bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of rhinitis – the specialist’s opinion
Authors: Van Cauwenberge
Published: March 2003

The aim of the guidelines in the International Consensus Report on the Diagnosis and Management of Rhinitis was to aid general practitioners (GPs) in the treatment of mild or moderate cases of seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and non‐allergic rhinitis. After the initial strategy of allergen avoidance, GPs have several medications at their disposal. For mild or occasional symptoms of SAR, an oral H1‐antihistamine or topical antihistamines or chromones are advised. For moderate symptoms, a topical nasal steroid can be used with or without an oral H1‐antihistamine supplemented if necessary with a topical antihistamine or chromone eyedrops. For PAR, patients should be advised on how to minimize their exposure to house‐dust mite (HDM) allergens. For intermittent symptoms, an oral H1‐antihistamine and an occasional oral decongestant can be used. For persistent symptoms, a topical nasal steroid is advised, possibly supplemented with an antihistamine. For non‐allergic rhinitis, irritant factors should be identified and avoided if possible. Topical or oral decongestants can be used for intermittent symptoms. Topical ipratropium bromide is useful for drying up watery rhinorrhea. For moderate symptoms, either a topical nasal steroid or topical ipratropium bromide should be used. For all the conditions, if treatment proves ineffective and symptoms are severe, then a specialist referral is appropriate. Investigations are conducted to identify causative allergens. Further treatment options include immunotherapy and minimal invasive surgery. A large clinical study is ongoing to validate the guidelines and enable the development of simpler therapeutic options according to symptom severity. In the meantime, the current guidelines provide a valuable guide to both the GP and the specialist.
Inflammatory mechanisms in childhood asthma
Authors: Warner  , Marguet  , Rao  , Roche  , Pohunek
Published: March 2003

There is now a reasonable body of data that would suggest that the immunopathology of asthma is similar, if not identical, in childhood asthmatics compared with adult asthmatics. Indeed, we now have evidence that much of the immunopathology is established within the airways of asthmatics very early after the onset of symptoms and, given the lack of correlation with duration of symptoms, may even antedate the first manifestations. There are, however, some differences with neutrophil recruitment being somewhat more prominent than has been recorded from adult observations. The utility of any inflammation parameter in identifying the real future asthmatics has yet to be studied in sufficient detail to define sensitivity, specificity and predictive value. Such studies will be an essential prerequisite to establishing very early intervention strategies, particularly if these involve the use of inhaled and/or oral corticosteroid.
Immunoregulatory networks in asthma
Authors: Le Gros  , Erb  , Harris  , Holloway  , McCoy  , Ronchese
Published: March 2003

It is now well established that a subset of T‐cell‐derived cytokines (termed Th2 cytokines) programme the timing and characteristics of atopic airway disease including mast‐cell sensitization, eosinophil and lymphocyte infiltration and recently mucus secretion. To date, attempts to devise ways to selectively limit the activities of Th2 cytokine‐producing cells have been frustrated. However, the recent identification of the molecules which direct the activation and maturation of T cells has led to some successful attempts to block the activities of Th2 cells in models of atopic airway inflammation. Some of the agents with the most potential include antagonists of the T‐cell costimulatory molecule CD28, local stimulators of the Th1 subset of cytokines such as the BCG vaccine and potentially, antagonists of the eotaxin chemokine receptor and agonists of the T‐cell costimulatory molecule CTLA‐4. Not only do such agonists and antagonists represent potential new therapies, they could represent a rich hunting ground for those who aim to determine the ways in which atopic airway disease can be diagnosed and understood.
Unique role of allergens and the epithelium in asthma
Authors: Thompson
Published: March 2003

The respiratory epithelium has been regarded as an inert barrier separating the human airway from the external world. Equally allergens have been perceived to be environmental proteins which interact with immunocompetent cells, activate inflammatory cells via IgE and promote the allergic response. However many allergens are biochemically active and are able to increase epithelial permeability and to stimulate epithelial cells to produce cytokines, adhesion receptors and MHC Class II expression. Thus the biochemical properties of allergens are likely to be important in enhancing the allergic responses and disease.
Leukotriene modifiers as novel therapeutics in asthma
Authors: Leff
Published: March 2003

After years of research, the components of slow‐reacting substance of anaphylaxis have been identified as the cysteinyl leukotrienes C4, D4, and E4. Leukotrienes are now known to be important mediators of chronic asthma. Leukotrienes cause bronchoconstriction, oedema, and mucus secretion in models of asthma and are produced in excess quantities in asthmatic patients. Leukotriene receptor antagonists and biosynthesis inhibitors have been produced to improve the signs and symptoms of asthma. These agents block laboratory challenges simulating chronic asthma such as exercise, allergen, and aspirin challenge. They also are effective in studies of chronic asthma in a wide variety of patient types demonstrating that leukotrienes are indeed important mediators of asthma. Over the next several years the appropriate place in asthma therapy for these new agents will be defined.
What can we learn from late‐onset and occupational asthma?
Authors: Papi  , Corbetta  , Fabbri
Published: March 2003

