bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitization to grass, ragweed, mugwort pollen allergens in Japanese monkeys (Macaca fuscata): preliminary report
Authors: Sakaguchi M. , Kobayashi C. , Inouye S. , Konaka A. , Yamada T. , Nigi H.
Published: March 2003

Background

The natural occurrence of Japanese cedar (CJ, Cryptomeria japonica) pollinosis has been reported in Japanese monkeys (Macaca fuscata). Furthermore, most of these monkeys with CJ pollinosis have immunoglobulin (Ig) E sensitization to Japanese cypress (Chamaecyparis obtusa) pollen. However, specific IgE to other pollens has not yet been reported.

Objectives

The present study was designed to investigate IgE sensitization of Japanese monkeys to grass, ragweed, and mugwort pollen.

Methods

Serum samples from 47 monkeys as a general population in one troop were collected at random. We measured specific IgE to grass, ragweed and mugwort pollen. Next, 10 monkeys with CJ pollinosis from the same troop were also examined for their IgE sensitization to grass, ragweed, and mugwort pollen.

Results

Of 47 monkeys, 13 (28%) had specific IgE to CJ pollen, 15 (32%) to grass pollen, five (11%) to ragweed pollen, and three (6%) to mugwort pollen. Furthermore, CJ pollinosis monkeys seemed to be sensitized to these pollen allergens with higher frequency; of 10 monkeys, 10 (100%) had specific IgE to CJ pollen, six (60%) to grass pollen, four (40%) to ragweed pollen, and two (20%) to mugwort pollen.

Conclusion

Japanese monkeys had specific IgE to grass, ragweed, and mugwort pollen in addition to CJ pollen.
Loratadine: a non‐sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation
Authors: Kay G. G. , Harris A. G.
Published: March 2003

Although equally potent at blocking the H1 receptor, first‐ and second‐generation antihistamines can be distinguished with respect to their different effects on the central nervous system (CNS). First‐generation antihistamines readily cross the blood–brain barrier leading to significant drowsiness, altered mood, reduced wakefulness, and impaired cognitive and psychomotor performance. This paper reviews of studies CNS functioning conducted with loratadine, a second‐generation H1‐receptor antagonist, at its therapeutic dose of 10 mg per day. Studies employing self‐report measures, such as diary cards, visual analogue scales, rating scales, and mood inventories have shown that the effect of loratadine on somnolence, fatigue, and mood was comparable to those found with placebo. In studies exploring physiological indices of CNS functioning, such as EEG‐evoked potentials, and sleep latency tests, loratadine has been shown to be free of CNS effects. In addition, studies have investigated the effects of loratadine on actual driving performance, and on tests of cognitive and psychomotor functioning. On all of these performance measures, loratadine has been shown to have effects comparable to placebo. In contrast, diphenhydramine, a common first‐generation antihistamine, usually available without a doctor's prescription, has significant adverse effects on vigilance, divided attention, working memory and psychomotor performance. Impairment has been shown to occur even in the absence of self‐reported sleepiness.
Arrhythmogenic mechanisms of non‐sedating antihistamines
Authors: Yap Y. G. , Camm A. J.
Published: March 2003

Antihistamines (H1‐receptor antagonists) are amongst the most frequently prescribed drugs worldwide for the treatment of allergic conditions. Recently, there have been reports that certain non‐sedating antihistamines, mainly terfenadine and astemizole, might be associated with the risk of rare but severe arrhythmias, namely torsades de pointes, particularly in overdosage, concomitant ingestion of imidazole or macrolide antibiotics and in patients with underlying cardiac or liver diseases. It has now been shown that the molecular target in human ventricle for the potassium channel blockade of antihistamine is HERG gene located in chromosome 7 that expresses the delayed rectifier IKr and appears to be involved in the congenital long QT syndrome. Mechanistic studies showed that blockade of IKr channels by these drugs leads to prolongation of the monophasic action potential (QT interval on surface electrocardiogram) which may then induce the development of early after‐depolarization and dispersion of repolarisation leading to torsades de pointes through re‐entry mechanism. There are still many questions that need to be answered such as the roles of other potassium channels (IKs, Ito, and Iped) and the relative expression of various potassium channels in different individuals which may be important in the pathogenesis of torsades de pointes with non‐sedating antihistamines. There is also a lack of information on the cardiac actions of newer non‐sedating antihistamines. It is hoped that with a better understanding of the arrhythmogenic mechanism of non‐sedating antihistamines, one will be able to identify those at risk patients and prevent any cardiac toxicity associated with antihistamines and ultimately death.
Fibrosis and airway remodelling
Authors: Redington
Published: March 2003

