bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphocyte activation by house dust allergen in asthma: analysis with monoclonal antibodies
Authors: KUS J.
Published: April 2006

Peripheral blood mononuclear cell (MNC) response to house dust (HD) stimulation in cultures was studied in a group of 35 subjects with asthma and a multiple positive skin test (ST) reaction to inhalant allergens including HD, and in 19 healthy controls. The MNC response to allergen stimulation was assessed by interleukin‐2 receptor (IL‐2R) expression identified with an anti‐Tac monoclonal antibody. Lymphocyte subpopulations of baseline and cultured cells were also analysed. The percentage of IL‐2R presenting cells increased significantly in HD‐driven cultures in the asthma group compared to controls. The increase in proportion of IL‐2R+ cells was closely related to the increase in CD4+ percentage of cultured cells and was accompanied by a decrease in proportion of CD8+ lymphocytes and monocytes/macrophages, suggesting that HD‐activated cells were CD4+ lymphocytes. Lymphocyte activation, measured by IL‐2R expression, was significantly higher in the group of asthmatics, and positive dual (early and late) skin reaction to HD, as compared to those with single early reaction.
On the use of absorbing discs to sample mucosal surface liquids
Authors: ERJEFÄLT INGRID , PERSSON C. G. A.
Published: April 2006

A common technique to sample airway mucosal ‘surface’ liquids is with absorbing discs of filter paper. The present study examined the efficacy of this technique by analysing tracheal liquids of control and capsaicin (0.1 nmol)‐exposed guinea‐pig airways. Mucosal fluids, obtained by topically applied discs or by a specific lavage procedure, and tracheal tissue were sampled. The animals had received FITC‐dextran (MW 70 kDa) intravenously and this specific plasma tracer was analysed in the sampled material. Under control conditions significantly more FITC‐dextran was found in the discs than in the tracheal lavage fluids (P < 0.001) despite the fact that the lavaged mucosal surface was much larger than that covered by the discs, Capsaicin significantly increased the content of FTTC‐dextran in all fluids sampled as well as in the airway tissue. In all cases concentrations of FITC‐dextran in the disc fluids did not differ much from that in the tissue samples. These data suggest that absorbing discs severely disturb the epithelial‐barrier function and sample subepithelial fluid and solutes including macromolecules. As demonstrated in this study by the elevated content of a plasma tracer molecule an inflammatory process may, nevertheless, be traced in the mixture of surface and tissue fluids that is sampled by the discs.
The‘nasal pool’device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions
Authors: GREIFF L. , PIPKORN U. , ALKNER U. , PERSSON C. G. A.
Published: April 2006

A‘nasal pool’(NP) device, a compressible plastic container with an adapted nozzle, was used to perform a continuous 10‐min nasal provocation and lavage. This novel technique brings known concentrations of agents into contact with a large and defined area of the nasal mucosal surface for extended periods of time. Simultaneously, the surface exudations/secretions of the same nasal mucosa are effectively sampled by the NP fluid. A concentration‐response study of histamine (80, 400 and 2000 μg/ml) was performed in 12 normal subjects on three different occasions. Exudation of plasma albumin into the lavage fluid was measured to quantitate the histamine‐induced airway inflammation. The effect of the dwell time on exudation was examined using histamine (400 μg/ml) instilled in the nasal cavity for time periods from 10 sec to 10 min. The time course of histamine‐induced plasma exudation response was studied by exposing the mucosa to histamine (400 μg/ml) for 12 min, with the NP renewed every minute. Allergen‐provocations were performed in subjects with hay fever and TAME‐esterase activity in the returned lavage fluid was determined to indicate the degree of response. Histamine produced a concentration‐dependent increase in albumin levels in the NP fluid; 123·3 ± 25·6, 213·8 ± 19·7 and 430·2 ± 32·0 μg/ml (mean ± s.e.m.), respectively. The time‐course study demonstrated that plasma exudation into the lumen occurred promptly and that the exudation response reached a maximum after exposure to histamine for 6–10 min. The dwell‐time experiments supported this finding. After 10 min the exudation appeared to decline despite the continued presence of histamine. Allergen provocation resulted in a concentration‐dependent increase in TAME‐esterase activity of the NP‐fluids. It is concluded that the NP technique provides new possibilities in studies of pathophysiology and pharmacology of human airway mucosa. With the NP technique controlled concentrations of mediators, drugs, tracers, etc. can be applied for desirable lengths of time on a well‐defined mucosal surface area. This particular area is gently and effectively lavaged during the presence of the NP fluid and when the fluid is recovered by decompressing the NP device.
Evidence of grass‐pollen allergenic activity in the smaller micronic atmospheric aerosol fraction
Authors: SPIEKSMA F. Th. M. , KRAMPS J. A. , VAN DER LINDEN A. C. , NIKKELS BEP H. , PLOMP A. , KOERTEN H. K. , DIJKMAN J. H.
Published: April 2006