Late‐onset asthma and occupational asthma may provide interesting models of human asthma to compare with the most frequent type of atopic early‐onset asthma. The discovery of similarities and discrepancies in the aetiology and pathogenesis of these different diseases might provide new insights on different mechanisms producing the same phenotype and, thus, by recognizing the different underlying mechanisms of the different forms of asthma, may allow better targeting of prevention and treatment. Occupational asthma, in addition to being a late‐onset asthma, provides the unique opportunity to study the development of asthma under measurable exposure conditions, and consequently to examine the effect of cessation of exposure which, at variance with allergen avoidance, is possible in most of the cases.
Animal models of asthma and chronic bronchitis
Authors: Drazen J. M. , Takebayashi T. , Long N. C. , DE Sanctis G. T. , Shore S. A.
Published: March 2003

Human asthma is characterized by three critical phenotypic traits: intermittent reversible airway obstruction, airway hyperresponsiveness and airway inflammation. In animal models of asthma, airway hyperresponsiveness is an important feature. This trait is characterized by an exaggerated bronchoconstrictor response that would have little physiological consequence in an otherwise unaffected or normal individual. In this article we explore two distinct facets of airway responsiveness. The first is the genetic basis for variations in airway responsiveness that occur in mice in the absence of any specific environmental manipulation. We demonstrate that standard genetic approaches can be successfully applied to the identification of regions of the mouse genome linked to the expression of airway hyperresponsiveness. The second topic addressed in this review is the change in airway responsiveness induced in rats by repeated exposure to sulphur dioxide gas. With daily exposure to high concentrations of sulphur dioxide gas, there is chronic injury and repair of epithelial cells. Over time, rats develop mucous hypersecretion, airway inflammation, increased airway resistance and airway hyperresponsiveness. This model has provided useful information on the mechanisms underlying the pathophysiological events that typify the chronic bronchitis in humans.
Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen‐presenting dendritic cell: influence of treatment with fluticasone propionate
Authors: Hoogsteden H. C. , Verhoeven G. T. , Lambrecht B. N. , Prins J.‐B.
Published: March 2003

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen‐presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose–response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV1), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP‐treatment of COPD patients, FEV1 remained stable, while FEV1 deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease‐specific aspects of inflammation, the anti‐inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.
Indoor survey of moulds and prevalence of mould atopy in Israel
Authors: Katz  , Verleger  , Barr  , Rachmiel  , Kiviti  , Kuttin
Published: March 2003

Background

Moulds are ubiquitous indoor as well as outdoor allergens and therefore potential candidates for indoor environmental control measures. However, very few studies have been performed to examine the significance of indoor moulds in allergic diseases and the effectiveness of measures to reduce the quantity of indoor moulds has not been established.

Objective

To determine the significance and the contribution of moulds to allergic manifestations.

Methods

Prevalence of allergic rhinitis and asthma in 395 members of a rural community were examined by questionnaire and examination of medical files. The atopic status in general and allergy to moulds was determined by skin‐prick tests (SPTs) to a panel of aeroallergens including Aspergillus, Penicillium, Alternaria and Cladosporium. A study of indoor mould levels was performed by placing SDA plates in 59 houses. The type of fungi and the number of colonies from each species were recorded.

Results

Forty‐two subjects, comprising 10.9% of the study group had positive SPT to moulds, 61.9% of those were classified as symptomatic. When taking into account individuals with a borderline positive SPT to moulds, an additional 23 had positive results. Of the 65 mould‐positive subjects, 48% were symptomatic and of the 13 who were allergic to moulds alone, only two had allergic symptoms. Viable moulds were recovered from all 59 houses examined. The most common isolated genus was Aspergillus, followed by Penicillium, Alternaria and Cladosporium. Aspergillus was also the most abundant mould in houses. There was no significant correlation between the abundance of moulds, positive SPT to that mould and symptomatology.

Conclusions

Viable moulds are common in houses in temperate climates. Allergy to moulds itself has a low predictive value to development of allergic symptoms, but allergy to moulds in otherwise atopic subjects increases the risk of symptomatic allergic disease.
Effect of fluticasone propionate aqueous nasal spray on allergen‐induced inflammatory changes in the nasal airways of allergic rhinitics following exposure to nitrogen dioxide
Authors: Wang  , Devalia  , Rusznak  , Bagnall  , Sapsford  , Davies
Published: March 2003

Background

The authors have recently demonstrated that prior exposure for 6 h to 400 p.p.b. nitrogen dioxide significantly enhances the early phase response of eosinophils in the nasal airways of allergic rhinitics to subsequent allergen provocation.

Objective

To investigate whether treatment with fluticasone propionate aqueous nasal spray (FP) can alter the inflammatory response in the nasal airways under these conditions.

