bluuebunny/crossref_metadata_2025 huggingface dataset:
Asthma: individual patient perspective and current unmet needs
Authors: Worstell
Published: March 2003

Today there is an array of medication options to treat asthma and state‐of‐the‐art guidelines to help diagnose and manage this chronic disease. Despite this, asthma morbidity and mortality rates are rising. There is an urgent need to direct educational programmes and health resources to address this disparity. A recent US survey of asthma patients and health‐care providers disclosed that a large number of asthma patients do not fully understand what control of asthma really means and what treatments are available. They underestimate the severity of their condition and over‐estimate how well their asthma is being controlled. More treatment choices provide the opportunity for better asthma control for more patients. However, more choices also mean an increased need for education so that the practitioners can determine the best treatment plan for each patient. Provider/patient communication must be enhanced to address patient cultural and lifestyle practices, including environmental exposures. These factors are as important as medication options for successful patient compliance in asthma control. This will require a change in clinician educator skills or more extensive use of ancillary asthma education in clinics. An interactive seminar for physicians on how to communicate better led to patient–physician encounters that were of shorter duration, had significant impact on the prescribing and communication behaviour of physicians, led to more favourable patient responses to physicians’ actions, and led to reductions in health care services use. Not all patient educational needs can be met in brief medical visits. Patient education and patient advocate organizations are essential to supplement education given by the physician. Patient organizations help develop culturally and linguistically appropriate educational materials and they organize patient assist systems that help patients exchange information, practice advice and emotional support.
Unmet needs in the treatment of asthmatic children and adolescents: 2
Authors: Björkstén
Published: March 2003

The five main unmet needs in the treatment of asthma in children and adolescents are the treatment of infants, the treatment of adolescents, the efficacy of medication, the lack of clinical trials in children and the need for prevention. Asthma is a dynamic disease that changes over time and there are several patterns of asthma in children. One of the greatest needs is to identify those children with chronic asthma where undertreatment is more of a problem than overtreatment. Although the treatment of asthma in children is the same in principle as adults, there are several practical difficulties with infants, such as accurately assessing lung function and administering drugs. Teenage asthma creates a distinct management problem. Not only is asthma underdiagnosed but acceptance of diagnosis and compliance is often poor. Existing therapies need to be used more effectively in adolescents. It is particularly important to establish a partnership with teenage asthmatics and motivate them to create their own treatment goals. This requires passing on knowledge. The efficacy of asthma medication may be different in children than in adults and clinical studies should be performed to optimize therapy with existing drugs. The only proven primary preventive measure to prevent wheezing and asthma is to avoid passive tobacco smoke exposure. Possible intervention strategies include early intervention with anti‐inflammatory therapy, allergen avoidance and vaccine approaches but more of them have proven efficacious. Although modern asthma treatment has improved patient quality of life and long‐term prognosis, there is still a need for further improvement.
Airway responsiveness to acetaldehyde in patients with asthma: relationship to methacholine responsiveness and peak expiratory flow variation
Authors: Prieto  , Sánchez‐Toril  , Brotons  , Soriano  , Casañ  , Belenguer
Published: March 2003

Background

Although airway hyperresponsiveness to inhaled acetaldehyde has been documented in Japanese patients with asthma, the response to this bronchoconstrictor agent has never been studied in Caucasians.

Objectives

The objectives of the study were to determine differences in airway responsiveness to acetaldehyde between asthmatic and healthy subjects, and to examine the relationship between acetaldehyde responsiveness and the variability of peak expiratory flow (PEF).

Methods

The response to methacholine and acetaldehyde challenges was measured in 81 non‐smoking adults (61 asthmatics and 20 normal controls). Subjects recorded PEF morning and evening for 14 days. The response to both bronchoconstrictor agents was measured by the PC20 (provocative concentration required to produce a 20% fall in FEV1). PEF variation was expressed as amplitude percentage mean, and as low percentage best (lowest PEF expressed as a percentage of the best PEF recorded).

