bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupational respiratory disease caused by acrylates
Authors: SAVONIUS B. , KESKINEN H. , TUPPURAINEN M. , KANERVA L.
Published: April 2006

Acrylates are compounds used in a variety of industrial fields and their use is increasing. They have many features which make them superior to formerly used chemicals, regarding both their industrial use and their possible health effects. Contact sensitization is, however, one of their well known adverse health effects but they may also cause respiratory symptoms. We report on 18 cases of respiratory disease, mainly asthma, caused by different acrylates, 10 cases caused by cyanoacrylates, four by methacrylates and two cases by other acrylates.
The aerodynamic characteristics of cat allergen
Authors: WOOD R. A. , LAHERI A. N. , EGGLESTON P. A.
Published: April 2006

To further characterize airborne cat allergen and a newly established cat challenge facility, airborne Fel d I levels and particle size distributions were studied in both the cat challenge room and home environments under different conditions of ventilation and physical activity. In the cat room, there has been a dramatic and continued rise in the concentration of airborne Fel d I since the room was established. No differences in total airborne Fel d I levels or particle size distribution were detected under widely differing rates of ventilation (40 air changes per hour vs 8 ac/hr vs < 1 ac/hr). Likewise, altering ventilation had little effect on the clearance of airborne antigen after disturbance. Significant increases in allergen levels were detected, however, after simply allowing the cats to leave their holding cage and move about the room, Feld I levels in homes ranged from 2–468.5 ng/m3 similar to the levels seen in the cat room without disturbance. Feld I particle size distribution was very consistent in both homes and the cat room with the majority of airborne Fel d I being detected on particles > 17 μm. Although very little allergen f < 15%) was detected on particles <4 μm, this important fraction was present under all conditions. We conclude that airborne cat allergen resides primarily on relatively large particles, that a small but consistent fraction is found on very small particles, and that neither allergen levels or particles size distribution are significantly influenced by ventilation.
Down modulation of L‐Selectin expression on eosinophils recovered from bronchoalveolar lavage fluid after allergen provocation
Authors: MENGELERS H. J. J. , MAIKOE T. , HOOIBRINK B. , KUYPERS T. W. , KREUKNIET J. , LAMMERS J‐W. J. , KOENDERMAN L.
Published: April 2006

In allergic asthma eosinophils infiltrate into the lung after allergen challenge. The mechanism of this cellular infiltration is not fully understood. L‐Selectin is involved in leucocyte‐endothelial cell recognition and participates in homing of leucocytes into sites of inflammation. To find indications for a role of L‐Selectin in the migration of eosinophils to the bronchoalveolar space we measured L‐Selectin expression on eosinophils in peripheral blood and bronchoalveolar lavage fluid (BAL) 4 hr after the early allergic reaction after allergen challenge. Nine patients with allergic asthma participated in the study. An eosinophil specific high depolarization signal enabled us to measure L‐Selectin expression on eosinophils in a FACS analysis without isolation of these cells. Eosinophils recovered from BAL showed a strong decrease of L‐Selectin expression compared to blood eosinophils. This decrease in L‐Selectin expression can be induced in vitro by activation of eosinophils with PMA or FMLP whereas priming of eosinophils during several hours with GM‐CSF did not influence L‐Selectin expression. Our results are a first indication that L‐Selectin may play a role during homing of eosinophils in the lung in asthma after allergen challenge. Moreover, the low expression of L‐Selectin on eosinophils in the lung is a further indication that these cells exhibit an activated phenotype.
Predominance of the major allergen (Alt a I) in Alternaria sensitized patients
Authors: KLEINE‐TEBBE J. , WORM M. , JEEP S. , MATTHIESEN F. , LØWENSTEIN H. , KUNKEL G.
Published: April 2006

Thirty‐nine patients sensitized to Alternaria were evaluated using titrated skin‐prick test (SPT), histamine release studies (HR), inhibition of RAST and immunoblotting studies. To determine the relevance of the major allergen, Alt a I, specific rabbit antibodies against Alt a I and Alt a B were used. The antibodies were preincubated at different concentrations: (i) with the Alternaria allergen dose required for maximum response in the HR assay (10 BU/ml) and (ii) with the Alternaria antigen coupled to RAST paper discs (1000 BU/disc). Dose dependent inhibition of histamine release (n= 30, x̄= 80%± 4%, IC30 = 0.69 μg/ml) and of RAST (n= 7, IC30 = 4.4 μg/ml) was found in all patients sensitized to Alternaria as indicated by allergen induced HR. The greater the response to Alternaria in HR, the higher the antibody concentrations necessary for inhibition (P<0.05). Immunoblot experiments (n=25) using SDS‐PAGE showed in all cases IgE‐ and IgG binding at approximately 28 kD, which is the size reported for the major allergen. All a I. In two cases, slight IgE binding at 45 and 66 kD was also found, while in two other patients, only IgE binding at 66 kD was seen. Our findings emphasize the major importance of Alt a I in patients sensitized to Alternaria.
Lymphocyte transformation test with house dust mite (Dermatophagoides pteronyssinus) in normal children, asthmatic children and asthmatic children receiving hyposensitization
Authors: VAN BEVER H. P. , BRIDTS C. H. , MOENS M. M. , DE RUCK T. E. , MERTENS A. V. , DE CLERCK L. S. , STEVENS W. J.
Published: April 2006

