bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating CLA+ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal‐related T‐cell receptor variable segments
Authors: Torres  , Gonzalez  , Corzo  , Giron  , Carvajal  , Garcia  , Pinedo  , Martinez‐Valverde  , Blanca  , Santamaria
Published: March 2003

Background

Atopic dermatitis is an allergic T‐cell mediated skin inflammation. Staphylococcus aureus colonization is very common in cutaneous atopic dermatitis lesions. The cutaneous lymphocyte‐associated antigen (CLA) is a T cell skin homing receptor that defines T lymphocytes associated with the cutaneous immune response.

Objective

To study whether CLA+ T cells from atopic dermatitis children present a selective expression for Staphylococcus aureus‐related TCR Vβ segments.

Methods

Peripheral blood T cells were stained with HECA‐452 (anti‐CLA) and a panel of TCR Vβ specific monoclonal antibodies and analysed by flow cytometry.

Results

Atopic dermatitis patients have a higher percentage of circulating CLA+ CD3+ lymphocytes compared with healthy controls. Patients with active atopic dermatitis during the study expressed a higher percentage of cells positive for the TCR Vβ2 and Vβ5.1 segments in the CLA+ but not in the CLA− subset. These TCR Vβs are recognized by staphylococcal superantigens. Moreover, there was an increased percentage of HLA‐DR+ expression by CLA+ Vβ5.1+ T cells in patients with active atopic dermatitis, but those patients whose eczema was inactive had very similar values to healthy controls regarding TCR Vβ and HLA‐DR phenotype in circulating CLA+ T lymphocytes.

Conclusion

Our data indicate that circulating skin‐homing T cells of patients with active atopic dermatitis contain an increased percentage of cells bearing TCR Vβ segments related with Staphylococcus aureus. Staphylococcus superantigens may therefore trigger expansion or at least circulation of appropriate CLA+ T cells.
Role of respiratory infection in onset of asthma and chronic obstructive pulmonary disease
Authors: Martinez F. D.
Published: March 2003

There is renewed interest in the possible role of events occurring during early life in determining predisposition to asthma and allergies. Among these events, respiratory illnesses associated with viral infections have been the matter of considerable research interest. There is now evidence suggesting that an immune response to viral infection in early life that is skewed toward an IgE‐ or an eosinophil‐mediated slant is predictive of persistent wheezing symptoms up to the age of 6 years. Genetic and environmental factors (specifically bacterial infection burden) may be important determinants of the maturation of immune responses from a default ‘Th‐2‐like’ at birth to mature, non‐Th‐2‐like responses. Homing of Th‐2‐like responses to the lung may be determined in part by inheritance of bronchial hyperresponsiveness, and in part by the progressive nature of chronic, uncontrolled airway inflammation. The main risk factor for the development of wheezing episodes in children who are not predisposed to allergic asthma is diminished airway function, which can also be detected shortly after birth. These children may stop wheezing later during childhood, but their levels of lung function track with age. It is tempting to speculate that chronic obstructive pulmonary disease may occur more frequently in these children.
Regional variations in grass pollen seasons in the UK, long‐term trends and forecast models
Authors: Emberlin  , Mullins  , Corden  , Jones  , Millington  , Brooke  , Savage
Published: March 2003

Background

Three sites in the UK have daily records of pollen spanning several decades, giving the longest data sets worldwide. Previous research on London data revealed decreasing severity of grass pollen seasons. This is often taken as a model for the whole country but comparisons with Derby and Cardiff, in different regions of local climate and land‐use, emphasize the need for regional studies.

Objective

The grass pollen seasons were analysed for three contrasting long‐term sites to provide regional insight into the changing incidence of hay fever.

Methods

Pollen was monitored by volumetric instruments using standard techniques. Data have been taken from 1961 to 1993 to examine variation in grass pollen seasons in relation to land‐use changes, cumulative temperatures and rainfall. Models were developed to predict total seasonal catches.

Results

At Cardiff the annual counts and severity increased in the 1960s, declined in the 1970s and rose again in the 1980s. At Derby and London the annual counts and severity declined but at different rates. Start dates have tended to become earlier at Cardiff and Derby, but later at London. Trends in annual counts and severity are similar to changes in grassland areas but they cannot be accounted for entirely by these. Weather in spring and early summer has tended to become warmer but there are no sustained patterns in June and July. No trends are apparent in the rainfall records for these months. The maximum explanation (r2≥ 95%) in forecast models was obtained using 10‐day aggregates of weather.

Conclusion

The contrasting patterns both in the pollen records and land‐use changes between the three sites emphasize the need for regional data. The predictive models achieved a high degree of explanation enabling pollen season severity to be forecast with high confidence shortly before the start date.
Carob is not allergenic in peanut‐allergic subjects
Authors: Fiocchi  , Restani  , Travaini  , Decet  , Gaiaschi  , Bernardo  , Riva
Published: March 2003

Background

The antigenic potential of proteins from the carob bean, a member of the legume family used as a food additive, have not so far been investigated and legumes share antigenic proteins with peanut, a potent trigger of anaphylaxis.

Objective

To assess the carob protein determinants of sensitization in peanut‐allergic children.

