bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in nasal metachromatic cells during allergen immunotherapy
Authors: OTSUKA H. , MEZAWA A. , OHNISHI M. , OKUBO K. , SEKI H. , OKUDA M.
Published: April 2006

We have investigated changes of nasal metachromatic cell number, nasal symptoms and nasal provocation at the third and sixth month during allergen immunotherapy. Twenty‐five subjects with perennial allergic rhinitis (house dust (23), Alternaria (2)) were divided into two groups: an immunotherapy‐treated group (n= 14) and a control group (n=11). At the first visit nasal symptom scores, nasal provocation reactions and the number of metachromatic cells in nasal mucosal epithelial scrapings were not significantly different between groups. At the third and sixth month after immunotherapy nasal symptom scores, nasal provocation and the metachromatic cells in epithelial scrapings were significantly reduced (P < 0.05) compared with the pretreatment values in the immunotherapy group, but unchanged in the control group. These results suggest that the reduction in metachromatic cell number at the nasal mucosal surface may be one of the mechanisms which could explain the improvement of nasal allergic symptoms by immunotherapy.
Clinical evaluation of a new in‐vitro assay for specific IgE, the immuno CAP system
Authors: LEIMGRUBER ANNETTE , MOSIMANN B. , CLAEYS M. , SEPPEY M. , JACCARD Y. , AUBERT V. , PEITREQUIN R. , NISOLI MARIE‐PIERRE , PÉCOUD A.
Published: April 2006

The Pharmacia CAP system is a new assay for specific IgE characterized by a new solid phase (hydrophilic polymer encased in a capsule). The CAP results were compared to those of the Phadebas IgE RAST and skin‐prick tests (SPT) performed in 145 subjects suffering from rhinitis and/or asthma with eight common inhalant allergens (total number of tests = 1160), Concording CAP/RAST results were found in 91% of the tests The CAP was positive in 78% and the RAST in 65% of the positive SPT. Conversely, the CAP was negative in 90.6% and the RAST in 96.4% of the negative SPT. A pattern ‘negative SPT, negative RAST and positive CAP’ was found in 56 tests (41) subjects): in four such subjects, the CAP posilivity was confirmed by a positive IgE crossed radio‐immunoclcctrophoresis. Three borderline positive results were found among 240 negative controls (serum from cord blood or non‐atopies). These data indicate that compared with SPT the CAP system is (a) more sensitive than the Pharmacia RAST and (b) does not seem less specific.
Skin prick testing using allergen‐coated lancets: a comparison between a multiple lancet device and a single lancet applied with varying pressures
Authors: PHAGOO S. B. , WILSON N. M. , SILVERMAN M.
Published: April 2006

Allergen‐coated lancets have been developed to simplify skin prick testing. The effect of variation in application pressure on the response to prick tests was assessed in 20 alopic subjects, and the results compared to the response obtained with a newly devised multiple lancet device (M LD), capable of holding up to eight lancets and of providing a standardized application pressure. A positive weal ( 7 mm2) using light pressure occurred in 2/20 subjects, compared with 14/20 after moderate pressure. The largest weals were obtained using hard pressure and with the MLD (all 20 subjects obtained positive weals) and there was no significant difference in weal si/e between the two. There was evidence of a late reaction in 4/17 subjects with the MLD and with hard pressure applied to a single lancet, but in only one with moderate and in none with light pressure. Thus both the early and late skin responses are dependent on the pressure applied. The newly designed MLD allows skin prick tests to be performed using a standard pressure. It is also convenient for multiple allergen testing of uncooperative children.
Purification and characterization of the major dog allergen, Can f I
Authors: SCHOU C. , SVENDSEN U. G. , LøWENSTEIN H.
Published: April 2006

An important dog‐hair and dander‐specific allergen Ag13 has been purified by means of immunoaffinity chromatography utilizing rabbit antibody specific for Ag13. Purity was judged to be very high as detected by crossed immunoelectrophoresis and SDS‐PAGE. The purified allergen was subjected to amino acid analyses. Molecular weight was about 22 kD in HPLC‐gel filtration and 25 kD in SDS PAGE with an additional band at 18 kD. In vitro IgE binding of the allergen was investigated by luminescence immunoassay (LIA) inhibition. Removal of Ag13 from dog hair and dander extract (DHD) removed 50 ± 1.5% of the IgE binding capacity. The purified allergen inhibited up to 56.5% of the IgE activity to DHD as measured with a pool of serum from dog‐allergic patients. Out of 26 dog‐allergic patients, 24 had a positive skin‐prick test to the allergen. Out of 23 dog‐allergic patients, 16 reacted with the allergen in IgE immunoblotting. We suggest that Ag13 be termed Can f I. The allergen will be a marker allergen for environmental dog hair and dander exposure.
Isolation and partial characterization of Bermuda grass pollen allergen, BG‐60a
Authors: SU S. N. , LAU G. X. , TSAI J. J. , YANG S. Y. , SHEN H. D. , HAN S. H.
Published: April 2006

