bluuebunny/crossref_metadata_2025 huggingface dataset:
House dust mite fauna of tropical Singapore
Authors: Chew  , Zhang  , Ho  , Lee
Published: March 2003

Introduction and aims

Sensitization to house dust mites is very common in the tropics. This study evaluated the dust mite fauna in Singaporean homes.

Methods

A total of 134 dust samples from 50 homes were evaluated. Dust mites were isolated, identified and quantified by standard techniques.

Results

Dust mites were isolated from 130/134 (97%) samples, with mites identified in all samples from sofas (n = 21) and carpets (n = 13), and 49/50 (98%) and 47/50 (94%) from mattresses and bedroom floors, respectively. All samples from sofas and carpets had more than 500 mites/g compared with 47/50 (94%) and 23/50 (46%) from mattresses and floors, respectively. Blomia tropicalis was the predominant mite (62% of total mites) followed by D. pteronyssinus (16% of total mites). Eight samples had a predominance of Sturnophagoides brasiliensis and Tarsonemus granarius. Other species that accounted ≈ 1% of mites identified included D. farinae, Austroglycyphagus malaysiensis, Cheyletus malaccensis, Malayoglyphus intermedius, Suidasia pontifica and Tyrophagus putrescentiae.

Conclusion

Dust mites were highly prevalent and present in high densities in Singaporean homes with B. tropicalis being the most prevalent species.
Residential characteristics influence Der p 1 levels in homes in Melbourne, Australia
Authors: DHARMAGE  , BAILEY  , RAVEN  , CHENG  , ROLLAND  , THIEN  , FORBES  , ABRAMSON  , WALTERS
Published: March 2003

Background

Exposure to house dust mite (HDM) allergens is an important risk factor for childhood asthma. Knowledge of environmental determinants of HDM allergen levels is essential before designing rational avoidance measures.

Aim

To investigate the effect of domestic characteristics on HDM allergen (Der p 1) levels in Melbourne homes.

Methods

Dust was collected from bed and floor of the bedrooms in 485 houses over a period of one year. Dust was analysed for Der p 1 levels using an enzyme‐linked immunosorbent assay. Temperature and relative humidity were measured at the visit. Details of residential characteristics were collected using a questionnaire. Statistically significant predictors of Der p 1 levels (P < 0.05) were identified using multiple linear regression.

Results

High levels of Der p 1 were observed in the floors (geometric mean 17.2 μg/g fine dust) as well as in the beds (geometric mean 20.3 μg/g fine dust). Der p 1 levels in the floor dust were significantly lower in winter and spring. They were higher in houses built before 1980 and those with central heating, weather board walls, damp bedrooms or fitted old wool carpets. Der p 1 levels in bed dust were significantly higher in houses built before 1980, with wooden floors built on stumps, with high relative humidity, with visible mould in the room, in beds with an old mattress or in beds without a quilt.

Conclusions

We would encourage construction of homes without carpets, wooden floors on stumps or weather board walls.
Mutant derivatives of the main respiratory allergen of cow are less allergenic than the intact molecule
Authors: KAUPPINEN  , ZEILER  , RAUTIAINEN  , RYTKÖNEN‐NISSINEN  , TAIVAINEN  , MÄNTYJÄRVI  , VIRTANEN
Published: March 2003

Background

Allergen immunotherapy offers an alternative for drug treatment in the management of allergic diseases. Because immunotherapy often induces side‐effects, less allergenic preparations would be beneficial.

Objective

The purpose of this study was to examine whether the allergenicity of a cow‐derived lipocalin allergen, Bos d 2, could be diminished by substituting or deleting carboxy‐terminal amino acids including the cysteine which forms a disulphide bond with a cysteine inside the molecule.

Methods

Four recombinant mutants of Bos d 2 were created by substituting or deleting the four most carboxy‐terminal amino acids. The immunological characteristics of the mutant preparations were compared with the unmodified rBos d 2 by Western blotting, ELISA inhibition, skin prick tests, and the proliferative responses of allergen‐specific T‐cell clones.

Results

In Western blot, one of the two monoclonal antibodies showed reduced binding to the preparations without the terminal cysteine. In contrast, the other monoclonal antibody, human IgE and rabbit immune serum bound equally well to all the preparations. ELISA inhibition analyses revealed, however, that the preparations without the terminal cysteine bound antibody less efficiently. They were needed 15–38 times more than the unmodified rBos d 2 to cause the same level of inhibition. Surprisingly, one of the mutants with the terminal cysteine but a mutated adjacent amino acid turned out to be the weakest in inducing skin reactivity. All the preparations stimulated well allergen‐specific T‐cell clones.

Conclusions

The results show that the allergenicity of a lipocalin allergen, Bos d 2, can be diminished by modifying the carboxy‐terminal end of the molecule. Modifications in the area which encompasses a disulphide bond impaired the antibody binding without affecting the T‐cell stimulatory capacity. It was also shown that in vivo tests are necessary for determining the allergenicity of a modified allergen.
Immunohistochemical investigation of the cellular infiltrates at the sites of allergoid‐induced late‐phase cutaneous reactions associated with pollen allergen‐specific immunotherapy
Authors: Eberlein‐König B. , Jung C. , Rakoski J. , Ring J.
Published: March 2003

Background

Reduction in the size of the allergen‐induced late‐phase reaction (LPR) is seen as a consequence of successful allergen specific immunotherapy.

