were found in old houses, without central heating, and in houses with lower income.

Conclusion:  In Polish children, CR allergen is a very important factor of sensitivity. Concentrations of Bla g 2 in homes are higher than previously reported in other European countries, and are strongly related to the houses' characteristics. Also, children with CR hypersensitivity have severe asthma more often than children with other allergies.
Cytokine production from sputum cells after allergenic challenge in IgE‐mediated asthma
Authors: Bettiol J. , Sele J. , Henket M. , Louis E. , Malaise M. , Bartsch P. , Louis R.
Published: March 2003

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways inflammation in allergic asthma. Induced sputum has become a widely used technique to assess airways inflammation.

Methods: By applying the technique of induced sputum to collect airways cells, we have assessed the spontaneous production of a set of cytokines, including interleukin‐4, 6, 10, interferon‐γ and tumour necrosis factor‐α, 6 h after a bronchial allergenic challenge with Dermatophagoides pteronyssinus (Dpt) in 12 sensitized asthmatics and compared the results obtained after inhalation of saline as control. A group of eight healthy non‐allergic subjects was enrolled to control for any non‐specific effect of Dpt. Cytokines were measured by a dynamic immunoassay during a 24‐h sputum cell culture.

Results: Allergen challenge in sensitized asthmatics caused an acute and a late bronchospasm together with a rise in sputum eosinophil counts. Afterwards allergen sputum cells from allergic asthmatics displayed a rise in their production of IL‐4 (P < 0.01), IL‐6 (P < 0.05) and IL‐10 (P < 0.05) when compared to saline. By this time sputum generation of IL‐4 in atopic asthmatics was greater than in healthy subjects (P < 0.001). Furthermore, in allergic asthmatics there was a strong correlation between the rise in interleukin‐4 production from sputum cells and the rise in sputum eosinophils (r = 0.87, P < 0.001).

Conclusions: Sputum cell culture is a useful model to assess cytokine production in allergic asthmatics who show a marked up‐regulation of Th2 cytokines following acute allergen exposure. The rise in sputum eosinophil count following allergen challenge strongly correlates with the rise in IL‐4 generation from sputum cells.
Mitigation of the action of wheat allergen by acidic oxidative potential water
Authors: Matsumoto T.
Published: March 2003

Background: Acidic oxidative potential water (AOPW) is strongly acidic, and contains active oxygen species and thus exhibits an oxidative potential to cause biochemical alterations of wheat proteins.

Methods: A commercial wheat allergen extract was treated with AOPW, and then analysed by means of SDS‐PAGE and the skin prick test in IgE‐mediated wheat allergic patients.

Results: The wheat extract comprised 70 kDa, 32 kDa and 30 kDa fractions, and the protein in the 70 kDa fraction was broken down into less than 14 kDa fractions by AOPW. AOPW mitigated 39% of the wheal reaction to the wheat extract in the skin prick test.

Conclusion: AOPW may be useful for enhancing the digestibility and lowering the allergenicity of wheat proteins.
Reactivity to potential cross‐reactive foods in fruit‐allergic patients: implications for prescribing food avoidance
Authors: Crespo J. F. , Rodríguez J. , James J.M. , Daroca P. , Reaño M. , Vives R.
Published: March 2003

Background: Prescribing therapeutic elimination diets in patients with fruit allergy should include recommendations on which other foods of the same family or group may be safely consumed. Evidence‐based data on the management of fruit allergy are lacking; therefore, advice may vary from just avoiding the offending fruit, to overly restrictive diets of the entire botanical family. The aims of this investigation were to assess clinical reactivity to potential cross‐reactive foods in fruit‐allergic patients, and the implications for prescribing specific therapeutic elimination diets.

Methods: Sixty‐five adults diagnosed with clinical allergy to one or more fruits were evaluated for IgE‐mediated allergy to other related foods, which might share cross‐reactive antigens. Those with actual allergy to some Rosaceae fruit (including peach, apple, apricot, plum, and almond) underwent skin prick testing (SPT), food‐specific IgE assessment by the Pharmacia CAP‐FEIA system, and oral challenges with the entire group. For those with allergy to other fruits (chestnut, melon, banana, kiwi, or avocado) immunologic and clinical reactivity to all five were evaluated. Since a number of people in the study also had proven clinically allergy to some nut or legume (peanut, sunflower seed, walnut, pistachio, or hazelnut), the reactivity to the entire set was investigated.