The term ‘airway remodelling’ is now widely used to refer to the development of specific structural changes in the airway wall in asthma. Particular interest has focused on subepithelial fibrosis, myofibroblast accumulation, airway smooth muscle hyperplasia and hypertrophy, mucous gland and goblet cell hyperplasia, and epithelial disruption. The presence of these features is generally accepted, but further studies are still required to define the changes occurring more precisely at the pathological and ultrastructural levels. Attention also needs to be directed towards the existence of such changes in small airways. The natural history of the response has not been well described: remodelling is present in the airways of asthmatic children and of adults with newly diagnosed asthma, and studies that have attempted to relate the extent of remodelling to disease severity have produced conflicting findings. The role of remodelling in the progressive decline in lung function leading to fixed airflow obstruction seen in some patients is also unclear. Epidemiological studies are currently hindered by the absence of a useful non‐invasive marker of remodelling. Airway remodelling is frequently assumed to be a consequence of chronic inflammation, but the precise relation between the remodelling and inflammatory components in asthma is unclear. The cellular and molecular events underlying the remodelling process are also poorly understood. There is therefore a need for the development and characterization of animal models that will allow these issues to be explored. Finally, the ability of currently available anti‐asthma therapies to prevent or reverse airway remodelling is uncertain. There is some evidence that early treatment with inhaled corticosteroids can lead to improved outcome in asthma but this needs confirmation. Studies addressing the ability of corticosteroid treatment to reverse established structural changes have not produced consistent findings, and there is little information with regard to other therapies such as theophylline and antileukotriene agents. Effective treatment of airway remodelling may require the development of novel therapies directed against appropriate targets.
Altered in vitro apoptosis of cultured mast cells prepared from an inbred strain of mice, NC/Kuj
Authors: Hiragun  , Morita  , Shindo  , Tanaka  , Kameyoshi  , Okabe  , Kanno  , Yamamoto
Published: March 2003

Background

An inbred strain of mice, NC, develops dermatitis associated with highly elevated serum IgE and dermal mast cell hyperplasia.

Objectives and methods

To clarify the mechanisms for the dermal mast cell hyperplasia in NC, we prepared bone marrow‐derived mast cells (BMMCs) from three strains of mice, NC/Kuj, C57BL/6 and BALB/c, and compare histamine contents, histamine release abilities, adhesive properties and apoptosis of the BMMCs.

Results

Compared with BMMCs obtained from C57BL/6 and BALB/c, NC/Kuj BMMC possessed higher histamine content and higher adhesive ability to plastic plates, although histamine release from BMMCs was found to be similar in the three strains. The most intriguing finding is the lack of apoptosis in the BMMCs from NC/Kuj upon growth factor deprivation as determined by DNA ladder formation and loss of membrane phospholipid asymmetry.

Conclusion

The altered in vitro properties of mast cells in NC/Kuj partially account for an increase of dermal mast cells, which might be involved in the development of skin lesions in NC.
Association between HLA genes and susceptibility to toluene diisocyanate‐induced asthma
Authors: Mapp  , Beghè  , Balboni  , Zamorani  , Padoan  , Jovine  , Baricordi  , Fabbri
Published: March 2003

Background

Only a small proportion of subjects exposed to isocyanates develop occupational asthma, suggesting individual predisposition. The human leucocyte antigen (HLA) class II molecules may play a crucial role in the development of the immune response to isocyanates.

Objectives

To investigate the role of HLA class II molecules in the development of toluene diisocyanate (TDI)‐induced asthma.

Subjects

Sixty‐seven asthmatic subjects and 27 asymptomatic exposed subjects (controls) were typed at the HLA class II DQA1, DQB1 and DRB1 loci by polymerase chain reaction (PCR)‐based techniques.

Results

The frequencies of DQA1*0104 and DQB1*0503 were significantly increased in asthmatics compared with asymptomatic exposed subjects, while DQA1*0101 and DQB1*0501 were significantly increased in asymptomatic exposed subjects. No significant difference was found in the distribution of DRB1 alleles between asthmatics and controls.

Conclusions

The results of this study indicate that HLA‐regulated immune mechanisms are involved in TDI‐induced asthma and that, in exposed subjects, specific factors may increase or decrease the risk of developing disease.
Occupational asthma caused by soybean flour in bakers—differences with soybean‐induced epidemic asthma
Authors: Quirce  , Polo  , Figueredo  , González  , Sastre
Published: March 2003

Background

Soybean dust has been identified as the causative agent of occupational asthma and asthma epidemics. Two main soybean hull allergens responsible for asthma outbreaks, Gly m 1 and Gly m 2, have been identified and purified.

Objective

The soybean allergens causing occupational asthma in exposed bakers were investigated and compared with those involved in epidemic asthma.

Methods

We report four bakers or confectioners with work‐related respiratory symptoms who were exposed to soybean flour used as a baking additive. The causative role of soybean flour was investigated by immunological tests and specific inhalation challenge tests. Soybean flour allergens causing occupational asthma were characterized by immunoblotting. Immunoglobulin (Ig) E‐reactivity to Gly m 1 and Gly m 2 was assessed using enzyme‐linked immunosorbent assay.

Results

Sensitization to soybean flour was demonstrated by skin and serological tests and was confirmed by positive inhalation tests. Bronchial challenge test to soybean flour extract elicited immediate or dual asthmatic responses. Immunoblotting with soybean flour and soybean hull extracts showed IgE‐binding mainly to high molecular weight (MW) allergens. There was an important individually different allergic response to inhalant soybean components. None of the patients showed IgE‐reactivity against Gly m 1 and only one patient showed IgE‐reactivity to the soybean hull allergen Gly m 2.

Conclusion

These bakery workers had developed IgE‐mediated occupational asthma to soybean flour. The allergens involved in occupational asthma caused by soybean flour are predominantly high MW proteins that are present both in soybean hull and flour, and they are different from the allergens causing asthma outbreaks, which are mainly low MW proteins concentrated in the hull.
Temporal patterns of mediator release during developing cutaneous late‐phase reactions
Authors: Zweiman  , Von Allmen
Published: March 2003

Background

Several inflammatory mediators have been found released in sites of cutaneous late phase reactions (LPR). However, the temporal pattern of their release during LPR development has not been characterized.