Objective

It was the aim of this study to characterize the cellular infiltrate at the sites of cutaneous LPR that may occur following injection of a depot pollen allergoid (Allergovit®) during immunotherapy and thereby determine the immunological nature of the response.

Methods

Punch biopsies were taken 24 h after subcutaneous injection of a depot pollen allergoid from eight patients that showed LPR and a further five patients that did not. Additional biopsies taken 24 h after injection of allergoid‐free depot in the same patients served as controls. Immunoenzymatic labelling of the cryostat sections with different antibodies was performed with the APAAP technique. Results were expressed as cells/field (400 × magnification).

Results

Similar dermal cellular infiltrations were seen following depot allergoid injections in patients both with and without LPR. Patients with LPR showed statistically significant increases in total cells, CD4+ cells, CD11c+ cells, CD45RO+ cells, CD45RB+ cells and activated eosinophils at the reactions sites as compared with control sites. In patients without LPR CD11c+ cells, HLA‐DR+ cells and CD45RA+ T cells increased significantly. CD8+, CD1a+, NP57+, CD23+ and CD25+ cells did not differ significantly in either group.

Conclusion

These results indicate that activation of T cells, monocytes/macrophages and eosinophils at the sites of LPR following injection of depot allergoid are comparable with those following injection of allergen. Even in the absence of a cutaneous LPR, subsets of T cells and monocytes/macrophages increased. These cell activations may reflect events associated with the mechanisms of allergoid‐based specific immunotherapy, and suggest that at least part of the late‐phase reaction may be independent of IgE.
The systemic safety of fexofenadine HCl
Authors: Mason J. , Reynolds R. , Rao N.
Published: March 2003

Fexofenadine is a highly specific, H1‐receptor antagonist with a safety profile similar to placebo. In placebo‐controlled trials of seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU), the type and incidence of adverse events were comparable in fexofenadine and placebo recipients. Fexofenadine does not impair performance in tests of driving or psychomotor performance and has been shown to improve quality of life in patients with SAR. Fexofenadine has a high margin of safety and is also well tolerated in subjects with renal or hepatic impairment, in children and the elderly. No clinically significant drug interactions have been identified. Fexofenadine is not associated with cardiotoxicity. Unlike some other antihistamines, such as loratidine or cetirizine [1, 2], fexofenadine is truly non‐sedating, showing no dose‐related increase in sedation, even at high doses [3, 4]. Fexofenadine is formulated and marketed as the hydrochloride salt. The recommended dose of fexofenadine HC1 is 120 mg daily for SAR (either as 120 mg once daily or 60 mg twice daily) or 180 mg once daily for CIU.
Electrophysiological effects of cetirizine, astemizole and d‐sotalol in a canine model of long QT syndrome
Authors: Weissenburger J. , Noyer M. , Cheymol G. , Jaillon P.
Published: March 2003

Observations of torsades de pointes during therapy with terfenadine and astemizole has raised concern about the cardiac safety of non‐sedating H1‐antagonist agents. We compared cetirizine, another compound of that class, to d‐sotalol and to astemizole in a model of acquired long QT syndrome.

Open‐chest surgery was performed in adult beagle dogs anaesthetized with halothane and thiopental. Bradycardia was produced with β‐adrenergic blockade and sinus node crush. Four left ventricular intramyocardial unipolar monophasic action potentials (MAP) were recorded during atrial pacing at basic cycle lengths (BCL) 400–1500 msec, before and during three successive 1‐h drug infusions (0.14, 0.45 and 1.4 mg/kg/h for astemizole and cetirizine and 1.1, 2.2 and 4.5 mg/kg/h for d‐sotalol).

Dose‐ and bradycardia‐dependent prolongations of MAP duration (MAPD) were produced by d‐sotalol (P < 0.001) and astemizole (P < 0.001) but not by cetirizine. At BCL 1500 ms, the three infusions of astemizole prolonged endocardial MAPD from 323 ± 8 msec (mean ± SE) at baseline to 343 ± 10, 379 ± 13 and 468 ± 26 msec, respectively (n = 9). Sotalol prolonged that MAPD from 339 ± 6 msec to 377 ± 7, 444 ± 15 and 485 ± 24 msec (n = 7). In contrast, cetirizine did not prolong MAPD: 341 ± 8 msec at baseline Vs 330 ± 8, 324 ± 9 and 323 ± 11 msec (n = 9). Drug‐induced increase in transmural dispersion reached +79 ± 19 msec after astemizole, +59 ± 21 msec after d‐sotalol and only +7 ± 11 msec after cetirizine. Runs of ventricular tachycardias and torsades de pointes occurred during dose three of astemizole (5/9 dogs) and d‐sotalol (4/7 dogs) but never during cetirizine.

In the present model, astemizole and d‐sotalol but not cetirizine prolonged MAPD and transmural dispersions of repolarization and produced torsades de pointes. These results suggest that the halothane‐anaesthetized bradycardic dog could be a valuable model to discriminate drugs for their class III effects and proarrhythmic potencies.
Cardiovascular safety of fexofenadine HCl
Authors: Pratt C. , Brown A. M. , Rampe D. , Mason J. , Russell T. , Reynolds R. , Ahlbrandt R.
Published: March 2003

Background

Certain first‐ and second‐generation H1‐receptor antagonists are associated with prolongation of the corrected QT interval (QTc) and, in rare instances, with ventricular dysrhythmias, including torsades de pointes ventricular tachycardia.

Objective

To assess the effect of fexofenadine HCl, a new non‐sedating antihistamine, on QTc.

