bluuebunny/crossref_metadata_2025 huggingface dataset:
UROMODULIN Mutations Cause Familial Juvenile Hyperuricemic Nephropathy
Authors: Turner J. J. O. , Stacey J. M. , Harding B. , Kotanko P. , Lhotta K. , Puig J. G. , Roberts I. , Torres R. J. , Thakker R. V.
Published: March 2003

Gout, which is commonly associated with hyperuricemia, affects 0.2% of the population. Hyperuricemia has a heterogeneous etiology that may be due to either over production and/or reduced renal clearance, of urate. In order to identify the mechanisms underlying reduced excretion of urate, we undertook positional cloning studies of familial juvenile hyperuricaemic nephropathy (FJHN), which is an autosomal dominant disorder characterized by hyperuricaemia, a low fractional renal excretion of urate, and chronic renal failure that is associated with interstitial fibrosis. The FJHN locus has been previously localized to a 22 centiMorgan interval flanked centromerically by D16S401 and telomerically by D16S3069, on chromosome 16p11-p13. This interval contains over 120 genes and we selected 13 renal expressed sequences to search for mutations in 5 unrelated FJHN families that contained 21 affected and 24 unaffected members. This revealed 5 heterozygous missense mutations (Cys77Tyr, Cys126Arg, Asn128Ser, Cys255Tyr and Cys300Gly) that altered evolutionary conserved residues in the gene encoding UROMODULIN. UROMODULIN, which is an 85 Kda glycoprotein, has roles in renal stone formation, the modulation of immune responses, and urothelial cytoprotection. The results of our studies, which have identified the gene causing FJHN, now indicate a further, novel role for UROMODULIN in urate metabolism.
Relationship between mite, cat, and dog allergens in reservoir dust and ambient air
Authors: Custovic A , Simpson B , Simpson A , Hallam C , Craven M , Woodcock A
Published: March 2003

Background: Standardized methods to measure allergen exposure are essential to assess the relationship between exposure, sensitization, and asthma. Most studies have measured allergen levels in reservoir dust, although air samples may be more representative as a measure of inhaled allergen. The aim of this study was to define the relationship between mite, cat, and dog allergen content in the reservoir dust and the levels in the ambient air.

Methods: Dust samples from the living‐room floor (LF) and sofa (S) were collected in 127 homes: 62 without and 65 with pets (31 dogs, 34 cats). Air samples were taken in the same room, with a high‐volume pump for 1 h (flow 60 l/min). Der p 1, Fel d 1, and Can f 1 were determined by mAb‐based ELISA.

Results: Airborne Der p 1 was below the detection limit (0.8 ng/m3) in all homes, with reservoir levels (GM and range) being 1.14 μg/g (0.2–66) and 1.15 μg/g (0.2–127) in LF and S, respectively. Airborne Can f 1 was detected in 40/62 homes without pets (range 0.6–12.4 ng/m3) and in all homes with dogs (range 0.5–99 ng/m3). In the multiple linear regression analysis, Can f 1 level in the LF was an independent correlate of the airborne Can f 1 (P=0.01, homes with dogs; P=0.04, homes without dogs). Fel d 1 was detected in the air in 16/62 homes without pets (range 0.16–1.8 ng/m3) and in all homes with cats (range 0.4–22.3 ng/m3). Fel d 1 level in the LF was an independent correlate of the airborne Fel d 1 in homes without cats (P=0.008), but airborne levels in homes with cats did not correlate with reservoir levels.

Conclusions: The aerodynamics of each allergen must be taken into account when assessing exposure: while levels in reservoir dust are the best available index for mite allergens, airborne levels might be more suitable for defining exposure to pets. If air samples are difficult to obtain, levels of Can f 1 and Fel d 1 in the LF samples should be used as a surrogate measure of personal exposure.
The patch test, skin prick test, and serum milk‐specific IgE as diagnostic tools in cow's milk allergy in infants
Authors: Vanto T , Koivikko A , Valovirta E , Juntunen‐backman K , Klemola T , Syvänen P , Varjonen E , Kalimo K , Koskinen P
Published: March 2003

We evaluated the value of the patch test, skin prick test, and milk‐specific IgE by CAP RAST in 301 infants with suspected hypersensitivity to cow's milk. The patch test was carried out with milk powder, and the skin prick test with cow's milk‐based formula. Hypersensitivity to cow's milk was determined with double‐blind, placebo‐controlled challenge. An immediate reaction to cow's milk challenge was observed in 100 infants (33%), a delayed reaction in 76 (25%), and a negative result in 125 (42%). Skin prick test wheals were significantly greater in infants with immediate reactions than in infants with delayed or negative reactions. Milk‐specific IgE was correlated with the skin prick test (r=0.78, P<0.001, n=268) but did not contribute to further discrimination of immediate reactions from delayed or negative reactions compared to skin prick test alone. In our study population, the skin prick test (diameter ≥3 mm) showed a specificity and sensitivity of 91% and 69%; the results for milk‐specific IgE (≥0.7 kU/l) were 88% and 58%, respectively. The patch test did not distinguish subjects with immediate or delayed reactions from those with negative reactions.
Experimental common cold increases mucosal output of eotaxin in atopic individuals
Authors: Greiff Lennart , Andersson Morgan , Svensson Christer , Andersson Eva , Linden Margareta , Myint Steven , Persson Carl G.A.
Published: March 2003

Background: In view of recent observations demonstrating that rhinovirus infections are associated with increased local activity of eosinophils, we hypothesized that eotaxin, a selective eosinophil chemoattractant, may be involved in eosinophil recruitment/activation in common cold infections.