In June 1988, during the grass‐pollen season in Leiden, The Netherlands, outdoor airborne paniculate matter was collected and separated into fractions according to aerodynamic sizes ( 10μm, 4·9–10μm, 2·7–4·9μm, 1·3–2·7μm, 0·6–1·3μm, 0·6μm), with a cascade impactor mounted on top of a high volume sampler. The different fractions were tested for the presence of grass‐pollen allergenic activity using a RAST‐inhibition assay: specific IgE‐antibody‐containing patient serum was applied on the particle‐loaded impaction strips, and the serum was recovered by descending elution for further analysis in the RAST. Simultaneously, continuous measurements were made of the airborne grass‐pollen concentration using a volumetric pollen trap. Sampling observations lasting 7–9 hr during a period with relatively high airborne grass‐pollen concentrations showed reliably detectable amounts of grass‐pollen allergen, not only in the first impaction stage where intact pollen were collected, but also in the lower stages collecting the smaller, paucimicronic and submicron atmospheric aerosol fraction. It is evident that this result has serious implications for the understanding of the bronchial symptoms frequently seen in hay fever patients on days with high pollen concentrations in the air.
Natural anti‐IgE auto‐antibodies interfere with diagnostic IgE determination
Authors: VASSELLA CLAUDIA C. , DE WECK A. L. , STADLER B. M.
Published: April 2006

A simple method is described which enables measurement of anti‐IgE antibodies in free form as well as in immune complexes of IgE and anti‐IgE. Anti‐IgE antibodies were purified from serum of one selected blood donor with highly elevated levels of such auto‐antibodies. These purified anti‐IgE auto‐antibodies inhibited the measurement of myeloma IgE. Purification also revealed that 98% of the subject's serum IgE was masked by anti‐IgE auto‐antibodies. Our data suggest that IgE determinations in sera containing anti‐IgE antibodies might be underestimated.
Salicylate pre‐treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin‐intolerant patients
Authors: NIZANKOWSKA E. , DWORSKI R. , SOJA J. , SZCZEKLIK A.
Published: April 2006

Aspirin (ASA) and other non‐steroidal anti‐inflammatory drugs, which are cyclo‐oxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA‐intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. However, salicylate moiety appears to interfere with aspirin inhibitory action on platelets and vascular COX. Such interaction, if present at the level of respiratory tract, may be of interest to pathogenesis of ASA‐induced asthma.

We performed a double‐blind, placebo‐controlled, randomized cross‐over study on the effect of choline magnesium trisalicylate (CMT, trilisate) pre‐treatment on ASA‐induced adverse reactions in nine patients. Pulmonary function tests, nasal symptoms score, PNIF and serum salicylate levels were monitored following challenges with threshold doses of ASA. Trilisate administered at a dose of 3000 mg daily for 3 days, offered a moderate protection against ASA‐induced symptoms; it diminished the severity and/or delayed the appearance of FEV1 fall. Maximal decreases in FEV1 as well as reaction intensity indexes were significantly lower (P < 0·02 and P < 0·002, respectively) after trilisate pre‐treatment as compared to placebo. Trilisate also attenuated nasal symptoms in three out of five patients. Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo‐oxygenase locus in the respiratory tract in ASA‐intolerant patients.
The inflammatory response in asthma exacerbation: changes in circulating eosinophils, basophils and their progenitors
Authors: GIBSON P. G. , DOLOVICH J. , GIRGIS‐GABARDO A. , MORRIS M. M. , ANDERSON M. , HARGREAVE F. E. , DENBURG J. A.
Published: April 2006

Circulating eosinophils, basophils and eosinophil/basophil (Eo/B) progenitors were examined in 12 patients at the time of an exacerbation of asthma accompanied by sputum eosinophilia and after resolution of the exacerbation with inhaled corticosteroid treatment. Differential counts were performed and peripheral blood non‐adherent mononuclear cells were cultured for 14 days in methyl‐cellulose to determine the number of Eo/B and granulocyte‐macrophage (GM) colonies without knowledge of the clinical conditions or findings. With resolution of the asthma exacerbation on beclomethasone therapy, there were significant falls in circulating eosinophils, basophils and Eo/B colonies whereas GM colonies were unchanged. To elucidate whether the observed changes could be due to systemic absorption or local action of inhaled corticosteroid, seven subjects with allergic rhinitis and no current evidence of lower airway inflammation (no symptoms of asthma and normal methacholine airway responsiveness) received 14 days' treatment with the same dose of inhaled beclomethasone or of placebo in a double‐blind randomized cross‐over study. No significant changes in airway function or in circulating cell counts were observed. The results suggest reduced production of eosinophils and basophils after the resolution of an exacerbation of asthma. This effect may be due to reduced levels of airway‐derived eosinophil‐basophil growth and differentiation factors.
Respiratory and immunological reactions among Shiitake (Lentinus edodes) mushroom workers
Authors: SASTRE J. , IBANEZ M. D. , LOPEZ M. , LEHRER S. B.
Published: April 2006

Four workers, the total work force employed at a Shiitake farm, developed cough and sputum production following a variable period of exposure to Shiitake mushrooms. All four had abnormal diffusing capacity and three had abnormal spirometry values. Chest roentgenograms demonstrated an interstitial pattern in one worker. Pulmonary function tests performed before and during several days of work demonstrated a significant decrease (> 20%) in forced vital capacity (FVC) and/or maximal midexpiratory flow (MMEF) in three workers. Although specific antibodies to an extract of Shiitake spores were detected in sera from three workers none were IgE. High levels of Shiitake spores were detected in growing rooms (> 106/m3) as well as other locations at the farm. Shiitake spore airborne antigen, detected by an immunochemical assay, was present in dust collected with a volumetric sampler from different locations at the farm. Antigenic determinants of Shiitake spore antigens, in common with antigens from other cultivated mushrooms (Agaricus and Pleurotus) were demonstrated by ELISA inhibition assay. This study demonstrates that workers exposed to high levels of Shiitake spores develop symptoms and laboratory findings suggestive of hypersensitivity pneumonitis (HP). Strict environmental control and the wearing of a face mask is probably needed to reduce the high risk of sensitization and possible development of immunological lung disease. Shiitake spores must be considered as an aetiological agent of mushroom workers' lung.
The spectrum of low molecular weight house dust mite (Dermatophagoides pteronyssinus) allergens with emphasis on Der p II
Authors: FORD S. A. , TOVEY E. R. , BALDO B. A.
Published: April 2006