In the first part of this study the proliferative response of lymphocytes (lymphocyte transformation test) to house dust mite (HDM) stimulation in cultures was studied in normal children (n= 16), asthmatic children who never received hyposensitization (HS) (n = 50) and asthmatic children receiving HS with HDM for at least 6 months (n = 20). The results are expressed as disintegrations per minute (d.p.m.) and as stimulation index (SI = d.p.m. in the presence of the allergen/d.p.m. in the control culture). A positive SI (> 2) was found in 54% of the asthmatic children who never received HS, in 30% of the asthmatics receiving HS and in none of the normal children. Furthermore, between asthmatics with and without HS, the SI was not statistically different, although asthmatics without HS tended to have a higher SI (median value: 2.13 vs 1.38) (P= 0.10). In a second series of experiments the effect of adding interleukin‐2 (IL‐2) to the lymphocyte cell culture was studied in asthmatic children with and without HS. Interleukin‐2 induced an additional stimulatory effect on the lymphoproliferative response to HDM and to phytohaemagglutinin in patients who never received HS, but had no effect in patients receiving HS. We conclude that HS treatment seems to have an inhibiting effect upon this proliferative response, not only inhibiting the degree of the allergen‐induced lymphocyte proliferation, but also inhibiting the sensitivity of proliferating lymphocytes for IL‐2. These inhibiting effects upon lymphocytic activation could be responsible for the anti‐inflammatory effects (i.e. suppression of the late asthmatic reaction) of HS.
Increased immune reactivity to house dust mites in adults with chronic rhinosinusitis
Authors: ARMENAKA M. C. , GRIZZANTI J. N. , ORIEL B. , ROSENSTREICH D. L.
Published: April 2006

Sixty‐three adults with symptomatic chronic rhinosinusitis had computerized tomegraphic (CT) scans of the paranasal sinuses, which were used to quantify disease severity. These patients were divided into three closely age‐ and sex‐matched groups: a CT scan‐negative group (chronic rhinitis only), a mild sinusitis group and a severe sinusitis group. Serum dust mite‐specific IgG levels were found to be significantly elevated in the sinusitis patients compared with a matched group of asymptomatic normal individuals. Levels were highest in the more severe sinusitis group, in which the mean titre was 559 U/ml and the incidence of litres greater than 400 U/ml was 48%, as compared with a mean titre of 139 U/ml and only a 10% incidence of litres greater than 400 U/ml in the normal subjects (P< 0.005 and <0.01). In contrast, although the frequency of immediate hypersensitivity to dust mite, as assessed by intradermal skin tests, tended to be higher in patients with sinusitis, it was not significantly different from normal individuals. The association between mite IgG and disease was most striking in the patient sub‐group with negative mile skin tests. In this group, mite IgG levels were significantly higher than normal, even in those patients with only chronic rhinitis. These findings demonstrate that increased serum levels of IgG against dust mites are strongly associated with chronic rhinosinusitis, especially in the sub‐group of patients who are not allergic to mites.
Allergen extracts. Standardization of preparations for bronchial provocation tests. A position paper
Authors: FRØLUND L. , BONINI S. , COCCO G. , DAVIES R. J. , DE MONCHY J. G. R. , MELILLO G. , PAUWELS R.
Published: April 2006

Standardization of allergen provocation tests of the airways requires standardization of each of the steps involved, including standardization of the extracts used. The value of international standards is emphasized and so is the determination of a clinically relevant potency. The allergen extracts used for bronchial provocation tests must be compared with qualitatively and quantitatively clinically relevant standards using complementary immunochemical and biological methods. Ideally the same extracts should be used for diagnosis (skin test, specific IgE determinations, provocations) and treatment (immuno‐therapy). The importance of the biological compared with the non‐biological methods is that the biological methods are established in allergenic patients in order to select a clinically relevant potency of the allergen in question, and this potency ought to be confirmed in clinical trials. Once established the biological potency of an in‐house preparation can be reproduced by supplementary in vitro methods. Very few commercial allergen preparations are available which fulfil the above‐mentioned criteria.
Detection of crossreactive determinants in grass pollen extracts using monoclonal antibodies against group IV and group V allergens
Authors: FAHLBUSCH B. , MÜLLER W.‐D. , DIENER CH. , JÄGER L.
Published: April 2006

Monoclonal antibodies (MoAb) to defined allergens of P. pratense were raised. Five of them were selected for detailed studies by means of immunoblotting after SDS–PAGE and IEF of extracts from P. pratense and L. perenne. Three antibodies (1D11, 3B2, 2D1) recognize structures with mol. wt of 29 and 34 kD and pI of 4.4‐7.7, corresponding to group V allergens. Two other MoAbs (2D8, 3C4) are directed against strong basic structures with a mol. wt of 50 kD and pI of 7.7‐9.9 according to group IV allergens. The specificity of antibodies was supported by direct ELISA with purified group V and IV allergens. The isolated allergens were characterized before by SDS‐PAGE and CIE and that allergenicity was detected with sera of patients with allergic rhinitis. Using our selected MoAbs crossreactive epitopes on group V and IV allergens have been excluded. Our antibodies have been used to detect crossreactivity in 14 grass pollen extracts. The evaluation of the pollen extracts has been performed by enzyme immunoassay (EIA) inhibition. One MoAb (3C4) is able to recognize group IV allergens in all grass species analysed whereas the MoAb 2D8 seems to identify group IV structures in selected grasses only. Binding to conserved structures of group V has been proved for MoAb 1D11. Other group V specific MoAbs (2D1, 3B2) identify similar, however incomplete, spectra. These results have been confirmed also by the dot immunobinding assay.
Precise area determination of skin‐prick tests: validation of a scanning device and software for a personal computer
Authors: POULSEN L. K. , LIISBERG C. , BINDSLEV‐JENSEN C. , MALLING H.‐J.
Published: April 2006