Methods

In a prospective, double‐blind, placebo‐controlled study 12 patients (median age 9.5 years) with a history of hyperreactivity to peanut (anaphylaxis) were assessed. Skin prick tests with a commercial peanut allergen, raw carob pulp, raw and cooked carob cotyledon formula were used to confirm the history. RAST for peanuts and cooked carob were used to evaluate sensitization to these proteins. Carob‐specific IgE were identified by immunoblotting analyses. Allergic reactivity was evaluated during double‐blind placebo‐controlled food challenges (DBPCFC; 5.5 g carob extract and cooked carob cotyledon formula).

Results

Peanut allergen‐induced skin prick test positivity in all children (confirmed during double‐blinded challenge in 6/12 patients), carob pulp in 3/12 patients, raw carob bean in 6/12, and cooked carob cotyledon formula in none. RAST were positive for peanut in all cases but negative for carob beans in 9/12 cases. Immunoblot analyses found peanut‐specific IgE in all cases and raw carob bean‐specific IgE in eight cases. Carob allergens were identified in the 17.5, 48, and 66 kDa MW bands. The least allergenic density was found for cooked carob proteins. There was no clinical reactivity with either raw or cooked carob during DBPCFC.

Conclusions

These data suggest that carob‐specific sensitization, apparent both in vitro and in SPTs, can be concordant with peanut allergy and that cooked carob can be ingested by children who are allergic to peanuts. That heat‐processing deactivates carob protein allergenicity has dietary implications for polyallergic children.
Cow's milk protein‐specific IgE concentrations in two age groups of milk‐allergic children and in children achieving clinical tolerance
Authors: SICHERER  , SAMPSON
Published: March 2003

Background

IgE‐mediated cow's milk protein allergy (CMPA) is usually outgrown in children by the age of 3 years. The immunological responses to cow's milk proteins in children who achieve tolerance, in comparison with those who remain allergic, however, are not well described.

Objective

To compare the level of cow's milk protein‐specific IgE among children with documented CMPA under the age of 3 years, another group over the age of 9 years (persistent allergy), and in another group of children in whom clinical tolerance developed.

Methods

Stored sera from children with CMPA were analysed for IgE antibodies specific for whole cow's milk, casein, whey, α‐lactalbumin (ALA), β‐lactoglobulin (BLG), and bovine serum albumin (BSA) using the Pharmacia CAP System FEIA.

Results

Within each group of CMPA children, the concentration of specific IgE antibody to casein proteins was not significantly different from that to whey proteins. However, children in the group with CMPA over 9 years of age had significantly greater concentrations of whole milk (P = 0.02) and casein‐specific (P = 0.04) IgE antibodies compared with the group of children with CMPA under age 3 years. Children under the age of 3 years had a higher median concentration of casein‐specific IgE (20.2 vs. 5.5, P = 0.04) than another group of 11 children (mean age 3.5 years), who later lost their milk allergy. Out of 16 children who lost sensitivity to milk, 75% had milk‐specific IgE levels below 14.3 kUA/L (median, 1.3 kUA/L).

Conclusions

Although a dominant allergenic milk protein fraction was not identified within either of the two age groups, those with persistent CMPA over age 9 years had significantly elevated levels of milk and casein‐specific IgE compared with younger children with CMPA.
Assessment of eosinophil granule proteins in various body fluids: is there a relation to clinical variables in childhood asthma?
Authors: KOLLER  , HALMERBAUER  , FRISCHER  , ROITHNER
Published: March 2003

Background

The eosinophil plays a central role in the inflammatory process in bronchial asthma. Recent studies have indicated that the assessment of eosinophil‐derived proteins in various body fluids could be used for monitoring disease activity of childhood asthma. Till now, no study exists which compared the levels of eosinophil‐derived proteins in various body fluids such as serum, nasal lavage fluid (NALF) and urine.

Objective

To investigate whether eosinophil granule proteins in different compartments were correlated and whether there is a relationship betweeen disease activity, pulmonary function and bronchial hyperreactivity.

Methods

Twenty‐eight children with atopic bronchial asthma were recruited. Serum, NALF and urine samples were obtained and assessed for eosinophil cationic protein (ECP) and eosinophil protein X (EPX). The levels of eosinophil proteins were analysed for a relationship with lung function variables, bronchial hyperreactivity and disease activity. Eleven healthy control subjects were used as controls.

Results

Median ECP and EPX concentrations in serum (31.4 and 74.8 μg/L vs 15.8 and 24.3 μg/L, respectively), NALF (9.9 and 44.9 μg/L vs 0 and 2.5 μg/L, respectively) and urine (49.4 vs 16.5 μg/mmol creatinine) were significantly raised in children with bronchial asthma compared with healthy control subjects. In addition, ECP and EPX levels in serum and urine samples were significantly higher in symptomatic patients compared with asymptomatic subjects with asthma. Although no relationship between eosinophil‐derived proteins in serum, NALF or urine and the level of nonspecific bronchial hyperreactivity could be detected, the concentrations of EPX in serum and urine were correlated with variables of pulmonary function.

Conclusion

Our findings demonstrate increased eosinophil activity in serum, NALF and urine derived from children with bronchial asthma. Due to the relationship between levels of eosinophil proteins in serum/urine samples and lung function, as well as significant concentration differences between symptomatic and asymptomatic asthmatic children, the assessment of eosinophil proteins in serum or urine samples appear to be more appropriate in monitoring disease activity than measurement of ECP or EPX in NALF. Thus, the determination of serum ECP/EPX or urinary EPX may be preferentially used in monitoring eosinophilic inflammation in childhood asthma.
Human immunoglobulin isotype profiles produced in response to antigens recognized by monoclonal antibodies specific to Anisakis simplex
Authors: Lorenzo  , Iglesias  , Audícana  , García‐Villaescusa  , Pardo  , Sanmartín  , Ubeira
Published: March 2003

Background

Anisakis simplex is a medically important pathogen which not only causes anisakiasis but may provoke allergy reactions, ranging from mild urticaria to anaphylactic shock.