In an earlier study we showed that Bermuda grass (Cynodon dactylon) pollen contains at least 12 IgE‐binding proteins that can be analysed by immunoblot technique. One of the active components (BG‐60) proved to be a basic protein of glycoprotein nature. It contained about 28% carbohydrate as determined from the dry weight and consisted of four molecules. One of the components was purified from the pollen extract by a combination of ammonium sulphate precipitation, ion‐exchange chromatography on carboxymethyl‐TSK, gel filtration on Ultrogel AcA 44 and chromatofocusing. Its molecular weight was approximately 60 kD by SDS PAGE and 34 kD by gel filtration chromalography. The isoelectric point of the antigen was about 9.7. The homogeneity of the antigen BG‐60a was assessed by one single are of immunoprecipitation both in immanodiffusion and crossed immunoelectrophoresis and by one single band after SDS‐PAGE. Its allergenicity was demonstrated by direct intradermal skin test on allergic patients and by examining IgE‐binding reactivity with allergic patients' serum.
Levocabastine: an effective topical treatment of allergic rhinoconjunctivitis
Authors: JANSSENS M. M.‐L. , VANDEN BUSSCHE G.
Published: April 2006

The new H1‐receptor antagonist levocabastine is the most potent antihislumine available, as shown in classical animal tests for antihistamine activity. Its effects also are very specific, with doses as high as 40000 times the effective antihistumine dose not displaying other pharmacological effects. In nasal and ocular provocation tests, levocabastine nasal spray and eye drops protected against allergen‐induced nasal and ocular symptoms. Twenty‐three clinical trials have been performed with levocabasline nasal spray in 1363 patients with allergic rhinitis. At a dose of two sprays per nostril twice daily (if necessary to be increased up to four times daily), levocabastine was significantly better than placebo and as good as or slightly better than cromoglycate in alleviating nasat symptoms. Good to excellent results were reported in about 60% of patients on levocabastine. compared with 37% with placebo and 47% with cromogly‐cate. Levocabastine eye drops were studied in 21 clinical trials including 1218 patients with allergic conjunctivitis. One drop per eye twice daily (up to four times daily) provided significantly better symptom control than placebo and similar effects as those observed with cromoglycate. Response rates were 71‐80% with levocabastine, 55% with placebo and 76% with cromoglycatce. Levocabastine has a fast onset of action, with 94% of patients experiencing symptom relief within 15 min after the first instillation of levocabastine eye drops. Three long‐term studies (10‐16 weeks' duration) showed absence of tachyphylaxis during prolonged treatment with levocabastine. The incidence of adverse experiences was similar for levocabastine, cromoglycate and placebo, for nasal spray as well as eye drops. Nasal and ocular irritation were the most frequently reported complaints. No consistent changes in haematological or biochemical variables were observed. Levocabastine promises to be a valuable topical alternative for the treatmenl of patients with allergic rhinoconjunctivitis.
Double‐blind comparison of levocabastine eye drops with sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis
Authors: AZEVEDO M. , CASTEL‐BRANCO M. G. , OLIVEIRA J. FERRAZ , RAMOS E. , DELGADO L. , ALMEIDA J.
Published: April 2006

The efficacy and tolerance of topical administration (one drop in each eye q.i.d.) of levocabastine (0‐5 mg/ml) was compared with that of sodium cromoglycate (20 mg/ml) and placebo in a 4‐week double‐blind trial in patients with seasonal allergic conjunctivitis. The investigator rated the treatment as globally good or excellent in significantly more patients treated with levocabastine (89%) than with cromoglycate (67%. P=0·03) or placebo (48%, P= 0·007). The patients felt that the treatment was more efficacious in 95% (levocabastine), 35% (cromoglycate) and 36% (placebo) of the cases in which they had taken previous antiallergic medication. Total symptom severity according to the patients' diary data was consistently lower with levocabastine than with cromoglycate or placebo for all ocular symptoms. The difference was mainly apparent at the beginning of treatment. The percentage of symptom‐free days was higher in the levocabastine group (53%) than in the cromoglycate (31%, P= 0·02) and the placebo group (34%, P= 0·08). Particularly at high‐pollen days, levocabastine was superior to cromoglycate in eliminating moderate or severe symptoms. Adverse effects did not occur more frequently with levocabastine or cromoglycate than with placebo. It is concluded that levocabastine is an efficacious, fast‐acting and well‐tolerated drug in the management of seasonal allergic conjunctivitis.
Detection of circulating histamine releasing autoantibodies with functional properties of anti‐IgE in chronic urticaria
Authors: GRATTAN C. E. H. , FRANCIS D. M. , HIDE M. , GREAVES M. W.
Published: April 2006

Circulating histamine releasing factor(s) have been demonstrated previously in chronic urticaria by an immediate weal‐and‐flare response to intradermal autologous serum injection. We have studied 25 chronic urticaria patients by in vivo skin testing with autologous sera and an in vitro histamine release assay using mixed leukocytes of healthy donors, to define the nature and functional properties of the serum factor(s). Twenty showed a weal response to autologous serum (mean ± s.e.m., 37.3±6.8 mm3). Weal formation was confined to ultrafiltered serum fractions > 100 kD in nine of nine patients. There was no response in 10 healthy controls or five patients with symptomatic dermographism. Fourteen chronic urticaria sera elicited histamine release > 10% (mean ± s.e.m., 44‐3%± 6 7) above basal levels from leukocytes of at least one of seven healthy donors. This in vitro response was also confined to ultrafiltered serum fractions > 100 kD in seven of seven sera and was present in IgG fractions of six of seven chronic urticaria sera that showed histamine releasing activity. Functional studies indicated that this histamine releasing autoantibody had the properties of anti‐IgE: chronic urticaria sera ‘desensitized’ basophil leukocytes to subsequent challenge with other chronic urticaria sera and to goat anti‐human IgE antibody; human myeloma IgE inhibited histamine release from leukocytes in response to chronic urticaria sera; removal of surface‐bound IgE by lactic acid “stripping” reduced histamine release in response to chronic urticaria sera and anti‐IgE and subsequent passive sensitization with IgE myeloma serum partially restored it, Stainable peripheral blood basophils/mm3 in chronic urticaria patients were significantly reduced (mean ± s.e.m., 7.9 ± 2 0) when compared to healthy controls (39.6 ± 44), P < 0.001. These results suggest that histamine releasing autoantibodies are important in the pathogenesis of chronic urticaria by stimulating or facilitating degranulation of basophils and cutaneous mast cells through cross‐linking cell surface IgE receptors.
Toluene diisocyanate produces an increase in airway tone that outlasts the inflammatory exudation phase
Authors: PERSSON C. G. A. , GUSTAFSSON B. , LUTS A. , SUNDLER F. , ERJEFÄLT I.
Published: April 2006