Methods: Twenty‐three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 (HRV 16) outside the pollen season. Sequential diluent and allergen (103 SQ‐U) challenges, each followed by nasal lavage, were carried out about 3 months before and 4 days after virus inoculation.

Results: Seventeen patients developed common cold and were further analyzed. Lavage fluid levels of eotaxin were increased at the height of active common cold (day 4 after inoculation) both at baseline (after diluent challenge) (P<0.01) and acutely after allergen challenge (P<0.05).

Conclusions: Common cold symptoms after nasal HRV 16 inoculation are associated with increased nasal mucosal output of eotaxin, suggesting that this chemokine is partly responsible for recruitment/activation of airway mucosal eosinophils in common cold infections.
Cow's milk IgE and IgG antibody responses to cow's milk formulas
Authors: Oldæus G , Björkstén B , Jenmalm MC , Kjellman N.‐I.M , Oldæus G
Published: March 2003

For comparison of the antigenicity and allergenicity of three cow's milk formulas, serum IgE antibodies to cow's milk, β‐lactoglobulin and casein, and IgG antibodies to β‐lactoglobulin were analyzed in 94 infants with a family history of allergy. They were participating in a randomized trial comparing the allergy prophylactic effect of feeding an extensively hydrolyzed (N), a partially hydrolyzed (PH), and a regular cow's milk formula (RM). Only infants who had been formula‐fed for 3 months or more were included. IgE antibodies to cow's milk proteins were more common in the RM group (22/34) than in the N (2/31) and PH groups (3/29). There was a strong correlation between sensitization to cow's milk and β‐lactoglobulin (r=0.85, P<0.001). The IgG responses to β‐lactoglobulin were low in the N group, intermediate in the PH group, and high in the RM group. High responses, as well as detection of IgE antibodies, were associated with development of atopic disease. The low antigenicity and allergenicity of the extensively hydrolyzed formula support its use in allergy prophylaxis. The partial hydrolysate seemed to be less suitable for this purpose.
Effect of pre‐ and postnatal tobacco smoke exposure on specific sensitization to food and inhalant allergens during the first 3 years of life
Authors: Kulig M , Luck W , Lau S , Niggemann B , Bergmann R , Klettke U , Guggenmoos‐Holzmann† I , Wahn U ,   Multicenter Allergy and Study Group, Germany
Published: March 2003

Background: The study aimed to assess the effect of pre‐ and postnatal tobacco smoke exposure on specific sensitization to food allergens and inhalant allergens during the first 3 years of life.

Methods: A total of 342 children of a prospective and observational birth cohort study on atopy (MAS) were included on the basis of a complete follow‐up of specific IgE measurements at the ages of 1, 2, and 3 years with available questionnaire information about the parental smoking habit at birth, 18 months, and 3 years of age. Study children were grouped into four exposure categories representing in utero and postnatal environmental tobacco smoke (ETS) exposure, and according to the number of cigarettes smoked by the parents. The effect on the development of allergic sensitization to food, outdoor, and indoor allergens by 3 years of age was determined by multiple logistic regression analyses.

Results: At the age of 3, children who were pre‐ and postnatally exposed to tobacco smoke had a significantly higher risk of sensitization to food allergens (odds ratio: 2.3, 95% C.I.: 1.1–4.6) than unexposed children. Children who were only postnatally exposed by a smoking mother also had a 2.2 times higher risk (95% C.I.: 0.9–5.9) of sensitization than unexposed children. These two categories (pre‐ and/or postnatal exposure) contribute to the significant overall effect of the tobacco smoke exposure (P≤0.02). No significant association between tobacco smoke exposure and specific sensitization to inhalant allergens was observed. The determining risk factors for this type of sensitization were atopic family history and mite‐ and cat‐allergen exposure levels.

Conclusions: During the first 3 years of life, both prenatal and postnatal tobacco smoke exposure has an adjuvant effect on allergic sensitization which seems to be restricted to allergens to which children are mainly exposed, in combination with the peak of the ETS exposure around the first birthday.
Suppressive activity of bronchial macrophages recovered by induced sputum
Authors: Fireman E , Onn A , Levo Y , Bugolovov E , Kivity S
Published: March 2003

Background: The immunomodulatory activity of macrophages was shown to be a crucial mechanism in the pathogenesis of asthma.

Methods: Induced sputum (IS) and methacholine challenge (MC) were carried out in 21 atopic subjects. Suppressive activity (SA) of sputum macrophages (SMO) was investigated on autologous peripheral lymphocytes (APL) proliferation in 12 of these patients and compared to the MC.

Results: In 10 of the 21 patients, the FEV1 was >80%; five of these had a nonreactive MC. Eosinophils and metachromatic cells correlated well (r=0.6442; P=0.0029), but not with the MC. The SA of SMO correlated (P=0.0152) with the MC: SMO enhanced APL proliferation in five patients with a positive MC, while SMO showed SA in five with a negative MC. Only two patients with suppressive SMO had a positive MC. Cytokine profiles from five patients showed that two patients with a negative MC had interleukin (IL)‐1α and β, IL‐6, and transforming growth factor (TGF)‐β transcripts, while two patients with a positive MC transcripted IL‐4 and IL‐5. One patient with a borderline MC transcripted IL‐5, but not IL‐4.

