Identification of 2 new allergens of Phoenix dactylifera using an immunoproteomics approach.

The date palm (Phoenix dactylifera) has a wide geographical distribution (Middle East, Mediterranean, central Africa, western Asia, Australia, and North America). Pho d 2, the major allergen of date palm pollen was recently identified as a profilin, yet little is known about the nature of the other pollen allergens from this tree. The objective of this study was to characterize clinically significant allergens other than profilins from P. dactylifera pollen using immunoproteomics. In order to reveal the proteins causing the allergy, we used serum from a patient monosensitized to date palm pollen extract who experienced asthma and rhinoconjunctivitis during the palm tree pollen season. The results revealed 2 novel immunoglobulin E-binding proteins not related to the cross-reactive allergen profilin. Individualized allergens of Pdactylifera that cause specific date palm pollen sensitization must be defined to determine the real prevalence of sensitization to this species.

Occupational rhinitis and bronchial asthma due to TBTU and HBTU sensitization.

Exposure to an increasing amount of products in the work environment is leading to new cases of occupational asthma among workers. We report the case of a worker at a pharmaceutical plant who developed occupational rhinitis and bronchial asthma due to HBTU: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate and TBTU: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate sensitization, two chemical products widely used in peptide synthesis and coupling. Skin tests (prick test) with HBTU and TBTU solutions in PBS were positive at a concentration of 1 mg/ml. Skin tests with the same solutions in 10 atopic controls yielded a negative result. Nasal challenge tests with these products were positive with HBTU at a concentration of 0.01 mg/ml and TBTU at a concentration of 1 mg/ml. In both cases PNIF (peak nasal inspiratory flow) decreased by more than 60% and severe sneezing and rhinorrhea were induced. Nasal challenge tests performed on 10 atopic controls with TBTU and HBTU at a concentration of 1 mg/ml were negative. We conclude that the patient presents occupational rhinitis and bronchial asthma due to TBTU and HBTU; the operational mechanism is probably immunological IgE-mediated given the positive prick tests and nasal challenge with these products.

Clinical efficacy and safety of a depigmented and glutaraldehyde polymerized therapeutic vaccine of Parietaria judaica.

BACKGROUND: The inhalation of Parietaria judaica pollen is a common cause of allergic respiratory diseases in the Mediterranean area. The objective of this study was to investigate the safety and clinical efficacy of a chemically modified (depigmented and glutaraldehyde-polymerized) vaccine of Parietaria judaica. METHODS AND RESULTS: Thirty patients with a well-documented clinical history of seasonal rhinitis and clinical sensitivity to Parietaria judaica pollen were included in a randomized trial during 12 months. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into 2 groups of 15 individuals; group A received the modified extract and group C did not receive specific immunotherapy. Any adverse event was recorded to assess safety. Symptom scores, symptomatic medication use and the results of specific nasal challenges (before and after 12 months of treatment) were recorded to evaluate clinical efficacy. The treatment schedule consisted of an incremental phase of 5 injections and a maintenance dosage of 0.5 ml per month. Each patient received 14 injections during this period. All the patients completed the trial and no adverse reactions related to immunotherapy were recorded. A significant difference (p < 0.001) in symptom scores and overall use of symptomatic medication was observed between the two groups, being both scores lower in group A. No significant differences in nasal sensitivity existed before treatment among the 2 groups. However, after 12 months, a significant difference (p < 0.05) was observed only in group A patients, who showed a significant improvement in specific nasal challenges. CONCLUSIONS: Immunotherapy with depigmented and glutaraldehyde-polymerized extract of Parietaria judaica pollen is safe and effective to treat patients with allergic rhinitis and clinical sensitivity to this pollen.

Cross-reactivity between Platanus pollen and vegetables.