Methods

Sixteen allergic, rhinitic patients were recruited for this double‐blind, randomized, cross‐over study and received either topical FP 200 μg once daily or matched placebo for 4 weeks. At the end of treatment, all underwent nasal lavage followed by a 6 h exposure to 400 p.p.b. NO2. Following exposure to NO2, nasal allergen challenge was performed and nasal lavage repeated. After a 4 week washout period, patients were given alternate treatment and tested as above.

Results

Analysis of eosinophil cationic protein (ECP) in lavage samples from patients treated with placebo, demonstrated that this was significantly increased from a median value of 2.3 ng/mL (range: 1.0–7.1) to 15.1 ng/mL (range: 1.5–40.0; P = 0.001) following exposure to NO2 and allergen challenge. However, in patients treated with FP, ECP concentrations only increased from 3.3 ng/mL (range: 0.2–9.2) to 5.1 ng/mL (range: 0.3–20.0; P = 0.034) following exposure to NO2 and allergen challenge. The difference of the changes in ECP concentration between the placebo and the FP‐treated group was significant (P = 0.003). Similarly, there was a significant increase in the number of eosinophils in nasal lavage after exposure to NO2 and allergen challenge in the placebo group, and this increase was inhibited in FP group (P = 0.002).

Conclusion

These results suggest that FP influences NO2‐ and allergen‐induced changes in eosinophil function, as well as eosinophil number in the nasal airway of allergic rhinitics.
The relationship between anthropometric measurements at birth: asthma and atopy in childhood
Authors: Gregory  , Doull  , Pearce  , Cheng  , Leadbitter  , Holgate  , Beasley
Published: March 2003

Background

Recent studies have reported that a large head circumference at birth is associated with an increased risk of raised serum IgE in adult life, and asthma during childhood.

Objective

To examine the relationship between head circumference and other anthropometric measurements at birth and asthma and indices of atopy in childhood.

Methods

The presence of asthma and measures of atopic status (total serum IgE level and skin prick tests to common allergens) were assessed prospectively in offspring of families participating in a community‐based genetic study in Southampton, UK. Measures of perinatal variables including birth weight, head circumference at birth, and gestational age were obtained from hospital records of 239 offspring aged 6–23 years.

Results

Children with a head circumference of 37 cm or more at birth had a relative risk of an elevated serum total IgE (> 150 IU) of 3.2 (95% CI 1.0–10.4). There were no consistent relationships between head circumference at birth and either skin prick positivity or the development of clinical asthma. There was no significant association between other perinatal markers and measures of atopic status or clinical asthma.

Conclusion

The study has identified that a large head circumference at birth is associated with an increased risk of an elevated total serum IgE in childhood. The reasons for this association, and the lack of an association with asthma are unclear and will require further research.
Do mite avoidance measures affect mite and cat airborne allergens?
Authors: Carswell  , Oliver  , Weeks
Published: March 2003

Background

Effective mite allergen avoidance measures are presumed to reduce airborne allergens yet the quantity in the air is rarely measured.

Objective

To monitor airborne allergen during a placebo‐controlled mite allergen avoidance study.

Methods

Bedrooms of 56 atopic asthmatic children were randomly allocated to hot washing and encasing covers + acaricide (active regime) or placebo treatment. Dust was collected from the mattress, bedding and carpets; airborne allergen was measured using Casella samplers and dust settling in open Petri dishes. Der p 1, Der p 2 and Fel d 1 were measured.

Results

After 24 weeks of mite allergen avoidance the Casella air‐samplers collected Der p 1 less frequently in active than placebo‐treated bedrooms (0 vs 29%, P < 0.05) and Petri dishes in the active group collected less than baseline (0.2 vs 0.6 ng/day P < 0.05). Homes without cats had less cat allergen than cat‐owning homes and when actively treated for 24 weeks showed a greater reduction (P = 0.03) in mattress cat allergen than the placebo group.

Conclusion

Encasing covers and hot washing of bed linen reduced mite aeroallergen (and mattress cat allergen in the absence of cats). This could mean dual benefits to a patient sensitive to both mite and cat.
Allergenic differences between the domestic mites Blomia tropicalis and Dermatophagoides pteronyssinus
Authors: CHEW  , YI  , CHUA  , FERNANDEZ‐CALDAS  , ARRUDA  , CHAPMAN  , LEE
Published: March 2003

Background

House dust mite allergens are the most important indoor allergens associated with asthma and rhinitis in Singapore and the tropics. Recent data to suggest that besides the Dermatophagoides spp., the domestic mite Blomia tropicalis (Bt) is also an important source of allergens in these regions.

Objective

To evaluate the degree of allergenic cross‐reactivity between Bt and D. pteronyssinus (Dp).

Methods

Cross‐reactivity between extracts of Bt and Dp was evaluated by fluorescent allergosorbent (FAST) inhibition studies and cross enzyme immunoelectrophoresis. Additionally, the major Dp allergens — Der p 1, Der p 2 and Der p 5, were also compared with the Bt extract by dot blot inhibition. Skin prick and intradermal end‐point titration were then carried out to compare the homologous allergens of the mite species, Blo t 5 and Der p 5.