Objetive

To investigate anti‐Anisakis isotype profiles in anisakiasis and Anisakis allergy patients.

Methods

Capture ELISA techniques were used to investigate the isotype profiles of antibodies specific for two defined Anisakis simplex antigens, in serum from Japanese patients with confirmed anisakiasis and from Spanish patients with allergy to Anisakis. The antigens were ‘UA2R antigens’ (two proteins with MW of 48 and 67 kDa, recognized by our monoclonal antibody UA2) and ‘UA3R antigens’ (two proteins with MW of 139 and 154 kDa, recognized by our monoclonal antibody UA3).

Results

Considering IgG, the two most frequent isotypes in the response to the UA2R antigens were IgG1 and IgG2, with IgG4 detected in only one case; in response to the UA3R antigens, by contrast, the two most frequent isotypes were IgG1 and IgG4 (though IgG2 remained reasonably frequent). As regards potential utility for serodiagnosis, 95% of the Japanese anisakiasis patients and 84% of the allergy patients showed detectable IgG1 antibodies to the UA3R antigens. Furthermore, all allergy patients showed IgE antibodies to these antigens.

Conclusion

Anisakis simplex contains antigens that induce responses which are differentially regulated. Because of their immunogenicity, immunodominance and allergenic nature, we consider that the 139/154‐kDa antigens recognized by our MoAb UA3 are good candidates for use in tests for the diagnosis of anisakiasis and of the allergy caused by this parasite.
Long‐term effects of corticosteroid nasal spray on nasal inflammatory cells in patients with perennial allergic rhinitis
Authors: Holm  , Godthelp  , Fokkens  , M. Severijnen  , Mulder  , Vroom  , Rijntjes
Published: March 2003

Background

The effect of long‐term topical nasal corticosteroid therapy on nasal inflammatory cells is unclear.

Objectives

To investigate the long‐term effect of fluticasone propionate aqueous nasal spray (FPANS) on nasal mucosal inflammatory cells and efficacy in a 1‐year study in patients with perennial allergic rhinitis.

Methods

In a 1‐year, double‐blind, placebo‐controlled study of duration we investigated the influence of a topical corticosteroid (FPANS), on Langerhans' cells (CD1a+ cells), T cells, mast cells, eosinophils and macrophages in nasal mucosa in 42 patients with perennial allergic rhinitis. Efficacy was evaluated by nasal symptom score.

Results

The FPANS group experienced significantly less sneezing and nasal itching compared with the placebo group. The total symptom score in the FPANS group declined significantly in comparison with baseline (P = 0.007) and placebo group (P = 0.009). After 1 year of active treatment, a significant decrease was seen in the epithelium in numbers of Langerhans' cells, CD3+, CD4+, CD8+ cells, mast cells and eosinophils. In the lamina propria, there was a significant decrease in eosinophils.

Conclusion

These findings show that FPANS treatment results in a decrease of nasal inflammatory cells. Furthermore, the efficacy of FPANS improves after prolonged treatment.
Eosinophil protein X and eosinophil cationic protein as indicators of intestinal inflammation in infants with atopic eczema and food allergy
Authors: Majamaa  , Laine  , Miettinen
Published: March 2003

Background

The aim of this study was to evaluate the presence of allergic intestinal inflammation in infants with food allergy and atopic eczema before and after elimination diet, and to evaluate the use of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) in the monitoring of inflammatory activity.

Methods

The study material comprised 25 infants with atopic dermatitis and food allergy. Thirteen healthy infants served as controls. Faecal and serum samples were collected before an elimination diet (on the first visit to the hospital) and approximately 3 months later for the determination of EPX and ECP.

Results

Before the elimination diet, infants with atopic dermatitis demonstrated markedly higher faecal concentrations of EPX and ECP than healthy controls (P = 0.0003, P < 0.0001, respectively). The faecal concentrations of EPX and ECP showed a distinct decrease as a result of an adequate elimination diet in patients with favourable clinical response (P = 0.0027, P = 0.004, respectively).

Conclusions

The results indicate the presence of marked intestinal inflammation in patients with atopic dermatitis and food allergy. The determination of faecal ECP and especially of faecal EPX provides a promising noninvasive tool in monitoring intestinal inflammation and disease activity in infants with atopic eczema and food allergy.
CNS effects of histamine H1 antagonists
Authors: Rihoux J. P. , Donnelly F.
Published: March 2003

An accurate evaluation of the functions of the human brain during the administration of drugs is one of the most complex tasks in medical science. In the case of H1 antihistamines, there are many biases that can explain why the interpretation of pharmacological data and those from clinical studies can be very difficult. First of all, the allergic disease itself may modify central nervous system (CNS) functioning and effective medical treatment may accordingly influence the self‐reported CNS sensations of patients. Moreover, the carefully selected populations that are enrolled both in pharmacological and clinical studies do not reflect the profile of patients who are trreated with such drugs on an everyday basis. Finally, studies of performance impairment and those relying on self‐reported sensations may give different and indeed conflicting results.It may be concluded that the various pronouncements on the CNS properties of H1 antihistamines must be treated with some caution.
Prescription‐event and other forms of epidemiological monitoring of side‐effects in the UK
Authors: Dunn N. , Mann R. D.
Published: March 2003