Objective

Determine hourly accumulation of mediator release in comparison with gross and inflammatory cell responses during developing LPR.

Methods

Skin chamber appended to sites of allergen and diluent control challenge with hourly collections. Then, study of exuding leucocytes in chamber bases.

Results

In the allergen‐challenged sites, histamine release peaked in the first hour, then low level release over the next 5 h. Lactoferrin release from neutrophils started by the second hour, likely associated with released IL‐8. Eosinophil cationic protein levels started increasing slightly later. The percentage of exuding leucocytes which were activated was significantly higher in the allergen challenge sites than in the control challenge sites

Conclusions

Both gross LPR and local inflammatory cell responses in the skin start soon after the immediate mast cell activation in IgE‐mediated responses. Such inflammatory responses include leucocyte activation and mediator release.
Endogenous interleukin‐10 suppresses allergen‐induced airway inflammation and nonspecific airway responsiveness
Authors: Tournoy  , Kips  , Pauwels
Published: March 2003

Background

The airway inflammation observed in asthma is orchestrated by activated Th‐2 lymphocytes relevant for the induction of altered airway responsiveness. An increasing body of evidence is accumulating that not only the pro‐inflammatory cytokines interleukin (IL)‐4 and IL‐5 but also the immunomodulating cytokines IL‐12 and possibly IL‐10 are crucial for regulating the allergic airway inflammation.

Objective

Since IL‐10 is capable of downregulating a broad spectrum of pro‐inflammatory cytokines, we wanted to address the role of endogenously produced IL‐10 in vivo in allergic asthma.

Methods

Knockout (IL‐10−/−) mice (C57BL/6‐IL10tm1Cgn) and wild‐type (WT) counterparts were immunized (day 0) and exposed (day 14–21) to ovalbumin (OVA). Airway inflammation and reactivity (AR), serum allergen‐specific IgE responses and cytokine profiles in the bronchoalveolar lavage fluid (BALF) were studied.

Results

The IL‐10−/− mice had more eosinophilic airway inflammation but comparable levels of allergen‐specific serum IgE compared to the WT mice after allergen challenge. The AR was comparably increased in the OVA challenged WT and IL‐10−/− mice vs sham‐exposed WT, but not vs sham‐exposed IL‐10−/− mice since these showed a higher baseline AR. IFN γ, IL‐4 and IL‐13 were comparable and IL‐5 was even lower in the BALF of the in IL‐10−/− mice compared to the similarly exposed WT mice.

Conclusion

These results indicate that IL‐10 plays an important and possibly direct role in the control of airway inflammation and responsiveness in an in vivo mouse model of allergy.
Complementary DNA cloning and expression of a newly recognized high molecular mass allergen Phl p 13 from timothy grass pollen (Phleum pratense)
Authors: Suck  , Petersen  , Hagen  , Cromwell  , Becker  , Fiebig
Published: March 2003

Background

Grass pollen extracts contain a range of different allergenic components that can be classified as having low, middle or high molecular mass. Almost 75% of patients allergic to grass pollen display immunoglobulin (Ig) E‐reactivity to allergens in the high molecular mass range of 55–60 kDa. These proteins have not yet been fully characterized on the protein and DNA level.

Objective

The aim of this study was to identify and characterize an allergen of the high molecular mass fraction of Phleum pratense pollen by N‐terminal protein sequencing and molecular cloning.

Methods

A previously uncharacterized allergen which migrates as a double band with a molecular mass of 55–60 kDa was biochemically purified and investigated by N‐terminal sequencing. Subsequently, a DNA primer was designed to amplify the corresponding cDNA using PCR. The cloned cDNA and deduced amino acid sequence were compared with sequence data bases. Immunoblots carrying the recombinant expression product were developed with monoclonal antibodies and sera derived from allergic subjects. The IgE‐binding capacity of natural and recombinant allergen was determined using EAST.

Results

The nucleic acid sequence as well as the deduced amino acid sequence consisting of 394 amino acids indicated homology with pollen specific polygalacturonases. Four potential sites for glycosylation and 16 cysteine residues were found. The recombinant expression product exhibited the same molecular size as the natural allergen and was clearly IgE‐reactive.

Conclusion

The newly characterized allergen Phl p 13, which shows homology with polygalacturonases, is clearly different from the allergen designated as Phl p 4 and therefore the high molecular mass fraction is composed of at least two different allergens. A possible reason why this important allergen has not been detected until now is that Phl p 13 and Phl p 4 are hardly separable by one dimensional SDS‐PAGE.
Experimental rhinovirus 16 infection increases intercellular adhesion molecule‐1 expression in bronchial epithelium of asthmatics regardless of inhaled steroid treatment
Authors: Grünberg  , Sharon  , Hiltermann  , Brahim  , Dick  , Sterk  , Van Krieken J. Han J. M.
Published: March 2003

Background

Rhinovirus infections in airway epithelial cells in vitro have been shown to upregulate intercellular adhesion molecule‐1 (ICAM‐1) expression. Epithelial ICAM‐1, in its dual role as the major rhinovirus receptor and as adhesion molecule for inflammatory cells may be involved in the pathogenesis of rhinovirus‐induced exacerbations of asthma.

Objective

We aimed to investigate the effect of experimental rhinovirus 16 (RV16) infection on ICAM‐1 expression in bronchial mucosal biopsies in asthma. In addition, the effect of 2 weeks pretreatment with inhaled budesonide (800 μg b.d.) on RV16‐associated changes in ICAM‐1 expression was studied.