Results

The two types of challenge yielded a similarly high level of sensitivity (100% for methacholine and 92% for acetaldehyde) and specificity (90 and 100%, respectively) to distinguish between asthma and controls. Asthmatic subjects were on average 265‐fold less sensitive to acetaldehyde than to methacholine. PC20 acetaldehyde correlated weakly but significantly with both indices of PEF variation (amplitude percentage mean: ρ = − 0.36, P = 0.004; low percentage best: ρ = 0.42, P = 0.001).

Conclusions

These results indicate that airway hyperresponsiveness to acetaldehyde is a sensitive and specific indicator for separating asthmatic and normal subjects. Airway responsiveness to methacholine or acetaldehyde and PEF variation are not reflecting the same pathophysiological process in the airways.
Dose‐related efficacy and tolerability of fluticasone propionate nasal drops 400 μg once daily and twice daily in the treatment of bilateral nasal polyposis: a placebo‐controlled randomized study in adult patients
Authors: Penttilä  , Poulsen  , Hollingworth  , Holmström
Published: March 2003

Background

Topical corticosteroids are the accepted medical adjunct to surgery in patients suffering from nasal polyposis. Fluticasone propionate (FP) is a potent, topically active corticosteroid which has been formulated as nasal drops specifically for the treatment of polyposis.

Objectives

To evaluate dose‐related efficacy and tolerability of FP nasal drops (FPND) in the treatment of mild to moderate bilateral polyposis; in a double‐blind, placebo‐controlled, multicentre international study.

Methods

Adult patients (n = 142) with bilateral nasal polyps were randomized to receive either FPND 400 μg once daily (o.d.), FPND 400 μg twice daily (b.i.d.) or placebo for 12 weeks. The majority then entered a further 12 week open period during which all patients received FPND 400 μg o.d. The primary efficacy endpoint was the physicians' visual assessment of polyp size. Secondary clinical endpoints were nasal blockage and overall rhinitis (0–3 scores), peak nasal inspiratory flow (PNIF), olfactory function tests, and requirement for polypectomy. The patients also kept twice daily records of symptom scores, peak nasal inspiratory flow (PNIF) and use of rescue medication.

Results

At the end of the 12 week randomized treatment period, polyp size was reduced significantly by FPND 400 μg b.i.d. as compared with placebo (P = 0.006). Clinical assessments of nasal blockage and overall rhinitis showed significant improvements at several stages of treatment with both doses of FPND. Clinic PNIF was also improved significantly by both doses of FPND in comparison with placebo, and FPND 400 μg b.i.d. was significantly more effective than 400 μg o.d. (P = 0.045). Patient diary card scores supported the clinical assessments. Two patients on placebo required polypectomy and all treatments were well tolerated with a similar incidence of adverse events.

Conclusion

FPND 400 μg once or twice daily is an effective and well‐tolerated treatment for bilateral nasal polyposis.
Detection of immunoglobulin antibodies in the sera of patients using purified latex allergens
Authors: Kurup  , Yeang  , Sussman  , Bansal  , Beezhold  , Kelly  , Hoffman  , Williams  , Fink
Published: March 2003

Background

Latex allergy is largely an occupational allergy due to sensitization to natural rubber latex allergens present in a number of health care and household products. Although several purified allergens are currently available for study, information on the usefulness of these purified, native or recombinant allergens in the demonstration of specific immunoglobulin (Ig) E in the sera of patients is lacking.

Objective

To evaluate the purified latex allergens and to demonstrate specific IgE antibody in the sera of health care workers and spina bifida patients with clinical latex allergy.

Methods

Two radioallergosorbent and an enzyme‐linked immunosorbent assay (ELISA) using latex proteins Hev b 1, 2, 3, 4, 6 and 7 along with two glove extracts and Malaysian nonammoniated latex (MNA) were evaluated to demonstrate IgE in the sera of health care workers and spina bifida with latex allergy and controls with no history of latex allergy.

Results

ELISA using the purified latex allergens demonstrated specific IgE in 32–65% health care workers and 54–100% of spina bifida patients with latex allergy. The corresponding figures for RAST were 13–48 and 23–85 for RAST‐1 and 19–61 and 36–57 for RAST‐2. These results were comparable with the results obtained with glove extracts and crude rubber latex proteins.