Methods

Dose‐tolerance, safety, and drug‐interaction studies with healthy volunteers; and clinical efficacy studies with seasonal allergic rhinitis patients were conducted. Twelve‐lead ECG data were collected pre‐ and postdosing or serially throughout these studies. Outliers were defined as QTc >440 msec with a ≥10 msec increase from baseline.

Results

Fexofenadine HCl at single doses up to 800 mg q.d. (once daily) and multiple doses up to 690 mg b.d. for 28 days in healthy volunteers resulted in no increases in QTc (recommended dose range is 120–180 mg daily); QTc changes were similar to placebo. Compared with placebo, there were no statistically significant QTc increases in patients receiving fexofenadine HCl 80 mg b.d. for 3 months, 60 mg b.d. for 6 months, or 240 mg q.d. for 12 months. No statistically significant increases in QTc were detected when fexofenadine HCl 120 mg b.d. was administered in combination with erythromycin (500 mg t.d.) or ketoconazole (400 mg q.d.) after dosing to steady‐state (6.5 days). In seasonal allergic rhinitis patients (n = 1160) treated with 40, 60, 120, or 240 mg b.d. fexofenadine HCl for 2 weeks, there were no dose‐related increases in QTc and no significant increases in mean QTc compared with placebo. Frequency and magnitude of QTc outliers with fexofenadine HCl and placebo were similar in all studies. No case of fexofenadine‐associated torsades de pointes has been observed in controlled trial experience with more than 6000 patients.

Conclusion

Fexofenadine HCl has been investigated more extensively for possible electrophysiological effects than any other antihistamine. Fexofenadine HCl has no significant effect on QTc, even at doses much higher than those used in clinical practice.
The bronchial microcirculation in asthma
Authors: Wilson
Published: March 2003

Airway wall remodelling in asthma involves a number of changes including increased vascularity, vasodilation and microvascular leakage. Evidence suggests that the number and size of bronchial vessels is increased in patients with asthma compared with normal controls. In particular, there may be increased numbers of vessels in patients with fatal asthma. Treatment with inhaled corticosteroids is now known to reduce this vascularity. Bronchial vessels may undergo proliferation in response to inflammatory stimuli. Many factors can induce angiogenesis including a range of mediators and growth factors. Others can cause a vascular response by causing vasodilation and microvascular leakage. Airway wall oedema is likely to be important in asthma but has not yet been quantified. It is thought that mast cells play a key role in modulating these vascular remodelling changes by releasing cytokines and growth factors. Many key issues remain to be resolved before we fully understand the role of the bronchial microcirculation in asthma. In the future, novel therapies may be directed towards angiogenesis, vasodilation and microvascular leakage.
Neural mechanisms in asthma
Authors: Joos  , Germonpré  , Pauwels
Published: March 2003

Advances in the understanding of neural mechanisms in asthma may provide novel therapeutic approaches in the treatment of asthma. Excessive activity of cholinergic nerves may be important in asthma. Dysfunction of M2 muscarinic receptors in asthma may lead to excessive bronchoconstriction and mucus secretion and can be induced in animal models by a range of stimuli including allergen, viral infection, ozone, eosinophil products and cytokines. Cholinergic mechanisms may be especially important in certain types of patients and anticholinergic agents provide protection against bronchospasm due to psychogenic factors or beta2‐blockers. Non‐adrenergic non‐cholinergic (NANC) mechanisms, both inhibitory (i‐NANC) and excitatory (e‐NANC), may play a significant role in the pathophysiology of asthma. The putative neurotransmitters, vasoactive interstinal polypeptide (VIP) and nitric oxide (NO), mediate neural bronchodilation in human airways. There does not appear to be a defect in the i‐NANC system in moderate or severe asthma. e‐NANC is mediated by the sensory neuropeptides substance P (SP) and the more potent bronchoconstrictor neurokinin A (NKA). Various studies suggest that the SP content of human airways is increased in asthma. Tachykinins are not only present in sensory nerves, but also are produced by inflammatory cells such as alveolar macrophages, dendritic cells, eosinophils, lymphocytes and neutrophils. They can be released into the airways by stimuli such as allergen and ozone. Evidence suggests that in addition to smooth muscle contraction, which is mediated mainly by NK2 receptors, tachykinins also cause mucus secretion, plasma extravasation and stimulate inflammatory and immune cells. These effects are mediated by NK1 receptors. Recent studies have shown that NK2 receptor antagonists such as saredutant partially inhibit NKA‐induced bronchoconstriction in asthmatics. Thus, tachykinin receptor antagonists have potential as therapies for asthma.
Unmet needs in the treatment of asthmatic children and adolescents: 1
Authors: Warner
Published: March 2003

The paediatric asthma guidelines have been successful in providing a uniform approach to the management of asthma for the medical profession as a whole. Unfortunately, the guidelines were generated without input from patients themselves and consequently do not consider issues that are important to patients such as a preference for oral treatment. Asthma is a heterogeneous group of conditions and the guidelines do not sufficiently define subgroups of patients and their particular needs. As a result, there has been a tendency to assume that all wheezing in infancy is asthma and this had led to gross overtreatment in certain patients. In contrast, severe asthma often remains underdiagnosed and undertreated. The most recent revision of the guidelines has classified asthma in terms of the patterns of disease; infrequent episodic, frequent episodic and chronic persistent. The treatment required for each of these groups is clearly defined and there is no need for stepwise therapy. Other changes to the guidelines will occur and are needed. None of the treatments available can modify the natural history of asthma; they control the symptoms not the disease process. Evidence from bronchial biopsies suggests that both inflammation and remodelling occur early, even before the first symptoms appear. We need to look for the factors in early life that predict which children will go on to develop asthma and intervene at that stage. Anti‐histamines and leukotriene receptor antagonists may be interesting as interventions in that respect. Two important unresolved issues are to understand what drives remodelling and inflammation, and to look at early life origins of asthma. These approaches may provide effective therapeutic targets and, ultimately, a means of prevention.
Comparison of incremental and bolus dose inhaled allergen challenge in asthmatic patients
Authors: Taylor  , Harris  , O'Connor
Published: March 2003