BACKGROUND: Several associations have been described between tree and plant pollens and certain foods. The objective of this study is to verify whether there is cross-reactivity between Platanus pollen and vegetable origin foods. METHODS: We selected 56 patients allergic to vegetable foods and subjected them to cutaneous tests with aeroallergens and vegetable foods. A statistical analysis was performed to evaluate the association of Platanus pollen with foods and with other aeroallergens. Later, a specific IgE determination was performed as well as a RAST (radioallergosorbent) inhibition experiment, to verify the existence of cross-reactivity in vitro. RESULTS: In the cutaneous tests we found a positive correlation between Platanus pollen and hazelnut, peanut, banana and celery. The results of the RAST inhibition experiment indicate an important cross-reactivity between the pollen of Platanus acerifolia and hazelnut and banana fruit, and an intermediate cross-reactivity with celery and peanut. CONCLUSION: We have described an association between the pollen of the Platanus tree and some vegetable foods such as hazelnut, banana, peanut and celery. This association could be explained by the in vitro IgE cross-reactivity detected.

Facial edema associated with thyroid autoimmunity.

BACKGROUND: There is growing evidence that some cases of chronic urticaria and angioedema are associated with thyroid autoimmunity. We present the case of a 42-year old woman with a two month long evolution of edema in the right hemiface associated with thyroid antibodies. METHODS: Skin tests were performed with a standard series of aeroallergens and foods and were negative. Epicutaneous tests were performed with a series of contact allergens with a negative result. The chest X-ray was normal. A complete blood count was performed with ESR, biochemistry study, proteinogram, coagulation, complement, rheumatoid factor, anti-nuclear antibodies, hydatidosis and hepatitis serologies, urine sediment and stool parasitology, which were normal. The TSH was normal and, among the thyroid antibodies, the thyroglobulin ones (492 IU/mL) were positive and the microsomal ones were negative. RESULTS: The edema remitted with the 2-month long thyroxin treatment. In spite of the clinical response, and although the thyroglobulin antibodies initially suffered a small decrease, they increased to values which greatly surpassed the initial ones, coinciding with a relapse of the facial edema, so that treatment was re-initiated with thyroxin, and the picture subsided again. CONCLUSIONS: Some cases of localized edema can be associated with thyroid antibodies and respond to treatment with thyroxin.

Comparison of the efficacy and safety of two preseasonal regimens of glutaraldehyde modified, tyrosine-adsorbed parietaria pollen extract over a period of three years in monosensitive patients.

The purpose of this study was to evaluate the clinical efficacy over a period of three years (1988-90) of two preseasonal dosage regimens of a Parietaria allergoid (Bencard Tyrosine Parietaria) in patients who were only sensitive to this pollen. Fifty patients were included (14 men and 36 women, age: mean, 28 years; range, 14-47 years). Twenty five patients (group A) were treated each january with the basic course of Bencard Tyrosine Parietaria. This consisted of injecting subcutaneously 0.5 ml from each of three vials, with one week between each injection. A further injection using the vial with the highest dose was given one week later. Each january and february, twenty five patients (group B) were treated with the basic course of Bencard Tyrosine Parietaria, repeating the last dose five times, with one week between each injection. Immunotherapy with a tyrosine-adsorbed Parietaria judaica allergoid is an effective method for mitigating nasal (p < 0.0001), bronchial (p < 0.005), conjunctival (p < 0.001) and palatal itching symptoms (p < 0.0001) in patients who are sensitive to this pollen. Sensitivity to Parietaria pollen, as verified by skin test and nasal challenge, decreased during immunotherapy (p < 0.001). Histamine release by peripheral blood basophils decreased during the course of the study, falling from 43.5 ng/ml to 12.3 ng/ml in group A and from 42.9 ng/ml to 10.0 ng/ml in group B; during the second and third years, IgG levels were increased one and four months after starting treatment with the extract, while this was not the case after ten months; IgE levels were also increased. Finally, overall tolerance to this immunotherapy product was good in almost all patients.

Biosynthesis inhibitors for leukotrienes in bronchial asthma.