Conclusions: These data support the theory that patients with reduced suppressive bronchial macrophages display clinical bronchial hyperreactivity.
Immunologic characterization of a recombinant American cockroach (Periplaneta americana) Per a 1 (Cr‐PII) allergen
Authors: Wang NM , Lee MF , Wu CH
Published: March 2003

Background: Previously, we have identified several Per a 1 (Cr‐PII) allergens from a λgt22A cDNA library of Periplaneta americana. This study aimed to sequence clone C42 and determine its molecular and antigenic properties.

Methods: The cDNA of C42 was sequenced and ligated into a bacteria expression vector, pET21. The recombinant proteins were purified by ion‐exchange and affinity chromatographies. Their antigenicities were analyzed by immunoblotting, ELISA, and binding inhibition with human IgE.

Results: The nucleotide of the cDNA has been sequenced and the deduced amino acid which encodes a 446‐amino‐acid protein (50 kDa) determined. The recombinant C42 protein can bind both anti‐Per a 1 monoclonal antibodies and human IgE and showed a 54.4% (12/22) skin reactivity in atopic patients. Sequence homology searches revealed a high degree of identity to two other members of the Per a 1 family, C17 and C6, and the German cockroach (Blattella germanica) Bla g Bd90K allergen. Interestingly, these allergens all contain internal repeats, and the crude B. germanica extract, Per a 1, and recombinant allergens share similar antigenic determinant(s) as defined by ELISA and IgE‐binding inhibition studies. In IgE‐binding epitope studies, an immunopositive C42 fragment was first identified from partial protease digestion. Overlapping peptides were then generated by expression of restriction enzyme fragments in E. coli. The shortest peptide, C42‐P560, identified by monoclonal antibodies and human specific IgE, can inhibit IgE binding to C42.

Conclusions: An additional Per a 1 allergen has been defined at the molecular level and characterized and preliminary results showed that a potential IgE‐reactive region is located within amino‐acid residue 358–446 of C42, which is an internal repeat. The results defined the boundaries of the antigenic site and will facilitate further epitope‐mapping studies.
The effect of immediate‐hypersensitivity reactions on the level of SLPI, granulocyte elastase, α1‐antitrypsin, and albumin in nasal secretions, by the method of unilateral antigen challenge
Authors: Westin U , Whil J‐å , Lundberg E , Ohlsson K
Published: March 2003

Background: The aim of this paper was to investigate the role of SLPI in patients with allergic rhinitis. From this point of view, we also examined leukocyte elastase, α1‐antitrypsin, and albumin.

SLPI is an inhibitor of serine proteases such as leukocyte elastase, cathepsin G, and mast‐cell chymase. Since chymase is considered to participate in mast‐cell degranulation and histamine release, SLPI might act as a regulator of allergic reactions. Recent interest has been focused on leukocytes and allergy. Since SLPI is a strong inhibitor of leukocyte elastase, we also focused on the function of elastase in allergic rhinitis.

Methods: We used the method of nasal lavage after unilateral nasal antigen challenge in atopic and healthy subjects. The ELISA quantified SLPI and elastase. Albumin and α1‐antitrypsin were quantified by electroimmunoassay. Gel filtration was used to separate native SLPI from its complex with elastase.

Results: There was a higher level of SLPI in lavage fluid from healthy subjects than from atopic patients. SLPI was increased on the contralateral side in atopic subjects after allergen challenge. The absence of increase in SLPI on the challenged side may be attributed to the increase in elastase and its binding to SLPI, which might have an effect on the immunoreactivity and interfere with the ELISA. It may then be assumed that there is an augmentation of SLPI on the challenged side as well. No increase was seen in healthy subjects. There was a higher concentration of elastase, α1‐antitrypsin, and albumin before antigen challenge in atopic patients outside the pollen season than in healthy subjects. As expected, an increase was also seen in the challenged side exclusively in atopic subjects.

Conclusions: The lower concentration of SLPI in nasal lavage fluid among the atopic patients than the healthy subjects indicates damaged mucosa. Neural reflexes are involved in SLPI release since there was an increase even in the contralateral nostril. A higher level of elastase and albumin before allergen challenge suggests chronic inflammation in nasal mucosa outside the pollen season. Leukocyte recruitment takes place in response to IgE‐mediated reactions, which are reflected in an increase in elastase in response to allergen challenge.
Indoor viable mold spores – a comparison between two cities, Erfurt (eastern Germany) and Hamburg (western Germany)
Authors: Koch A. , Heilemann K.‐J. , Bischof W. , Heinrich J. , Wichmann H.E.
Published: March 2003

Background: In eastern Germany, the prevalence of allergies is lower than in western Germany for both children and adults. Several reasons for this fact have been discussed, although it is still not completely understood. One purpose of the epidemiologic study “Indoor and genetic factors in asthma and allergy” (INGA) is to compare exposure to mold spores in two German cities. Therefore, 405 homes in Erfurt (east) and Hamburg (west) were visited twice by trained investigators between June 1995 and May 1997.

Methods: Samples of settled dust were taken by vacuuming from the carpet in the living room. Sieved house dust was diluted and plated on DG18 agar. The analyses were carried out in duplicate in the same laboratory.

Results: No significant difference could be shown for the total and for single genera (Alternaria, Aspergillus, Cladosporium, and Penicillium) in concentration of spores of viable fungi in settled house dust between Erfurt and Hamburg. Seasonal variation of the mold picture, with highest values in August, could be identified both indoors and outdoors.