Toluene diisocyanate (TDI) is a causative agent in occupational asthma. Through an oral catheter TDI, 0·03 μl, dissolved in 0·02 ml olive oil. was superfused on the tracheobronchial mucosa of anaesthetized guinea‐pigs. TDI induced plasma exudation into both airway tissue and lumen (peak effect: 5 hr; duration ∼ 17 hr). Light microscopy examinations demonstrated that the epithelium was not disrupted by this process (and that microvessels are abundant just beneath the epithelium). At days 6 and 21 after exposure to TDI PAS‐positive cells were increased, but no other histological alterations were found. Also, the occurrence of peptide‐containing nerve fibres was not altered by TDI. After TDI‐exposure the airway smooth muscle tone was elevated as examined in vitro at base‐line and at concentration‐response to carbachol. The largest increases in tone were recorded 21 days after exposure to TDI. The abnormally large tone was not associated with an increased thickness of the smooth muscle layer nor was it associated with reduced effects of either β2‐agonist (terbutaline) or xanthine‐ (theophylline) relaxants. It is concluded that TDI‐induced plasma exudation into guinea‐pig airways occurs for 17 hr without disrupting the epithehal lining and without causing major changes in the airway peptidergic innervation. Both the airway tone, and the number of mucous cells, are increased for at least 3 weeks after exposure to TDI.
The effect of a single oral dose of prednisolone or cetirizine on inflammatory cells infiltrating allergen‐induced cutaneous late‐phase reactions in atopic subjects
Authors: VARNEY V. , GAGA M. , FREW A. J. , DE VOS C. , KAY A. B.
Published: April 2006

The effect of a single dose of prednisolone (20 mg) or cetirizine (10 mg) on the immunohistology of the cutaneous late‐phase reaction was determined in a double‐blind, placebo‐controlled, cross‐over study in 12 atopic allergic individuals. The subjects were challenged with intradermal allergen (30 BU) 2 hr after ingestion of the drugs or placebo. The magnitude of the cutaneous reactions were determined at 15 min, 6 and 24 hr, and skin biopsies performed at 24 hr. Cetirizine produced a 50% average inhibition of the immediate weal and flare response (P=0.001) and a 27% average inhibition of the 6 hr late‐phase induration (NS). Prednisolone reduced the immediate (27%, P=0.03) and significantly inhibited the late‐phase reaction (53%, P=0.02). Prednisolone significantly inhibited infiltration of CD45+ (total leucocytes), neutrophil elastase+, EG2+ (activated eosinophils) and CD25+ (IL‐2R) cells (P=0.017, 0.005, 0.005 and 0.032 respectively). CD3, CD4, CD8 and HLA‐DR expression was also inhibited but this was not significant. Cetirizine also reduced the numbers of EG2+ cells, particularly those with high counts before treatment but the overall results were not significant. No other changes in the cellular infiltrate were demonstrated when cetirizine was compared with placebo. These findings indicate a single dose of prednisolone significantly reduces leucocyte infiltration and activation as well as the magnitude of the cutaneous late‐phase reaction.
Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients
Authors: CRIMI N. , PALERMO F. , OLIVERI R. , PALERMO B. , POLOSA R. , MISTRETTA A.
Published: April 2006

Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double‐blind order. Inhaled NKA produced a dose‐related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 × 10−9 mol.

We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects. However, further studies are necessary to investigate the exact role and the mode of action of tachykinins in human airways.
Dust from carpeted and smooth floors. V. Cat (Fel d I) and mite (Der p I and Der f I) allergen levels in school dust. Demonstration of the basophil histamine release induced by dust from classrooms
Authors: DYBENDAL T. , ELSAYED S.
Published: April 2006