The post‐marketing surveillance (PMS) of drugs is necessary because of the limited size of the clinical safety database at the time of marketing. The principal hypothesis‐generating methods of PMS are spontaneous reporting (e.g. the yellow card) and Prescription Event Monitoring. These methods are discussed in this chapter and certain basic pharmacoepidemiological issues that are relevant are briefly reviewed.
Total and specific IgE (house dust mite and intestinal helminths) in asthmatics and controls from Gondar, Ethiopia
Authors: Selassie  , Stevens  , Cullinan  , Pritchard  , Jones  , Harris  , Ayres  , Newman Taylor
Published: March 2003

Background

The role, if any, of parasitosis in the development of asthma remains incompletely understood; both ‘protective’ and ‘predictive’ associations have been reported. We report a study which examined immunoglobulin (Ig) E responses to two common helminths in asthmatics living in Ethiopia.

Objective

To compare the frequencies of specific IgE antibodies to Ascaris and Necator species and to Der p 1 among 84 adult asthmatics and a referent group of nonasthmatics.

Methods

A case‐control analysis.

Results

Total IgE levels were not different between the two groups. The presence of specific IgE to Der p 1 was strongly associated with asthma (P = 0.001). Raised levels of Ascaris‐(P = 0.010) and Necator‐ (P = 0.001) specific IgE antibodies were more common among referents; there were no associations between specific IgE production to Der p 1 and either of the two parasites.

Conclusion

These findings confirm the association between Der p 1 sensitization and asthma among urban, adult Ethiopians. While they also indicate a negative relationship with two indicators of helminth infestation it appears that this is not mediated through the immunological response to common aeroallergens.
Indoor determinants of Der p 1 and Der f 1 concentrations in house dust are different
Authors: Gross  , Heinrich  , Fahlbusch  , Jäger  , Bischof  , Wichmann
Published: March 2003

Background

Exposure to mite allergens is a major risk factor for sensitization and the development of asthma. Der p 1 and Der f 1 content in homes and probably the proportion of both antigens is highly variable even in the same geographical area.

Objective

We investigated specific indoor determinants of Der p 1 and Der f 1 concentrations in house dust of two German cities, Erfurt and Hamburg (n = 405 homes).

Methods

Mite allergen levels were determined using monoclonal antibodies against Der p 1 and Der f 1 by the ELISA method. Indoor relative humidity and temperature were monitored continuously in the homes over 1 week. The characteristics of homes and occupants were assessed by questionnaire to obtain information on factors which may have an impact on the mite antigen concentration in house dust. These determinants were studied by multivariate regression analysis.

Results

The correlation between concentrations of Der p 1 and Der f 1 inside the homes was weak (r = 0.29–0.35), indicating that different determinants are relevant. Concentrations of the allergens were significantly higher on lower floors (ratios 2–8 times, Der p 1, Der f 1), on old mattresses (ratios 3–13 times, Der p 1, Der f 1), in post‐war buildings (ratio 6 times, Der p 1), for non‐central heating (ratio 2 times, Der p 1), for old carpets (ratio 3 times, Der p 1) and for the presence of a dog in the house (ratio 3 times, Der f 1). Furthermore, mite concentration increases with raising relative humidity (ratio 1.03 per 1%, Der p 1) and with decreasing temperature (ratio 0.86 per 1 °C, Der p 1) indoors.

Conclusion

Both Der p 1 and Der f 1 concentrations should be measured in house dust, since they are only weakly correlated and have different determinants.
Biochemical and immunological characterization of a recombinant precursor form of the house dust mite allergen Der p 1 produced by Drosophila cells
Authors: Jacquet  , Haumont  , Massaer  , Daminet  , Garcia  , Mazzu  , Jacobs  , Bollen
Published: March 2003

Background

The major house dust mite allergen Der p 1 elicits strong IgE antibody responses in patients suffering from mite allergy.

Objective

This study reports the expression and characterization of a recombinant precursor form of Der p 1 secreted as ProDer p 1 from insect cells.

Methods

The cDNA coding for ProDer p 1 was cloned downstream to the gp67 signal peptide, starting from commercial cDNA encoding Der p 1 and PCR‐amplified ProDer p 1 genomic fragment. ProDer p 1, expressed in Drosophila cells and purified from culture medium, was compared to Der p 1 isolated from mite culture, in terms of glycosylation, enzymatic activity as well as IgG‐ and IgE‐binding capacity.

Results

Sequence analysis of the genomic clone of ProDer p 1 revealed that, besides two introns in the mature Der p 1 coding sequence, two introns were also present in the propeptide coding sequence. ProDer p 1 was purifed to homogeneity by a combination of ion‐exchange, hydroxyapatite and gel filtration chromatographies. The precursor form of Der p 1 could be processed in vitro into mature Der p 1 under acidic and reducing conditions. Carbohydrate analysis clearly indicated that ProDer p 1 expressed from insect cells was glycosylated and that glycan structures were located only in the prosequence. ProDer p 1 displayed a similar immunoreactivity towards IgE, monoclonal and polyclonal IgG antibodies compared to natural Der p 1. Specific activity measurements using synthetic substrates clearly indicated that, contrary to natural Der p 1, ProDer p 1 was totally enzymatically inactive.