Conclusions: Beccause that outdoor concentration is the main influence on indoor concentration of mold spores from June to October, we recommend sampling from November to May to evaluate exposure to indoor mold spores.
ICAM‐1 and α3β1 expression by bronchial epithelial cells and their in vitro modulation by inflammatory and anti‐inflammatory mediators
Authors: Vignola A. M. , Bonsignore G. , Siena L. , Melis M. , Chiappara G. , Gagliardo R. , Bousquet J. , Bonsignore G. , Merendino A. M.
Published: March 2003

Background: Adhesion molecules are involved in inflammatory and repair processes of the bronchial epithelium. ICAM‐1 is mainly involved in inflammatory reactions, whereas integrins, such as α3β1, are mainly involved in repair processes.

Methods: Using bronchial biopsies from 10 asthmatics and eight controls, we first evaluated by immunohistochemistry expression of α3β1 and ICAM‐1 in intact and damaged epithelium. Then, using the human pulmonary epithelial cell line WI‐26 VA, we studied, by flow‐cytometry, the modulation of ICAM‐1 and α3β1 expression, and, by ELISA, the release of fibronectin by proinflammatory cytokines, such as IL‐5, and anti‐inflammatory cytokines, such as IL‐4, TGF‐β, and EGF.

Results: α3β1 expression was slightly higher in asthma than in controls, as well as in damaged epithelium than in undamaged epithelium. ICAM‐1 expression was higher in asthma than in controls, and similarly distributed in intact or damaged epithelium. In vitro, α3β1 was significantly increased by TGF‐β, EGF, and IL‐4, and significantly decreased by IL‐5. Fibronectin release was significantly increased by TGF‐β and IL‐4, unchanged by EGF, and slightly but significantly decreased by IL‐5. ICAM‐1 expression was significantly decreased by TGF‐β and IL‐4, unchanged by EGF, and significantly increased by IL‐5.

Conclusions: These differences in adhesion molecule expression and fibronectin release may be important in epithelial cell inflammation and repair.
Sensitivity to fungal allergens is a risk factor for life‐threatening asthma
Authors: Black P. N. , Udy A. A. , Brodie S. M.
Published: March 2003

Background: Previous studies have suggested that sensitivity to Alternaria and Cladosporium may be risk factors for life‐threatening asthma. We have investigated this by studying the relationship between skin tests for fungal spores and admission to an intensive care unit (ICU) for asthma.

Methods: Skin prick tests for fungal spores (Alternaria tenuis, Cladosporium cladosporoides, Helminthosporium maydis, and Epicoccum nigrum), cat dander, house‐dust mite (Dermatophagoides pteronyssinus), and a seven‐grass mix were performed in three groups of patients: patients admitted to an ICU with an attack of asthma; those who had received emergency treatment for asthma but had not been admitted to an ICU, and those who had never required emergency treatment for their asthma.

Results: Twenty of 37 patients (54%) admitted to the ICU had a positive skin test for one or more fungal allergens compared with 15/50 patients (30%) in each of the other groups (P=0.005). The ICU patients were no more likely to have positive skin tests for the grass mix, cat dander, or house‐dust mite than the other patients.

Conclusions: A positive skin test for fungal allergens is a risk factor for admission to an ICU with an acute attack of asthma.
Severe atopic dermatitis is associated with sensitization to staphylococcal enterotoxin B (SEB)
Authors: Breuer K. , Wittmann M. , Bösche B. , Kapp A. , Werfel T.
Published: March 2003

Background:
Staphylococcus aureus has been identified as a possible trigger factor in atopic dermatitis (AD). Some 30–60% of S. aureus strains isolated from patients with AD are able to produce exotoxins with superantigenic properties, mostly staphylococcal enterotoxins A, B, C, and D (SEA–D) and toxic shock syndrome toxin‐1 (TSST‐1). Recently, it was demonstrated that the presence of IgE antibodies to SEA and SEB is correlated with the severity of skin lesions in children with AD. To determine the relevance of staphylococcal enterotoxins in adult patients with AD, we investigated the relationship between the severity of skin lesions and sensitization to SEA and SEB.

Methods: Clinical severity was determined by the SCORAD index. Circulating IgE antibodies to SEA and SEB, serum eosinophil cationic protein (ECP) levels, and urine eosinophil protein X (EPX) levels were measured.

Results: The skin condition was significantly worse in patients sensitized to SEB than in unsensitized patients. Serum ECP and urine EPX levels were found to be significantly higher in SEB‐sensitized patients, confirming the higher degree of cutaneous inflammation.

Conclusions: Our results demonstrate a relationship between severity of skin lesions and sensitization to SEB in adult patients with AD, but a relationship between disease activity and sensitization to SEA could not be shown.
Clinical and immunologic effects of long‐term sublingual immunotherapy in asthmatic children sensitized to mites:a double‐blind, placebo‐controlled study
Authors: Pajno G. B. , Morabito L. , Barberio G. , Parmiani S.
Published: March 2003

Background: Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy. We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy (SLIT) in asthmatic children with mite‐induced respiratory allergy.

Methods: Twenty‐four patients (age range 8–15 years), suffering from mild to moderate asthma, with single sensitization to mite allergen, were enrolled. After a 1‐year observation phase, patients were randomly allocated to one of two groups, and were given SLIT (sublingual‐spit) as drops for 2 years according to a double‐blind, placebo‐controlled (DBPC) design. Symptoms/medication scores (diary card), visual analog scale, and immunologic parameters (house‐dust‐mite [HDM]‐specific IgE, and total HDM‐specific IgG and IgG4) were determined during the observation phase and during the DBPC treatment period.