Sixty dust samples from schools in Norway were analysed for major allergens from cat and mite after sampling with the regularly used vacuum cleaners for 5 days and with a new model vacuum cleaner for 10 days, respectively. The major feline allergen Felis domesticus allergen I (Fel d I) was detected in all the classrooms, with ranges from 12 to 16 840 ng/m2 floor area. The mean Fel d I concentration was about 11 times higher per unit area carpeted floors as compared with smooth floors after the 10 days sampling period. Mite allergens Dermatophagoides pteronyssinus allergen I (Der p I) and Dermatophagoides farinae allergen I (Der f I) were detected in very low concentrations, with ranges from <1 ng to 104 ng/m2 floor area. These findings suggest that the school is a protective environment against mite infestation, while the prevalence of cat allergens in classrooms seems higher than previously assumed. Basophil histamine release was measured after provocation with 20 dust extracts from 10 different schools. In nine of the 10 schools examined, the basophil histamine release caused by challenge with carpet dust was higher than the corresponding release with smooth floor dust. The calculated floor areas in each school in which dust led to 15% histamine release were from 2 to 55 times larger for smooth floors compared with carpeted floors. These results emphasize previous findings regarding higher allergen concentrations in classrooms with carpeted floors.
Regulation of IgE production in pre‐sensitized animals: in vivo elimination of alveolar macrophages preferentially increases IgE responses to inhaled allergen*
Authors: THEPEN T. , McMENAMIN C. , GIRN B. , KRAAL G. , HOLT P. G.
Published: April 2006

Intratracheal inoculation of dichloromethylene diphosphonate encapsulated in liposomes leads to the rapid accumulation of this drug in alveolar macrophage (AM) phagolysosomes, and the death of the majority of these cells over the ensuing 24–48 hr. The technique is highly selective for phagocytes and has no detectable side‐effects on other cells in the lung. The present experiments demonstrate that following AM depletion, pre‐sensitized animals respond to aerosol challenge via secondary serum IgE (but not IgG) responses, and the accumulation of large numbers of allergen‐specific and non‐specific antibody forming cells in respiratory tract regional lymph nodes and in lung and airway tissues; the latter comprise both IgE and IgG plasma cells, which were detected in the approximate ratio of 2.5:1. Moreover, aerosol challenged AM‐depleted animals develop large mononuclear cell infiltrates in the lung and airways, which includes a substantial CD4+ T‐cell component. These results suggest a major role for AM in regulating the magnitude of secondary IgE responses to inhaled allergen.
Protein and allergen content of commercial skin test extracts for soybeans*
Authors: HERIAN A. M. , BUSH R. K. , TAYLOR S. L.
Published: April 2006

The protein and allergen contents of four commercial soybean skin test extracts were tested by SDS‐PAGE and immunoblotting using sera from soy‐allergic adults. Polyacrylamide gels stained with Coomassie Blue showed an absence of several major soybean proteins, particularly those at higher molecular weights. The acidic subunits of glycinin and beta‐conglycinin, major soybean storage proteins, appear to be absent or present in much reduced amounts. Immunoblots with soy‐allergic sera indicate alteration, reduction, or loss of IgE‐binding in the commercial extracts as compared to extracts of soy flour. In one soy‐allergic patient, skin tests revealed a negative response to three of the commercial soybean extracts and a mild response to one extract. Defatted soy flour obtained from two of the four extract manufacturers was extracted in the laboratory using a standard procedure for the isolation of soybean proteins. In one case, the extract still had an abnormal protein profile on gel electrophoresis while in the other case, the new extraction procedure gave significantly improved extraction of soy protein. Preparation methods appear to be partially responsible for the variable allergen content in commercial soybean skin test extracts.
Prediction of annual variations in atmospheric concentrations of grass pollen. A method based on meteorological factors and grain crop estimates
Authors: SUBIZA J. , MASIELLO J. M. , SUBIZA J. L. , JEREZ M. , HINOJOSA M. , SUBIZA E.
Published: April 2006

We performed an aerobiologic observation of the grasses present in Madrid for 14 years (1978–1991), using volumetric air samplers. The counts obtained show that the major grass pollen release period (average daily grass pollen counts >50 grains/m3 of air) occurs in the months of May and June, although lower counts can occur some days from the end of January onward. There are wide year‐to‐year variations in total atmospheric grass pollen counts, expressed as the total sum of the mean daily concentrations from April 1st to July 30th (ranging from 2568 to 6624). A strong, statistically significant correlation, based on Spearman's rank test and/or simple and multiple linear regressions, was found between the total grass seasonal count and preseasonal rainfall from October to March (R2= 0.64; P= 0.0429). The meteorological variable which gave the correlation with greatest statistical significance (R2= 0.97; P= 0.0016) was the average monthly preseasonal humidity from October to March. A good correlation was also found between March estimates of wheat, rye and barley crops and the total grass count (R2= 0.73; P= 0.006). A model was designed from the above mentioned humidity variable through a multilinear regression analysis, and it was possible to predict, at the beginning of April, total seasonal counts for 1989 (predicted = 5468; actual = 4410; average error = 24%), 1990 (5033; 6090; – 17%)and 1991 (3930; 2568; 53%). These data may help clinicians to predict and prepare themselves for the intensity of the grass pollen season and to explain yearly variations in the severity of symptoms.
The long‐term effect of nedocromil sodium on the maximal degree of airway narrowing to methacholine in atopic asthmatic subjects
Authors: SONT J. K. , BEL E. H. , DIJKMAN J. H. , STERK P. J.
Published: April 2006