Conclusions

The expression of an enzymatically inactive and highly antigenic ProDer p 1 zymogen molecule could be a suitable strategy for the development of in vitro diagnosis test as well as for specific immunotherapy.
Transepithelial migration of activated eosinophils induces a decrease of E‐cadherin expression in cultured human nasal epithelial cells
Authors: Kobayashi  , Terada  , Hamano  , Numata  , Konno
Published: March 2003

Background

The damage of respiratory epithelium in allergic diseases has a close correlation with the extent of eosinophil infiltration. It seems to be a good possibility that eosinophil infiltration could induce the changes in the expression of the epithelial cell adhesion molecules, which play a key role in the maintenance of structural and functional rigidity of epithelium.

Objective

We observed the expression of E‐cadherin in cultured human nasal epithelial cells (HNECs) to study whether could it be affected by transepithelial migration of inflammatory cells, especially eosinophils.

Methods

In vitro study of the transmigration assay was designed using various types of inflammatory cells and HNEC monolayers. Various assays of each experimental group were done under the stimulation of interleukin‐5 (IL‐5) and/or platelet activating factor (PAF). Subsequently immunohistochemistry for E‐cadherin was performed in the HNECs. The intensity of immunofluorescence of E‐cadherin was quantified using confocal laser scanning microscopy (CLSM) system and compared before and after the transmigration.

Results

The mean intensity of immunofluorescence for E‐cadherin decreased significantly after the transmigration of any types of inflammatory cells. Above all, the migration of eosinophils treated with IL‐5 and PAF had an eminent effect on the decrease, whereas the degranulation extracts derived from eosinophils activated by IL‐5 and secretory IgA (sIgA) did not affect the intensity.

Conclusion

This work suggests that transepithelial migration of inflammatory cells can directly induce the decrease in epithelial E‐cadherin expression. Furthermore, the most prominent change was induced by transmigration of activated eosinophils, which might be caused by some mechanisms independent of the eosinophil contents. The decrease in E‐cadherin expression may trigger the damage of epithelial barrier, which contributes to the pathogenesis of allergic diseases.
Lipid‐transfer proteins as potential plant panallergens: cross‐reactivity among proteins of Artemisia pollen, Castanea nut and Rosaceae fruits, with different IgE‐binding capacities
Authors: DÍaz‐Perales A. , Lombardero M. , SÁnchez‐Monge R. , GarcÍa‐Selles F. J. , Pernas M. , FernÁndez‐Rivas M. , Barber D. , Salcedo G.
Published: March 2003

Background

Lipid‐transfer proteins (LTPs), but not Bet v 1 homologues, have been identified as major allergens of apple and peach in the Rosaceae fruit‐allergic population in the Mediterranean area. Many of these patients show cosensitization to mugwort pollen. LTPs have an ubiquitous distribution in tissues of many plant species, and have been proposed as a novel type of plant panallergens.

Objective

We sought to isolate LTPs from Artemisia pollen and from a plant food not belonging to the Rosaceae family, such as chestnut nut, and to compare their amino acid sequences and IgE‐binding capacities with those of apple and peach LTPs.

Methods

Allergens (LTPs) were isolated by different chromatographic methods (gel‐filtration, ion exchange and/or reverse‐phase HPLC), and characterized by N‐terminal amino acid sequencing and MALDI analysis. Specific IgE‐quantification and immunodetection, as well as immunoblot and ELISA inhibition assays, were carried out using sera from patients allergic to both apple and peach.

Results

Purified LTPs from Artemisia pollen and from chestnut seed showed molecular masses about 9 700d, and 43–50% sequence identity with the equivalent allergens of apple and peach in the first 30 N‐terminal residues, which comprise about one third of the total amino acid sequence. A similar degree of sequence identity (50%) was found between the Artemisia and chestnut proteins. Both isolated LTPs bound specific IgE of sera from Rosaceae fruits allergic patients. However, substantially lower values of specific IgE‐binding and maximum ELISA inhibition percentages were obtained for Artemisia and chestnut LTPs when compared to those from apple and peach.

Conclusion

LTPs from Artemisia pollen and chestnut crossreact with allergens (LTPs) of Rosaceae fruits, but significant differences in specific IgE‐binding capacities were observed among members of the plant LTP family. Thus, further studies are needed to evaluate the clinical significance of the observed cross‐reactivities of plant LTPs.
Intolerance to hydrolysed cow's milk proteins in infants: clinical characteristics and dietary treatment
Authors: Carroccio A. , Cavataio F. , Montalto G. , D'Amico D. , Alabrese L. , Iacono G.
Published: March 2003

Background

Multiple food intolerance in infants, including intolerance to extensively hydrolysed proteins (HP), is often difficult to treat. However, few data have been reported on clinical outcome and dietary treatment of these patients.

Aims

To evaluate the clinical characteristics of patients with HP‐intolerance and the long‐term outcome of treatment with ass' milk.

Patients and Methods

This study included 21 HP‐intolerant infants (15 males, median age at diagnosis 2 months) treated with an ass' milk‐based diet and 70 cow's milk (CM) intolerant infants (40 males, median age at diagnosis 3 months) treated with casein hydrolysate milk‐based diet. All patients were followed‐up for a median period of 4 years. Both HP‐intolerance and intolerance to other foods were diagnosed according to the double‐blind placebo‐controlled procedure. Formal CM‐challenges were conducted at yearly intervals until tolerance was demonstrated. At diagnosis and after one year of the respective diets, the following growth parameters were determined: relative weight for sex and age, relative weight for height and height z‐score.