When skin‐prick tests (SPTs) are used quantitatively, the circumference of the weal and/ or the flare is outlined using a felt tip pen, and transferred to paper by adhesive tape. The aim of the study was to develop and validate a procedure, objectively and precisely determining these areas after transfer to paper. A system was developed enabling the drawing of the area of weal or flare to be read by a hand‐held scanner and calculated on a personal computer. Areas in the 5‐500 mm2 range could be determined with day‐to‐day and interoperator coefficients of variation (CVs) of 3.3% and 1.1%, respectively. Accuracy was determined in two ways: by correlation to cutting/weighing of four times enlarged SPT areas (r2= 0.0, P< 0.0) and by measuring standardized areas (deviations less than intra‐assay CV, i.e. 1‐2%). For comparison, CVs of alternative methods were also determined: eight different areas (9‐76 mm2) were evaluated in quadruplicate using the SPT‐scanner (CV=1.1%), by cutting/weighing of paper (CV = 2.2%), by digitizing (CV = 4.4%) or by measuring longest and orthogonal diameters (CV= 13.13%). In conclusion, the scanning device and software provides an objective and reproducible procedure for rapid determination of SPT areas. When areas are determined by scanning, digitizing or cutting/weighing the variations in area determination becomes negligible compared to the variations of the entire skin test procedure.
Reversibility of the allergen‐provoked late asthmatic response by an inhaled β2‐adrenoceptor agonist
Authors: TWENTYMAN O. P. , HOLGATE S. T.
Published: April 2006

There is uncertainly about the relative contributions of bronchial smooth muscle contract ion. mucosal oedema and mucus plugging lo airflow obstruct ion in the allergen induced late asthmatic response (LAR).

We systematically studied the ability of the inhaled β2‐agonist salbutamol to reverse the LAR in eight subjects after allergen bronchoprovocation. Salbutamol reversed the LAR by restoring FEV1, to a level similar to the initial value measured at the same time of day (18.00 h)on the previous evening. For the eight subjects studied, this initial FEV1 value, measured after abstaining from β‐agonists for 8 h, was a mean ±SEM 90.7 ± 5.6% of predicted, which suggests further bronchodilation may have been possible at this time. We then studied six of the eight subjects in an identical protocol with saline challenge substituted for allergen bronchoprovocation to answer the question whether further bronchodilation was possible at that time after salbutamol in the absence of an LAR. After salbutamol on the allergen challenge day the FEV1 for the six subjects was 84.1 ± 7.0% of predicted, compared with 94.0 ± 3.7% of predicted at the same point on the saline challenge day (p < 0.05).

We conclude that, although the LAR may be effectively reversed by β2‐agonists, there is evidence for some residual airway narrowing, presumably related lo mucosal oedema, exudate and mucus plugging.
Two‐dimensional immunoblot analysis of allergens of Cladosporium herbarum
Authors: ZHANG L. , CURRAN I. , MURADIA G. , RODE H. , VIJAY H. M.
Published: April 2006

In the present study, allergens of Cladosporium herbarum were analysed by SDS‐PAGE. two‐dimensional gel electrophoresis and immunoblot. The SDS‐PAGF under reduced conditions followed by western blotting analysis revealed 10 human IgE‐binding components with molecular masses ranging from 15 to 143 kDa. Within the same molecular mass range, five components were detected under non‐reduced conditions. Examination of the specificities of 10 individual sera revealed that two patients were sensitive to almost all the allergens, whereas the majority reacted with only some components. Two‐dimensional immunoblot was employed to further analyse the allergens in the extract. A silver‐stain of the two‐dimensional gel revealed that there were more than 30 different protein components visible in the extract, Immunoblot of the proteins separated under denatured conditions disclosed that 17 spots were reactive with human atopic sera.
In vitro basophil histamine‐releasing activity of circulating IgG1 and IgG4 autoanti‐IgE antibodies from asthma patients and the demonstration that anti‐IgE modulates allergen‐induced basophil activation
Authors: SHAKIB F. , SMITH S. J.
Published: April 2006

In this study we have examined the relationship between the in vitro basophil histamine‐releasing activity of human IgG anti‐IgE, isolated as euglobulin fractions from sera of asthmatic patients, and its IgG1/IgG4 subclass distribution. In particular, we have investigated whether IgG anti‐IgE modulates allergen‐induced basophil activation. The study has revealed that only a small proportion of IgG anti‐IgE samples triggered histamine release from basophils of an asthmatic individual (4/21; 19%), a hay fever sufferer (4/10; 40%) and a healthy person (7/21; 33%). The basophil histamine‐releasing activity of IgG anti‐IgE did not seem to be determined by the IgG1/IgG4 subclass composition of the IgG anti‐IgE preparation used. Furthermore, we have demonstrated that autoanti‐IgE antibodies modulate allergen‐induced basophil histamine release. The three modulatory effects exerted by IgG anti‐IgE antibodies on allergen‐triggered basophil activation (i.e. additive, synergistic and blocking) were not dependent on the subclass nature of IgG anti‐IgE or the use of histamine‐releasing anti‐IgE preparations. Our data suggest that IgG anti‐IgE antibodies in asthma patients may consist of two functionally distinct subpopulations: those which up‐regulate (pro‐allergic) and those which down‐regulate (anti‐allergic) the allergic release of mediators from mast cells and basophils.
Sensitization to storage mites in house dust mite (Dermatophagoides pteronyssinus) allergic patients. Comparison of a rural and an urban population
Authors: EBNER C. , FELDNER H. , EBNER H. , KRAFT D.
Published: April 2006