Background

Attenuation of airway responses to inhaled allergen is increasingly used to evaluate anti‐asthma drugs. Many studies use different allergen challenge methods and the presence of the late asthmatic response can be identified by a screening challenge with inhalation of incremental doses of allergen. Once defined, subsequent challenges are often administered as a constant dose based on the dose from the screening challenge. Previously, constant dose challenges have been employed but never validated.

Objective

A comparative study of two methods of delivering inhaled allergen by evaluating the responses of an incremental dose allergen challenge and the same cumulative dose administered as a bolus over a single inhalation.

Methods

Thirty‐five male patients with mild allergic asthma underwent incremental dose challenge followed 3–6 weeks later by a bolus dose challenge. Bronchoconstrictor responses were expressed as the maximum percentage fall in FEV1 from baseline during the early (0–2 h) and late (4–10 h) asthmatic responses and area under the percentage change in FEV1‐time curve (AUC).

Results

There were no significant differences between the challenges. The mean ± sem fall in FEV1 following incremental and bolus dose challenge was 33.1 ± 1.8% and 29.9 ± 2.2% during the early response, and 36.9 ± 2.4% and 34.0 ± 3.1% during the late response, respectively. The mean ± sem AUC following incremental and bolus dose challenge was 35 ± 3 and 33 ± 3 Δ%FEV1/h for the AUC0–2 h, 147 ± 12 and 139 ± 16 Δ%FEV1/h for the AUC4–10 h, and 204 ± 14 and 190 ± 19 Δ%FEV1/h for the AUC0–10 h, respectively.

Conclusion

Bolus dose allergen challenge is a safe method to administer inhaled allergen in clinical trials with a valid response when compared with incremental dose allergen challenge.
Tear levels of interferon‐γ, interleukin (IL) ‐2, IL‐4 and IL‐5 in patients with vernal keratoconjunctivitis, atopic keratoconjunctivitis and allergic conjunctivitis
Authors: Uchio  , Ono  , Ikezawa  , Ohno
Published: March 2003

Background

A predominance of TH2 activity in chronic allergic diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), has been suggested recently. However, there is no published study on tear levels of cytokines of the two different subgroups, TH1 and TH2, in patients with ocular allergy.

Objectives

We measured interferon (IFN)‐γ, interleukin (IL)‐2, IL‐4 and IL‐5 levels in tears by ELISA, to determine whether the levels of these cytokines are elevated in allergic ocular diseases when compared among patient groups and normal controls.

Methods

Tear levels of IL‐2, IFNγ, IL‐4 and IL‐5 were measured by ELISA using samples from patients with VKC, AKC (AKC‐NP, without proliferative lesions; and AKC‐P, with proliferative lesions), allergic conjunctivitis (AC) and normal subjects. The levels of these cytokines in tears and the clinical severity of AD were also compared.

Results

Tear IL‐4 level in patients with AKC was significantly higher than those in VKC, AC and controls, and tear IL‐4 levels in patients with AKC‐P vs VKC differed significantly. Tear IL‐5 levels in patients with diseases associated with proliferative lesions, VKC and AKC‐P, were higher than those in AC and normal controls. However, tear level of IL‐5 in patients with AKC‐P was significantly higher than that in AKC‐NP. Although the dermatological severity of AD correlated significantly with tear IL‐4 level, IFNγ, IL‐2 and IL‐5 levels did not correlate with dermatological severity of AD.

Conclusion

These results indicate that the TH2‐like cytokines play an important pathophysiological role in severe ocular allergic conditions such as AKC and VKC and that tear level of IL‐5 may be a candidate marker to evaluate the clinical status of ocular allergy. The different patterns of tear levels of IL‐4 and IL‐5 among ocular allergic diseases may reflect the origin and immunological basis of these cytokines.
The search of latex sensitization in spina bifida: diagnostic approach
Authors: Nieto  , Mazón  , Estornell  , Nieto  , Reig  , García‐Ibarra
Published: March 2003

Background

Sensitization to latex has become a major problem in children with spina bifida. Life‐threatening reactions may occur in these patients, therefore the search of latex sensitization must be an active task in all of these children.

Objective

To design an approach for the diagnosis of latex sensitization in children with spina bifida.

Methods

We studied 100 consecutive unselected patients. Skin prick tests with a commercial latex extract were performed, latex‐specific serum immunoglobulin (Ig) E was determined by CAP test, and risk factors were studied. Originally, patients with an area of latex skin test > 50% of the area of histamine and/or CAP class ≥ 3 were considered sensitized to latex. Diagnostic tests were also performed in a control group of 51 atopic and nonatopic children.