Results

FAST inhibition studies showed low to moderate cross‐reactivity between the two dust mite extracts (maximum cross‐inhibition, 60%). Native allergens studied by cross enzyme immunoelectrophoresis using mite allergic sera also showed similar results but with at least four cross‐reactive IgE binding antigens. Dot blot inhibition studies using allergens of Dp, Der p 1, Der p 2, and Der p 5, showed little cross‐reactivity between these allergens with components of the crude Bt extracts. Further, evaluation of a recombinant allergen of Bt, Blo t 5, showed low levels of cross‐reactivity even with its homologous Dp counterpart, Der p 5.

Conclusion

These results provide evidence that Bt allergens are distinct and have relatively low to moderate cross‐reactivity with Dermatophagoides spp. allergens. Bt allergens should therefore be included in the diagnostic panel for the evaluation of allergic disorders in the tropics, and the development of new diagnostic and therapeutic strategies should include allergens of Bt.
IgE reactivity and cross‐reactivity of Japanese monkeys (Macaca fuscata) to Japanese cedar (Cryptomeria japonica) and cypress (Chamaecyparis obtusa) pollen allergens
Authors: KOBAYASHI  , NIGI  , SAITO  , IDE  , TANIGUCHI  , INOUYE  , SAKAGUCHI
Published: March 2003

Background

The natural occurrence of Japanese cedar (Cryptomeria japonica, CJ) pollinosis has been reported in Japanese monkeys (Macaca fuscata). However, the reactivity to Japanese cypress (Chamaecyparis obtusa, CO) pollen allergens in these monkeys has not yet been reported.

Objectives

The present study was designed to investigate the reactivity to CO pollen allergens in monkeys sensitized to CJ pollen allergens.

Methods

Serum samples from 40 monkeys naturally sensitized to CJ pollen allergens were collected from four troops. We measured the specific IgE to CO pollen allergens and examined the reactivity to the allergens by intradermal test. Cross‐reactivity between CJ and CO pollen allergens was examined by ELISA inhibition method. Furthermore, we examined the sensitivity to the allergens by histamine release assay from leucocytes.

Results

All 40 monkeys had specific IgE to crude and purified major allergens (Cha o 1) of CO pollen. The monkeys showed a positive reaction to CO pollen allergens in the intradermal test. Allergenic cross‐reactivity between Cha o 1 and Cry j 1 (a major allergen in CJ pollen) was also observed. Specific histamine release to both the major allergens was noted in two monkeys with CJ pollinosis.

Conclusion

Japanese monkeys sensitized to Japanese cedar pollen allergens also demonstrate reactivity to Japanese cypress pollen allergens.
Allergy to bovine β‐lactoglobulin: specificity of immunoglobulin E generated in the Brown Norway rat to tryptic and synthetic peptides
Authors: Miller K. , Meredith C. , Selo I. , Wal J.‐M.
Published: March 2003

Background

Animal models which reflect the induction and development of food‐allergic reactions are important in the identification of allergenic potential of food proteins and peptides. A number of rat strains, including PVG, Hooded Lister and Brown Norway have been shown to produce immunoglobulin (Ig) E antibodies to food proteins as well as to inhaled allergens. Previous work in our laboratory using the Brown Norway (BN) rat has shown that specific IgE is produced following administration of ovalbumin and milk products via both enteral and parenteral route; this has allowed us to rank ovalbumin, lactoferrin and bovine serum albumin in terms of their inherent allergenic potential and has enabled us to demonstrate that milk protein allergens recognized by the systemically‐sensitized animal are consistent with those recognized by sera from cow's milk‐allergic patients (the most common allergens recognized were β‐lactoglobulin and the α, β and κ‐caseins).

Objective

To demonstrate that the BN rat model can be used to identify the major IgE‐binding peptides from β‐lactoglobulin, a known human food allergen, and that those IgE‐binding peptides are similar to those recently identified using sera from cow's milk‐allergic patients.

Methods

BN rats were exposed to β‐lactoglobulin or to semiskimmed milk via the intraperitoneal route in the presence of the adjuvant carrageenan. Specific IgE raised against β‐lactoglobulin was determined by a direct enzyme immunoassay using acetyl‐cholinesterase substrate; specific IgG responses were also monitored. Overlapping synthetic peptides and tryptic peptides were used within the ELISA to identify the major and minor IgE‐binding immunoreactive sequences.

Results

In terms of comparative immunogenicity, there appeared to be sequences that were predominantly IgE‐ or IgG‐reactive. IgE‐dominant regions were amino acid sequences 21–40, 41–60, 107–117 and 148–168 whereas sequences 1–24, 67–77, 82–92, 85–95 and 117–127 appeared more selective for IgG antibody recognition. An increased capacity to induce specific IgE was observed when the allergen was present in the context of whole food.