summary

In this study, sera collected from 50 patients (24 females, 26 males) with Type I allergy to house dust mite (Dermatophagoides pteronyssinus) were investigated for IgE antibodies specific for eight different mite species including storage mites of the families Pyroglyphidae, Glycyphagidae and Acaridae. According to their environment the patients were divided into two groups. Group I consisted of 24 (11 women, 13 men) farmers working and living in rural regions of Austria (Styria. Lower Austria), group II included 26 citizens of Vienna (13 women, 13 men). As expected, RAST investigations revealed a higher rate of sensitization to storage mites in the farmer group. Comparing the two patient groups, sensitization to Lepidoglyphus destructor and Tyrophagus putreus was markedly increased in the farmer group. However, the sensitizalion rate to storage miles was also considerably high in city dwellers. Elevated levels of IgE specific for Euroglyphus maynei were more frequently observed in the urban collective. RAST‐inhibition experiments suggest a partial crossreactivity between house dust mites and storage mites. In their living environment, patients with perennial Type I allergy are exposed to multiple different mite‐derived allergens in addition to the well‐known house dust mite allergens. These allergens lead to sensitization and are therefore of clinical importance.
Nasal challenge shows pathogenetic relevance of specific IgE serum antibodies for nasal symptoms caused by hexahydrophthalic anhydride
Authors: NIELSEN J. , WELINDER . , OTTOSSON H. , BENSRYD I. , VENGE P. , SKERFVING S.
Published: April 2006

Abstract. Hexahydrophthalic anhydride (HHPA) is a component of some epoxy resin systems, A high fraction of HHPA‐exposed workers display nasal symptoms, and some of them have specific serum antibodies. To test the pathogenetic relevance of the antibodies, nasal challenge tests were performed with a conjugate of HHPA and human serum albumin (HSA) at three increasing concentrations. Eleven subjects, who were IgE‐sensitized against HHPA (positive in RAST and in skin‐prick test against the HHPA‐HSA conjugate), and who reported work‐related nasal symptoms, had a significant increase of nasal symptoms and a decrease of nasal inspiratory peak flow after the challenges. The symptoms were associated with specific serum IgE, but with IgG. Further, significant increases were found in eosinophil and neutrophil counts, and in levels of tryptase, and albumin, whereas no clear rise was recorded for eosinophil cationic protein in nasal lavage fluid. Nine subjects, who were not sensitized, but who complained of work‐related nasal symptoms, and 11 subjects, who were not sensitized and had no symptoms, displayed no significant change in any of these parameters. It is concluded that the symptoms in some of the workers were caused by an IgE‐mediated mast cell degranulation. followed by an inflammatory reaction, engaging eosinophil and neutrophil cells.
Isolation and denomination of an important allergen in baking additives: α‐amylase from Aspergillus oryzae (Asp o II)
Authors: BAUR X. , CHEN Z. , SANDER I.
Published: April 2006

Abstract. The commercially available α‐amylase from Aspergillus oryzae which is widely used as a baking additive was compared with a highly purified enzyme preparation. We used enzyme allergosorbent test (EAST), EAST inhibition, sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), isoelectric focussing, immunoblotting, and N‐terminal amino acid sequencing to characterize the causative allergen. Our screening comprised 89 partially selected bakers. Forty‐three (48%) of them had work‐related respiratory symptoms; 14 (32%) of whom were sensitized to the baking additive. Significant immunological differences could not be found between crude and purified sample with the exception that the latter one produced nearly twice as high antibody values. Iodine starch staining demonstrated that the component which was exclusively or predominantly bound by IgE antibodies of symptomatic bakers represents the active α‐amylase. According to the International Union of Immunological Societies (IUIS) nomenclature, the term Asp o II is suggested for this important occupational allergen.
Incidence and risk factors for latent sensitization to chymopapain: predictive skin‐prick tests in 700 candidates for chemonucleolysis
Authors: MONERET‐VAUTRIN D. A. , FELDMANN L. , KANNY G. , BAUMANN A. , ROLAND J. , PERE P.
Published: April 2006