Airway hyperresponsiveness in asthma is characterized by increased airway sensitivity and by excessive maximal airway narrowing. Long‐term inhalation therapy with nedocromil sodium has been shown to reduce increased airway sensitivity in asthma. However, it is unknown whether it also attenuates excessive airway narrowing. We studied the long‐term effects of nedocromil on the maximal degree of airway narrowing to methacholine. Twenty‐seven atopic asthmatic adults (21–39 years), with a measurable maximal‐response plateau on the dose‐response curve (20–55% fall in FEV1), were randomly allocated into two parallel treatment groups. They received either inhaled nedocromil 4 mg q.i.d. or placebo, for 8 weeks following a 2 week baseline period. Every 2 weeks, complete dose‐response curves to inhaled methacholine were obtained. The response was measured by FEV1 and by volume history standardized partial expiratory flow‐volume curves (V̇40p). A maximal‐response plateau was considered if three or more of the highest data points fell within a 5% response range, the maximal response being the average value on the plateau (MFEV1, MV̇40p). Airway sensitivity was defined as the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20FEV1) or 40% fall in V̇40p (PC40V̇40p). Twenty‐four subjects completed the study. Baseline FEV1 or V̇40p did not change during either treatment (P>0.07). There were no significant changes in MFEV1, or MV̇40p during treatment with nedocromil (P>0.07). Neither were these changes significantly different between the two groups (P>0.25). During treatment with nedocromil there was an increase in PC20FEV1 and PC40V̇40p, which was maximal at 6 weeks (mean change±s.d.: 1.0±0.9 doubling dose (DD), and 0.8±0.7 DD, respectively, P= 0.002). The changes in PC20 and PC40 were significantly different between the nedocromil and the placebo group (P<0.05). We conclude that long‐term treatment with nedocromil, in spite of reducing airway sensitivity, does not reduce the maximal degree of airway narrowing to methacholine in mild to moderate asthmatics. This suggests that nedocromil may not be sufficient in the prevention of excessive airway narrowing in asthma.
Can fatal asthma be prevented?—a personal view
Authors: SERAFINI U.
Published: April 2006

An increase in the mortality rate from asthma in several countries has been observed in recent years, notwithstanding the great improvement in pathophysiological findings and the introduction of new effective therapeutic agents. The phenomenon is difficult to explain but the causes of death and identification of high‐risk patients have been widely studied. It is suggested that the most vital aim for physicians is the avoidance of those factors which may contribute to death from asthma. These are particularly: inadequate assessment of its severity by patients, general practitioners and hospital doctors, and inadequate and inappropriate treatment. From the diagnostic point of view, the measurement of airflow rates is necessary to establish the diagnosis in terms of reversibility, quantify the severity and assess the response to therapy. The different entity of reversibility of bronchial obstruction is due to the various mechanisms intervening in different patients. After adequate treatment, according to our observations, the reversibility is more complete in young people and when the duration of the disease is less than 2 years. Trigger factors must also be considered. From the therapeutic point of view, considering that the most important alteration in asthma is the inflammation of bronchial structures with intervention of several inflammatory cells and of numerous different chemical mediators, physicians have to apply treatment aimed at reducing inflammation rather than relying on symptomatic bronchodilator remedies. Treatment should be divided into three phases, according to symptoms: induction, consolidation and maintenance. Finally, on the basis of data here presented and of clinical experience, the essential measures for the prevention of asthma mortality are reported. If general practitioners take them into account, deaths from asthma will be reduced to a minimum.
Variability of crossreactivity of IgE antibodies to group I and V allergens in eight grass pollen species
Authors: VAN REE R. , DRIESSEN M. N. B. M. , VAN LEEUWEN W. A. , STAPEL S. O. , AALBERSE R. C.
Published: April 2006

Crossreactivity to Dactylis glomerata, Festuca rubra, Phleum pratense, Anthoxanthum odoratum, Secale cereale, Zen mays, and Phragmites communis of IgE antibodies against Lol p I or Lol p V was investigated by means of RAST‐inhibition. Within a group of sera the degree of crossreactivity was demonstrated to be highly variable. Individual sera were not always equally crossreactive to all pollen species. A high degree of crossreactivity for Group I allergens did not necessarily implicate the same for Group V. Group I and Group V representatives were found to be present in all eight species. It was demonstrated that within this group of grass species significant quantitative and qualitative differences exist, with respect to Group I and Group V allergens. Species with a low phylogenetic affinity to Lolium perenne, like Zea mays and Phragmites communis showed a very low degree of reactivity, even when measured with the most crossreactive sera. A higher taxonomic relationship however, did not always implicate a closer antigenic resemblance. Antigenically both allergens from Zea mays are more similar to Lol p I and Lol p V, than the analogues in Secale cereale.
Influence of a positive family history and associated allergic diseases on the natural course of asthma
Authors: ROORDA R. J. , GERRITSEN J. , VAN AALDEREN W. M. C. , KNOL K.
Published: April 2006

The outcome of childhood asthma was studied in a cohort of 406 asthmatic children, with emphasis on the influence of family history for allergic disease, as well as the influence of associated allergic diseases on prognosis. Sixty‐two per cent had a positive family history for atopy. In young adulthood no differences, either in symptoms or lung function were demonstrated in comparison to subjects with a negative family history. Fifty‐two per cent of the children had no other allergic disease, 48% had either eczema or hay fever or both. When subjects were stratified based on associated allergic disease, no differences in outcome in adulthood were revealed either. It is concluded that neither a positive family history, nor concurrent associated allergic diseases in the child contribute to the prognosis of asthma from childhood to young adulthood. Therefore, environmental factors as well as patient characteristics (including lung function level, level of bronchial responsiveness) are likely to be more important for the prognosis.
The allergen specific B‐cell response during immunotherapy
Authors: SPARHOLT S. H. , OLSEN O. T. , SCHOU C.
Published: April 2006