Methods

The study had a parallel, placebo‐controlled design in 25 steroid‐naive nonsmoking atopic asthmatic subjects. After 2 weeks budesonide (BUD) or placebo (PLAC) pretreatment bronchoscopy was performed 2 days before (day −2) and 6 days after (day 6) RV16 inoculation (on days 0 and 1). Immunohistochemical staining for ICAM‐1 was performed on snap‐frozen bronchial biopsies. ICAM‐1 staining intensity on the basal epithelial cells was scored semiquantitatively from 1 (weak) to 3 (intense). Similarly, epithelial intactness was noted (1 = basal cells only, 2 = basal and parabasal cells, 3 = intact epithelium).

Results

ICAM‐1 scores were not significantly different between the groups at day −2 (P ≥ 0.08). Subsequent RV16 infection was associated with a trend towards an increase in ICAM‐1 expression in the BUD‐group (P = 0.07), whereas the increase was significant in the PLAC‐group (P = 0.03). However, the increase was not significantly different between the groups (P = 0.74). Epithelial intactness score was not different between the groups before RV16 infection (P ≥ 0.07), and no significant changes were observed in either group (P ≥ 0.59). Moreover, ICAM‐1 score did not correlate significantly with epithelium score in either group, at any time‐point (P ≥ 0.27).

Conclusion

We conclude that an RV16 common cold in atopic asthmatic subjects is associated with increased ICAM‐1 expression in the bronchial epithelium, which is not related to epithelial intactness. Glucocorticoid treatment does not appear to prevent the RV16‐associated increased ICAM‐1 expression. This suggests that other treatment modalities are required to protect against the spreading of infection during rhinovirus‐induced exacerbations in asthma.
Nasal hyperosmolar challenge with a dry powder of mannitol in patients with allergic rhinitis. Evidence for epithelial cell involvement
Authors: Koskela H. , Di Sciascio M. B. , Anderson S. D. , Andersson M. , Chan H.‐K. , Gadalla S. , Katelaris C.
Published: March 2003

Background

The responses to airway hyperosmolar challenges probably involve various inflammatory mediators. However, it is not fully understood which cell type/types are the source of these mediators. Potential cell types include mast cell, epithelial cell and the sensory c‐fibre nerve cell.

Objective

To clarify which cell types are involved with the mediator response to hyperosmolarity in the human airway.

Methods

Ten healthy subjects, 11 patients with nonactive allergic rhinitis, and nine with active allergic rhinitis were challenged intranasally with mannitol powder, and with sham provocation, on separate days. Symptoms were assessed by visual analogue scales and nasal patency by measuring the nasal peak inspiratory flow (nPIF). Nasal lavage fluid levels of α2‐macroglobulin (an index of plasma extravasation), substance P (an index of sensory nerve cell activation), tryptase (an index of mast cell activation) and 15‐hydroxyeicosatetraenoic acid (15–HETE, an index of epithelial cell activation) were analysed.

Results

Immediate, although transient burning was the most prominent symptom in all groups whereas only the patients with active rhinitis experienced a fall in nPIF. Mannitol significantly increased the nasal lavage fluid 15‐HETE levels in the allergic patients (P < 0.01 vs the sham challenge), but not in the healthy subjects. The increase in 15‐HETE correlated with nasal symptoms for itching (rs = 0.65, P = 0.019) and burning (rs = 0.72, P = 0.009). Detectable levels of tryptase was found only in five allergic subjects. Lavage levels of substance P and α2‐macroglobulin did not not change.

Conclusion

Epithelial cell seems to be involved with the mediator response to airway hyperosmolar challenge. The roles of sensory c‐fibre nerve cell and mast cell remained less clear.
IgE and IgG antibody responses to recombinant Alt a 1 as a marker of sensitization to Alternaria in asthma and atopic dermatitis
Authors: Vailes L. D. , Perzanowski M. S. , Wheatley L. M. , Platts‐Mills T. A. E. , Chapman M. D.
Published: March 2003

Background Sensitization to Alternaria alternata is a risk factor for the development of wheezing and asthma. Alt a 1 is the major Alternaria allergen causing sensitization in asthmatics. Some atopic dermatitis (AD) patients have very high immunoglobulin (Ig)E antibody (ab) to Alternaria as analysed by Pharmacia CAP, however, it is not clear whether these are specific responses or whether Alt a 1 is involved in disease symptoms.

Objective The aim of this study was to analyse specific IgE and IgG ab responses to recombinant Alt a 1 in asthmatic and AD patients and to compare these results to IgE ab against Alternaria measured by CAP.

Methods Sera from individuals who were IgE positive to Alternaria by CAP were obtained from 58 patients with asthma/rhinitis, 19 patients with AD, and 20 patients with cystic fibrosis (CF) who were included as specificity controls. IgE and IgG ab to recombinant Alt a 1 were measured by radioimmunoassay (RIA).

Results Of 43 asthma/rhinitis patients having an Alternaria CAP score > 2, a high percentage (93%) had both IgE and IgG ab to Alt a 1, emphasizing its importance as a major allergen. Only, 47% of AD patients with CAP score greater than 2 had ab to Alt a 1, and their levels were low when compared to the asthmatics. For CF controls, 75% of these patients had no IgE ab to Alt a 1, and those which were positive to Alt a 1 by RIA were also positive by CAP. Overall, patients with a low CAP (1–2) had a low prevalence (20–30%) of IgE or IgG ab to Alt a 1.