Results

During the study period, multiple food intolerance was documented in 21/21 HP‐intolerant infants (ass' milk group) and in 20/70 infants with CM‐intolerance but tolerating HP (casein hydrolysate group) (P < 0.0001). In the ass' milk group, the more frequent food intolerances were toward soya, oranges, tomatoes and fish; goat's milk intolerance was demonstrated in five out of six patients receiving this food, and sheep's milk derivatives intolerance in four out of seven; these patients tolerated ass' milk. During the study period 3/21 patients in the ass' milk group became ass' milk intolerant; they showed vomiting (one cases) or diarrhoea (two cases). A lower percentage (52%) of patients in the ass' milk group became CM‐tolerant during the study period than in the casein hydrolysate group (78%) (P < 0.01) and the age of the children at CM‐tolerance was higher in the ass' milk than in the casein hydrolysate‐treated children (P < 0.05). At diagnosis, a higher frequency of cases with elevated serum total IgE and specific IgE to CM antigens (P < 0.01) was observed in the ass' milk group. No difference was recorded between the two treatment groups in any of the growth parameters considered either at diagnosis or during the follow‐up.

Conclusions

HP‐intolerant patients showed a higher frequency of persistent food intolerance and of multiple food intolerance than patients tolerating casein hydrolysate. Ass' milk feeding was confirmed as a safe and valid treatment of the most complicated cases of multiple food intolerance.
Efficacy and tolerability of fluticasone propionate nasal drops 400 μg once daily compared with placebo for the treatment of bilateral polyposis in adults
Authors: Keith P. , Nieminen J. , Hollingworth K. , Dolovich J.
Published: March 2003

Background

Chronic eosinophilic rhinosinusitis underlies a range of respiratory disorders including nasal polyposis. Surgical and medical methods are used to control polyps, with topical steroids commonly being used for their anti‐inflammatory properties. Fluticasone propionate nasal drops (FPND) is a formulation developed specifically for an effective and well tolerated corticosteroid treatment of nasal polyposis.

Objectives

To assess efficacy and tolerability of FPND in the treatment of bilateral nasal polyposis in adults.

Methods

This multicentre, randomized, parallel‐group study compared FPND 400 μg once daily (o.d.) with placebo for 12 weeks in adult patients with mild to moderate bilateral polyposis. The primary efficacy endpoint was visual assessment of polyp size by the physician at monthly clinic visits. Nasal blockage, rhinitis, peak nasal inspiratory flow (PNIF), olfactory function and requirement for polypectomy were also assessed at visits. The patients kept diary card records of symptoms, PNIF, and use of rescue antihistamine. Additional safety data were provided by a 12‐week open extension, when all patients received FPND 400 μg o.d.

Results

After 12 weeks double‐blind treatment with FPND (n = 52) or placebo (n = 52), polyp size was reduced in 27% and 16% of patients, respectively; clinical reduction of nasal blockage significantly favoured FPND over placebo (55% vs 22%; P = 0.002), and clinic PNIF had increased significantly with FPND (by 52 L/min vs −3 L/min for placebo; P < 0.001). Diary card measurements showed significant benefits of FPND vs placebo for daily PNIF, nasal blockage, rhinitis and use of loratadine rescue medication. Both treatments were well tolerated and no serious adverse events occurred during randomized treatment. Epistaxis was more frequent with FPND than placebo but was generally mild and did not result in withdrawals. Mean serum cortisol levels did not change significantly with either treatment.

Conclusion

This study showed FPND 400 μg o.d. to be an effective and well tolerated treatment for bilateral nasal polyposis in adults.
The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus
Authors: Wan H. , Winton H. L. , Soeller C. , Taylor G. W. , Gruenert D. C. , Thompson P. J. , Cannell M. B. , Stewart G. A. , Garrod D. R. , Robinson C.
Published: March 2003

There have been only a few studies of how allergens cross the airway epithelium to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain several proteolytic enzymes. Group 1 allergens are cysteine peptidases, whilst those of groups 3, 6 and 9 have catalytic sites indicative of enzymes that mechanistically behave as serine peptidases. We have previously shown that the group 1 allergen Der p 1 leads to cleavage of tight junctions (TJs), allowing allergen delivery to antigen presenting cells.

In this study we determined whether HDMFP serine peptidases similarly compromise the airway epithelium by attacking TJs, desmosomes and adherens junctions.

Experiments were performed in monolayers of MDCK, Calu‐3 or 16HBE14o‐epithelial cells. Cell junction morphology was examined by 2‐photon molecular excitation microscopy and digital image analysis. Barrier function was measured as mannitol permeability. Cleavage of cell adhesion proteins was studied by immunoblotting and mass spectrometry.

HDMFP serine peptidases led to a progressive cleavage of TJs and increased epithelial permeability. Desmosomal puncta became more concentrated. Cleavage of TJs involved proteolysis of the TJ proteins, occludin and ZO‐1. This was associated with activation of intracellular proteolysis of ZO‐1. In contrast to occludin, E‐cadherin of adherens junctions was cleaved less extensively. Although Calu‐3 and 16HBE14o‐cells expressed tethered ligand receptors for serine peptidases, these were not responsible for transducing the changes in TJs.