Results: Twenty‐one patients completed the study. At the beginning of the treatment, no difference in environmental allergenic pressure could be shown between the groups. After 2 years of therapy, there was a significant decrease in asthmatic symptoms (P=0.0001) and medication use (P=0.0001) in the active group compared to the placebo group. The visual analog score on overall asthma symptoms improved in the SLIT group (P=0.0001), but not in the placebo group. Nevertheless, the immunologic results did not show significant differences in HDM‐specific IgE and total HDM‐specific IgG or IgG4 between the active and placebo groups (P=NS). No relevant side‐effects were recorded throughout the study.

Conclusions: Our results suggest that treatment for 2 years with SLIT is clinically safe and effective in significantly decreasing respiratory symptoms in children with mild to moderate asthma sensitized to HDM. On the other hand, the lack of changes of the immunologic parameters calls for further investigations with special reference to kinetics and mechanism(s) of action of this mode of treatment.
Mechanisms involved in airway obstruction: the role of smooth muscle
Authors: Mazzarella G. , Stendardi L. , Grazzini M. , Scano G.
Published: March 2003

Structural changes in the airway walls that are probably driven by mediators released as a consequence of chronic allergic inflammation are prominent features of asthma. However, it is not clear how each of the many changes that occur in the airway wall contribute to altered airway function in asthma. Collagen deposition in the subepithelial matrix, around and inside the smooth muscle, would be expected to oppose the effect of smooth‐muscle contraction. Conversely, geometric factors would result in exaggerated airway narrowing for a given degree of smooth‐muscle shortening; decreased airway wall stiffness and increased airway narrowing for a given amount of force generated by the smooth muscle. Degradation of the matrix may alter the coupling between muscle and lung recoil, allowing exaggerated smooth‐muscle shortening. Increase in muscle mass associated with preservation of its contractile capacity could be the most important contributor to exaggerated airway narrowing.
Predictors of house‐dust‐mite allergen concentrations in dry regions in Australia
Authors: Vanlaar C. H. , Downs S. H. , Mitakakis T. Z. , Leuppl J. D. , Car N. G. , Peat J. K. , Marks G. B.
Published: March 2003

Background: House‐dust‐mite allergen content differs between houses and is thought to be a function of the housing characteristics and furnishing choices that affect indoor microclimate and mite proliferation. The importance of these features may differ with regional climates.

Methods: Concentrations of mite allergen were analysed as a function of housing features. Information on housing features was collected by questionnaire in 50 houses in two towns in a dry inland region of Australia. Mite allergen (Der p 1) was measured by ELISA in dust samples collected on five occasions over 2 years from beds and floors.

Results: Der p 1 was detected in all houses. Many housing features did not influence mite allergen concentrations. However, the presence of evaporative cooling increased mite allergen by 3.34‐fold in beds (P=0.007) and 3.94‐fold in floors (P=0.003). Mite allergen was threefold higher in mattresses >5 years old, and synthetic and feather duvets tended to have higher and lower levels of mite allergen, respectively.

Conclusions: In houses in dry, inland regions of Australia, evaporative cooling and older mattresses are associated with higher concentrations of mite allergen. Alternative forms of air conditioning to evaporative cooling may be useful for control of mite allergen in dry regions.
Comparison of quantitative ELISA and semiquantitative Dustscreen™ for determination of Der p 1, Der f 1, and Fel d 1 in domestic dust samples
Authors: Lau S. , Schulz G. , Sommerfeld C. , Wahn U.
Published: March 2003

Background: Quantitative ELISA kits used for the measurement of indoor all_ergens are time‐consuming. Therefore, an immunodot assay (Dustscreen™) has been introduced, so that results can be obtained within 4 h. In order to assess the potential applications of the new method, we compared quantitative ELISA methods and Dustscreen.

Methods: We compared the measurements of the mite all_ergens Der p 1 and Der f 1, and Fel d 1 by both Dustscreen and one brand of ELISA in 82 dust samples, and we also compared the measurement of the cat all_ergen Fel d 1 by Dustscreen and a different brand of ELISA in 77 dust samples. Optimum dilutions of dust extracts were compared between the ELISA and the immunodot assay. The nonparametric coefficient of correlation (Spearman's rank) was calculated for each all_ergen.

Results: The immunodot assay was easy to perform. There was a good correlation between the results of the ELISA and Dustscreen (Der p 1: r=0.98, Der f 1: r=0.93, and Fel d 1: r=0.98). However, the coefficient of variation varied between 50% and 100% for Fel d 1 above 100 000 ng/g in Dustscreen. No cockroach all_ergen (Bla g 2) was detected in domestic dust samples in Berlin, and lower concentrations of group 2 all_ergen of mite (from not detectable to 19 500 ng/gm; median concentration 2000 ng/g) were found than mite group 1 all_ergens (sum of Der p 1 plus Der f 1: median 12 350 ng/g, minimum n.d., maximum 153 120 ng/g).

Conclusions: Our results indicate that quantification of indoor all_ergens in house‐dust samples can be performed easily with Dustscreen, and both the technology and methodology are satisfactory.
Increased plasma eotaxin in atopic dermatitis and acute urticaria in infants and children
Authors: Hossny E. , Aboul‐Magd M. , Bakr S.
Published: March 2003

Background: The previously reported eotaxin overexpression in the lesional skin of atopic dermatitis (AD) led us to the assumption that circulating levels of eotaxin may be elevated too. We sought to investigate the plasma expression of eotaxin in children with skin all_ergy in relation to clinical activity and type of lesions.

Methods: Plasma eotaxin was assayed in 78 infants and children, of whom 16 had AD, 19 had acute urticaria (AU), and 43 were healthy matched subjects. Seven children in the group of AU were resampled for plasma eotaxin after clinical remission.