Results

After performing a receiver‐operating characteristics curve for both tests we recommend skin tests > 25% of the area of histamine (sensitivity − SEN = 79%, specificity − SPE = 100%, positive predictive value − PPV = 100%, negative predictive value − NPV = 90%), or CAP class ≥ 2 (SEN = 88%, SPE = 100%, PPV = 100%, NPV = 94%) as diagnostic cut‐off points. The anamnesis had a SEN of 44% for diagnosis, and a SPE of 100%. Latex sensitization was associated with more than 5 operations (OR = 8, 95% CI = 3–21.3), a personal history of atopy (OR = 11.5, 95% CI = 2.3–57.1), and serum total IgE ≥ 2 z‐units (OR = 4, 95% CI = 1.6–10).

Conclusion

For the routine evaluation of children with spina bifida, we propose a diagnostic algorithm with skin prick tests as a first step and CAP second.
Possible mechanism of bronchoprotection by SIN‐1 in anaesthetized guinea pigs: roles of nitric oxide and peroxynitrite
Authors: Kanazawa  , Hirata  , Yoshikawa
Published: March 2003

Background

S‐morpholinosydnonimine (SIN‐1) is thought to generate peroxynitrite. Recent reports suggested that peroxynitrite possessed a potent vascular relaxant activity via guanylate cyclase activation. However, no previous studies have examined the relaxant effect of peroxynitrite on airway smooth muscle.

Objective

To determine the mechanism of bronchoprotection by SIN‐1, considering in particular the involvement of nitric oxide (NO) and peroxynitrite.

Methods

Peroxynitrite formation was assayed by monitoring the oxidizing activity of dihydrorhodamine 123, and NO was measured polarographically as a redox current in vitro. We examined the effect of SIN‐1 delivered to the airway by ultrasonic nebulization against bronchoconstriction induced by acetylcholine in anaesthetized guinea pigs.

Results

SIN‐1 produced peroxynitrite in a time‐ and concentration‐dependent manner, but did not produce NO in vitro. However, when mixed with glutathione (GSH) and bronchoalveolar lavage fluid (BALF), peroxynitrite formation by SIN‐1 was inhibited and SIN‐1 induced the release of NO. SNAP (S‐nitroso‐N‐acetyl‐penicillamine) and SIN‐1 each inhibited acetylcholine‐induced bronchoconstriction in a dose‐dependent manner in vivo. Though GSH alone did not have any effect on baseline airway resistance and acetylcholine‐induced bronchoconstriction, pretreatment with GSH significantly enhanced SNAP‐ and SIN‐1‐induced bronchoprotection. In addition, pretreatment with carboxy‐PTIO, a NO scavenger, completely inhibited bronchoprotective effect of SNAP on acetylcholine‐induced bronchoconstriction, but partially inhibited SIN‐1‐induced bronchoprotection.

Conclusion

These findings demonstrated that SIN‐1 is a potent peroxynitrite‐releasing compound and caused significant bronchoprotection against acetylcholine. The mechanism of bronchoprotection by SIN‐1 appears to be mediated by peroxynitrite but also at least in part through NO regeneration, which may involve GSH and airway thiols as a consequence of exposure to peroxynitrite.
Clinical relevance of food additives in adult patients with atopic dermatitis
Authors: Worm  , Ehlers  , Sterry  , Zuberbier
Published: March 2003

Background

Adverse reactions to food play an important role in the pathogenesis of atopic dermatitis (AD). In infancy and childhood, food allergies are observed in up to 30%, whereas nonallergic hypersensitivity reactions (pseudoallergic reactions) towards food additives have been reported to occur between 2 and 7%. By contrast, sensitizations towards food allergens are rarely of clinical relevance in adults and little data is available on nonallergic hypersensitivity reactions. To date the role of pseudoallergic reactions as an aggravating factor in AD of adult patients remains controversial. However, many adult patients report on food‐related aggravation of the disease and nonallergic hypersensitivity reactions have been incriminated repeatedly.

Objective

To elucidate the relevance of food additives in adult patients suffering from AD.

Methods

Fifty patients were monitored over 4 weeks under regular diet followed by 6 weeks of a diet omitting known pseudoallergens. Skin status of patients was assessed every 2 weeks by a standardized scoring, and serum eosinophilic cationic protein (ECP) was determined before and after diet.

Results

Nine of fifty patients dropped out, 26 showed a significant improvement of the Costa‐score by 57%. In 23/26 patients a corresponding reduction of serum ECP level by 52% on average was determined. Responder patients (24/26) were orally challenged with food rich in pseudoallergens followed by double‐blind exposure to food additives (n = 15). A worsening of the eczema was seen in 19/24 patients after intake of pseudoallergen‐rich food and in 6/15 patients after exposure to food additives.

Conclusion

These results indicate that a subgroup of adult patients with AD clinically improve on low‐pseudoallergen diet but only a small subgroup respond to oral provocation with food additives.
The challenge procedure influences the extent of allergen‐induced urinary excretion of leukotriene E4
Authors: Kumlin  , Dahlén
Published: March 2003

Background

Cysteinyl‐leukotrienes are central mediators in asthma and urinary leukotriene E4 (LTE4) is a reliable marker of their endogenous formation.

Objective

This study tested the hypothesis that the procedure used for allergen bronchoprovocation influences the bronchoconstrictor response and the amount of LTE4 excreted following allergen challenge.

Methods

Seven atopic asthmatic men underwent two allergen bronchoprovocations 4 weeks apart. The same total dose of allergen was given at both sessions, cumulatively on one occasion and as a single dose at the other session. Urine was collected in hourly samples before and after challenge and LTE4 was measured with previously validated methodology.