Conclusions

These studies provide evidence that the immune system of the BN rat and humans — at least in the case of milk allergens — is recognizing similar protein allergens and indeed, at the molecular level, similar peptide epitopes.
Experimental models of skin inflammation
Authors: Clough G.
Published: March 2003

The skin is the most accessible organ of the body in which to view the inflammatory process and its pharmacological modulation. However, there are relatively few studies in which the response of the dermal vasculature to inflammatory stimuli has been assessed quantitatively or the chemical mediators of the response measured directly. The mechanisms underlying these responses remain unclear despite the fact that altered microvascular function plays an important part in a number of clinical conditions. This paper describes recent studies in which an experimental model of inflammation in the skin has been used to investigate the pharmacological mechanisms underlying microvascular responses. As allergen‐induced cutaneous weal and flare responses are mediated mainly by histamine, we first set out to characterize the vascular responses using the intradermal injection of histamine as a first step, experimental model of allergic skin disease. To quantify the inflammatory responses and to explore the mediator mechanisms underlying them we have combined the techniques of scanning laser Doppler imaging of blood flux and dermal microdialysis to make simultaneous measurements of changes in skin blood flow and the release of mediators within the weal and flare response to intradermal injection of histamine in human skin, in vivo.
Unmet needs in adult asthma
Authors: Chung
Published: March 2003

Guidelines have been developed to provide an objective framework for the effective management of asthma. They are based on a mix of sound clinical practice and evidence‐based medicine. The aims of asthma management are to ensure that the patient is symptom free and living an unrestricted life with normal physical activity, lung function normalized as much as possible, using minimum therapy, that exacerbations are kept to a minimum and mortality is reduced or abolished. In practice, however, these aims are not being met. Thus, unmet needs exist in asthma and need to be addressed. One particular unmet need is poor delivery of asthma care. Undertreatment of asthma is common, especially in severe asthma. However, studies suggest that some patients with severe asthma do not respond to any available treatments. Many outcome measures have been used in asthma and different outcomes will ensue according to which outcome measure is chosen, which in turn depends on the population studied. Asthma is a heterogeneous disease and there is heterogeneity in the response to treatment. However, at present there are no means to determine which patients will be a responder or non‐responder to a particular treatment. In clinical trials of potential new asthma treatment we need to target the patient population more carefully according to the selected outcome measure, which should reflect the patient's perspective.
Prevention of latex allergy by selection of low‐allergen gloves
Authors: Mahler  , Fischer  , Fuchs  , Ghannadan  , Valent  , Fartasch  , Kraft  , Schuler  , Valenta
Published: March 2003

Background

In recent years the prevalence of type I allergy to latex has continuously increased, in particular among healthcare workers, to about 10%. While most forms of type I allergy caused by other environmental allergens can be treated by pharmacotherapy or specific immunotherapy, minimizing exposure to latex proteins may represent an effective preventive measure for latex allergy.

Objective

To investigate whether it is possible to select by in vitro and in vivo testing low‐allergen latex gloves for prevention of latex allergy.

Methods

We obtained separate extracts by standard aqueous extraction from the inner and outer surfaces of 15 different commonly used (10 examination, five surgical) glove brands. The extracts were analysed by quantitative (bicinchoninic protein assay, immunoglobulin [Ig] E‐ELISA, ELISA competition) and qualitative (SDS‐PAGE, silver staining, IgE immunoblotting) methods for their protein and allergen contents. In addition, the glove extracts were analysed for their capacity to induce basophil histamine release and immediate skin reactions.

Results

Extracts from different glove brands contained cross‐reactive IgE epitopes. However, IgE binding studies, basophil histamine release and skin testing showed that different glove brands and their inner and outer surfaces contained widely varying protein and allergen contents. While the determination of total protein contents was not sufficient to identify low‐allergen gloves, IgE measurements, basophil histamine release and skin testing were in good agreement and allowed to select low‐allergen products.

Conclusion

We suggest the use of low‐allergen latex products identified by IgE binding, basophil histamine release assays and skin testing as a feasible preventive measure for latex allergy.
Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin‐intolerant asthma
Authors: Yoshida  , Sakamoto  , Ishizaki  , Onuma  , Shoji  , Nakagawa  , Hasegawa  , Nakabayashi  , Amayasu
Published: March 2003

Background

Albeit its exact pathogenesis is still ambiguous; aspirin‐intolerant asthma is one of several types of asthma for which antileukotriene therapy is useful, because it is widely accepted that bronchial over‐production of leukotrienes may be involved in its pathogenesis. Pranlukast (8‐[p‐(4‐phenylbutyloxy) benzol] amino‐2‐(tetrazol‐5‐yl)‐4‐oxo‐4H‐1‐benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, is now widely used in the treatment of asthma.

Objective

This study was designed to investigate the protective effect of pranlukast on airway sensitivity to sulpyrine provocation testing, bronchial responsiveness to methacholine provocation testing, and to investigate whether this protective activity is associated with a reduction in aspirin‐induced excretion of urinary LTE4 (uLTE4), a marker of the cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin‐induced asthma.

Methods

We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin‐intolerant asthma; those who were in stable clinical condition and were hypersensitive to sulpyrine provocation testing were allocated to this study. A double‐blind, randomized, crossover design was used. uLTE4 was measured using combined reverse‐phase high‐performance liquid chromatography (rp‐HPLC)/enzyme immunoassay.