Abstract. Seven hundred patients were investigated prospectively before undergoing chemonucleolysis. A past history of allergy and/or previous exposure to papain, either in food, beverages or drugs, was sought, and a skin‐prick test with chymopapain was performed. Based on the results obtained, the subjects were classified into four groups: Group I– 225 non‐atopic non‐papain‐exposed subjects; Group II–285 non‐atopic papain‐exposed subjects; Group III–69 atopic non‐papain‐exposed subjects; and Group IV– 121 atopic papain‐exposed subjects. Latent sensitization to papain was observed in 0.4% of subjects in Group I, 3.16% in Group II, 5.8% in Group III and 7.4% in Group IV. The odds ratios were 13.8 for atopy and 7.3 for exposure to papain. Interaction between atopy and papain exposure did not result in a significantly greater risk. Neither sex nor age nor a history of a previous drug reaction were risk factors. Only one patient out of the 23 who were sensitive to papain had no risk factor. The 677 skin‐test negative patients then underwent chemonucleolysis and none of them had an anaphylactic reaction. This was significantly less frequent: (P= 0‐04) than the incidence in a random population (0.45%). Prick tests performed 6 weeks and 6 months after chemonucleolysis revealed newly acquired sensitization in 36% of the patients. Atopy was not a risk factor for this event. Three points are discussed: (i) the negative predictive value of skin‐prick tests with chymopapain is confirmed; (ii) subjects likely to be sensitized are atopic and/or have been exposed previously to food or drugs containing papain and therefore they can be identified pre‐operatively by a questionnaire; (iii) atopy is a risk factor for the induction of specific IgE to allergens internalized via a mucosal surface but not for those that are injected parenterally.
Occupational asthma caused by two herb materials, Dioscorea batatas and Pinellia ternata
Authors: PARK H. S. , KIM M. J. , MOON H.‐B.
Published: April 2006

Abstract. There have been very few cases of occupational allergies caused by herb materials. In this paper, we report a case of occupational asthma and rhinitis caused by two herb materials. Dioscorea batatas and Pinellia ternata which are known as Sanyak and Banha respectively. The patient had strong positive responses to grass pollens and cat fur, as well as to Sanyak and Banha extracts on skin‐prick tests. Bronchoprovocation tests showed a dual asthmatic response to Sanyak whereas only an early asthmatic response to Banha. Serum specific IgE and IgG4 antibodies to Sanyak were detected by enzyme‐linked immunosorbent assay (ELISA) but there was no specific IgE antibody binding to Banha. In order to further characterize the allergenie component of these extracts, sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and electroblotting studies were also performed. Three IgE binding components (29000, 57000, 63000 Da) were detected within the Sanyak extracts, but no IgE‐binding component was noted within the Banha extracts. It is suggested that Sanyak can induce IgE‐mediated bronchoconstriction in an exposed worker. Further studies are needed to investigate the pathogenetic mechanism triggered by Banha.
Allergenic characterization of Acarus siro and Tyrophagus putrescentiae and their crossreactivity with Lepidoglyphus destructor and Dermatophagoides pteronyssinus
Authors: JOHANSSON E. , JOHANSSON S. G. O. , van HAGE‐HAMSTEN M.
Published: April 2006

Allergenic components in extracts of Acarus siro and Tyrophagus putrescentiae were identified by sodium dodecyl sulphate‐polyacrylamide (SDS‐PAGE) and immuno‐blotting. Five and four allergenic components, respectively, were visualized with sera from farmers sensitized to storage mites. The highest frequency of IgE‐binding was to a 15kDa component of A. siro (7/9 sera) and a 16kDa component of T. putrescentiae (23/29 sera). The allergenic crossreactivity of A. siro and T. putrescentiae with Lepidoglyphus destructor and Dermatophagoides pteronyssinus was studied with an immunoblotting inhibition technique. Crossreactivity between D. pteronyssinus on the one hand and A. siro and T. putrescentiae on the other, was shown, as the IgE reactivity to a 25 kDa component of D. ptertonyssinus was inhibited to the same degree by extracts of A. siro, T. putrescentiae and D. pteronyssinus. However, D. pteronyssinus was a poor inhibitor of the allergenic components of A. siro and T. putrescentiae. Strong cross‐reactivity was also shown between L. destructor and the allergenic components of A. siro and T. putrescentiae, while the latter mite species only to a very low degree inhibited the allergenic components of L. destructor.
Non‐invasive assessment of bronchial inflammation in asthma: no correlation between eosinophilia of induced sputum and bronchial responsiveness to inhaled hypertonic saline
Authors: IREDALE M. J. , WANKLYN S. A. R. , PHILLIPS I. P. , KRAUSZ T. , IND P. W.
Published: April 2006

Bronchial inflammation in mild asthma has been investigated using bronchoscopical techniques. The safety of bronchoscopy in patients with more severe asthma has been questioned. We have used the non‐invasive technique of hypertonic saline (HS) inhalation to induce sputum samples for cellular analysis whilst simultaneously yielding a measure of bronchial responsiveness. Ten normal subjects and a heterogenous group of 24 asthmatic patients (range % predicted FEV1 43.3‐111.5) underwent HS challenge. Sputum samples induced were analysed. Total and differential cell counts between the two groups were compared. The association between bronchial responsiveness to HS and sputum cell counts was examined in the asthma group. Mean maximum fall in FEV1 for normal subjects was 4.0 (2.1‐5.9, 95%CI)% after saline. Geometric mean PD20HS for asthma patients was 7.7 (range 0.68‐40.92) ml. Adequate sputum samples were obtained from 9/10 normals and 23/24 asthmatic patients. Sputum from normal subjects contained a median of 3.8 (2.8‐8.1, interquartile range)% eosinophils compared with 17.6 (8.9‐34.1)% in sputum from asthma patients (P < 0.001). Sputum from asthma patients contained fewer of all other cell types compared with normals, with the difference in macrophages reaching significance. There was no correlation between PD20HS and cell count for any cell type in asthma subjects. Analysis of induced sputum represents a simple, safe, non‐invasive and well‐tolerated method of assessment of bronchial inflammation, suitable for use in patients with a range of asthma severity. There was no relationship between inflammation, as assessed by sputum cell counts and a measure of ‘Indirect’ bronchial responsiveness.
In vitro and in vivo effect of glucocorticoids on IgE and IgG subclass secretion
Authors: KLEBL F.H. , WEBER G. , KALDEN J. R. , NÜSSLEIN H. G.
Published: April 2006