Results

The mean (± se) drop in FEV1 was not significantly different between the cumulative (29 ± 2.4%) and the single dose challenge (25 ± 2.8%). There was a significant increase in post‐challenge levels of urinary LTE4 after both sessions. The peak excretion of LTE4 occurred 1 h following the maximal drop in FEV1 for both challenges. However, the post‐challenge increase in urinary LTE4 was significantly larger at the cumulative session. In fact, the net increase (post‐challenge minus prechallenge) of urinary LTE4 was more than twofold higher after the cumulative session (AUC 0–3 h post‐challenge: 46.7 ± 8.2 vs 22.1 ± 9.8, P < 0.05).

Conclusion

The peak excretion of urinary LTE4 occurred within 2 h after the termination of either challenge but the magnitude of urinary excretion of LTE4 was larger when cumulative challenge was performed. The findings are important to consider when designing studies where allergen‐induced urinary excretion of LTE4 is an outcome variable.
Identification and characterization of a group 2 conifer pollen allergen from Chamaecyparis obtusa, a homologue of Cry j 2 from Cryptomeria japonica
Authors: Yasueda  , Saito  , Sakaguchi  , Ide  , Saito  , Taniguchi  , Akiyama  , Inouye
Published: March 2003

Background

Not only Cryptomeria japonica (Japanese cedar) pollen but also that of Chamaecyparis obtusa (Japanese cypress) induces the allergic symptoms of Japanese cedar pollinosis. However, allergens from C. obtusa pollen have not been as well characterized as those from C. japonica pollen.

Objective

We sought to identify and characterize a homologue of the second major allergen of C. japonica pollen, Cry j 2, from the pollen of C. obtusa.

Methods

An allergen homologous to Cry j 2 was identified in C. obtusa pollen extract by immunoblot analysis, probed with anti‐Cry j 2 monoclonal antibodies and purified by a series of column chromatographic steps.

Results

The allergen isolated from the extract showed a slightly diffuse band of 45 kDa and closely spaced double‐bands of 42 and 45 kDa on SDS‐PAGE, under reducing and non‐reducing conditions, respectively; the bands were approximately 5–7 kDa larger than those of Cry j 2. In 24 of 30 residues, the N‐terminal amino acid sequence of the allergen was identical with corresponding sequence in Cry j 2. Most patients with pollinosis who were IgE antibody‐positive to Cry j 2 were shown to be IgE antibody‐positive to this allergen, and the IgE antibody levels to both allergens were highly correlated.

Conclusion

The results indicate that the allergen isolated from C. obtusa pollen in this study is a homologue of Cry j 2. The allergen was designated as Cha o 2 according to the WHO/IUIS Allergen Nomenclature Subcommittee recommendation.
Regulation of the release of eosinophil cationic protein by eosinophil adhesion
Authors: Xu  , HÅkansson
Published: March 2003

Background

Varying release of eosinophil granule proteins depending on the stimulus and environmental factors has previously been reported.

Objective

To investigate the degranulation from adherent eosinophils by using mixed granulocytes.

Methods

Granulocytes isolated by Percoll gradient centrifugation were incubated on plates coated with plasma and tissue fibronectin, fibrinogen or human serum albumin (HSA) and stimulated with Mn2+, phorbol‐myristate‐acetate (PMA), formyl‐methionyl‐leucyl‐phenylalanine (f‐MLP) and combinations thereof, respectively. The release of eosinophil cationic protein (ECP) was measured by radioimmunoassay.

Results

Unstimulated eosinophils incubated in wells coated with plasma and tissue fibronectin, fibrinogen or HSA did not release any ECP. Furthermore, Mn2+ (5 mmol/L) did not induce release of ECP despite the fact that adhesion of eosinophils to these four proteins was induced. PMA stimulated a dose‐dependent release of ECP. Contemporaneous stimulation of eosinophils with PMA and Mn2+ induced a dramatically increased release of ECP regardless of which protein the eosinophils were adhering to. A small but significant release of ECP was found when eosinophils incubated on plates coated with fibrinogen and HSA were stimulated by f‐MLP. Contemporaneous stimulation of eosinophils with f‐MLP and Mn2+ did not induce any synergistic effect on the release of ECP. On the contrary, Mn2+ inhibited the release of ECP induced by f‐MLP from eosinophils. Serum‐opsonized Sephadex particles stimulated a potent increase of the release of ECP up to 12%–14% in the presence of plasma fibronectin and, in particular, fibrinogen. The kinetics of eosinophil adhesion and degranulation showed that the cellular adhesion preceded the degranulation response and that the degranulation patterns depend on the stimuli and environment.

Conclusion

The present study indicated that cellular adhesion plays an important role in the regulation of eosinophil degranulation, but that adhesion and degranulation can be induced separately.
In vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroids
Authors: Ghaffar  , Christodoulopoulos  , Lamkhioued  , Wright  , Ihaku  , Nakamura  , Frenkiel  , Hamid
Published: March 2003

Background

The allergen‐induced late nasal response is associated with a high local expression of interleukin (IL) ‐4, a TH2‐type cytokine implicated in immunoglobulin (Ig) E production, tissue eosinophilia and other events considered to be relevant to allergic inflammation. Interaction of IL‐4 with its receptor activates at least two distinct signalling pathways that culminate in the transcription of specific target genes. One pathway involves the activation of a transcription factor termed signal transducer and activator of transcription factor 6 (STAT6).

Objective

To investigate the expression of STAT6 in the allergen‐induced late nasal response and to examine the effect of local steroid treatment on STAT6 expression.