Results

Pranlukast protected against analgesic‐induced bronchoconstriction through mechanisms that were not related to the bronchodilator property, but were related to the improvement both of bronchial hyperresponsiveness and hypersensitivity to analgesic (P < 0.005 and P < 0.0001). Pranlukast showed little effect on excretion of uLTE4.

Conclusion

These results support the hypothesis that cysteinyl leukotriene is one of the most important components in the pathogenesis of aspirin‐intolerant asthma. Pranlukast improves not only hypersensitivity to analgesic, but also bronchial hyperresponsiveness in aspirin‐intolerant asthma. It is also possible that pranlukast has another anti‐asthmatic effect besides that of a leukotriene receptor antagonist.
Infiltration of cytotoxic T cells in drug‐induced cutaneous eruptions
Authors: Yawalkar  , Egli  , Hari  , Nievergelt  , Braathen  , Pichler
Published: March 2003

Background

Previous in vitro data indicate that perforin containing drug‐specific cytotoxic T cells are involved in cutaneous drug reactions.

Objective

The aim of this study was to investigate the in situ expression of perforin and granzyme B together with the nature of the inflammatory infiltrate in acute drug‐induced exanthem. Furthermore, expression of interleukin (IL)‐12 and interferon (IFN)‐γ, which are known to stimulate cytotoxic T cells, was investigated.

Methods

Skin biopsy specimens were obtained from 10 patients with a generalized maculopapular exanthem and from nine controls with normal skin. Expression of CD3, CD4, CD8, CD56, CD1a, CD68, CD25, HLA‐DR, CD54, perforin, granzyme B, IL‐12 and IFNγ was analysed using immunohistochemistry.

Results

In contrast to the controls, the skin of patients with an exanthem was mainly infiltrated by T cells (CD4 > CD8) and showed a marked enhancement of perforin and granzyme B immunostaining. Double immunostaining revealed that perforin and granzyme B were expressed in both CD4+ and CD8+ cells, which were partly located at the dermoepidermal junction and in the epidermis. In addition, strong immunreactivity for IL‐12 and IFNγ was observed in the mononuclear cells infiltrate, indicating that these cytokines may be important in activation of these cytotoxic T cells.

Conclusion

The increased numbers of perforin and granzyme B containing T cells infiltrating the dermoepidermal junction may contribute to the damage of epidermal cells, which is frequently observed as a typical feature of interface dermatitis in drug‐induced exanthem. Our data provide further evidence that cytotoxic T cells play an essential role in cutaneous drug reactions.
Diagnosis of venom allergy by flow cytometry. Correlation with clinical history, skin tests, specific IgE, histamine and leukotriene C4 release
Authors: Sainte‐Laudy  , Sabbah  , Drouet  , Lauret  , Loiry
Published: March 2003

Background

Potent allergens such as hymenoptera venoms are capable of inducing severe and life threatening clinical reactions. Percentage of false negative results obtained by the usual diagnostical methods is comprised between 10 and 25%

Objective

Evaluation of the sensitivity and the specificity of cellular tests and particularly evaluation of a new flow cytometric method.

Methods

Forty‐five allergic patients having experienced a local, a systemic reaction or an anaphylactic shock and 10 controls having undergone hymenoptera stings without clinical reactions were selected on the basis of the clinical history, skin tests and specific IgE. Three cellular tests were performed on the same cell suspensions and in the presence of 2 ng/mL of rIL3: histamine release (RIA), leukotriene C4 release (ELISA) and basophil activation test (flow cytometry after double anti‐IgE FITC, anti‐CD63 PE labelling).

Results

As compared to the clinical history, sensitivities of skin tests, specific IgE, flow cytometry, histamine release and leukotriene release were, respectively; 85%, 88%, 100%, 89% and 100%. Flow cytometric analysis of basophil activation showed a significant decrease of the mean fluorescence density and number of IgE positive cells and a significant increase of the number of CD63 positive cells. The 10 controls tested by flow cytometry were negative.

Conclusion

As compared to the clinical history and to the other parameters tested here, flow cytometry showed a high sensitivity and a high specificity. The excellent correlation observed between this method and the other cellular tests such as histamine and leukotriene release are in favour of the specificity of flow cytomery and in favour of the use of this method for venom allergy diagnosis.
The high molecular mass allergen fraction of timothy grass pollen (Phleum pratense) between 50–60 kDa is comprised of two major allergens: Phl p 4 and Phl p 13
Authors: Suck R. , Hagen S. , Cromwell O. , Fiebig H.
Published: March 2003

Background

More than 70% of the patients allergic to grass pollen exhibit IgE‐reactivity against the high molecular mass fraction between 50 and 60 kDa of timothy grass pollen extracts. One allergen from this fraction is Phl p 4 that has been described as a basic glycoprotein. A new 55/60 kDa allergen, Phl p 13, has recently been purified and characterized at the cDNA level.