The paper examines the allergen specific B‐cell response in peripheral blood from patients undergoing immunotherapy with house dust mite extract. The 12 patients were part of a double blind placebo controlled study, and they were treated with either Dermatophagoides pteronyssinus (n= 4), Dermatophagoides farinae extract (n= 3) (Alutard SQ, ALK, Denmark) or placebo (n= 5). Blood was taken every fortnight on day seven after hyposensitization and tested for IgM, IgG, IgA and IgE antibody secreting cells (AbSC) to D. pteronyssinus and D. farinae allergens and for the total number of immunoglobulin secreting cells (IgSC). The data showed a maximum of approximately 120 Der f I + II specific AbSC/106 mononuclear cells (MNC). A comparison of specific AbSC to the major allergens of the two house dust mites demonstrated that there was no measurable species specificity in the B‐cell response that could be correlated to immunotherapy with either of the two extracts. The specific IgM, IgG, and IgA response to Der f I + II was examined in the placebo (39 measurements) and the actively treated (56 measurements) groups, and the results demonstrated a significant rise in specific IgM and IgA AbSC following immunotherapy. The number of specific IgG AbSC did not change. There was a mean of less than one specific IgE AbSC/106 MNC, and no detectable change following the treatment. It is speculated that immunotherapy to inhalant allergens causes the induction of specific IgA AbSC. It would then be these partly differentiated plasma cells that are detected on their way to the bronchial or gut mucosa to exert their protective function mediated by allergen specific secretory IgA.
Effect of topical application with capsaicin on skin responses to bradykinin and histamine in man
Authors: CRIMI N. , POLOSA R. , MACCARRONE C. , PALERMO B. , PALERMO F. , MISTRETTA A.
Published: April 2006

Pre‐treatment with topical capsaicin is known to induce neuropeptide depletion from sensory nerve endings and it is a useful pharmacological tool to evaluate the contribution of these nerves to skin injury and inflammation. To investigate the relative contribution of sensory neural stimulation to the action of bradykinin and histamine, a randomized, double‐blind study has been undertaken evaluating the effect of topical capsaicin pre‐treatment on the responses to intradermal injections of both agonists in 12 healthy volunteers. Capsaicin pre‐treatment caused significant inhibition of the immediate mean flare responses (95% CI) to both bradykinin (from 51.5 [39.7–63.3] mm2 to 16.2 [8.0–24.5] mm2) (P < 0.01) and histamine (from 108.4 [80.4–136.4] mm2 to 52.3 [37.1–67.1] mm2) (P < 0.01). Topical capsaicin elicited a significant inhibition of the weal response induced by histamine, the mean weal area being reduced from 14.8 (12.6–17.0) mm2 to 12.1 (10.1–14.1) mm2 (P < 0.05). In addition, the effect of topical capsaicin was to completely inhibit the bradykinin induced weal response compared to control, the mean weal area (95% CI) being reduced from 13.4(11.4–15.4) mm2 to 8.2 (5.3–11.0) mm2 (P < 0.01). Our findings show that repealed topical application with capsaicin led to a significant reduction of the skin responses to intradermal injections with both agonists, and particularly with bradykinin. The weal responsiveness to bradykinin may entirely follow neuropeptide release from sensory nerves within the skin and the same applies to the flare response, although this is not completely inhibited by topical application with capsaicin.
Bronchial responsiveness to exercise in a random sample of 494 children and adolescents from Copenhagen
Authors: BACKER V. , ULRIK C. S.
Published: April 2006

To investigate the bronchial response to exercise, we studied a random sample of 494 children and adolescents, aged 7–16 years, from Copenhagen. Exercise challenge consisted of steady running on a 10% sloping treadmill for 6 min in a climate chamber. Furthermore, in 464 subjects a histamine challenge test was also performed. Of the 494 subjects studied, 81 (16%) had at least 10% and 30 (6%) at least 15% reduction in FEV1 within 15 min after exercise. Twenty‐nine (6%) subjects had bronchial hyperresponsiveness to both histamine and exercise, 48 (10%) subjects had bronchial hyperresponsiveness to exercise, but histamine responsiveness within the normal range, whereas 340 (73%) subjects had neither bronchial hyperresponsiveness to exercise nor inhaled histamine. With regard to the presence of asthma defined as substantial exercise induced bronchoconstriction (Δ‐FEV1≥10%), exercise testing may not be appropriate for identifying clinical asthma in a random sample, because the highest predictive value of a positive lest was 25%. On the other hand, a history of clinical asthma was frequently associated with increased bronchial responsiveness to exercise (77%). In conclusion, 16% of a random sample of children and adolescents had abnormal bronchial responsiveness to exercise (ΔFEV1≥10%), 6% of the subjects had a ΔFEV1≥15%. Furthermore, because of a low predictive value of a positive test, the exercise challenge test has only a supplementary role in the detection of clinical asthma in population samples.
IgE antibodies to Pityrosporum orbiculare and Staphylococcus aureus in patients with very high serum total IgE
Authors: NORDVALL S. L. , LINDGREN L. , JOHANSSON S. G. O. , JOHANSSON S. , PETRINI B.
Published: April 2006