Analysis by protein blotting of sera from 96 different house dust mite‐allergic subjects revealed previously unrecognized complexity of low molecular weight (MW) (< 20 kD) IgE‐binding proteins in extracts of whole bodies of Dermatophagoides pteronyssinus. Of 11 different IgE‐binding components of MW < 20 kD identified, two (MW ∼ 16 kD and ∼ 15 kD), showed both a high frequency (88% and 49% respectively) and a high intensity of IgE‐binding. The ∼ 16 kD component, identified as allergen Der p II, showed the highest frequency of IgE antibody reactivity of any of the major D. pteronyssinus allergens including Der p I and Der p III.
Prophylactic treatment of grass pollen‐induced asthma with cetirizine
Authors: DIJKMAN J. H. , HEKKING P. R. M. , MOLKENBOER J. F. , NIEROP G. , VANDERSCHUEREN R. , BERNHEIM J. , VAN GANSE E. H.
Published: April 2006

In a double‐blind randomized parallel‐group study, six investigators enrolled 43 subjects to study the prophylactic effect of 10 mg cetirizine b.i.d. on grass pollen‐induced asthma. The control group received 60 mg b.i.d. terfenadine, given to avoid withdrawals from the trial because of hay fever symptoms. Subjects were included in the study between the appearance of the first symptoms of hay fever and those of pollen‐induced asthma. The hay fever and asthma symptoms, visual analogue scores (VAS), FEV1 and self‐assessment data on complaints, salvage treatment and peak‐flow values were statistically analysed. Both treatments were well tolerated, with a low and similar incidence of side‐effects. During the last 3 weeks of treatment, six (32%) of the 19 subjects on cetirizine who were evaluable for efficacy remained free of asthma complaints, and another two (10%) had only a single minor attack. None had a grade 3 (incapacitating) attack. Conversely, only one (5%) of the 20 evaluable subjects on terfenadine remained complaint free, and all others (95%) had multiple attacks, which incapacitated three (15%) of them. Nasal obstruction, dyspnoea, morning peak flow, consumption of β2‐mimetics and an efficacy index on asthma, combining complaints and rescue drug consumption, were significantly better on cetirizine (P < 0·05). It is concluded that cetirizine is able to prevent the exacerbation of asthma induced by grass pollen.
Sequence analysis of cDNA coding for a major house dust mite allergen, Der f I
Authors: DILWORTH R. J. , CHUA K. Y. , THOMAS W. R.
Published: April 2006

A cDNA clone‐coding for Der f I, a major allergen from the house dust mite Dermatophagoides farinae has been isolated and sequenced. It codes for a putative 18‐residue signal peptide, an 80‐residue proenzyme region, and a 223‐residue mature protein with a derived molecular weight of 25 191. The deduced amino‐acid sequence shows significant homology to other cysteine proteases in the proregion as well as in the mature protein. Sequence alignment of the mature Der f I protein with the homologous allergen Der p I from the related mite D. pteronyssinus revealed a high degree of homology (81%) between the two proteins, as predicted by previous sequencing at the protein level. In particular, the residues comprising the active site of these enzymes and the cysteine residues were conserved. A potential N‐glycosylation site was present at an equivalent position in both mite allergens. It is anticipated that the availability of recombinant Derf I will facilitate epitope mapping studies and studies of T‐cell function in mite allergy by providing high levels of pure allergen.
The heterogeneity of human IgE exemplified by the passive transfer of D2O sensitivity
Authors: MACDONALD SUSAN M. , WHITE JANE M. , KAGEY‐SOBOTKA ANNE , MACGLASHAN D. W. , LICHTENSTEIN L. M.
Published: April 2006

Basophil responsiveness to histamine‐releasing factors (HRF) is limited to cells from atopic donors; this response can be transferred passively to non‐reactive hasophits by IgE molecules from the sera of donors who are intrinsically responsive to HRF [1], Deuterium oxide (D2O) also causes mediator release from the basophils of atopic asthmatic subjects [2]. To assess whether basophil responsiveness is IgE dependent, and, if so, whether this release revealed IgE heterogeneity, we tested the ability of sera from HRF responders (IgE+) and non‐responders (IgE ‐) to sensitize basophils to D2O. Both purified IgE + and unpurified sera from an HRF responder were passively used to sensitize basophils whose IgE had been removed by lactic acid treatment. As a control, an IgE‐ myeloma‐containing serum was used for passive sensitization. In five experiments, histamine release in the presence of 44% D2O was 9 ± 2% and 46 ± 4% using control IgE‐ and lgE+ sensitized cells, respectively. The non‐responder serum, even at higher IgE levels, did not sensitize the cells for D2O release. If the IgE receptors on lactic‐acid treated cells were first exposed to serum from an IgE‐ donor, sensitization to DiO by IgE+ was blocked. The percentage histamine release to D2O was directly related to both the amount of IgE+ used for passive sensitization and the concentration of D2O used for release. These experiments further support the concept of IgE heterogeneity and suggest that the occupancy of IgE receptors on the basophil surface ‘activate’ the cell to make it more responsive to various stimuli.
Group V allergens in grass pollens. I. Purification and characterization of the group V allergen from Phleum pratense pollen, Phl p V
Authors: MATTHIESEN F. , LøWENSTEIN H.
Published: April 2006