Objective

The relative importance of the two high molecular mass allergens has been characterized with respect to their IgE‐binding frequency and capacity.

Methods

Both high molecular mass allergens were biochemically purified and subjected to nitrocellulose strips. About 306 sera obtained from subjects allergic to grass pollens were used to determine specific IgE‐binding frequency to Phl p 4 and Phl p 13. IgE‐binding of allergens was quantified by ELISA measurements. Pre‐adsorption of sera with purified allergens and subsequent incubation of nitrocellulose‐blotted timothy grass pollen extract was performed to determine whether or not Phl p 4 and Phl p 13 represent the whole high molecular mass allergen fraction. Proteolytic stability of both allergens was investigated by addition of protease Glu‐C.

Results

More than 50% of 300 patients displayed IgE‐binding with both allergens. Clear differences concerning the immunological properties of Phl p 4 and Phl p 13 were confirmed by individual IgE reactivities. Quantification of specific IgE for both allergens revealed comparable values. For complete inhibiton of IgE‐binding in the high molecular mass range preincubation of sera with both allergens was necessary. Interestingly, inhibition of strong reacting sera with Phl p 13 eliminated not only reactivity of the 55/60 kDa double band, but in addition a ‘background smear’. Whilst undenatured Phl p 4 was resistent to proteolytic digestion with Glu‐C, native Phl p 13 was degraded rapidly.

Conclusion

Phl p 4 and Phl p 13 are immunologically different and must both be considered as major allergens. They are judged to be important candidates for potential recombinant therapeutics that may provide a basis for improved immunotherapy.
The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut‐allergic children
Authors: Primeau  , Kagan  , Joseph  , Lim  , Dufresne  , Duffy  , Prhcal  , Clarke
Published: March 2003

Background

Peanut‐allergic patients are affected by a condition which forces them and their families to exercise extreme dietary vigilance and experience constant uncertainty throughout their lives.

Objective

To compare the quality of life and family relations of children and adults with a peanut allergy to that of children and adults with a rheumatological disease.

Methods

Patients with a confirmed diagnosis of peanut allergy or a rheumatological disease completed (for children less than 18 years, by proxy) self‐report questionnaires regarding the impact of their condition on their quality of life and family relations. A vertical visual analogue scale and the Impact on Family Questionnaire (IFQ) served as outcome measures.

Results

One hundred and fifty‐three peanut‐allergic children were compared with 69 children with a rheumatological disease while 37 peanut‐allergic adults were compared with 42 adults with a rheumatological disease. The parents of peanut‐allergic children, compared to the parents of children with a rheumatological disease, reported that their children had significantly more disruption in their daily activities. Furthermore, the parents of peanut‐allergic children reported more impairment in the familial‐social dimension of the IFQ. Conversely, adults with a chronic rheumatological disease reported more disruption in their family relations than peanut‐allergic adults.

Conclusion

Given the considerable disruption in daily activities and family relations reported by the parents of peanut‐allergic children, accurate diagnosis of peanut allergy is essential. Our work should make health care professionals dealing with children with confirmed peanut allergy more aware of the support that these families may require. Furthermore, we hope to motivate food industries to offer more ‘peanut free’ products to decrease the dietary restrictions of these patients while minimizing their potential for accidental ingestion.
Analysis of induced sputum before and after withdrawal of treatment with inhaled corticosteroids in asthmatic patients
Authors: Giannini D. , Di Franco A. , Cianchetti S. , Bacci E. , Dente F. L. , Vagaggini B. , Paggiaro P. L.
Published: March 2003

To assess whether sputum eosinophilia predicts the recurrence of asthma symptoms after withdrawal of therapy in moderate stable asthmatics on low‐dose inhaled corticosteroids.

Randomized, double‐blind, placebo‐controlled study involving 30 subjects with stable asthma, asymptomatic, with low PEF variability measured over two run‐in weeks, on treatment with low‐dose inhaled beclomethasone dipropionate (BDP, 250 µg b.i.d. in the last 3 months). At the end of the run‐in, all patients underwent a methacholine challenge test and sputum induction (T1). They then stopped therapy and received either placebo (20 subjects, study group) or BDP at the same dose as in the previous 3 months (10 subjects, control group). They continued to monitor PEF and symptom score for 3 months, or until asthma symptoms recurred (diurnal and nocturnal symptom score ≥2 on two consecutive days). At the end of the study (T2), i.e., either within 5 days from the beginning of asthma symptoms or after 3 months in subjects without recurrence of asthma symptoms, all subjects repeated the methacholine challenge test and sputum induction.

In the placebo‐treated group, sputum eosinophils at T1 were significantly higher in subjects who subsequently developed recurrence of asthma symptoms (n = 7) after cessation of treatment than in subjects who remained asymptomatic for 3 months (8.2% [0–56.6] vs 0.9% [0–11], P < 0.05). At the time of recurrence of asthma symptoms, sputum eosinophil percentages significantly increased (from 8.2% [0–56.6] to 16.6% [5.8–73.6], P < 0.05). The positive predictive value of sputum eosinophils for the recurrence of asthma symptoms was 71%, while the negative predicting value was 84%. In the BDP‐treated control group, none of the subjects experienced recurrence of asthma symptoms, and sputum eosinophil percentages measured at the beginning (T1) and at the end (T2) of the study were similar.