Conclusion IgE and IgG ab to Alt a 1 in asthmatics are good markers for sensitization to Alternaria. Although AD patients gave high Alternaria CAP scores, they had low or undetectable levels of IgE to Alt a 1, suggesting that other Alternaria allergens may be important in AD or that the CAP results are non‐specific. Recombinant allergens may provide more specific measures of sensitization to fungi.
Wasp venom immunotherapy induces a shift from IL‐4‐producing towards interferon‐gamma‐producing CD4+and CD8+T lymphocytes
Authors: Schuerwegh A. J. , De Clerck L. S. , Bridts C. H. , Stevens W. J.
Published: March 2003

BackgroundVenom immunotherapy (VIT) has proven to be very effective in hymenoptera venom anaphylaxis. However, the underlying immunoregulatory mechanisms of venom immunotherapy remain poorly understood. Recent studies measured the total amount of cytokine in culture supernatans, suggesting a shift in cytokine production from Th2 to a Th1 cytokine profile during VIT. We wanted to examine the contribution of specific T lymphocyte subpopulations, which is impossible using an extracellular method to determine cytokines in supernatants.

ObjectiveThe present study was designed to evaluate the effect of VIT on the percentages of type 1 (IL‐2, interferon‐gamma (IFN‐γ)) and type 2 (IL‐4) CD4+and CD8+T lymphocytes of patients with wasp venom anaphylaxis during immunotherapy.

MethodsPeripheral blood mononuclear cells of 20 individuals with a history of wasp sting anaphylaxis and a positive serum wasp venom specific IgE were isolated andin vitrostimulated with phorbol‐12‐myristate‐13‐acetate and ionomycin before VIT, at the end of a 5‐day semirush VIT and at 6 months during VIT. Three‐colour flow cytometric analysis was used for intracellular cytokine (IL‐2, IFN‐γ, IL‐4) detection in CD4+(CD3+CD8−) T lymphocytes and CD8+(CD3+CD8+) T lymphocytes.

ResultsAt the end of a 5‐day semirush VIT, there was a significant decrease in percentage of IL‐4‐producing CD4+and CD8+T cells, compared with cytokine‐producing cells before VIT (P = 0.0002 and 0.004). After 6 months of VIT, patients showed an increased number of IL‐2‐producing stimulated CD4+and CD8+lymphocytes compared with values before VIT (P = 0.002 andP = 0.0003). A higher amount of IFN‐γ‐producing stimulated CD4+and CD8+cells was found after 6 months of VIT (P = 0.001 andP = 0.0006). There was no correlation between cytokine‐producing cells and specific IgE for wasp.

ConclusionVenom immunotherapy induced a shift from IL‐4‐producing towards IFN‐γ‐producing CD4+as well as CD8+T lymphocytes.
Eosinophilic rhinitis accompanies the development of lower airway inflammation and hyper‐reactivity in sensitized mice exposed to aerosolized allergen
Authors: Hellings P. W. , Hessel E. M. , Van Den Oord J. J. , Kasran A. , Van Hecke P. , Ceuppens J. L.
Published: March 2003

Background Allergic rhinitis is a risk factor for the development of asthma. About 80% of asthmatic patients also have rhinitis. However, the pattern of induction of allergic rhinitis and asthma remains unclear.

Objective The purpose of this study was to investigate the development of upper airway inflammation in mice during the development of an asthma‐like disease and after an acute allergen provocation.

Methods BALB‐c mice were sensitized intraperitoneally (i.p) to ovalbumin (OA, days 1–13) and were challenged with aerosols of either OA or saline on 8 consecutive days (days 33–40). In a second experiment, chronic exposure for 8 days was followed by 10 days of rest and then an acute nebulized allergen provocation was performed (day 50). Inflammatory parameters were investigated at different time‐points.

Results Upper and lower eosinophilic airway inflammation were simultaneously induced in the course of repeated inhalations of nebulized OA, as shown by analyses of nasal and broncho‐alveolar lavage fluids and histological sections of the nose and bronchi. Mice that developed bronchial hyper‐responsiveness also had increased thickness of the nasal mucosa on magnetic resonance image (MRI) scans. When chronic exposure was followed by acute allergen provocation, the latter caused a systemic increase in IL‐5 levels, with a concomitant rise in blood and airway eosinophils, primarily in the nose.

Conclusions Simultaneous induction of eosinophilic inflammation in the nose and lungs was found in a mouse model of respiratory allergy. These findings support the viewpoint that upper and lower airway disease represent a continuum of inflammation involving one common airway and provide evidence for the concept of global airway inflammation after inhalation of allergen.
Opiate‐sensitivity: clinical characteristics and the role of skin prick testing
Authors: Nasser S. M. S. , Ewan P. W.
Published: March 2003

Background The value of skin prick testing in opiate‐sensitive individuals is uncertain as opiates cause non‐specific weals by direct degranulation of mast cells.

Objective To define whether skin prick test (SPT) responses to opiates in opiate‐sensitive individuals are different to those seen in the normal population and to describe the clinical characteristics of this group of subjects.