An allergen from Phleum pratense (timothy) pollen. Phl p V, has been isolated by a combination of copper chelate affinity chromatography and ion exchange chromato‐graphy. Phl p V binds IgE from serum of grass‐sensitized donors as revealed in immunoelectrophoretic techniques and in SDS PAGE immunoblot, and luminescence immunoassay (LIA) inhibition experiments indicate that the allergen represents a significant part of the IgE binding capacity of the extract. In immunoelectrophoresis, Phl p V is revealed as a single precipitate. However, molecular weight studies show that Phl p V consists of at least two isoforms with similar immunochemical properties, but with different molecular size. After SDS‐PAGE treatment purified Phl p V is identified as two IgE‐binding components. Phl p Va and Phl p Vb, with molecular weights 33 and 29 kD. After HPLC gel filtration, Phl p Va and Phl p Vb are identified in the major 30‐kD eluate. After Sephadex G75 gel filtration of whole pollen extract, Phl p V is identified in fractions corresponding to molecular weights 47 and 25 kD. The 47‐kD fraction corresponds to Phl p Va/Phl p Vb as seen in SDS‐PAGE, while the 25‐kD component presumably corresponds to a degradation product present in whole pollen extract. The NH2‐terminal sequence of Phl p V, corresponding to approximately 10% of the molecule, has been determined. The sequence shows minor variations in some residues and contains besides many alanine residues also hydroxyproline; the sequence reveals no homologies to any known NH2 terminal sequence of other proteins. The ammo acid composition, revealing 26 mote % alanine and no cysteine, does not show any similarities to other known amino acid compositions of allergens. From the amino acid composition determination and an immunoelectrophoretic comparison. Phl p V is estimated to represent 6% (w/w) of the whole pollen extract.
Group V allergens in grass pollens. II. Investigation of group V allergens in pollens from 10 grasses
Authors: MATTHIESEN F. , LøWENSTEIN H.
Published: April 2006

In an earlier study an allergen from Phleum pratense (timothy) pollen. Phl p V. has been isolated and physicochemically characterized. In this study Phl p V and immunochemically simitar components from other grass pollens (group V allergens) have been investigated using immunoelectrophoretic techniques. To study the allergenic importance of the group V allergens, the allergenic compositions of 10 grass pollen extracts were investigated in crossed radioimmunoelectrophoresis (CRIE) using 20 sera from grass pollen‐allergic donors. Group V allergens were identified using monospecific rabbit antibodies raised against Phl p V, anti‐phl p V, which react with other group V allergens usually producing dense precipitates in immunoelectrophoresis. In this way group V allergens were identified in eight extracts, and when present the precipitate corresponding to the group V allergen was the dominant IgE binding precipitate. All identified group V allergens bound IgE in at least 17 of the 20 investigated sera. Monospecific rabbit antibodies raised against the group I allergen of Lolium perenne (rye grass), anit‐Lol p I. do not precipitate group V allergens, indicating that there are no immunochemical similarities between group I and group V allergens. In SDS‐PAGE anti‐Phl p V identifies IgE‐binding components with molecular weights between 26 and 33 kD. In contrast, anti‐Lol p I binds to components of slightly higher molecular weight. Apparently, the group V components are allergens that are physicochemically and immunochemically distinct from group I allergens.
Lack of dose‐response effect of terfenadine on resting bronchomotor tone in patients with asthma
Authors: PATEL K. R. , GHOSH S. K. , MATCHAM J.
Published: April 2006

Bronchodilatation data from three, four‐period cross‐over studies were combined to assess the effect of oral terfenadine 60, 120, 180 mg and placebo on the airways of 26 patients with atopic asthma. Mela‐analysis of these data showed that mean changes in FEY1 from pre‐dose to 4 hr were 11.4, 14.6 and 11.8% for the three doses of terfenadine, respectively, and −2.9% for placebo. There was a significant treatment effect (P= 0.0001) but no effect of dose. Terfenadine, a non‐sedating histamine H1‐receptor antagonist, caused bronchodilatation in a single dose. Whether this efTect is sustained with long‐term treatment requires further investigation.
Delayed generation of thrombin in clotting blood of atopic patients with hayfever and asthma
Authors: SZCZEKLIK A. , SCHMITZ‐SCHUMANN M. , KRZANOWSKI M. , SR C. VIRCHOW
Published: April 2006

There have been several reports on alterations of platelet function and raised plasma heparin levels in symptom‐free atopic subjects. Either of these can affect formation of thrombin in vivo. In 25 symptom‐free atopic patients and 32 healthy volunteers we studied the generation of thrombin in blood emerging from a standardized skin microvasculature injury, which also served to determine bleeding time. Generation of thrombin was delayed in atopies. They produced significantly less thrombin (P<0.01) during the early and central phase of haemostasis. The amount of thrombin generated was inversely correlated to bleeding time, which in atopies was on average 50 sec longer than in controls (P= 0.055). Two hours after ingestion of 500 mg aspirin, this difference increased up to 150 sec, although the individual responses varied markedly (P= 0.08), while the generation of thrombin became strongly depressed in both groups. The possible clinical relevance of the delayed formation of thrombin in atopy awaits further studies.
Exposure and sensitization to dust mite allergens among asthmatic children in Sao Paulo, Brazil
Authors: ARRUDA L. K. , RIZZO M. C. , CHAPMAN M. D. , FERNANDEZ‐CALDAS E. , BAGGTO D. , PLATTS‐MILLS T. A. E. , NASPITZ C. K.
Published: April 2006