Sputum eosinophil percentages may vary over a wide range in asthmatic subjects, although regularly treated and apparently well controlled. However, high sputum eosinophil percentages are related to early recurrence of asthma symptoms after cessation of inhaled corticosteroids.
Quantification of group 5 grass pollen allergens in house dust
Authors: Fahlbusch B. , Hornung D. , Heinrich J. , Dahse H.‐M. , JÄger L.
Published: March 2003

Background

It is widely known and accepted that grass pollen is a major outdoor cause of hay fever. However, it is of virtual importance for grass pollen allergic patients with symptoms all the year round to know the concentration of grass pollen allergens in their homes.

Objective

The main objective of this study was to quantify the amount of grass pollen allergen in mass units (μg Phl p 5) in dust settled indoors and to detect the distribution of allergenic activity in different sampling locations of homes. Furthermore, we studied the seasonal fluctuation of allergen content in dust samples.

Methods

We adapted the two site binding assay for detection of group 5 grass pollen allergens in samples from randomly selected homes in Hamburg (n = 371), Erfurt (n = 396), Hettstedt (n = 353), Zerbst (n = 289) and Bitterfeld (n = 226), Germany. Dust samples were collected from floor of living room (LR), bedroom (BR) or children's room (CR) and mattress (MA) during period of June 1995 to August 1998. The amount of the major grass group 5 allergens was detected in μg/g dust.

Results

Phl p 5 was detected in 67% of the samples analysed (n = 4760). The range was between undetectable (< 0.03 μg/g dust) and 81 μg/g dust. Phl p 5 levels were significantly higher in the dust from LR (geometric mean 0.117 μg/g dust) or BR/CR floors (geometric mean 0.098 μg/g dust) than in mattresses (geometric mean 0.043 μg/g dust). We observed seasonal fluctuation of indoor Phl p 5 levels with peak in June but also annual differences. Thus Phl p 5 content indoors reflects also the different quantities of pollen counts of annual courses. During pollination period we found two times higher Phl p 5 levels (0.172 μg/g dust, P < 0.001) than outside of grass pollination season (0.095 μg/g dust). The indoor Phl p 5 levels outside of season seem to be independent of pollination before. We suppose that settled pollen grains or allergenic material from outdoor particles carried indoors via footwear and clothes accumulates in house dust.

Conclusion

Although we not known how the allergens in settled dust are equilibrated with those in the air, the considerable high level of Phl p 5 in indoor dust even during periods when no grass pollen is present in the atmosphere may be an important cause of pollen‐allergy symptoms outside of season.
Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease?
Authors: Droste J. H. J. , Wieringa M. H. , Weyler J. J. , Nelen V. J. , Vermeire P. A. , Van Bever H. P.
Published: March 2003

Background

One of the mechanisms evoked to explain the increasing prevalences of asthma and allergy, in particular among children, is the ‘Western lifestyle’ or ‘hygiene’ hypothesis. As early childhood infections are assumed to hold a protective effect on the development of asthma and allergies, the use of antibiotics at that sensitive age may lead to an increased risk of asthma and allergy.

Objective

The aim of this study is to investigate the association between the use of antibiotics in the first year of life and the subsequent development of asthma and allergic disorders.

Methods

In a population‐based sample of 7‐and‐8‐year‐old children questionnaire and skin prick test data were collected from 1206 and 675 subjects, respectively. Prevalence rates of asthma, allergic disorders and skin test positivity were compared between children with and without early life use of antibiotics, taking into account other possible risk factors including early respiratory infections. The effect of genetic predisposition was investigated by stratified analyses of children with and without parental hay fever.

Results

The use of antibiotics during the first year of life was significantly associated with asthma (OR = 1.7, 95% CI 1.0–3.1), hay fever (OR = 2.3, 95% CI 1.3–3.8) and eczema (OR = 1.3, 95% CI 1.0–1.8). No significant relationship was found with skin test positivity (OR = 1.1, 95% CI 0.7–1.7). After stratification for the presence of parental hay fever, children without parental hay fever did not show any significant associations between antibiotics use and asthma or allergy, whereas in children with parental hay fever the use of antibiotics was significantly related with asthma (OR = 2.3, 95% CI 1.1–5.1), hay fever (OR = 2.8, 95% CI 1.5–5.1) and eczema (OR = 1.6, 95% CI 1.0–2.6), and of borderline statistical significance with skin test positivity (OR = 1.6, 95% CI 0.9–3.0).

Conclusion

Early childhood use of antibiotics is associated with an increased risk of developing asthma and allergic disorders in children who are predisposed to atopic immune responses. These findings support recent immunological understanding of the maturation of the immune system.