Methods The SPT responses of eight opiate‐sensitive subjects to morphine 10 mg/mL, pethidine (meperidine) 50 mg/mL and papaveretum 15.4 mg/mL at four different concentrations (undiluted, 1/10, 1/50 and 1/100) were compared with the responses of 100 (32 atopic) non‐opiate‐sensitive control subjects. Four of the opiate‐sensitive subjects had a clinical history of asthma, rhinitis or urticaria on occupational exposure to morphine. One subject developed urticaria with codeine, one developed urticaria and asthma with morphine and diamorphine and two subjects reacted to intravenous papaveretum with anaphylaxis or urticaria. Five out of the eight cases had opiate sensitivity confirmed by single‐blind placebo‐controlled oral challenge.

Results Skin prick tests to all three opiates were not significantly different when the eight opiate‐sensitive subjects were compared with either the entire normal control group or the subgroup of 47 definite opiate‐tolerant controls that had previously received opiates for clinical indications. Furthermore, there were no significant differences in size of opiate SPT responses between atopic and non‐atopic control subjects. In the control subjects, there was a positive correlation in SPT weal size between the three opiates.

Conclusion Skin prick testing is not useful in the diagnosis of opiate sensitivity and placebo‐controlled challenge should be considered.
Identification of β‐lactoglobulin‐derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy
Authors: Inoue R. , Matsushita S. , Kaneko H. , Shinoda S. , Sakaguchi H. , Nishimura Y. , Kondo N.
Published: March 2003

Background Cow's milk allergy impairs the health and development of many infants since it deprives them of adequate nutrition. Cow's milk fractions contain many allergens, and β‐lactoglobulin (BLG) is one of the major allergens.

Objective The purpose of this study was to determine T cell epitopes, antigen‐presenting molecules and cytokine production by T cells in relation to BLG. The results can provide new therapeutic possibilities of using analogue peptides of BLG for infants with cow's milk allergy.

Methods Using a mixture of a panel of overlapping synthetic peptides that cover the entire BLG molecule, we established polyclonal BLG‐specific short‐term T cell lines and clones from peripheral blood mononuclear cells of four patients with allergy to cow's milk carrying most of the common human leucocyte antigen (HLA) haplotypes seen in the Japanese population. We then identified the T cell epitopes and antigen‐presenting molecules, and measured the production of cytokines interleukin (IL)‐4, IL‐5 and interferon‐γ in the culture supernatants.

Results The T cell lines established from the four patients responded to seven different peptides. Three of the peptides stimulated the T cells of two donors, regardless of the HLA types. The patterns of inhibition of the proliferative responses of the cell lines by anti‐HLA class II antibodies were heterogeneous; three were mainly inhibited by anti‐HLA‐DR mAbs, and the other was inhibited by anti‐HLA‐DQ mAbs. High levels of IL‐5 were produced by these T cell lines.

Conclusions Patients' T cells recognized BLG in association with a variety of HLA‐DR or ‐DQ as antigen‐presenting molecules. Although some peptides did have a more potent T cell stimulatory activity than others, the T cell receptor ligands formed with the BLG molecule are heterogeneous. Peptides for the desensitization of T cells of the patients with cow’s milk allergy need to be designed keeping in mind the different requirements in different ethnic groups.
Elevated serum concentrations of β‐tryptase, but not α‐tryptase, in Sudden Infant Death Syndrome (SIDS). An investigation of anaphylactic mechanisms
Authors: Buckley M. G. , Variend S. , Walls A. F.
Published: March 2003

BackgroundSudden Infant Death Syndrome, (SIDS) or cot death, remains the most common category of post‐perinatal death in the UK. By definition, the cause of death is unknown, but a long‐standing theory is that some of these deaths could be the result of anaphylaxis.

ObjectiveTo investigate the potential contribution of anaphylactic mechanisms to deaths in infancy by determining relative levels of α‐ and β‐tryptases and both total and allergen‐specific IgE in sera from groups of infants whose deaths were attributed to SIDS or to other causes.

MethodsSerum samples were collected at the time of post‐mortem examination from infants whose death was classed as SIDS (n = 40) and from a comparison group in which cause of death had been established (n = 32). Serum tryptase concentrations were measured with a radioimmunoassay with monoclonal antibody G5 which detects primarily β‐tryptase or an ELISA with antibody AA5 which has equal sensitivity for α‐ and β‐tryptases. Levels of total IgE and IgE specific for casein, β‐lactoglobulin, house dust mite and moulds were determined.

ResultsAnalysis of the results of the two assays for tryptase indicated that levels of the β‐like tryptase (the form secreted on anaphylactic degranulation) were significantly higher in serum from infants with SIDS compared with those whose death was explained. There was no evidence for an increase in serum levels of α‐tryptase (the variant secreted constitutively from mast cells). Total levels of serum IgE did not differ between the two groups and, reflecting the low circulating IgE concentrations in infancy, an elevation in IgE specific for the panel of allergens was not detected.

ConclusionsIn a proportion of SIDS victims there may be increased serum levels of β‐like tryptase, a marker for anaphylaxis. The failure to detect an increase in α‐tryptase would suggest that mast cell hyperplasia is not a feature of cot death. The nature of the inciting agents remains unclear, but anaphylaxis deserves serious consideration as a possible cause of sudden death in infancy.
Sputum induction: effect of nebulizer output and inhalation time on cell counts and fluid‐phase measures
Authors: Belda J. , Hussack P. , Dolovich M. , Efthimiadis A. , Hargreave F. E.
Published: March 2003

Background A knowledge of the factors that can affect induced sputum results is essential in order to standardize the procedure.

Objective We investigated the influence of nebulizer output on sputum cell counts and fluid phase measurements at increasing times of sputum induction.