A group of 20 mite allergic asthmatic children aged 6‐12 years old. living in Sao Paulo, Brazil, was studied regarding their degree of sensitization to house dust mites and exposure to mite allergens in their homes. In 18 out of 20 houses at least one dust sample was obtained which contained > 10 μg Der p I/g of dust. The highest levels of Dermatophagoides pteronyssinm allergens, Der p I and Group II, were measured in bedding samples (geometric mean 38.4 and 36.6 μg/g, respectively), followed by bedroom floor, TV room and kitchen. Mite allergen levels in Brazilian houses were as high as those reported to be associated with sensitization and acute attacks of asthma in other parts of the world. In keeping with previous reports that D. farinae is rarely found in Brazil, Der fl was undetectable or found in very low levels (<0.5 μg/g). Levels of cat allergen Pel d I of > 8 μg/g of dust were obtained only in 2 houses only. Cockroach allergen Bia g I was detected in five out of 20 houses. Levels of IgE antibodies to D. pteronyssinus were > 200 RAST U/ml in 19 out of 20 children (geometric mean 1588 RAST U/ml). IgE antibodies to cat, cockroach, A. fumigatus, ragweed and rye grass pollens were undetectable or <80 RAST U/ml. IgE antibodies to the mite Blomia tropicalix were also measured, and levels >200 RAST U/ml were observed in 13 out of 20 sera. Immunoabsorption studies demonstrated that the bulk of the IgE‐ antibody to B. tropicafis (64%) was to species‐specific allergens and that 36% were cross‐reactive with D. pteronyssinus. The implication of our results is that management of children with asthma in São Paulo should include skin testing for allergy to both Dermatophagoides and B. tropicalis as well as recommendations about environmental control of house dust mite exposure.
Relationships of haptoglobin level to FEV1, wheezing, bronchial hyper‐responsiveness and allergy
Authors: KAUFFMANN F. , FRETTE C. , ANNESI I. , ORYSZCZYN M.‐P. , DORE M.‐F. , NEUKIRCH F.
Published: April 2006

The relationships of haptoglobin level to respiratory and allergic parameters have been assessed in an epidemiological study conducted in a working population surveyed twice 5 years apart. At the first survey conducted in 892 working men, haptoglobin level was significantly related to FEV1 (r=−0·18; P < 0·001) and smoking habits. After adjustment for smoking, a history of wheezing was significantly related to lower haptoglobin level, A second survey conducted in 304 men of the original sample 5 years later confirmed that haptoglobin was related to FEV1 (r=−0·21; P < 0·001) and that wheezing was significantly related to hypohaptoglobinaemia (lower decile; P= 0·04). Men who exhibited bronchial hyper‐responsiveness to methacholine had haptoglobin levels 0·35 g/1 higher than those who did not (P= 0·01), Haptoglobin level was unrelated to IgE level and skin prick tests. These results support the hypothesis of the role of inflammation in both lower lung function and bronchial hyper‐responsiveness. They suggest that some heterogeneity exists within subjects with a history of wheezing.
Larval exoantigens from ascarid nematodes are potent inducers of histamine release from human blood basophils
Authors: NIELSEN B. WINDELBORG , LIND P. , HANSEN B. , NANSEN P. , SCHIØTZ P. O.
Published: April 2006

Histamine release (HR) from washed human blood cells after challenge with the excretory‐secretory antigens (ES) of the parasitic nematodes Toxocara canis and Ascaris suum was studied, employing a recently developed microfibre–based assay combined with hyperosmolar release media for maximal sensitivity.

Blood samples were obtained from 30 patients suspected of parasite infection and 11 healthy volunteers serving as controls. Specific antibodies of IgE, IgG1 and IgG4 subclasses were determined by ELISA.

Virtually no HR could be provoked by ES in the 11 controls. In contrast, HR was seen in 16 patients after challenge with T. canis ES and in II patients with A. suum ES. In the majority of these. HR was detectable after challenge with ES protein concentrations of less than 1 ng/ml. and the maximal HR obtained with ES was greater than that seen with optimal concentrations of anti‐IgE.

The HR after ES antigen challenge correla ed with the amount of specific IgE in patient plasma, and coincided with the presence of specific IgGi and IgG4.
Factors confounding genetic linkage between atopy and chromosome 11q
Authors: MOFFATT M. F. , SHARP P. A. , FAUX J. A. , YOUNG R. P. , COOKSON W. O. C. M. , HOPKIN J. M.
Published: April 2006

The results of testing for linkage between atopy and the chromosome 11 marker D11S97 is shown for all the 723 subjects genotyped by us up to January 1992. Lod score estimations were confounded by the high population prevalence of atopy, maternal inheritance of atopy at the 11q locus, genetic heterogeneity, and excess of atopy in families not ascertained through a single proband. Affected sib‐pair analysis shows evidence for linkage which is not dependent on the definition of atopy or model specification. We suggest that presentation of sib‐pair data will be suitable for meta‐analysis of the different studies of genetic linkage and atopy.
Genetic analysis of atopy in three large kindreds: no evidence of linkage to D11S97
Authors: RICH S. S. , ROITMAN‐JOHNSON B. , GREENBERG B. , ROBERTS S. , BLUMENTHAL M. N.
Published: April 2006