Serum IgE antibodies were detected with the radioallergosorbent test (RAST) to a panel of allergens which included Pityrosporum orbiculare, Candida albicans, Trichophyton rubrum, Cladosporium herbarum, Staphylococcus aureus, animal dander, deciduous tree pollens, grass pollens and foods in 81 consecutive patients with total IgE ≥ 3000 kU/1. Data on atopic and infectious disease characteristics were collected by a questionnaire. IgE antibody concentrations to P. orbiculare were significantly higher than to the other fungi and of the same magnitude as those to animal danders and pollens. High levels of P. orbiculare IgE antibodies were associated with current eczema, especially when it was the only atopic manifestation and demanding specialist care. IgE antibodies to P. orbiculare had the best explanatory value for current eczema in logistic regression analysis. Head‐neck‐face dermatitis was also associated with high levels of specific IgE to the yeast. IgE antibodies to S. aureus were detected in few patients and at low concentrations. Six patients had a history of systemic staphylococcal infections and presented a clinical picture, which was very similar to the hyperimmunoglobulinaemia E syndrome. Among the six were the two cases with the highest levels of IgE antibodies to S. aureus. The demonstration of high levels of IgE antibodies to P. orbiculare, which is a major part of human normal skin microflora, suggests that allergy to this yeast plays an important pathogenic role in eczema.
Autologous bacteria induce chemotaxis of peripheral blood mononuclear cells (MNC) from non‐atopic asthmatics
Authors: ŻAK‐NEJMARK T. , MAŁOLEPSZY J. , KRAUS‐FILARSKA M. , NADOBNA G. , JUTEL M. , STANKIEWICZ M.
Published: April 2006

The chemotactic response of peripheral blood MNC from healthy subjects and non‐atopic asthmatics against the respective pathogen isolated and cultured from sputum of individual patients was investigated. We found that the wide range of concentrations of autologous bacteria induced chemotaxis of MNC from asthmatics but showed no influence on MNC from healthy subjects. This finding might explain the mechanism of lymphocyte accumulation in the lungs of non‐atopic asthmatics.
Effects of cytokines on human basophil chemotaxis
Authors: TANIMOTO Y. , TAKAHASHI K. , KIMURA I.
Published: April 2006

Basophil chemotactic activity (BCA) of eight recombinant human (rh) cytokines was examined. Highly purified basophils were obtained by Percoll discontinuous gradients, followed by negative selection using flow cytometry. Then BCA was measured by means of modified Boyden chamber method. Both interleukin (IL)‐3 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) had much more potent BCA than complement C5a, leukotriene B4 and platelet activating factor, well known as granulocyte chemotactic factors. Chemotaxis rather than chemokinesis was shown in chequerboard analysis of basophil migration induced by IL‐3 and GM‐CSF. Relatively high concentrations of IL‐5 also induced basophil migration, although predominantly chemokinetic. IL‐8 had apparent BCA, which was not so high as that of C5a. In contrast, IL‐2, IL‐4, interferon(IFN)‐γ and granulocyte colony‐stimulating factor (G‐CSF) had no significant BCA. These findings suggest that IL‐3, IL‐5, GM‐CSF and, perhaps, IL‐8 have an effect on basophil migration as well as modulation of basophil mediator release and may provide some insight into the basophil accumulation observed in late‐phase allergic responses.
IgE, IgG, IgG1 and IgG4 patterns in yellow jacket allergic patients during immunotherapy with a venom depot extract
Authors: JEEP S. , MEYSEL U. , KUNKEL G.
Published: April 2006

Using immunoblot studies, detailed antibody patterns were performed with the sera of 10 yellow jacket allergic patients undergoing specific immunotherapy with a yellow jacket venom SQ‐depot extract (ALK, Denmark). Five males and five females (age range 10–65, mean 48 years) were investigated. All patients had a history of systemic reactions after an insect sting and a positive skin‐prick test at a dose of at least 100 μg/ml yellow jacket venom.

Yellow jacket venom (ALK) was separated on a 7.5–20% SDS–PAGE, transferred to nitrocellulose (NC), and then the NC‐strips were incubated with the patients’sera. For detection of IgE, IgG, IgG1 and IgG4, an alkaline phosphatase linked 2nd antibody was used. Prior to immunotherapy, a strong IgE binding was detected at 25 kD in nine of 10 patients, representing Antigen‐5 (Ag‐5) as major allergen. Reactivity to this antigen was also present with the other immunoglobulin classes, although not as marked. In addition, a second frequent IgG and IgG1‐binding band was seen at 35 kD (phospholipase A). Only weak or no binding to this band was found with IgE and IgG4. Binding to hyaluronidase (43 kD) was seen only in three cases.

During immunotherapy, a significant increase in IgG and particularly IgG4 staining was found with Ag‐5, whereas hyaluronidase induces mainly an IgG1 response and phospolipase A showed only a weak IgG response. In addition, the formation of new IgG4 binding to proteins in the region of about 70–90 kD was found in most patients. The dose necessary for the induction of this antibody formation was ≥ 150.00 SQ yellow jacket venom. We conclude that the increase in the total amount of specific IgG4 to an allergen extract (protein mixture) during immunotherapy gives no information about the increase of IgG4 to the patient's special major allergen.
Diagnostic value of skin and laboratory tests in cow's milk allergy/intolerance
Authors: RÄSÄNEN L. , LEHTO M. , REUNALA T.
Published: April 2006