Conclusions

When used simultaneously, latex proteins Hev b 2 and Hev b 7 reacted significantly with specific serum IgE in 80% of health care workers and 92% of spina bifida patients with latex allergy by ELISA technique, while this combination gave lower positivity when the RASTs were used. By the addition of Hev b 3, specific IgE was detected in all spina bifida patients with latex allergy. Both RASTs failed to show specific IgE in the control subjects, while the ELISA showed significant latex‐specific IgE in 22% of controls.
Inhibition of CD23 processing correlates with inhibition of IL‐4‐stimulated IgE production in human PBL and hu‐PBL‐reconstituted SCID mice
Authors: Mayer  , Bolognese  , Al‐Mahdi  , Cook  , Flamberg  , Hansbury  , Khandekar  , Appelbaum  , Faller  , Marshall
Published: March 2003

Background

CD23, the low affinity serum immunoglobulin E (IgE) receptor, is upregulated on B cells following interleukin (IL)‐4 stimulation and is concomitantly cleaved to generate soluble CD23 (sCD23) fragments with cytokine‐like activity.

Objective

Compounds that selectively inhibit the proteolytic release of CD23 to generate sCD23 were assessed for their ability to inhibit IgE production in order to evaluate the contribution of sCD23 in the production of human IgE as well as the ability of such compounds to block IgE production.

Methods

IgE production was measured in IL‐4‐stimulated human peripheral blood lymphocytes (PBL) and PBL‐reconstituted SCID mice in the presence of a broad‐spectrum matrix metalloprotease (MMP) inhibitor, a compound selective for inhibition of CD23 processing over MMPs and an anti‐CD23 mAb, MHM6.

Results

The two compounds were equipotent in inhibiting IgE production without inhibition of IgG production by IL‐4/anti‐CD40‐stimulated PBL. Soluble CD23 release was also shown to precede IgE accumulation in the cell‐free medium. Addition of compound at later times other than day 0 in the 14 day assay resulted in progressively less inhibition of both IgE and sCD23, and exactly paralleled the effect of an anti‐CD23 mAb, MHM6 on IgE levels. Both compounds also inhibited the release of CD23 from human RPMI 8866 cells adoptively transferred i.p. to mice. Doses required for inhibition of CD23 correlated well with the doses required for inhibition of IgE production in IL‐4‐challenged hu‐PBL‐SCID mice. IgE was selectively inhibited over total IgG in the SCID mice as well.

Conclusions

Inhibition of CD23 processing alone is sufficient to inhibit IL‐4‐stimulated IgE production both in vitro and in vivo.
Cloning of the minor allergen Api g 4 profilin from celery (Apium graveolens) and its cross‐reactivity with birch pollen profilin Bet v 2
Authors: Scheurer  , Wangorsch  , Haustein  , Vieths
Published: March 2003

Background

Profilin is a panallergen that is recognized by IgE from about 20% of birch pollen‐ and plant food‐allergic patients. A subgroup of celery‐allergic patients shows IgE‐reactivity with this minor allergen. To investigate the IgE‐binding potential and cross‐reactivity of celery profilin at the molecular level, this study was aimed at the cloning and immunological characterization of this allergen.

Objectives

Cloning, expression and purification of profilin from celery tuber to characterize its immunological properties and its cross‐reactivity with birch pollen profilin.

Methods

Cloning of celery profilin was performed by polymerase chain reaction using degenerated primers and a 5′RACE method for the identification of the unknown 5′‐end of the cDNA. Expression was carried out in Escherichia coli BL21 (DE3) using a modified vector pET‐30a. The recombinant profilin was purified by affinity chromatography on poly l‐proline coupled to sepharose. Immunological characterization was performed by immunoblotting, EAST and IgE‐inhibition experiments.

Results

The coding region of the cDNA of celery profilin was identified as a 399‐bp open reading frame, coding for a protein of 133 amino acids with a calculated molecular weight of 14.3 kDa. The deduced amino acid sequence of the corresponding protein showed high identity with other plant profilins (71–82%) recently described as allergens. Celery profilin was isolated as highly pure nonfusion protein. The IgE‐reactivity of celery profilin was similar to that of natural protein. Seven of 17 celery‐allergic patients tested presented specific IgE‐antibodies to the recombinant protein tested by immunoblotting. Inhibition experiments showed high cross‐reactivity of IgE with both profilins from celery and birch pollen. Moreover, the biological activity of recombinant celery profilin was demonstrated by a histamine release assay.