Methods

Inferior turbinate biopsies were obtained from subjects with allergic rhinitis out of the allergen season. Subjects were then randomized into topical steroid‐ (n = 6) and placebo‐treated (n = 6) groups in a double‐blind fashion. After a 6‐week treatment period, a second nasal biopsy was performed 24 h after local challenge with allergen. STAT6 immunoreactivity was examined in biopsy specimens by immunocytochemistry using a specific monoclonal antibody. Numbers of inflammatory cells (CD3+ T cells and MBP+ eosinophils) and IL‐4 mRNA+ cells were investigated by immunocytochemistry and in situ hybridization, respectively.

Results

STAT6 immunoreactivity was detected in all biopsies studied and localized predominantly to inflammatory tissue of the nasal mucosa. After allergen challenge, expression of STAT6 was markedly increased in placebo‐treated patients (P < 0.01). By confocal microscopy, STAT6 was localized to the cytoplasm and the nucleus of positively‐staining cells. The allergen‐induced increase in STAT6 immunoreactive cells was not observed in the steroid‐treated patients. The change in STAT6 immunoreactivity after allergen challenge correlated significantly with the change in numbers IL‐4 mRNA+ cells (r = 0.74, P = 0.006) and CD3+ T cells (r = 0.76, P = 0.004), but not MBP+ eosinophils.

Conclusion

This study provides the first evidence of increased STAT6 expression in vivo in human allergic inflammation. The results support a role for STAT6 and IL‐4 in the pathogenesis of late nasal response and show that decreases in STAT6 expression parallel the reduction in IL‐4 expression that occurs with topical steroid treatment.
Prevalence of sensitization to Tetranychus urticae in greenhouse workers
Authors: Navarro  , Delgado  , Sanchez  , Orta  , Martínez  , Palacios  , Martínez  , Conde
Published: March 2003

Background

Tetranychus urticae (TU) is a macroscopic mite which infests a large number of plants of economic interest worldwide. It has recently been described as a cause of occupational allergic disease in greenhouse workers. However, there are no epidemiological data concerning the prevalence of TU allergy in an unselected exposed population.

Objective

The aims were to study the prevalence of TU sensitization among greenhouse workers and its relationship to the working environment and to personal factors.

Methods

We studied 246 consecutive greenhouse workers, recruited directly from the field. A clinical and epidemiological questionnaire, a skin‐prick test (SPT) to TU and common allergens and TU‐specific IgE (RAST) determinations were performed. Seventy‐five healthy volunteers and 152 atopic patients were used as a control group.

Results

The prevalence of a positive SPT to TU was of 25%. Forty‐five workers (19%) were TU‐allergic, occurring more often in atopic greenhouse workers (P < 0.0001). Seven per cent showed asymptomatic sensitization. The time of exposure to TU was significantly greater in the TU‐allergic patients (P < 0.05). The probability of sensitization to TU was 3.7 times greater in exposed than in non‐exposed subjects (P < 0.0001).

Conclusions

In this study, the prevalence of TU sensitization was 25%. There were significant associations with TU allergy and atopy and the time of exposure to TU.
Diagnostic accuracy of sputum outcomes in chronic stable asthma
Authors: Rosi  , Ronchi  , Grazzini  , Duranti  , Scano
Published: March 2003

Background

Asthma with non‐remitting airflow obstruction may not always be differentiated from COPD with airway hyperreactivity. Many attempts have been made to find useful markers for the distinction between these two disorders.

Objective and methods

In order to help the finding of a useful marker for the diagnosis of asthma in the population of patients with airway obstruction we analysed the diagnostic accuracy of sputum eosinophils and sputum ECP in 91 patients with asthma, 15 patients with chronic bronchitis, 32 patients with chronic obstructive pulmonary disease (COPD) and 20 controls subjects, by performing ROC analysis.

Results

Sputum eosinophils were above the normal range of our laboratory (0–3.7%) in 48 asthma patients and in six COPD patients, while sputum ECP (normal range < 85 μg/L) was high in 65 asthma patients, in 24 COPD patients and in nine chronic bronchitis patients. The ROC analysis revealed that sputum eosinophils count (AUC = 0.82) was more accurate than both sputum ECP levels (AUC = 0.56) (P < 0.0001) and β2‐reversibility (AUC = 0.53) (P = 0.0001) in differentiating asthmatic from non‐asthmatic subjects (COPD, chronic bronchitis patients and normal subjects). The diagnostic accuracy of ECP was similar to that of bronchial reversibility (P = 0.76). When ROC analysis was performed by including only patients with airway obstruction (36 asthmatics with airway obstruction and COPD patients), both eosinophil count (AUC = 0.77) and β2‐reversibility (AUC = 0.66) were more accurate than ECP measurement (AUC = 0.39) in discriminating asthmatics from COPD patients (P < 0.00001 and P = 0.04, respectively).

Conclusion

Sputum eosinophils seem to be valid markers for detecting asthma in a population of patients with airway obstruction. Moreover, the higher diagnostic accuracy of eosinophils in the sputum compared to sputum ECP and bronchial reversibility reinforces the role of cytological analysis of sputum in the diagnosis of chronic stable bronchial asthma.
Airway inflammation and hyperresponsiveness to adenosine 5′‐monophosphate in chronic obstructive pulmonary disease
Authors: Rutgers  , Timens  , Tzanakis  , Kauffman  , Van Der Mark  , Koëter  , Postma
Published: March 2003

Background

Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation.