This article reviews the literature on the effects of leukotrienes in asthma. In particular, the ability of recently developed synthesis inhibitors to attenuate the asthma causing effects of leukotrienes is examined. MEDLINE (1966-1996), EMBASE (Excerpta Medica; 1974-1996), and other biomedical and drug directory databases were searched to identify English-language articles (basic science, clinical trial research, and review articles) and abstracts of conference proceedings on biosynthesis inhibitors for leukotrienes and related terms. Leukotrienes are endogenous molecules formed by the breakdown of a membrane constituent, arachidonic acid, via the 5-Lipoxygenase enzyme pathway. This pathway ultimately produces several species of leukotrienes with various biologic activities, including generalized inflammatory effects associated with asthma: increased vascular permeability, enhanced mucous production, and decreased mucociliary transport. The biosynthesis inhibitors for leukotrienes attenuated the response to inhaled leukotrienes and allergen challenges (MK-0591; MK-886; AA-681; A-64077; ZD-2138). These agents produced beneficial effects in cold, exercise (A-64077) and aspirin-induced asthma (A-64077; ZD-2138), as well as clinical asthma. Many of these medications appear to be effective in the treatment of asthma (BAYX-1005; MK-0591; MK-886; AA-681; A-64077; ZD-2138; U-60257; FR-110302; BI-6239; A-78773; ABT-761; L-746530; L-699333; ZM-230487). Further clinical research is needed to determine which patients would benefit most from their use.

Leukotrienes and their antagonists in allergic disorders.

Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of allergic rhinitis and asthma. Strategies for inhibition of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. The leukotrienes antagonists, with particular reference to asthma and allergic rhinitis, is reviewed in this paper. In studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as LY-171883, SK&F-104353, ICI-204219, ONO-1078, MK-751, MK-0679, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. NZ-107 was studied for its effect on airway inflammation caused by intratracheal injection of LTB4 or IL-5, or by inhalation of PAF, and by cell activation. Analysis of the BAL fluid revealed that both induced eosinophilia and neutrophilia were suppressed. Surprisingly, although PAF and superoxide generation were inhibited in macrophages and eosinophils, NZ-107 had no effect on neutrophil activation. U-75302 was studied in guinea pigs and inhibited LTB4 induced chemotaxis of eosinophils in vitro and antigen-induced lung eosinophilia in vivo. Further studies are needed to clarify the exact mechanism by which these compounds provide beneficial effects.

[Treatment of asthma using aerosols]. / Tratamiento del asma con aerosoles.

The vast majority of clinicians in Europe now prescribe beta-2 agonists as first-line therapy for patients with asthma. Inhaler devices may deliver rapidly acting (beta-2 sympathomimetics) and more slowly acting (anticholinergic) bronchodilator therapy as well as prophylactic medication (sodium cromoglycate and topical corticosteroids). The metered dose inhaler (MDI) is most often prescribed, but at least 50% of patients cannot use this device efficiently and 10-15% of those who can, develop an inefficient technique. The vast majority of those patients are able to use a single-dose dry power inhaler. Recent studies have shown that a multidose dry power system can be used by most patients and is preferred to the MDI by over two-thirds of patient. The large volume spacer systems have been shown to be as good as the MDI and nebulizer systems in the management of asthma, and they are easier to use than the MDI. Nebulisers are of value in chronic asthma in children who cannot use other delivery systems. The role of nebulisers for the domiciliary treatment of asthma in adults, however, remains controversial.

[Comparative study] of beclomethasone and budesonide, with same posology (400 micrograms every 12 hours), in the control of cortico-dependent intrinsic asthma]. / Estudio comparativo entre beclometasona y budesonida, a igual posología (400 micrograms cada 12 horas), en el control del asma intrínseco corticodependiente.

Inhaled steroids have rendered an undoubtful benefit in the control of airway inflammation of the asthmatic patients. Our objective was to compare clinical efficacy between budesonide (BUD) and beclomethasona depropionate (BDP), when administered at equal doses (800 micrograms/24 hours). A two ways crossed open clinical trial was designed. Thirty-three steroid dependent chronic asthmatic patients (18 females, 15 males) were included. Ages ranged from 29 to 73 years (mean = 52.5 +/- 11.7). All subjects suffered a severe asthma, with several years of activity (mean = 11.7 +/- 7.8), insufficiently controlled by inhaled steroids and bronchodilators, who required regular systemic steroids supply. The parameters compared were: the patients subjective symptoms punctuation (cough, expectoration, thoracic noises, exercise induce dyspnea and dyspnea at rest), salbutamol needs (number of inhalations/day), additional prednisone needs, sputum eosinophil counts, FEV1 measurement and inespecific bronchial reactivity control (PD20 methacoline). After a baseline week patients received one of the drugs for 6 weeks and, after a lavage week, the other drug was administered for another 6 weeks. All patients improved with both therapies. We got the following conclusions: 1) a significative decrease in salbutamol (p < 0.05-0.001) and prednisone needs (p < 0.05-0.001); 2) this decrease has been more important during BUD therapy, although without significative differences; 3) no significant variations in sputum eosinophils, FEV1 or bronchial reactivity were observed; 4) both drugs, when administered at equal doses, have probed to be equally effective in severe steroid dependent asthma control.