Both genetic and environmental influences have been implicated in the pathogenesis of atopic disease. A recent report suggested that a major gene providing susceptibility to atopy was transmitted in a pattern consistent with autosomal dominant inheritance and evidence was presented that places the disease locus near the D11S97 marker on human chromosome 11q. In this report, we present three large, highly characterized pedigrees in which atopy is transmitted in a pattern consistent with autosomal dominant inheritance. Genotypes at the D11S97and HLA loci were evaluated using both lod score and sib pair methods of analysis. In these pedigrees, we reject close to moderate linkage (up to 10 cM) of atopy with both D11S97 and HLA.
Genetic analysis of the linkage between chromosome 11q and atopy
Authors: LYMPANY P. , WELSH K.I. , COCHRANE G. M. , KEMENY D. M. , LEE T. H.
Published: April 2006

Previous work has suggested that there is a genetic predisposition for the development of both asthma and atopy. A recent study has also shown that there is a striking link between chromosome 11q and the IgE response underlying asthma and rhinitis. To further assess the linkage between chromosome 11q and atopy, we have studied nine families of two and, in many instances, three generations with the index case having asthma and/or atopy. Using two restriction fragment length polymorphism probes associated with the regions 11q12‐q13.2, namely PYGM and INT2, we have been unable to confirm a significant link between this region of chromosome 11q and atopy as defined by a positive skin‐prick test and or a raised specific IgE and/or a raised total IgE.
A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid
Authors: GIBSON P. G. , WONG B. J. O. , HEPPERLE M. J. E. , KLINE P. A. , GIRGIS‐GABARDO A. , GUYATT G. , DOLOVICH J. , DENBURG J. A. , RAMSDALE E. H. , HARGREAVE F. E.
Published: April 2006

This study evaluated a research method to examine an exacerbation of asthma induced by corticosteroid withdrawal. Ten non‐smoking adult asthmatics who were stable on treatment with inhaled steroid underwent a graded reduction of the daily dose by 200 μg at weekly intervals until an exacerbation of symptoms occurred. A daily symptom, peak expiratory flow rate (PEF) and medication diary was kept. Weekly clinic visits were used to assess symptoms, spirometry, methacholine airway responsiveness (expressed as the provocative concentration to cause a fall in FEV1 of 20%, PC20), circulating eosinophils, basophils and their progenitors (Eo/B‐CFU), and sputum inflammatory cells. The laboratory tests were performed blind to the clinical details. Each subject developed an exacerbation of symptoms, on average at 16 (70–26) days after the onset of steroid reduction. This was accompanied by a deterioration in each of the objective measures. There was a fall in FEV1 by 320 ml (s.e.m. 9.5) and in PC20 from 0.8 to 0.43 mg/ml. Circulating eosinophils rose from 114 (24) × 103/ml to 227 (50) × 103/ml and Eo/B‐CFU rose from 31 (5.6) to 44(11.3)/106 cells. Sputum developed in five subjects and contained 36 (5.2)% eosinophils and 1.98 (0.21)% metachromatic cells (mast cells or basophils). The symptom diary and weekly questionaire were demonstrated to be valid and responsive to change. A deterioration indicated by the daily symptom score preceded changes in PEF. Treatment by an increase in steroid was followed by reversal of each of the changes. We conclude that this research method can safely produce and examine a mild exacerbation of asthma, and that an increase in airway inflammation is an early feature.
Mechanisms and patient compliance of dust‐mite avoidance regimens in dwellings of mite‐allergic rhinitic patients
Authors: KNIEST F. M. , WOLFS B. J. , VOS H. , DUCHEINE B. O. I. , VAN SCHAYK‐BAKKER M. J. , DE LANGE P. J. P. , VOS E. M. P. , VAN BRONSWIJK J. E. M. H.
Published: April 2006

We report on the mechanisms, the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens, taking into account both allergen contamination and the developmental success of pyroglyphid Acari. Twenty patients with persisting rhinitic complaints were selected and matched. Although the patients had performed some conventional dust and mite avoidance measures (patient compliance was 90%), the dwellings proved to be a stimulus for mite development. Moisture problems due to faulty construction and excessive moisture production were common. Since humidity conditions could not be changed at short notice, the 20 homes were subjected to the new variants of mite allergen avoidance based on intensive cleaning without (control) and with an acaricide incorporated (acaricidal cleaner [Acarosan]). After the carrying out of conventional avoidance measures, these patients still had allergic symptoms, and dust from only 23 to 52% of their textile objects was under the proposed guanine (mite faeces indicator) risk level. Only the acaricidal cleaner was able to decrease the allergenic mite load (and the burden of the patients) significantly in this 12 month period. With respect to mite‐extermination, acaricidal cleaning was 88% better than intensive cleaning. Reduction of guanine was 38% better in the Acarosan treatment group.

Clinical results have been reported elsewhere. A significant difference in favour of the acaricidal cleaning was seen in both subjective (as regards symptoms) and in objective data (total IgE). Another 50 patients were questioned. About 90% were willing to spend two weekends (70%), or at the most one weekend (20%) per year sanitizing the dwelling by cleaning it with the whole family.