Results: Thirty‐four of those tested (52%) were found to be clinically allergic to more than one fruit, so 125 allergic reactions occurred in the 65 patients. Peach, melon, kiwi, apple, and banana accounted for 72% of allergic reactions. Forty‐two (65%) had sensitization to pollens, causing seasonal allergic rhinitis and/or asthma, and 18 (28%) were sensitized to latex. The 65 with IgE‐mediated fruit allergy underwent 351 additional SPT and food‐specific IgE determinations with potential cross‐reactive foods considered in this study; 223 (64%) of these results were positive. The routine challenges with potential cross‐reactive foods uncovered 18 further reactions in 14 (22%) out of 65 (to avocado in seven; apricot in three; plum in one; almond and peanut in one; banana and hazelnut in one; avocado, banana and kiwi in one). Only 8% (18/223) of positive results for SPT, or food‐specific IgE levels of greater than 0.35 kUA/l to potential cross‐reactive foods investigated in this study, were clinically relevant.

Conclusion: Elimination diets that rely on total group avoidance, or only on the results of allergy testing, might have resulted in unnecessary restriction of 205 foods in the 65 people studied. The lack of routine oral challenges with related fruits—before prescribing dietary restriction—may have allowed 18 food reactions in one‐fifth (14/65) of patients to be overlooked.
Prevalence of occupational allergy to Chrysanthemum pollen in greenhouses in the Netherlands
Authors: Groenewoud G. C. M. , De Jong N. W. , Burdorf A. , De Groot H. , Van Wÿk R. Gerth
Published: March 2003

Background: An increasing number of allergic complaints appear to have occurred among Chrysanthemum greenhouse employees. The aim of this study was to estimate the prevalence of work‐related allergic symptoms and the prevalence of sensitization to pollen of different members of the Chrysanthemum family.

Methods: We studied 104 employees who were invited to answer an extensive questionnaire and to complete a rhinitis quality of life questionnaire. In addition, they were skin prick tested on location with inhalant allergens and home‐made pollen extracts of seven different members of the Chrysanthemum family. Radio‐allergo‐sorbent tests were performed to confirm IgE‐mediated reactions.

Results: Work‐related symptoms were reported in 56.7% of all cases, with the main symptom being rhinitis. Sensitization to Chrysanthemum pollen was found in 20.2% of the employees without one member of the Chrysanthemum family in particular being most prevalent. Sensitization to Chrysanthemum pollen was considered to be an important risk factor for the occurrence of work‐related symptoms of the upper airways. Furthermore, inhalant atopy as well as sensitization to common airborne pollen including mugwort were closely associated with sensitization to Chrysanthemum what might be suggestive for cross‐sensitization.

Conclusions: There is a high prevalence of work‐related symptoms in Chrysanthemum greenhouses. In one‐third of the employees these symptoms were caused by an IgE‐mediated allergy caused by the pollen of the flowers. Inhalant atopy appeared to have a great impact on the development of such a sensitization. Measurements to reduce the pollen exposure are necessary to prevent a further increase of this occupational allergy.
Neutrophil chemokines in cultured nasal fibroblasts
Authors: Rudack C. , Hermann W. , Eble J. , Schroeder J.‐M.
Published: March 2003

Background: To gain insight into the mechanisms responsible for tissue neutrophil immigration in sinusitis, primary nasal fibroblasts are analyzed for synthesizing and delivering neutrophil chemokines.

Methods: Primary nasal fibroblast cell culture was treated with tumor necrosis factor (TNF)‐α concentrations of 20 and 200 ng/ml for 2, 8, 24 and 72 h. Chemokine concentrations in supernatants were determined by enzyme‐linked immunoassay (ELISA) and chemokine mRNA expression in fibroblasts was measured by reverse transcriptase polymerase chain reaction (RT‐PCR). Biological chemotactic activity was identified by three‐step high‐performance liquid chromatography (HPLC) and by bioassay measuring neutrophil chemotaxis in a single Boyden chamber system.

Results: Interleukin (IL)‐8 and growth‐related oncogene (GRO)‐α were induced in nasal fibroblast culture by proinflammatory stimulus. After 24 h of stimulation neutrophil chemotactic activity only was detected for IL‐8. Granulocyte chemotactic protein (GCP)‐2 mRNA was already significantly up‐regulated after 2 h of stimulation.

Conclusion: Induction of IL‐8 protein dominates chemokine synthesis 24 and 72 h after stimulation, whereas induction of GCP‐2 mRNA seems to have a role in the early phase after 2 h of exposition with TNF‐α.
Roasted hazelnuts – allergenic activity evaluated by double‐blind, placebo‐controlled food challenge
Authors: Hansen K. Skamstrup , Ballmer‐Weber B. K. , Lüttkopf D. , Skov P. S. , Wüthrich B. , Bindslev‐Jensen C. , Vieths S. , Poulsen L. K.
Published: March 2003

Background: Allergy to hazelnuts is a common example of birch pollen related food allergy. Symptoms upon ingestion are often confined to the mouth and throat, but severe systemic reactions have been described in some patients. The aim of the study was to evaluate the reduction in allergenicity by roasting of the nuts.

Methods: Double‐blind, placebo‐controlled food challenges (DBPCFC) with roasted hazelnuts (140°C, 40 min) were performed in 17 birch pollen allergic patients with DBPCFC‐confirmed food allergy to raw hazelnuts. The effect of roasting was further evaluated by skin prick test (SPT), histamine release (HR), measurement of specific IgE, and IgE‐inhibition experiments.