[Non-sedative antihistaminics in the treatment of chronic urticaria]. / Los antihistamínicos no sedantes en el tratamiento de la urticaria crónica.

Antihistamines are the drugs of choice in the symptomatic relief of chronic idiopathic urticaria; however, the usefulness of classic antihistamines has been limited by side effects. In the 1980s a new class of antihistamines has been developed that maintains effectiveness and produces less side effects (eg anticholinergic side effects, daytime sedation, etc). This review analyzes each of the new nonsedating antihistamines commercially available in Spain (astemizole, ebastine, cetirizine, loratadine and terfenadine) and evaluates its clinical efficacy and safety in the treatment of chronic idiopathic urticaria.

[Comparative study between 10 and 20 mg of cetirizine in the symptomatic treatment of seasonal allergic rhinoconjunctivitis]. / Estudio comparativo entre 10 y 20 mg de cetirizina en el tratamiento sintomático de la rinoconjuntivitis alérgica estacional.

Our patients with seasonal allergic rhinoconjunctivitis usually present severe clinical symptoms. A single daily dose of cetirizine 10 mg might be insufficient for these patients. To investigate this hypothesis we compared clinical efficacy and adverse side effects between two daily doses of cetirizine, 10 and 20 mg. We designed a comparative open randomized study, including 38 patients, with hay fever sensitized to local pollens (grass, olive, parietaria judaica, chenopodium album, artemisia vulgaris and plantago lanceolata) diagnosed by clinical history and a positive skin prick test (wheal > 3 mm), 20 women and 18 men, aged 17 to 57 years (x: 31.32 +/- 9.73), living in the same geographic area. Randomly, after a week run in period, 21 subjects received a daily dose of cetirizine 10 mg during 2 weeks, and the other 17 received 10 mg twice a day. The symptomatic score used was based on: sneezes number, nasal itching, nasal secretion, nasal congestion, ocular itching, lacrimation, weight gain, sedation and additional methylprednisolone usage. All symptoms were scored on a 0-3 scale (0: absent; 1: mild; 2: moderate; 3: severe). A mean 8 points daily score during the previous week was required for recruitment. Nasal eosinophilia was determined at baseline and at the end of treatment. The study was conducted in may 1992. We did not find significant differences between the two groups, except in sneezes number and sedation. Both groups improved their symptoms, in comparison with the basal week (p < 0.01) and reduced their oral steroid use (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effectiveness of various methods of diagnosing hypersensitivity to Alternaria.

This study was undertaken for two reasons: 1) It is more difficult to diagnose hypersensitivity to molds than to other allergens, so an evaluation of diagnostic tests was needed. 2) Alternaria is the principal cause of mold sensitization in our area. Sixty-six patients (20 +/- 4 years) were selected and divided into two groups. Group A was made up of patients with rhinitis and/or asthma due to Alternaria sensitization. Group B consisted of patients sensitized to other allergens and patients with nonrespiratory allergic disorders. Skin tests (prick and intradermal), challenge tests (conjunctival, nasal, and bronchial), and specific IgE determination were performed for all patients. A biologically standardized extract of Alternaria tenuis (Alergia e Inmunología Abelló, S. A., Madrid, Spain) obtained from a single batch was used for all tests. Our diagnostic criterion was a clinical history of rhinitis or asthma that coincided with the results of nasal/bronchial challenge. The diagnostic value of the other tests was compared to this criterion. In the group of rhinitic patients, skin tests and conjunctival challenge were more sensitive than specific IgE determination. In asthmatic patients, the most sensitive techniques were nasal and conjunctival challenges, followed by prick and intradermal skin tests, and, lastly, serum specific IgE determination. When rhinitis and asthma were considered jointly, the most sensitive test was conjunctival challenge, followed by skin-prick and intradermal tests. All tests had the same specificity, regardless of disorder. Nasal challenge was positive in all patients. Skin tests are easy to perform, cheap, non-traumatic for the patient, and sufficiently specific and sensitive for the diagnosis of Alternaria hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine release following the administration of iodinated contrast media during cardiac catheterization.