The authors of this report consider acaricidal cleaning to be a significant improvement in the management of mite‐allergic diseases, such as rhinitis. Compared with the replacement of home textiles, this treatment is less expensive and more effective. Patient compliance is acceptable, but depends on acceptance by physicians and the initial motivation and consequent burden on the patient.
Respiratory allergies (bronchial asthma and rhinitis) due to sensitization of type I allergy to red spider mite (Panonychus ulmi KOCH)
Authors: KROIDL R. , MAASCH H. J. , WAHL R.
Published: April 2006

The inhabitants of a fruit growing area often report spontaneously of sensitization to the red spider mite (RSM) (Panonychus ulmi KOCH). These are for the most part sensitizations with low clinical symptoms (rhinitis, conjunctivitis and erythema). Severe clinical developments with bronchial asthma have been observed. We investigated six patients working in a fruit growing area sensitized by RSM. The sensitizations corresponded to a Type I allergy. Skin tests and provocation tests (nasal as well as bronchial) with RSM showed immediate reactions and RAST positive results were obtained using RSM allergen disks. RAST measurements of sera from nine house‐dust mite Dermatophagoides pteronyssinus allergic patients using RSM allergen disks showed RAST‐class > 1 for eight patients. RAST inhibition and immunoprint suggest a possible cross‐reaction between RSM and D. pteronyssinus.
Anti‐inflammatory effects of nedocromil sodium: inhibition of alveolar macrophage function
Authors: BORISH L. , WILLIAMS J. , JOHNSON S. , MASCALI J. J. , MILLER R. , ROSENWASSER L. J.
Published: April 2006

The IgE‐dependent activation of mononuclear phagocytic cells through their capacity to express low affinity IgE receptors (FcεRII) has been proposed as a mechanism for the development of airways inflammation in allergic asthma. This FcεRII expression leads to the IgE‐dependent production of the potent pro‐inflammatory cytokines IL‐1β and TNF‐α. Expression by monocytes of FcεRII is regulated by several cytokines including interleukin‐4, γ‐ and α‐interferons, and granulocyte‐macrophage and macrophage colony stimulating factors. An anti‐inflammatory effect of nedocromil on monocytes has been proposed as a possible mechanism for its anti‐asthma activity. We therefore investigated the capacity of nedocromil to modulate mononuclear phagocyte FcεRII expression and cytokine production. We used an anti‐FcεRII antibody and flow cytometric analysis to assess the capacity of nedocromil to modulate cytokine‐induced FcεRII expression in normals and asthmatics. Monocytes, THP‐1 monocyte leukaemia cells, and alveolar macrophages were exposed to varying concentrations of these cytokines for 48 hr at 37°C with or without the additional presence of nedocromil (1–10 μm) and the per cent of monocytes expressing FcεRII was determined. No changes in FcεRII expression were observed. Subsequently, we investigated the capacity of nedocromil to affect the capacity of IgE plus anti‐IgE complexes, allergen, and LPS (16 hr/37°C) to stimulate IL‐1β and IL‐6 production. No changes were observed when nedocromil was applied concomitant with the stimulus. However, pre‐treatment (30 min) with nedocromil was associated with a 59.5±5.6% inhibition of IL‐6 production stimulated by allergen and 34.5±5.1% by anti‐IgE. In conclusion, nedocromil does not modulate mononuclear phagocytic cell FcεRII expression but does suppress IgE‐dependent cytokine production. This may represent an important anti‐inflammatory action of nedocromil in the treatment of reactive obstructive airways disease.
Month of birth and allergic disease at the age of 10*
Authors: WJST M. , DOLD S. , REITMEIR P. , STIEPEL E. , VON MUTIUS E.
Published: April 2006

The relationship between month of birth and asthma, hay fever and skin sensitization to mixed grass pollen was analysed in a population‐based cross‐sectional study in Munich and Bavaria 1989–1990 of 6535 10‐year‐old children. The relative risk of developing atopic disease is calculated by comparing the prevalence in a single month with the prevalence of all other months. A slightly increased risk of developing allergic skin sensitization for grass pollen (n= 1128) was found for February (odds ratio, 1.3, 95% confidence interval 1.0–1.6), May (1.4, 1.1–1.8) and June (1.3, 1.0–1.6). For hay fever (n= 379) an increase was found for May (1.5, 1.0–2.1) and for allergic asthma (n= 271) for August (1.4, 1.0–2.1). A protective effect was observed for certain months of birth; September for allergic sensitization (0.8, 0.6–1.0), October for asthma (0.6, 0.3–1.0) and November for hay fever (0.6, 0.3–0.9). The occurrence of hay fever and positive prick test is explained by the seasonal variation of atmospheric grass pollen and the peak in August of asthmatic patients by house dust. Date of birth appears therefore to slightly influence the risk of developing an allergic sensitization and allergic diseases.
Divergent immune responses to respiratory and contact chemical allergens: antibody elicited by phthalic anhydride and oxazolone
Authors: DEARMAN R. J. , KIMBER I.
Published: April 2006

In previous studies we observed that exposure of mice to the contact allergen 2,4‐dinitrochlorobenzene (DNCB) and the respiratory allergen trimellitic anhydride (TMA) resulted in qualitatively different immune responses characteristic of selective Th1 ‐ and Th2‐type T helper cell activation respectively. The purpose of the present investigation was to determine whether the effects recorded with DNCB and TMA are characteristic of immune responses to contact and respiratory chemical allergens in general. Experiments have been performed with phthalic anhydride, a known human respiratory sensitizer, and with oxazolone, a potent contact allergen. Under conditions of exposure where both chemicals elicited an IgG anti‐hapten antibody response, only phthalic anhydride caused an increase in the serum concentration of IgE. Furthermore, like TMA, phthalic anhydride preferentially induced IgG2b rather than IgG2a antibody. In contrast, oxazolone, like DNCB, induced a markedly stronger IgG2a than IgG2b antibody response.