Results: The plasma eotaxin levels in AD (median=158 pg/ml, mean [SD]=168 [61] pg/ml) were significantly higher than the control values (median=60 pg/ml, mean [SD]=59.5 [18.5] pg/ml). Not only did patients with AU demonstrate elevated plasma eotaxin levels (median=126 pg/ml, mean [SD]=124 [33] pg/ml), but also a significant decline occurred on follow‐up. The coexistence of angioedema with AU did not cause any further increase in plasma eotaxin expression. Plasma eotaxin levels were significantly higher in AD than in AU, probably reflecting the chronic nature of eczematous AD lesions. The plasma eotaxin levels did not correlate with serum total IgE, peripheral blood absolute eosinophil count, or age of the patients. However, there was a positive correlation between age and plasma eotaxin in the control group.

Conclusions: Our findings imply that circulating levels of eotaxin increase in AD and during flares of AU, probably to serve in the recruitment and activation of eosinophils. It may also represent a biomarker of lesional activity.
Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine‐induced nasal response in healthy adult volunteers
Authors: Wang D.Y. , Hanotte F. , De Vos C. , Clement P.
Published: March 2003

Background: Cetirizine, an effective H1‐receptor antagonist, is a racemate mixture of two enantiomers: levocetirizine (R enantiomer) and dextrocetirizine (S enantiomer).

Methods: To investigate the pharmacologic activity of the two enantiomers of cetirizine, we conducted a randomized, double‐blind, four‐way, crossover study to assess the effect of treatment with 5 mg levocetirizine, 5 mg dextrocetirizine, and 10 mg cetirizine and matched placebo, on histamine‐induced changes in the nasal airways of 24 healthy volunteers. Four hours after a single oral intake, all subjects were challenged by nasal aerosol application with increasing doubling concentrations (from 0.25 to 32 mg/ml) of histamine in both nostrils. Nasal resistance was measured by passive anterior rhinomanometry (PAR), and changes in histamine threshold were calculated together with the absolute number of sneezes after each challenge.

Results: Both levocetirizine and cetirizine significantly attenuated the histamine‐induced increase in nasal airway resistance by nearly 50% (from a median resistance of 2.51 Pa per cm3/s to 1.29 and 1.31 Pa per cm3/s, respectively) at the maximal concentration, and they concomitantly increased the histamine threshold by fourfold (from 8 to 32 mg/ml), compared with placebo. Sneezing was also attenuated by both levocetirizine and cetirizine. However, these antihistaminic effects were not seen with dextrocetirizine.

Conclusions: This study shows a similar activity of levocetirizine and cetirizine on the inhibition of histamine‐induced increase in nasal resistance, indicating that the antihistaminic properties of cetirizine are probably attributable to levocetirizine.
Health‐related quality of life assessment in young adults with seasonal allergic rhinitis
Authors: Majani G. , Biardini I. , Giardini A. , Senna G.E. , Minale P. , D'Ulisse S. , Ciprandi G. , Canonica W.
Published: March 2003

Background: In health‐related quality of life (HRQL) studies on allergic rhinitis, both disease‐specific and generic questionnaires have been extensively used. Seasonal allergic rhinitis (SAR) has been studied mainly by focusing on symptomatology. The present study aimed to evaluate the SAR‐HRQL by means of two questionnaires, the Medical Outcome Study Short Form Health Survey (SF‐36) and a new instrument examining satisfaction in 32 aspects of daily life: the Satisfaction Profile (SAT‐P).

Methods: Thirty‐three patients with SAR (aged 33.5±8.5 years; 12 men, 21 women) were evaluated during and 2 months after the pollen season. Data were compared with reference samples by t‐test, and baseline and follow‐up HRQL scores were compared by a matched‐pair test.

Results: Patients' HRQL scores collected during the pollen season were significantly lower than reference sample data in many SF‐36 scores and in one SAT‐P item. No differences emerged between SF‐36 and SAT‐P scores collected outside the pollen season and reference sample scores. Compared to baseline, outside the pollen season, patients reported significantly higher scores in the following SF‐36 scales: physical functioning (P=0.002), physical role (P=0.00001), bodily pain (P=0.01), and vitality (P=0.008); and significantly higher scores in only two SAT‐P items (physical well‐being [P=0.009] and resistance to stress [P=0.01]).

Conclusions: Our data confirm the utility of using symptomatologic and health‐status questionnaires in evaluating the HRQL of SAR patients. More general quality of life questionnaires may prevent the symptomatologic and functional problems from being adequately recognized and managed. SAT‐P can be a fruitful additional tool in HRQL evaluation.
The relation between fungal propagules in indoor air and home characteristics
Authors: Ren P. , Jankun T. M. , Belanger K. , Bracken M. B. , Leaderer B. P.
Published: March 2003

Background: Questionnaires are commonly used in epidemiologic studies to obtain information about house characteristics in order to predict the household aeroallergen exposure levels. However, the reliability of the predictions made with the questionnaires has not been evaluated. To address this issue, we compared objectively measured fungal propagules including the most frequently isolated mold genera (i.e., Alternaria, Aspergillus, Cladosporium, Penicillium, etc.) in a large sample of homes and compared these measured values to the questionnaire‐determined household characteristics.