Hydrocortisone (HC) as well as its synthetic derivatives have been shown to strongly enhance interleukin‐4 (IL‐4)‐induced in vitro IgE synthesis. To investigate possible effects on IgG subclasses, peripheral blood mononuclear cells (PBMC) were incubated with different glucocorticosteroids in the absence or presence of IL‐4. The glucocorticoids alone led to a strongly enhanced secretion of IgG 1, IgG2 and IgG3, but not IgG4. The addition of IL‐4 induced marked increases in IgG1 and IgG4, no changes in IgG3, but a consistent decrease in IgG2 synthesis. In order to find out whether these profound in vitro effects of corticosteroids are also reflected by changes in antibody serum levels during steroid treatment, 10 healthy volunteers took 25 mg prednisone for 7 consecutive days. We could not observe any significant changes of IgE or IgG subclass serum levels during or after this period. However, cell cultures performed after the glucocorticoid treatment revealed a marked decrease in the ability to produce IgG4 and a significantly lower potential to produce IgE in response to IL‐4 alone or IL‐4 and HC. We conclude that, although strongly implicated by the in vitro results, glucocorticosteroid treatment does not result in an increased allergy risk.
House dust mite allergen (Der p I) and respiratory symptoms in children: a case‐control study
Authors: VERHOEFF A. P. , VAN STRIEN R. T. , VAN WIJNEN J. H. , BRUNEKREEF B.
Published: April 2006

The association between house dust mite allergen in house dust and childhood respiratory symptoms was investigated in a case‐control study of 259 children with reported chronic respiratory symptoms and 257 control children without reported respiratory symptoms. The Der p I concentration in floor dust of the living room and bedroom and in mattress dust was determined using an enzyme immunoassay. Venous blood samples were taken from all children for serum IgE determination against house dust mite (Dermatophagoides pteronyssinus) by radioallergosorbent assay (RAST). A questionnaire was administered to the parents of the children to elicit information about the home, about changes made to the home in the past in relation to respiratory symptoms, and about a number of risk factors for childhood respiratory disease. In 83% of the dwellings of cases and 89% of those of controls, Der p I concentrations higher than 2000 ng/g were found, and in 54% of the dwellings of cases and 57% of those of controls, the concentrations exceeded 10 000 ng/g dust. In a crude analysis, cases were generally exposed to lower Der p I concentrations than controls. Restriction of the analysis to cases sensitized to dust mites, and non‐sensitized controls, taking the type of floor covering into account, showed not significantly higher Der p I concentrations in bedroom floor dust of cases. However, restriction of the analysis to cases sensitizied to dust mites and cases not sensitized to house dust mites — adjusting for allergen avoidance measures taken in the past — revealed a positive association between the Der p I concentrations in bedroom floor dust and mattress dust and sensitization. This finding indicates that allergen avoidance measures modify current exposure to Der p I. This obscures the relationship between the exposure to mite allergens and sensitization, and hampers the estimation of the association between exposure to house dust mite allergens, sensitization and the development of respiratory symptoms.
Total serum IgE and FEV1 by respiratory symptoms and obstructive lung disease in adults of a Norwegian community
Authors: OMENAAS E. , BAKKE P. , EIDE G. E. , ELSAYED S. , GULSVIK A.
Published: April 2006

Background: The importance of total serum IgE level on lung function impairment has not been established in a general population.

Objective: The aim of this cross‐sectional community study was to examine the relationship between total serum IgE and level of lung function in adults, and whether this relationship differed by sex, age, smoking habits or by respiratory symptom and disease status.

Methods: A stratified random sample of 18–73 year old adults from the general population were invited to spirometry and serum analyses of total and specific IgE. Of 1512 subjects invited, 82% met and performed complete examinations.

Results: Increasing level of total serum IgE was related to reduced lung function (P<0.01) given as sex, age, and height standardized residuals of one second forced expiratory volume (SFEV1). Subjects with total serum IgE in the highest vs the lowest tertile had a mean SFEV1 of ‐0.58 vs ‐0.28, corresponding to age and height adjusted FEV1 differences of 120 and 150mL in women and men, respectively. The relationship between IgE and lung function impairment did not differ significantly by sex, age or smoking habits. In subjects with obstructive’lung disease increasing level of total serum IgE was more negatively associated with lung function level than in subjects with respiratory symptoms alone. No relationship was observed in a symptomatic subjects. This was confirmed in a multiple linear regression analysis adjusting for sex, age, smoking habits and lifetime smoking consumption showing that SFEV1 was predicted by an interaction between total serum IgE level and symptom and disease status (P < 0.01). This interaction remained after excluding subjects (n= 105) having specific IgE antibodies.