HDMFP serine peptidases cause cleavage of TJs. This study identifies a second general class of HDM peptidase capable of increasing epithelial permeability and thereby creating conditions that would favour transepithelial delivery of allergens.
Alpha‐1‐antitrypsin is present in the specific granules of human eosinophilic granulocytes
Authors: Johansson B. , Malm J. , Persson T. , Janciauskiene S. , Andersson P. , Carlson J. , Egesten A.
Published: March 2003

Eosinophils may be found at sites of inflammation, for example in asthma, allergy and helminthic infestation, but their role in human inflammatory disease is unclear.

In the present study, we investigated the presence of alpha‐1‐antitrypsin (AAT), a serine proteinase inhibitor, in human eosinophils.

When lysates of highly purified eosinophils were subjected to Western blotting, with a chemiluminescent substrate, immunoreactive bands were seen. An ELISA was developed to measure the AAT content, which was found to be about 100 ng/5 × 106 eosinophils, about 50 ng/5 × 106 neutrophils, and about 25 ng/5 × 106 monocytes. Immunoelectron microscopy showed localization of AAT to the specific granules of eosinophils. During prolonged incubation of eosinophils, no significant increase in the total amount of AAT could be detected by ELISA. However, there was an increased level of AAT in the medium, in parallel with a decrease in the intracellular AAT content, suggesting release of preformed AAT. Apparent complex formation between iodinated elastase and AAT in eosinophil lysates provided evidence that the AAT is functionally active.

On the basis of these findings it is suggested that by releasing AAT, eosinophils may, in a microenvironment, play a role in counteracting the tissue damage caused by serine proteinases released by neutrophils in inflammatory conditions.
NAC Manchester Asthma and Allergy Study (NACMAAS): risk factors for asthma and allergic disorders in adults
Authors: Simpson B. M. , Custovic A. , Simpson A. , Hallam C. L. , Walsh D. , Marolia H. , Campbell J. , Woodcock A
Published: March 2003

Asthma and atopic disorders are the most common chronic diseases in the developed countries. Knowledge of the risk factors for these disorders may facilitate the development of preventive strategies aimed at reducing prevalence rates.

To investigate the risk factors for asthma and allergic diseases in a large number of adults who are the parents of children in the National Asthma Campaign Manchester Asthma and Allergy Study.

All pregnant women and their partners attending ‘Booking’ antenatal clinics were invited to take part in the study. Questionnaire data were collected including the history of asthma and other atopic diseases, pet ownership and smoking habits, and skin prick tests were performed. The prevalence of atopy and the risk factors for asthma and allergic disorders were investigated in all subjects who completed the questionnaire and underwent skin testing. Statistical analysis was carried out using logistic regression. Initially, risk factors were assessed by univariate analysis to see how each potential explanatory variable affected the probability of having allergic disease. Variables were then tested in a forward stepwise multivariate analysis.

In 5687 adult subjects there was a very high (48.2%) prevalence of atopy, and 9.7% of subjects had a diagnosis of asthma. In a multivariate regression analysis sensitization to dust mite, cat, dog and mixed grasses were all independently associated with asthma. The odds ratios for current asthma increased with the increasing number of positive skin tests (any two allergens – OR 4.3, 95% CI 3.3–5.5; any three allergens – OR 7.0 95% CI 5.3–9.3; all four allergens – OR 10.4, 95% CI 7.7–14; P < 0.00001). Dog ownership (OR 1.31, 95% CI 1.10–1.57; P = 0.003) and current smoking (OR 1.36, 95% CI 1.15–1.62; P = 0.0004) were significantly and directly associated with ’asthma ever’. Thirteen per cent of participants reported a history of eczema. In the multivariate analysis the strongest independent associate of eczema was sensitization to dog (OR 1.37, 95% CI 1.14–1.63, P < 0.0001). Apart from dog, the strength of the association between sensitization to common allergens and eczema appeared to be much lower than in the case of asthma. The prevalence of hay fever was high (20.6%), and in the multivariate analysis the association between sensitization to pollen and hay fever was extremely strong (OR 13.6, 95% CI 11.3–16.3; P < 0.0001).

The results of the current study emphasize the importance of sensitization to indoor allergens in asthma. However, evidence of a possible direct role of allergen exposure in asthma causation remains unclear.
Does tobacco smoke prevent atopic disorders? A study of two generations of Swedish residents
Authors: Hjern A. , Hedberg A. , Haglund B. , Rosén M.
Published: March 2003

Background Earlier studies have given conflicting results regarding the effect of exposure to tobacco smoke on atopic sensibilization.

Methods A cross‐sectional study of present and former smoking habits in relation to atopic disorders from data on 6909 young and middle‐aged adults (16–49 years) and their 4472 children (3–15 years) from the Swedish Survey of Living Conditions in 1996–97.