Methods: As part of a prospective cohort study on the relation between residential allergen exposure and development of asthma in neonates, fungal air samples were collected from infant bedrooms and main living areas in 1000 homes in the Northeast USA, from December 1996 to January 1999. A Burkard portable air sampler was used in combination with DG‐18 and MEA agars. A questionnaire was used to obtain information on host and house characteristics that may have an impact on the presence of fungal propagules in the air. This included information on observation of moisture problems (e.g., water leakage or damage, and mold or mildew growth), ventilation and heating facilities, building age and type, number of occupants, annual household income, presence of pets and pests, cleaning regimens, etc.

Results: The number of CFU/m3 air collected on MEA was significantly higher than on DG‐18 (means, respectively, 1033.5 and 846.0 CFU/m3) (P<0.0005). However, there was no significant difference between the numbers of CFU/m3 air collected from the main living area and from the infant bedroom. There was only a very weak relationship between the house characteristics, as described by questionnaire, and the presence of fungal propagules in indoor air. Only the temperature, relative humidity, season, and cats inside homes had a statistically significant impact on the presence of fungal propagules in indoor air.

Conclusions: The presence of fungal propagules in indoor air cannot be reliably predicted by home characteristics. Actual measurements are required for fungal exposure assessment, and the use of only one medium to collect samples in one location in a home might be adequate to represent residential levels of fungi in indoor air.
In utero and perinatal complications preceding asthma
Authors: Annesi‐Maesano I. , Moreau D. , Strachan D.
Published: March 2003

Background: It has been suggested that pregnancy and early life may influence the development of asthma in the offspring, but published studies have not carefully controlled for potential biases.

Methods: In a large British birth cohort of 4065 natural children of 2583 mothers, we investigated whether in utero and perinatal influences contribute to the development and the severity of asthma in childhood, allowing for possible confounders of the relationship, and considering the nonindependence of familial data.

Results: Child asthma (10.1%) was more frequently reported by mothers when there had been health complications during pregnancy (prevalence=14.3%; adjusted odds ratio [ORadj]=2.01; 95% confidence interval, 1.52–2.67), labor, or delivery (19.3%, ORadj=1.35, 1.01–1.81); child illness or health complications during the first week of life (22.6%, ORadj=1.35, 1.01–1.82); and birth weight of <2.5 kg (7.0%, ORadj=1.57, 1.10–2.25). Specific causes of health complications during pregnancy which significantly related to asthma were early or threatened labor (ICD: 644) (4.8%, ORadj=1.58, 1.03–2.40) and the malposition or malpresentation of the fetus (ICD: 652) (1.6%, ORadj=3.63, 1.47–8.91).

Conclusions: The results provide further evidence that in utero and perinatal factors may increase the risk of developing asthma.
Chicken serum albumin (Gal d 5*) is a partially heat‐labile inhalant and food allergen implicated in the bird‐egg syndrome
Authors: Quirce S. , Marañón F. , Umpiérrez A. , De Las Heras M. , Fernández‐Caldas E. , Sastre J.
Published: March 2003

Background: Chicken serum albumin (α‐livetin) has been implicated as the causative allergen of the bird‐egg syndrome. However, the clinical relevance of sensitization to this allergen has not been confirmed by specific challenge tests and environmental sampling. We investigated whether chicken albumin can be detected in air samples collected in a home with birds, and whether sensitization to this protein may cause respiratory and food allergy symptoms. The heat resistance of chicken albumin and the possible cross‐reactivity with conalbumin were also investigated.

Methods: We studied eight patients with food allergy to egg yolk who also suffered from respiratory symptoms (rhinitis and/or asthma) caused by exposure to birds. Sensitization to egg yolk and bird antigens was investigated by skin and serologic tests. Hypersensitivity to chicken albumin was confirmed by specific bronchial, conjunctival, and oral provocation tests.

Results: All patients had positive skin tests and serum IgE against egg yolk, chicken serum, chicken meat, bird feathers, and chicken albumin. The presence of airborne chicken albumin in the domestic environment was confirmed. Specific bronchial challenge to chicken albumin elicited early asthmatic responses in six patients with asthma. An oral challenge with chicken albumin provoked digestive and systemic allergic symptoms in the two patients challenged. IgE reactivity to chicken albumin was reduced by 88% after heating at 90°C for 30 min. ELISA inhibition demonstrated only partial cross‐reactivity between chicken albumin and conalbumin.

Conclusions: Chicken albumin (Gal d 5) is a partially heat‐labile allergen that may cause both respiratory and food‐allergy symptoms in patients with the bird‐egg syndrome.
An allergen from Olea europaea pollen (Ole e 7) is associated with plant‐derived food anaphylaxis
Authors: Florido Lopez J. F. , Quiralte Enriquez J. , Arias de Saavedra Alías J. M. , Saenz de San Pedro B. , Martin Casañez E.
Published: March 2003

Background Several cross‐reacting proteins have been identified as responsible of the co‐occurrence of pollinosis and plant‐derived food allergy. This association has been mainly described in the birch–apple syndrome but other pollens such as Olea europaea and other fruits may also contain homologous proteins.

Objective To evaluate the associations between sensitization to allergens of Olea europaea pollen and confirmed plant‐derived food allergy, in addition to investigate if any pattern of clinical hypersensitivity of food allergy reaction (oral allergy syndrome (OAS) or anaphylaxis) and/or any fresh fruit or nut allergy, are associated to one or several Olea pollen allergen(s).

Methods One‐hundred and thirty‐four consecutive patients diagnosed with pollinosis by Olea were studied. Of these patients only 40, reported adverse reaction to plant‐derived food. Twenty‐one (group A) were classified as OAS and 19 (group B) as anaphylaxis. Skin‐tests with six Olea pollen allergens and several groups of fruits, were performed. Double‐blind placebo‐controlled food challenge (DBPCFC), confirmed the diagnostics of food allergy with the exception of patients who suffered previous anaphylactic reaction.