Methods Eighteen adults with stable asthma inhaled an aerosol of 3% hypertonic saline to induce sputum after 7, 14 and 21 min on 2 days separated by 48 h. On one day, in random order, the ultrasonic nebulizer used had a relatively low output of 0.87 mL/min (particle size 5.58 µm mass median aerodynamic diameter, MMAD) and, on the other, a higher output of 1.90 mL/min (particle size 4.14 µm MMAD). The sputum was selected from each expectorate and examined blind to the induction procedures.

Results With both nebulizers, the 14‐ and 21‐min samples were lower in weight, neutrophils, eosinophils, eosinophil cationic protein (ECP) and interleukin (IL)‐8 and higher in macrophages. The higher output nebulizer induced sputum with higher cell viability and lower ECP and IL‐8.

Conclusion The results identify that the volume of hypertonic saline inhaled in sputum induction influences the fluid‐phase measurements. The duration of induction does alter the cell counts and suggests that the later expectorated sputum samples originate from more peripheral airways. The results draw attention to the need to standardize the volume and time of nebulization to accurately interpret and compare results.
Dietary fats and asthma in teenagers: analyses of the first Nutrition and Health Survey in Taiwan (NAHSIT)
Authors: Huang Song‐Lih , Pan Wen‐Harn
Published: March 2003

Background The occurrence of asthma may be associated with dietary factors.

Objective To examine the association between nutrient intake and physician‐diagnosed asthma and allergic rhinitis.

Methods A stratified, multiple‐staged sampling design was used to select study areas, in which household interviews were carried out to gather information on health status and 24‐h food recall. Data from 1166 adolescents, 13–17 years of age, were analysed.

Results In univariate analysis, total calorie and energy‐adjusted fat intake were associated with the prevalence of asthma, whereas vitamin A and vitamin C intake showed negative association with asthma. Multivariate logistic regression was used to adjust for sex and levels of urbanization; intake of saturated fats was associated with increased risk (OR = 2.02 for an increase of one SD, 95%CI 1.40–2.90), while monounsaturated fats were inversely related to asthma (OR = 0.65 for an increase of one SD, 95%CI 0.43–0.99). Vitamin C intake in the lowest quartile was associated with elevated risk for asthma with marginal significance (OR = 1.81, 95%CI 0.88–3.71, P = 0.10). None of the nutritional factors was associated with allergic rhinitis.

Conclusion Results from this cross‐sectional survey suggest that saturated and monounsaturated fats may have different effects on airway inflammation.
A randomized, double‐blind trial of the effect of glucocorticoid, antileukotriene and bβ‐agonist treatment on IL‐10 serum levels in children with asthma
Authors: Stelmach I. , Jerzynska J. , Kuna P.
Published: March 2003

Background Levels of an immunoregulatory and anti‐inflammatory cytokine IL‐10 are reduced in asthmatic airways, potentially contributing to more intense inflammation. Triamcinolone has anti‐inflammatory properties and the anti‐inflammatory effects of montelukast and formoterol have been discussed.

Objective The purpose of this study was to define the effect of treatment with triamcinolone, montelukast and formoterol on the serum level of IL‐10, eosinophil blood counts, eosinophil cationic response (ECP) and clinical parameters (symptom score, FEV1 and PC20H) in children with moderate asthma.

Methods An 8‐week, placebo‐controlled and randomized, double‐blind trial was carried out. The subjects were 91 children with moderate atopic asthma who were allergic to dust mite. Patients were randomly allocated to receive 400 µg triamcinolone (n = 19), 5 or 10 mg (according to age) montelukast (n = 18), 24 µg formoterol (n = 18) or placebo (n = 36).

Results Seventy‐nine children completed the study. After treatment with triamcinolone and montelukast the level of IL‐10 in blood serum significantly increased, eosinophil blood counts and ECP levels significantly decreased and all clinical parameters improved; treatment with formoterol had no effect on IL‐10 level, eosinophil blood counts in serum and bronchial hyper‐reactivity; ECP level significantly decreased after treatment and asthma symptoms and FEV1 improved significantly. Mean IL‐10 levels in serum before and after treatment with triamcinolone were 7.23 pg/mL with 95% CI, 6.74 –7.72% and 14.24 pg/mL with 95% CI, 11.6–16.88%, respectively (P < 0.001); with montelukast they were 6.59 pg/mL with 95% CI, 6.26–7.23% and 10.94 pg/mL with 95% CI, 8.24–12.65%, respectively (P < 0.002); with formoterol they were 7.06 pg/mL with 95% CI, 6.61–7.52% and 7.04 pg/mL with 95% CI, 6.15–7.93%. We found statistically significant correlations between serum level of IL‐10 and serum level of ECP after treatment with triamcinolone and montelukast.

Conclusion This study demonstrates that one possible way by which triamcinolone and montelukast contribute to inhibition of inflammation is by increasing IL‐10 levels.
Cloning and molecular characterization of the Hevea brasiliensis allergen Hev b 11, a class I chitinase
Authors: O'Riordain G. , Radauer C. , Hoffmann‐Sommergruber K. , Adhami F. , Peterbauer C. K. , Blanco C. , Godnic‐Cvar J. , Scheiner O. , Ebner C. , Breiteneder H.
Published: March 2003

Background In the last 10 years type‐I allergy against proteins from Hevea brasiliensis latex has become an acknowledged medical issue. Fruit‐allergic patients represent one risk group for developing latex allergy. Class I chitinases have been identified from chestnut, avocado and banana as relevant allergens. The chitin binding (hevein) domain from these class I chitinases has been postulated to bear the important IgE binding epitopes.