The applicability of a panel of five skin and laboratory tests in the diagnosis of cow's milk allergy/intolerance (CMAI) was investigated. The tests used were prick and patch tests, RAST, basophil histamine release test (BHRT) and lymphocyte proliferation test (LPT). Twenty‐two atopic children who had experienced either immediate or delayed cutaneous symptoms upon challenge with cow's milk (CM), and 12 non‐milk‐allergic controls with atopic dermatitis (AD) were included in the study. RAST, prick test, BHRT and LPT to CM and patch test to α‐casein were positive in the CMAI group and non‐milk‐allergic atopic controls as follows: 59% and 33%, 57% and 0%, 55% and 17%, 77% and 17%, 33% and 0%. RAST, prick test and BHRT were more often positive in children exhibiting immediate reactions, and patch test and LPT more often positive in those having delayed reactions to CM. The panel of five tests detected 21/22 children with CMAI and gave false‐positive results in 5/12 of non‐milk allergic controls. The sensitivity and specificity of the panel in the diagnosis of CMAI were 95% and 58%, respectively.
Inhibition profiles of sodium cromoglycate and nedocromil sodium on mediator release from mast cells of human skin, lung, tonsil, adenoid and intestine
Authors: OKAYAMA Y. , BENYON R. C. , REES P. H. , LOWMAN M. A. , HILLIER K. , CHURCH M. K.
Published: April 2006

We have studied an aspect of the functional heterogeneity of human mast cells, namely responsiveness to the inhibitory effects of sodium cromoglycate and nedocromil sodium. The effects of these drugs were examined on the release of histamine and PGD2 from mast cells of human skin, lung, tonsils, adenoids and intestine. A high concentration, 1000 μM, of sodium cromoglycate was required to significantly inhibit histamine release from lung and tonsillar mast cells. Nedocromil sodium, 1000 μM, was more effective than sodium cromoglycate against histamine release from lung, tonsillar and adenoidal cells. Both compounds showed tachyphylaxis in lung and tonsillar mast cells but not in adenoidal and intestinal mast cells. In contrast, in intestinal mast cells, the effect of nedocromil sodium was weaker and more variable than sodium cromoglycate. Skin mast cells differed from mast cells of the other anatomical sites in being unresponsive to sodium cromoglycate and nedocromil sodium. Our results confirm that high concentrations of sodium cromoglycate and nedocromil sodium are required to achieve even modest inhibition of mediator release from human mast cells under in vitro conditions. Notwithstanding this, the results also indicate that differences exist among skin, lung, tonsillar, adenoidal and intestinal mast cells with respect to their sensitivity to sodium cromoglycate and nedocromil sodium, thus extending our knowledge of functional heterogeneity within the human mast cell populations.
Optimized preparation of Aspergillus fumigatus extracts for allergy diagnosis
Authors: LITTLE S. A. , LONGBOTTOM J. L. , WARNER J. O.
Published: April 2006

Extracts of Aspergillus fumigatus are required for the measurement of specific antibodies that are important indices in the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). This study investigated the effect of different culture conditions on the production and release of antigenic and allergenic proteins of A. fumigatus. Increasing the incubation temperature from 25°C to 37°C altered the production of proteins by the mycelium which resulted in the release of a greater number of proteins that reacted with precipitating antibodies. Static sporulating cultures produced a much wider antigenic spectrum than shake cultures although the number of precipitating proteins (5 and 3 respectively) and major IgE binding proteins (5 and 3 respectively) was not greatly altered. The widest range of proteins bound by precipitating antibody or IgE from ABPA serum were released into the culture filtrate during 28 day static incubation at 37°C. The resultant extract proved useful for screening patients for specific IgE and will provide a starting material for the identification of individual antigens or allergens.
Lack of role for mononuclear cell‐derived histamine releasing factors in occupational asthma due to western red cedar
Authors: FREW A. J. , CHAN H. , YEUNG M. CHAN
Published: April 2006

Occupational asthma due to Western Red Cedar (WRCA) is attributed to sensitization to plicatic acid (PA), but does not appear to be dependent on PA‐specific IgE antibodies. Exposure to PA induces histamine release in vivo and in vitro, so if IgE is not important. other mechanisms of histamine release must presumably operate in WRCA, To explore the possible role of histamine‐releasing factors in WRCA, peripheral blood mono‐nuclear cells were obtained and cultured with PA, PA‐albumin conjugate plica tic acid‐human serum albumin (PA‐HSA).grass pollen or Concanavalin A using a standard histamine releasing factor (HRF) generation protocol. Supernatants were dialysed to remove endogenous histamine and then assayed for histamine releasing activity using human basophils as targets and a Con A‐induced bulk supernatant as an internal HRF standard. In contrast to some previous reports, spontaneous HRF release from the peripheral blood mononuclear cells (PBMC) of WRCA patients (n= 9) and atopic asthmatic subjects (n= 5) was not elevated compared with the non‐asthmatic controls (n= 11; five atopic and six non‐atopic). Both PA and PA‐HSA induced the production of small amounts of HRF by PBMC of WRCA patients, but a similar degree of HRF generation was also observed in PBMC from the atopic asthmatic, atopic non‐aslhmatic, and non‐atopic subjects. The contrast, grass pollen induced the production of HRF by PBMC from the subjects with positive skin tests to grass pollen but not by PBMC of non‐atopic subjects, confirming that our methods and assay were capable of detecting antigen‐specific HRF production. Since neither PA nor PA‐HSA induced significantly elevated HRF production from PBMC of WRCA patients, it seems unlikely that PA‐induced HRFs play a substantial role in the pathogenesis of WRCA.