Results The prevalence of allergic asthma and allergic rhino‐conjunctivitis decreased, in a dose–response manner (P = 0.03 and P = 0.004, respectively), with increasing exposure to tobacco smoke in the adult study population. This pattern was little changed when potential confounders (sex, age, education, domicile, country of birth) were entered into a multivariate analysis: the adjusted odds ratio (OR) for allergic rhino‐conjunctivitis was 0.5 (0.4–0.7) for those who smoked at least 20 cigarettes a day and OR 0.7 (0.6–0.9) for those smoking 10–19 cigarettes, compared with those who reported that they never had smoked Former smokers had a tendency for a slightly lower risk: OR 0.9 (0.8–1.0). In a multivariate analysis, children of mothers who smoked at least 15 cigarettes a day tended to have lower odds for suffering from allergic rhino‐conjunctivitis, allergic asthma, atopic eczema and food allergy, compared to children of mothers who had never smoked (ORs 0.6–0.7). Children of fathers who had smoked at least 15 cigarettes a day had a similar tendency (ORs 0.7–0.9).

Conclusions This study demonstrates an association between current exposure to tobacco smoke and a low risk for atopic disorders in smokers themselves and a similar tendency in their children. There is a need for further studies with a prospective design to certify the causal direction of this association. Smoking habits and atopic disorder in parents should not be considered independent variables in epidemiological studies of the connection between exposure to tobacco smoke and atopy in children.
The importance of housing characteristics in determining Der p 1 levels in carpets in New Zealand homes
Authors: Wickens K. , Mason K. , Fitzharris P. , Siebers R. , Hearfield M. , Cunningham M. , Crane J.
Published: March 2003

Background A previous study of homes in Wellington, New Zealand showed that having carpets on floors was the most important determinant of floor Der p 1 levels, but there was much unexplained variability between houses in carpet levels.

Objective To determine to what extent housing characteristics might explain this variability in Der p 1 levels between houses.

Methods We returned to a selection of houses with carpets and sampled living room dust from 1 square metre for 1 min and from the whole floor at 5 m2 per min. Der p 1 levels were estimated by double monoclonal antibody ELISA and are expressed as geometric mean µg/g and µg/m2 (95% confidence intervals). Questionnaires were used to collect information on housing characteristics.

Results Der p 1 levels were significantly higher in the 1 square metre sample (40.0, 31.9–50.2 µg/g; 53.4, 41.4–68.9 µg/m2) than in the whole room (25.8, 21.3–31.1 µg/g; 5.3, 3.8–7.4 µg/m2). However, results from the different sampling methods were correlated (r = 0.51, P = 0.001 for µg/g and r = 0.58, P = 0.001 for µg/m2). After controlling for possible confounders, houses with insulation or a room or garage below the living room had approximately half the Der p 1 concentration (P = 0.05 for both samples) and the amount of Der p 1 per m2 (P = 0.004 for the 1 square meter sample, P = 0.06 for the whole room sample) than houses without these features. Having more than two children was associated with higher levels of Der p 1 in 1 square meter, significant (P = 0.05) for µg/m2. Carpet underlay less than 8 mm thick was associated with an almost 3‐fold increase in ug/m2 Der p 1 (P = 0.03) and a 1.6‐fold increase in ug/g Der p 1 (P = 0.08) in the whole room sample, when compared with thicker carpet underlays.

Conclusion The presence of insulation is the single most important housing characteristic explaining the between‐house variability in Der p 1 levels on carpeted living room floors.
Increased expression of cytosolic phospholipase A2, 5‐lipoxygenase and 5‐lipoxygenase‐activating protein in rat peritoneal macrophages during ovalbumin‐induced sensitization
Authors: Escoubet‐Lozach L. , M'Rini C. , Rey A. , Béraud M. , Lepert J.‐C. , Courtade M. , Frisach M.‐F. , Pipy B.
Published: March 2003

Background Macrophages are involved in immediate hypersensitivity reactions by their ability to release leukotrienes involved in the symptomatology of allergy. To date it is unknown whether this ability to secrete leukotrienes has been favoured by modifications, occurring during the sensitization phase, of the enzymes involved in leukotriene metabolism.

Objective We used ovalbumin‐sensitized rats to study the expression of cytosolic phospholipase A2 (cPLA2), 5‐lipoxygenase (5‐LO) and 5‐lipoxygenase‐activating protein (FLAP) in peritoneal macrophages during active sensitization. We compared basal and challenged (PMA, A23187 and allergen) arachidonic acid (AA) metabolism of macrophages from control (cPM) and sensitized (sPM) rats. Then we tested, in cultured cPM, whether IL‐4, the predominant cytokine of sensitization process, could reproduce the enzymatic modifications occurring in macrophages during sensitization.

Methods cPLA2, 5‐LO and FLAP expression was assessed by Western blotting. The arachidonic acid (AA) metabolism study was performed after incorporation of tritiated AA in macrophages and analysis of secreted tritiated eicosanoids.

Results Ovalbumin‐sensitization of rats increased cPLA2, 5‐LO and FLAP expression in peritoneal macrophages. These increased expressions were not paralleled by modifications of basal and PMA‐ or A23187‐stimulated AA metabolism of sPM. However, when macrophages encountered the specific allergen for a second time, sPM secreted higher levels of leukotrienes than cPM. IL‐4 induced FLAP expression in cPM but had no effect on cPLA2 and 5‐LO expression.

Conclusion Active sensitization of rats induces an increase, in peritoneal macrophages, of the enzymes involved in leukotriene metabolism. The increased leukotriene secretion of sPM in response to ovalbumin challenge may be favoured by this increased expression of cPLA2, 5‐LO and FLAP that, however, is not able to lead to modifications of macrophage AA metabolism in any circumstance. Our results also suggest that IL‐4 is not the major element originating the enzymatic modification induced by sensitization in peritoneal macrophages.