Results: In 5/17 patients the DBPCFC with the roasted nuts were positive. The symptoms were generally mild and included OAS (oral allergy syndrome) in all patients. Roasting of the nuts significantly reduced the allergenic activity evaluated by SPT, HR, specific IgE, and IgE‐inhibition. Immunoblotting experiments with recombinant hazelnut allergens showed sensitization against Cor a 1.04 in 16/17 patients and against Cor a 2 in 7/17 patients. None of the patients were sensitized to Cor a 8. Challenge‐positive patients did not differ from the rest in IgE‐binding pattern.

Conclusions: All the applied methods indicated that roasting of hazelnuts reduces the allergenicity, but since 5/17 birch pollen allergic patients were DBPCFC‐positive to the roasted nuts, ingestion of roasted hazelnuts or products containing roasted hazelnuts can not be considered safe for a number of hazelnut allergic consumers. For patients with a history of severe allergic symptoms upon ingestion of hazelnuts, thorough and conscientious food labelling of hazelnuts and hazelnut residues is essential.
Immunostimulatory DNA‐based therapeutics for experimental and clinical allergy
Authors: Horner A. A. , Takabaysahi K. , Zubeldia J. M. , Raz E.
Published: March 2003

Although allergen immunotherapy (IT) has been shown to modulate allergic hypersensitivities, its efficacy is limited. Recently, in various models of experimental allergy, a number of reagents which we have termed immunostimulatory DNA‐based therapeutics have proven highly effective in both the prevention and reversal of Th2 mediated hypersensitivity states. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS‐ODN), and physical allergen: ISS‐conjugates (AIC), and immunomodulation with ISS‐ODN alone. Results from our laboratory have shown that immunostimulatory DNA‐based therapeutics may be effective for the reversal of allergic hypersensitivity states in humans and several clinical trials have already been initiated. This review will focus on our laboratory's experience with immunostimulatory DNA‐based therapeutics in various murine models of allergy and their potential utility in the treatment of allergic patients.
Low molecular weight PTP–IL‐4RA interaction in atopy predisposition
Authors: Bottini N. , Mao X.‐Q. , Borgiani P. , Saccucci P. , Stefanini L. , Greco E. , Fontana L. , Shirakawa T. , Hopkin J. M.
Published: March 2003

We recently described a protective effect of the low molecular weight protein tyrosine phosphatase (LMPTP) BC genotype, associated with the highest total enzymatic activity, against high serum IgE levels both in the English and the Italian populations. Here we test the hypothesis of a role of LMPTP in the negative modulation of IL‐4 signal transduction checking for genetic interaction between interleukin‐4 receptor alpha chain (IL‐4RA) genetic polymorphisms and LMPTP polymorphism in the predisposition to high total IgE levels in the English population. We find a significant interaction between LMPTP polymorphism and the intracellular Gln/Arg polymorphism in position 551 of IL‐4RA. Our data support the hypothesis of a direct or indirect biochemical interaction between LMPTP and IL‐4RA resulting in different modulation of IL‐4 signal transduction among joint genotypes.
X‐inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency
Authors: Yorifuji Tohru , Muroi Junko , Uematsu Ayumi , Tanaka Koichi , Kiwaki Koji , Endo Fumio , Matsuda Ichiro , Nagasaka Hironori , Furusho Kenshi
Published: March 2003

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It is X‐linked and hemizygous new‐born males usually suffer fatal hyperammonemia. In contrast, carrier females manifest variable phenotypes, ranging from asymptomatic carriers to those with severe hyperammonemia. In order to understand the correlation between X‐inactivation status and the clinical phenotype of carrier females with this disorder, we analyzed the X‐inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and two daughters with severe manifestation. In addition, we obtained tissue samples from various parts of the liver of one of these daughters and analyzed X‐inactivation patterns and the residual OTC activities. The X‐inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype. However, the X‐inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. Interestingly, the degree of X‐inactivation varied considerably, even within the same liver.
The assent of a nation: genethics and Iceland
Authors: McInnis Melvin G
Published: March 2003

The Icelandic parliament passed legislation authorizing the establishment of a national health sector database which will be sponsored financially by private enterprises through DeCode Genetics Inc. Health related data will be gathered from patients, without their informed consent, from all points of contact with Icelandic public and private health care providers. A centralized data curator will ‘non‐personalize’ the identity of the subjects in a one‐way coding system which the government and DeCode Genetics argue overrides the need for informed consent. This legislation is in conflict with the European Data Protection Act, which requires informed consent for the collection of personal data. The law raises many ethical questions regarding the central tenets of informed consent, the power of government, the rights of the human subject, and finally, the responsibility of the clinician balancing commitments of the patient and research.