Results All patients, showed a positive skin prick test (SPT), against one or more of Olea europaea allergens. Sensitization to Ole e 7, was more frequent (P = 0.02) in patients from group B. A total of 84 DBPCFC were performed with 44% positive results. Challenge confirmed at least the 50% of positive SPT in any case (peach: 68.42%; pear: 50%; melon: 71.42% and kiwi: 53.84%). In patients from group B, significant association with O. europaea pollen allergens were found between positive SPT to Rosaceae fruits and Ole e 3 (P = 0.045) and Ole e 7 (P = 0.03); Cucurbitaceae and Ole e 7 (P = 0.03) and Actinidiaceae with Ole e 3 (P = 0.04).

Conclusions The results of this study, establish a new spectrum of associations between pollens and plant‐derived foods: sensitization to olive profilin (Ole e 2) is not more frequent in OAS patients. Patients with anaphylactic reaction after eating fruit are also sensitized to Ole e 7, a LTP present in Olea pollen, and suffer pollinic symptoms. Finally a polcalcin (Ole e 3) could be also associated to Olea pollen respiratory and food allergy.
No effect of oral treatment with an intestinal bacterial strain, Lactobacillus rhamnosus (ATCC 53103), on birch‐pollen allergy: a placebo‐controlled double‐blind study
Authors: Helin T. , Haahtela S. , Haahtela T.
Published: March 2003

Background: Oral probiotic bacteriotherapy with Lactobacillus rhamnosus has given promising results in small children with food allergy. We studied the effects of similar therapy in teenagers and young adults, who were allergic to birch pollen and apple food and had intermittent symptoms of atopic allergy and/or mild asthma.

Methods: We conducted a double‐blind, placebo‐controlled study, in which respiratory and eye symptoms and use of medications in two groups were compared. Open oral challenge tests with a slice of apple were performed trice: before, during and after the birch‐pollen season. There were 18 patients in each group. They used Lactobacillus rhamnosus for 5.5 months; 2.5 months before the pollen season, 1 month during the season (May), and 2 months after.

Results: The results were negative. The treatment did not alleviate the symptoms of the patients or reduce their use of medication during the birch‐pollen season or the subsequent 2 months. The treatment did not significantly affect the symptoms caused by apple in the oral challenge tests.

Conclusions: We found no indication of a beneficial treatment effect in our patients. As the number of patients was relatively small, conclusions should be drawn with caution.
Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three‐year prospective study
Authors: Pifferi M. , Baldini G. , Marrazzini G. , Baldini M. , Ragazzo V. , Pietrobelli A. , Boner A.L.
Published: March 2003

Background: Although widely practiced for over 80 years, the role of specific immunotherapy (SIT) in pediatric asthma treatment is still controversial. We assessed the effects of a 3‐year period of subcutaneous administration of a standardized preparation of Dermatophagoides pteronyssinus (D pt) on the respiratory health in a group of asthmatic children monosensitized to house dust mite (HDM).

Methods: A randomized clinical trial was performed after 1‐year run‐in period. Fifteen children receiving SIT for HDM and 14 controls (four drop‐outs), matched for age, allergen sensitization, asthma severity, lung function, and non‐specific bronchial reactivity (BHR), were studied during the 3‐year treatment period. During the whole trial, respiratory symptoms, pharmacological and respiratory function parameters were regularly evaluated. Skin prick tests and methacholine challenge were performed at the beginning and end of the study.

Results: In the SIT group significant improvement in asthmatic symptoms and marked reduction in drug intake was observed. The SIT group also showed a significant decrease in non‐specific bronchial BHR. No new sensitivity occurred during the study period in the SIT group only. No major local or systemic side‐effects were reported during the study.

Conclusions: Our results confirm that SIT is effective in asthmatic children sensitive to mites. It is associated with a decrease in BHR and it may prevent the development of new sensitizations in monosensitized subjects.
The relationship between alveolar epithelial proliferation and airway obstruction after ozone exposure
Authors: Jang A.‐S. , Choi I.‐S. , Koh Y.‐I. , Park C.‐S. , Lee J.‐S.
Published: March 2003

Background:  Proliferating cell nuclear antigen (PCNA) is a component of multiprotein complexes that are expressed during cell proliferation. Ozone induces cell necrosis and a consequent increase in cell proliferation.

Methods:  To investigate the effects of acute ozone inhalation on cell proliferation and airway obstruction in BALB/C mice, we examined enhanced pause (Penh) as an index of airway obstruction and PCNA expression by immunohistochemical staining.

Results:
 Compared with controls that received filtered air, the ozone‐exposed groups had increased PCNA expression in the alveolar epithelial cells. In rank order, the highest PCNA index was found following 2.0 p.p.m. ozone exposure. In the 2.0 p.p.m. ozone group, there was a PCNA index of 16.83 ± 0.57% (mean ± SEM;
P
< 0.01), compared with 4.25 ± 0.5% at 0.12 p.p.m., 6.83 ± 0.60 at 0.5 p.p.m and 12.16 ± 0.48% at 1 p.p.m. Following ozone exposure, Penh was increased in a dose‐dependent manner. There was a significant correlation between the PCNA index in alveoli and Penh (
r
 = 0.63,
P < 0.01).

Conclusions:  These data suggest that ozone can induce alveolar epithelial cell proliferation in a dose‐dependent manner, and that alveolar epithelial cell proliferation is correlated with airway obstruction.