Conclusion: Increasing total serum IgE level was associated with progressively lower lung function in a general adult population after taking other predictors of impaired Spiro metric lung function into account, though dependent on the subjects’respiratory symptom and disease status. Variation in prevalences of respiratory symptoms and obstructive lung disease in previous examined populations may thus explain conflicting observations of the association between total IgE and airflow impairment.
The differential release of eosinophil granule proteins. Studies on patients with acute bacterial and viral infections
Authors: KARAWAJCZYK M. , PAUKSEN K. , PETERSON C. G. B. , EKLUND E. , VENGE P.
Published: April 2006

Background: Harlier in vitro studies have suggested that the eosinophil may release its granule proteins selectively depending on the stimulus to which the cell is exposed.

Objective: The object of the present study was to study the question of selective release in vivo by means of serum measurements of the two eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) in acute infections.

Methods: Fourty‐six subjects with acute infections were studied before treatment, 20 with bacterial infections and 26 with viral infections. Serum ECP, EPO and MPO were measured by specific RIA.

Results: In acute bacterial infections ECP, but not EPO. was significantly raised in serum (P < 0.0001) compared with non‐infected healthy subjects. In acute bacterial infections ECP was significantly correlated to the levels of the neutrophil marker myeloperoxidase (MPO) (rs= 0.96, P < 0.0001) but not to EPO. In acute viral infections neither ECP nor EPO were on average raised. However, almost 20% the patients had elevated levels of both proteins. In the viral infections the serum‐levels of ECP and EPO were correlated (rs= 0.63, P < 0.001), but no correlation was found with MPO

Conclusion: It is concluded that eosinophils are activated during acute bacterial infections and that this activation results in the preferential mobilisation of ECP. The simultaneous assay of the two eosinophil proteins, ECP and EPO. may give new insight into the role of the eosinophil in disease.
A placebo‐controlled study of fluticasone propionate aqueous nasal spray and beclomethasone dipropionate in perennial rhinitis: efficacy in allergic and non‐allergic perennial rhinitis
Authors: SCADDING G. K. , LUND V. J. , JACQUES L. A. , RICHARDS D. H.
Published: April 2006

Background: Fluticasone propionate is a new potent, topically active corticosteroid with ncgligahle oral bioavailability. Data on its comparative efficacy in perennial allergic and non‐allergic rhinitis are limited.

Objective: To compare the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200μg once or twice daily with beclomethasone dipropionate aqueous nasal spray (BDP) 200μg twice daily and placebo in patients with allergic and nonallergic perennial rhinitis.

Methods: The 12‐week study had a multicenlre, double‐blind, randomized, parallel group design. Efficacy was assessed from symptom scores recorded on daily diary cards.

Results: FPANS 200μg once or twice daily was significantly better than placebo but not better than BDP in relieving the nasal symptoms of rhinitis. FPANS at either dose was equally effective in the treatment of allergic and non‐allergic perennial rhinitis. There were few adverse events and no treatment‐related abnormalities in laboratory measurements in either FPANS‐treated group. Comparisons between treatment groups indicated that FPANS was as well tolerated as placebo and BDP at the doses studied.

Conclusions: In the majority of patients FPANS 200μg once daily is as effective as BDP 200μg twice daily in the relief of perennial allergic rhinitis.
Clonal analysis of CD4 mediated accessory function on the effector activity of human CD4+ T cell subsets
Authors: LAMB J. R. , FAITH A. , HIGGINS J. A. , VERHOEF A. , SCHNEIDER P. , YSSEL H. , O'HEHIR R. E.
Published: April 2006

Background: It has been reported for the peripheral T cell repertoire that CD4 molecules may enhance adhesion between T cells and antigen presenting cells and, through their physical association with T cell antigen receptors, contribute to signal transduction.

Objective: The aims of this study were to determine if the modulation of CD4 molecules had differential effects on T cell recognition, antigen induced cytokine (IL‐4 and IFNγ), release and the induction of specific anergy for human TH‐0, TH‐1 and TH‐2 cells.

Methods: A panel of anti‐CD4 antibodies was examined for its ability to modulate T cell proliferation, cytokine production and tolerance induction in house dust mite (TH‐0 and TH‐2) and influenza haemagglutinin (TH‐1) specific human CD4+ T cell clones all restricted by DRB1*1101 and isolated from dust mite allergic individuals.

Results: We observed that anti‐CD4 antibodies may inhibit or enhance antigen mediated T cell proliferation, which may reflect the differential requirements of T cells for selective functions of CD4. Furthermore, IFNγ and IL‐4 production was differentially modulated depending on the specificity of the anti‐CD4 antibody and the clone of T cells. However, pretreatment of T cells with anti‐CD4 antibody alone neither induced nor enhanced the susceptibility of T cells to peptide mediated anergy.

Conclusion: Antigen recognition by different subsets of human CD4+ T cells has differential requirements on CD4, whereas the induction of specific anergy appeared to be independent of the functions of CD4 molecules. Antigen induced IFNγ production was more susceptible than IL‐4 to the inhibitory effects of anti‐CD4 antibodies. Furthermore, it appeared that certain anti‐CD4 antibodies can dissociate antigen induced IFNγ and IL‐4 production, and may downregulate IFNγ synthesis without inhibiting antigen dependent proliferation.
Cloning, sequencing and expression in Escherichia coli of Pha a 1 and four isoforms of Pha a 5, the major allergens of canary grass pollen
Authors: SUPHIOGLU C. , SINGH M. B.
Published: April 2006

Background: The pollen of canary grass, which was introduced as a pasture grass from Europe, is a major allergen source in the external environment of southern Australia. This study was performed to characterize the major recombinant allergens of canary grass pollen. It is anticipated that recombinant allergens may be useful in diagnosis and immunotherapy of grass pollen induced allergies.