Objective To clone the cDNA of an allergenic latex class I chitinase, to express the recombinant protein and to determine its IgE cross‐reactivity with hevein (Hev b 6.02).

Methods A full‐length cDNA coding for a class I chitinase has been isolated from Hevea latex RNA by reverse transcription followed by PCR. The chitinase encoding sequence has been subcloned into the pMAL expression vector and expressed in E. coli as a fusion protein to maltose binding protein. The highly enriched recombinant protein fraction has been tested for its IgE binding capacity in immunoblots and ELISA. Furthermore, the pathogenesis‐related function of the recombinant protein was tested in a fungal growth inhibition assay.

Results The Hevea brasiliensis latex chitinase, designated Hev b 11, displays 70% identity to the endochitinase from avocado and its hevein‐domain 58% to hevein (Hev b 6.02). The recombinant Hev b 11‐maltose binding protein is recognized by latex‐ and fruit‐allergic patients with IgE binding in both, ELISA and immunoblots. Pre‐incubation of sera with rHev b 11‐maltose binding protein showed an overall 16% inhibition of subsequent binding to rHev b 6.02‐maltose binding protein on solid phase. The growth of F. oxysporum was inhibited in a dose dependent manner by addition of rHev b 11‐maltose binding protein to the culture.

Conclusions Hev b 11, a class I chitinase, is another allergen from Hevea latex with a chitin binding domain and displays a different IgE binding capacity compared with hevein.
The involvement of sensory neuropeptides in airway hyper‐responsiveness in rabbits sensitized and challenged to Parietaria judaica
Authors: D'Agostino B. , Advenier C. , De Palma R. , Gallelli L. , Marrocco G. , Abbate G. F. , Rossi F.
Published: March 2003

Background C‐fibres have received considerable attention in the context of airway hyper‐responsiveness (AHR), in fact several lines of evidence suggest that tachykinins might be involved in the pathogenesis of AHR.

Objective The aim of this study was to investigate the role of capsaicin‐sensitive sensory C‐fibres and tachykinins in rabbits sensitized to the major allergen of Parietaria judaica pollen (Par j1).

Methods Airway responsiveness was determined by exposing sensitized rabbits to cumulative concentrations of aerosolized histamine before and after an allergic challenge and after a pre‐treatment with either vehicle or capsaicin or tachykinin receptor antagonists. Bronchoalveolar lavage was performed following histamine challenge and total and differential cell counts were performed.

Results In sensitized rabbits, an AHR to inhaled histamine was observed 24 h after a Par j1 challenge. Capsaicin pre‐treatment inhibited the AHR achieved 24 h following antigen exposure (P < 0.01). Pre‐treatment with the tachykinin NK2 receptor antagonist, SR 48968, significantly reduced the antigen‐induced AHR (P < 0.05), while pre‐treatment with tachykinin NK1 (SR 140333) and NK3 (SR 142801) receptor antagonists did not significantly modify it. Bronchoalveolar lavage fluid obtained from vehicle and capsaicin‐treated rabbits challenged with Par j1 exhibited no significant differences in total and differential cell counts.

Conclusions Parietaria judaica‐induced AHR in immunized rabbits was shown to be inhibited by pre‐treatment with capsaicin, an effect that is not related to an action on the associated pulmonary infiltration of eosinophils. The involvement of NK2 receptor stimulation in this phenomenon also suggests that NK2 receptor antagonists may be useful for investigating mechanisms of bronchopulmonary alterations in asthmatic patients.
Airway inflammation in thunderstorm asthma
Authors: Wark P. A. B. , Simpson J. , Hensley M. J. , Gibson P. G.
Published: March 2003

Background Epidemics of acute asthma associated with thunderstorms occur intermittently worldwide, though airway inflammation during these acute episodes has not been characterized. The aim of this study was to characterize airway inflammation in thunderstorm asthma.

Methods Cases were recruited after presentation to the emergency room with acute asthma immediately following a thunderstorm (n = 6). They were compared to two control groups: a group of atopic asthmatics that had presented with acute asthma to the emergency room prior to the thunderstorm (n = 12), and a second group of corticosteroid naïve asthmatics who presented to the emergency room in the prior 12 months (n = 6). Subjects had spirometry, sputum induction and allergy skin tests acutely and at review 4 weeks later.

Results Thunderstorm (TS) cases were more likely to have a history of hay fever and grass pollen allergy, and less likely to be on inhaled corticosteroids (ICS) prior to presentation. Cases and control groups had a similar degree of moderate to severe acute airway obstruction (P = 1.0). TS cases had elevated sputum eosinophils (14.8% of total cell count) compared to controls (1%, 2.6%, P < 0.01). TS cases had higher sputum eosinophil cationic protein (ECP; 11 686 ng/mL) compared to controls (1883, 3300, P = 0.02) acutely. TS cases had more cells positive for IL‐5 (30%) compared to controls (1, 1.5%, P = 0.02). When adjusted for ICS use, TS cases had a risk ratio for elevated sputum eosinophils of 2.4 (1.23–4.69).

Conclusion Thunderstorm asthma is characterized by airway inflammation with IL‐5‐mediated sputum eosinophilia and eosinophil degranulation. These results are consistent with allergen exposure as the cause of the exacerbation, and are consistent with the thunderstorm‐induced grass pollen deluge as the cause of epidemic asthma after thunderstorms.