These data provide confirmatory evidence that chemical respiratory allergens and chemical contact allergens elicit qualitatively different immune responses which reflect their clinical effects in man.
Topical vasoconstrictor (oxymetazoline) does not affect histamine‐induced mucosal exudation of plasma in human nasal airways
Authors: SVENSSON C. , PIPKORN U. , ALKNER U. , BAUMGARTEN C. R. , PERSSON C. G. A.
Published: April 2006

Mucosal exudation of almost unfiltered plasma proteins, plasma‐derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine‐induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double‐blind, randomized, cross‐over and placebo‐controlled study with pretreatment with a single dose oxymetazoline chloride (5 μg or 50 μg; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30‐min intervals during this period. The concentrations of two exudative indices, N‐alpha‐tosyl‐l‐arginine methyl ester (TAME)‐esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique.

Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine‐induced plasma exudation. It is concluded that histamine‐induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical α‐adrenoreceptor‐mediated vasoconstriction. It is further suggested that the antiblockage effect of oxymetazoline can be utilized in nasal research without interfering with the exudative indices which appear on the mucosal surface as a quantitative reflection of the airway tisue involvement in inflammatory processes.
Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia
Authors: PEAT J. K. , TOVEY E. , MELLIS C. M. , LEEDER S. R. , WOOLCOCK A. J.
Published: April 2006

The relation of house dust mite allergen levels to asthma and allergy was examined in two population samples of children aged 8–11 years in northern New South Wales. We studied 805 children in Lismore (a hot, humid, coastal region) and 770 in Moree/ Narrabri (a hot, dry inland region). Respiratory symptoms were measured by questionnaire, bronchial hyperresponsiveness (BHR) by histamine inhalation test, and allergy by skin‐prick tests. Current asthma was defined as the presence of both wheeze in last 12 months and BHR. Der p I levels were measured in dust from the bed and floors in the homes of 57 randomly selected children in the coastal region and of 74 inland children. Der p I levels were significantly higher by the coast (83.0 vs 11.2 μg/g, P < 0.001). House dust mite sensitivity was of similar prevalence in both regions (28.6 vs 26.4%, n.s.) but Alternaria sensitivity was higher inland (4.0 vs 15.2%P < 0.001). Bronchial responsiveness was more severe in coastal children sensitized to house dust mites and in inland children who were sensitized to Alternaria. The adjusted odds ratios for current asthma in children sensitized to house dust mites were 21.3 (95% CI 10.5, 43.2) by the coast and 2.7 (95% CI 1.3, 5.4) inland, and in children sensitized to Alternaria were 3.4 (95% CI 1.3, 9.1) in the coastal region and 5.6 (95% CI 3.1, 10.1 inland. These studies suggest that high house dust mite allergen levels in a humid, subtropical region act to significantly increase bronchial responsiveness in sensitized children, and that Alternaria allergens have a similar but less potent action in a dry, rural region.
Familial occurrence of atopic disease: genetic versus environmental factors
Authors: ÅBERG N.
Published: April 2006

Cumulative life prevalence of atopic disease (any of reported symptoms of asthma/ wheezy bronchitis, allergic rhinitis, eczema and urticaria) was studied by means of a questionnaire in 19814 (7‐, 10‐ and 14‐year‐old) Swedish school children and their parents. Maternal history was found to be twice as common as paternal history. The children of affected mothers contracted atopic disease in the same proportion as the children of affected fathers yielding twice as many affected children with affected mothers than with affected fathers. The strongest parental influence on childhood disease was seen for multiple symptoms and for congruent symptoms with both parents. The number of children with both parents affected was 1.6 times larger than expected. A possible dose‐response effect in polygenic inheritance is discussed as well as assumed impact of environmental factors with a tendency to familial clustering.
IgG and IgA subclass antibodies against Aspergillus umbrosus in farmer's lung disease
Authors: KAUKONEN K. , SAVOLAINEN J. , VIANDER M. , KOTIMAA M. , TERHO E. O.
Published: April 2006

Fifty patients with farmer's lung disease (FL), 20 asymptomatic exposed farmers, and 18 healthy controls were investigated for total IgG and total IgA, as well as subclass antibody levels against Aspergillus umbrosus, the most common fungus to which FL patients in Finland have been exposed. Enzyme‐linked immunosorbent assay (ELISA) revealed significantly elevated levels of specific total IgG and IgA antibodies in the sera of patients during the acute phase of the disease. Both IgG1 and IgG2 subclass antibodies and both IgA1 and IgA2 subclass antibodies were significantly associated with the disease. The antibody levels decreased during the first 3 months, when mould exposure was avoided and when an oral 6‐week steroid treatment was administered. During the next 12 month follow‐up, the mean antibody levels continued to decrease, even though re‐exposure might have occurred. The results (with sensitivity 94% and specificity 95%) imply that in addition to the measurement of A. umbrosus‐specific IgG, determination of both A. umbrosus‐specific IgG1 and IgA might also be useful in the scrodiagnosis of acute stage of FL.