Objective: To clone major canary grass pollen allergens and assess their nucleotide and amino acid sequence homologies with other grass pollen allergens. This sequence information may then be useful in T and B cell epitope mapping studies.

Methods: A canary grass pollen λgtl 1 cDNA expression library was constructed and screened with sera of grass‐pollen‐sensitive patients. IgE‐reactive clones were isolated, sub‐cloned into Escherichia coli, sequenced and, along with the deduced amino acid sequences, compared with other sequences in nucleotide and amino acid databases.

Results: One of the clones encoded the group 1 allergen of canary grass pollen, Pha a 1, with a deduced amino acid sequence identity of 88.8% with Lol p 1, from rye‐grass pollen, 88.1% with Hol 1 1, from velvet grass pollen and 86.6% with Phi p 1, from timothy grass pollen. The other clones (e.g. clones, 5, 14, 28, 29) encoded polymorphic forms of Pha a 5. These polymorphic forms showed between 60.6–95.5% nucleotide and 40.1–81.7% deduced amino acid sequence identities with each other. Moreover, they shared significant sequence identity with other group 5 allergens from rye‐grass, timothy and Kentucky bluegrass pollens.

Conclusions: Group 1 and four isoforms of group 5 allergens of canary grass pollen have been cloned and upon sequencing demonstrated strong nucleotide and amino acid sequence identities with other group 1 and 5 grass pollen allergens.
Effects of PBMC‐derived histamine‐releasing factors on histamine release from human skin and lung mast cells
Authors: OKAYAMA Y. , BRZEZIŃSKA‐BŁASZCZYK E. , KUNA P. , KAPLAN A. P. , CHURCH M. K.
Published: April 2006

Background: A field of study which has attracted much recent interest is the ability of mononuclear cells and neutrophils to interact with hislamine releasing cells by production of specific histamine releasing factors (HRFs). However, almost all of these studies have been performed on basophils rather than human mast ceils.

Objective: We have investigated the effects of lyophilized fractions of HRF preparations on histamine release from human skin and lung mast cells.

Methods: Lyophilized fractions of HRF preparations include crude supernatant from mononuclear cell/platelet (crude), void peak from union exchange chromatography column (void), second peak from anion exchange chromatography (peak 2), neutrophil‐activating peptide‐2 (NAP‐2), which was purified from void peak at molecular weight of 8‐12 kDa, and monocyte chemotactic‐activating factor (MCAF). Mast cells were enzymatically dispersal.

Results: Crude (24.2μg/mL‐2.42mg/mL), void (5.4μg/mL‐0.54mg/mL). peak 2 (3.5μg/mL‐0.35mg/tnL), and NAP‐2 (1‐20μg/mL) failed to release hislamine from lung mast cells. In skin mast cells, only higher concentrations of crude and void caused minimal release of histamine. MCAF up to micromolar concentrations failed to have an effect on mast cells from either source, However, these HRFs induced histamine release from human basophils. We also explored whether HRFs and stem cell factor could act as either priming agents for each other or for anti‐IgE. The response of skin mast cells to all these preparations was not enhanced by preincubation in stem cell factor at 1 ng/mL. nor did the HRFs and MCAF enhance the response of skin mast cells to anti‐IgE.

Conclusion: These results suggest that these HRFs have no significant effect on dispersed human cutaneous and lung mast cells.
Evaluation of the allergic/irritant potential of air pollutants: detection of proteins modified by volatile organic compounds from oilseed rape (Brassica napus ssp. oleiferd) using electrospray ionization‐mass spectrometry
Authors: BUTCHER R. D. , GOODMAN B. A. , DEIGHTON N.
Published: April 2006

Background
Upward trends in allergy and asthma rates have been reported in most western societies, including the UK, where around 15–20% of the population now suffer from allergy or asthma. Scientific proof of the causes of these increases relics on accurate assessment of exposure and standardized diagnostic tests, such as for specific IgE in blood serum and skin testing. For many air pollutants it has proven difficult to assess an individual's exposure outside an occupational environment and reliable test development is hampered by not knowing whether an allergic or irritant mechanism is involved. These problems are particularly evident in the controversial issue of whether airborne releases from oilseed rape can cause health effects.

Objective
To develop a method for evaluating the allergic/irritant potential of air pollutants and to assess whether the volatile organic compounds emitted by oilseed rape have this potential.

Methods
Proteins were exposed in vitro to volatile organic compounds emitted by oilseed rape. Electrospray ionization‐mass spectrometry was used to detect any resultant protein modifications.

Results
Dimethyl disulphide. thiocyanic acid methyl ester and 2‐methyl‐propaneni‐trile were able to modify human proteins. In addition, two isothiocyanates which can be emitted by damaged oilseed rape also have this ability. The major products emitted by undamaged oilseed rape, terpenes, a sesquiterpene and a terpene alcohol did not have this property, but the possible role of their oxidized products is discussed

Conclusion
Some of the volatile organic compounds emitted by oilseed rape have the potential to be allergens irritants. Standardized modified proteins produced by this method should prove useful for biomonitoring human exposure in molecular epidemic‐logical studies as well as in diagnostic tests. This method should find further application in investigations into the possible health effects of other environmental pollutants.