This study was motivated by the discrepancy in the results of published studies on the amount of histamine released following the intravascular administration of iodinated contrast media (ICM) in humans. From a group of patients due to undergo cardiac catheterization, we selected 45 subjects with no history of atopy. A central blood sample (left ventricle) was taken from each subject before and at various times following the administration of the ICM. We determined total and basal histamine levels in every sample. We did not find any significant difference in the total histamine concentration between the samples taken before and after the administration of the ICM; but the basal histamine concentration rose from 5.32 ng/ml to 11.26 ng/ml (p less than 10(-9)). This increase was inversely proportional to the time that had elapsed between the administration of the ICM and the taking of the sample (p less than 0.01). We believe that the inconclusiveness of the results from studies on histamine release following the administration of ICM may be explained by the dilution and inactivation of histamine in the systemic circulation.

Cross-reactivity among five major pollen allergens.

We have studied the cross-reactivity between L. perenne, S. cereale, P. pratense, C. dactylon, and Ph. communis. The results obtained demonstrate that L. perenne, S. cereale, and P. pratense have strong cross-reactivity. C. dactylon has a number of allergens that cross-react with the rest of the grasses studied but they are minor allergens. Ph. communis possesses a moderate cross-reactivity with the species of the group but it has, as well, individual allergens.

[Immediate hypersensitivity to fruits and vegetables and pollenosis]. / Hipersensibilidad inmediata a frutas y verduras y polinosis.

Various works have been published, mainly by Scandinavian authors, in which a partial immunological identity has been found to exist between birch pollen and hazelnut and apple. However, our attention has been particularly drawn to the high proportion of people who are allergic to the apple and other fruits, which in some cases has been as much as 50 and 70%, and in whom an oral pruritus alone is considered sufficient a symptom of allergies to certain foodstuffs. However due to the fact that the incidence of allergies to fruit in patients who suffer from pollen-related allergies is much lower in this area, being in the order of 7%, and because of the absence of birch, we decided to carry out our investigation in the opposite direction to that chosen by the Scandinavian researchers. That is to say, from the point of view of patients suffering from allergies to fruits and vegetables (these being the foodstuffs which most frequently produce allergic reactions in our own particular environment) we decided to investigate: 1) which foodstuffs, according to clinical history, are most frequently responsible for producing allergies; 2) their possible co-existence with pollen related allergies; 3) which pollens are responsible for producing a higher rate of positive results in patients; 4) and finally, by means of the RAST inhibition technique, to discover it a cross-reactivity might exist between these pollens and the peanut or the pea. We chose 40 patients (19 females and 21 males), between the ages of 5 and 49 years old, whose clinical history showed beyond a shadow of a doubt that they displayed symptoms of immediate hypersensitivity after the ingestion of certain fruits and/or vegetables. The technique employed in the skin tests was that of scratch of the skin from the backs of the patients (in a prone position), systematically using fresh natural foodstuffs, and at the same time trying to ensure that they were of the same type as those that had originally produced the above-mentioned symptoms in the patients. On 193 occasions we carried out passive transfers (the Prausnitz-Küstner method or P.K.), and on 13 patients we carried out oral provocative tests (cases with positive scratch and uncertain clinical histories). With regard to the pollens, we used glycerine-based antigens of the type: Lolium perenne, Olea europeae, Artemisia vulgaris and Parietaria officinalis of Dome/Hollister-Stier, and the Bencard gramineae.(ABSTRACT TRUNCATED AT 400 WORDS)