Objective

To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5′‐monophosphate (AMP) in COPD.

Methods

We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean ± SD, age 63 ± 8 years, FEV1% predicted 56 ± 13%), six without BHR (age 60 ± 6 years, FEV1% predicted 65 ± 11%) and 11 healthy nonatopic controls without BHR (age 58 ± 8 years, FEV1% predicted 104 ± 11%) participated in the study.

Results

Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm2; range, 30–1340 vs 280 cells/mm2; range, 110–450, P = 0.045; and median, 2.7%; range, 0.5–8.5 vs 0.6%; range, 0–0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid.

Conclusion

We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.
Lack of linkage between chromosome 5q23–33 markers and IgE/bronchial hyperreactivity in 67 Scottish families
Authors: Mansur  , Christie  , Turner  , Bishop  , Markham  , Helms  , Morrison
Published: March 2003

Background

Raised serum immunoglobulin E (IgE) and bronchial hyperreactivity (BHR) are risk factors for the expression of the asthma phenotype. Previous studies have reported evidence for linkage between these traits and markers on the 5q23–33 cytokine gene cluster.

Objective

To test for linkage between total serum IgE/BHR and microsatellite markers which map to the 5q23–33 region in an ethnically distinct cohort of families from Aberdeen, Scotland.

Methods

We performed a linkage study between five polymorphic markers (spanning the chromosome 5q23–33 region) and total serum IgE and BHR traits. A cohort of 67 families, who were recruited originally to study the natural history of wheeze, were clinically characterized and genotyped for D5S404, IL4, IRF‐1, IL9, D5S436 markers. Linkage analyses were performed using the nonparametric Haseman‐Elston algorithm for the quantitative trait log IgE, and the nonparametric LOD score (NPL‐score) of the GENEHUNTER package for the qualitative traits serum IgE and BHR.

Results

The results of the nonparametric linkage analysis using either the Haseman‐Elston algorithm or NPL‐score were consistent and showed no evidence for linkage with IgE. There was also no evidence for linkage between the BHR traits (at cut‐off values of PD20FEV1 < 8 mmol and 16 mmol) and any of the tested five microsatellite markers.

Conclusions

This study presents evidence against the presence of a gene with a major effect on total serum IgE or BHR in the 5q23–33 region, in this ethnic group.
Effect of a 4‐week treatment with theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid‐naive asthmatics
Authors: Louis  , Bettiol  , Cataldo  , Sele  , Henquet  , Radermecker
Published: March 2003

Background

The precise mechanism of action of theophylline in asthma is not fully understood but recent data have drawn attention to its potential anti‐inflammatory effect.

Objective

The purpose of this study was to assess the effect of theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid‐naive asthmatics.

Method

We performed a 4‐week randomized double‐blind, placebo‐controlled, parallel group study in 21 mild to moderate steroid‐naive asthmatics whose sputum eosinophilia was found twice > 5% during the run in period. Eleven subjects received 600 mg/24 h theophylline for the first 2 weeks and 900 mg/24 h for the last 2 weeks while 10 subjects took a placebo for 4 weeks. Sputum was induced after 2 and 4 weeks of treatment and 1 week after stopping the treatment. The sputum samples were compared for their cell counts, eosinophil cationic protein (ECP) levels and eosinophil chemotactic activity using micro‐Boyden chambers.

Results

Serum theophylline concentrations reached 7 and 11 μg/mL at V3 and V4, respectively. Intragroup comparisons showed that theophylline, but not placebo, caused a significant reduction in sputum eosinophil counts at V3 (62 ± 10% from baseline, P < 0.01) and a strong trend at V4 (67 ± 16% from baseline, P = 0.07) when compared to baseline. The intergroup difference obtained after comparing the area under the curve over the 4 week treatment period only approached the statistical significance (P = 0.08). At baseline the fluid phase of the sputum contained a significant eosinophil chemotactic activity which was inhibited after a 4‐week treatment by theophylline (P < 0.01) but not by placebo. The mean sputum theophylline levels after 4 weeks of treament (1.7 μg/mL) was lower than that required to cause significant inhibition of eosinophil chemotaxis in vitro.

Conclusion

Theophylline decreases the natural sputum eosinophil chemotactic activity present in asthmatics. However, when using a small sample size, the 35% reduction in sputum eosinophilia achieved by theophylline failed to reach statistical significance when compared to that seen after placebo.
Preliminary criteria for the definition of allergic rhinitis: a systematic evaluation of clinical parameters in a disease cohort (II)
Authors: Ng M. L. S. , Warlow R. S. , Chrishanthan N. , Ellis C. , Walls R. S.
Published: March 2003

Background

This study is a development of the work done in ‘Preliminary criteria for the definition of allergic rhinitis: a systematic evaluation of clinical parameters in a disease cohort (I)’.

Objective

We sought to develop criteria which could be routinely used to define allergic rhinitis.

Methods

A total of  47 allergic rhinitis and 23 normal subjects were evaluated with a detailed questionnaire and history, physical examination, serum total immunoglobulin (Ig) E, skin prick tests and serum EAST's.

Results

Based on this data, we developed a preliminary scoring system by which a reliable diagnosis of allergic rhinitis can be made, which is based on the prevalence adjusted strength of association delta (∂) rank values described in this report. Cumulative frequency histograms were constructed for allergic rhinitis and normal subjects in a variety of configurations.

Conclusion

A simple scoring system which can be used to diagnose allergic rhinitis on a routine basis was developed in this study.