Conclusions

Celery profilin is an important allergenic compound in celery and shows high homology to birch pollen profilin, Bet v 2. According to the revised IUIS allergen nomenclature, we suggest naming the celery profilin Api g 4. In addition to the cross‐reacting major allergens Api g 1 and Bet v 1, birch pollinosis and associated allergies to celery can therefore additionally be explained by the cross‐reactivity between homologous profilins. Moreover, recombinant Api g 4 may be used for target‐specific diagnosis and structural analyses.
Production and characterization of monoclonal antibodies to serine proteinase allergens in Penicillium and Aspergillus species
Authors: Lin W.‐L. , Chou H. , Tam M. F. , Huang M.‐H. , Han S.‐H. , Shen H.‐D.
Published: March 2003

Background

Alkaline and/or vacuolar serine proteinases are major allergens in prevalent airborne Penicillium and Aspergillus species.

Objective

The object of this study is to generate and characterize monoclonal antibodies against these serine proteinase allergens.

Methods

BALB/c mice were immunized individually with the Penicillium citrinum culture medium or the crude extract and culture medium preparations of Aspergillus fumigatus. Hybridoma cells that secrete monoclonal antibodies against serine proteinase allergens were selected by immunoblotting. Antigens in three different Penicillium (P. citrinum, P. notatum and P. oxalicum) and two different Aspergillus species (A. fumigatus, and A. flavus) recognized by these monoclonal antibodies were analysed by sodium dodecyl sulphate and two‐dimensional polyacrylamide gel electrophoresis immunoblotting and N‐terminal amino acid sequence analysis.

Results

Four (PCM8, PCM10, PCM16 and PCM39) and one (FUM20) monoclonal antibodies against serine proteinase allergens were generated after fusion of NS‐1 cells with spleen cells obtained from BALB/c mice immunized with antigens from P. citrinum and A. fumigatus, respectively. Immunoblotting results showed that PCM8 reacted with an alkaline serine proteinase allergen in P. citrinum and P. notatum. PCM10 and PCM39 reacted with the alkaline serine proteinase in two Penicillium (P. citrinum, P. notatum) and two Aspergillus species (A. fumigatus, and A. flavus) tested. PCM16 reacted with the alkaline serine proteinase allergen in P. citrinum, A. fumigatus and A. flavus but not with that in P. notatum. MoAb FUM20 reacted with the alkaline serine proteinase allergen in two Aspergillus species (A. fumigatus and A. flavus) but not with that in two different Penicillium species (P. citrinum, P. notatum) tested. Among these five monoclonal antibodies generated, only PCM39 and FUM20 can react with the vacuolar serine proteinase allergen in P. notatum, P. oxalicum and in A. fumigatus. The 35 kDa P. citrinum component that reacted with FUM20 has an N‐terminal amino acid sequence of DSPSVEKNAP.

Conclusion

Five monoclonal antibodies against different epitopes of the serine proteinase major allergens in prevalent Penicillium and Aspergillus species were generated in the present study. Antibodies obtained may be useful in the characterization and standardization of serine proteinase allergens in crude fungal extracts.
Early introduction of inhaled steroids in wheezing children presenting in primary care. A pilot study
Authors: Baxter‐Jones A. D. G. , Helms P. J.
Published: March 2003

Background

Recurrent wheezing illness in childhood is a frequent reason for consultation in both primary and secondary care and whilst there is widespread support for the earlier introduction of inhaled corticosteroids(ICS) concerns remain about potential adverse systemic effects.

Objective

We sought to identify the feasibility and size of study required to assess the benefits, adverse effects and cost‐effectiveness of early introduction of ICS.

Methods

We entered 86 children (mean age 4.5 years) with at least two consecutive wheezing episodes into a pragmatic randomized controlled trial. All children were already being prescribed β2‐agonist and those allocated to ICS were prescribed twice daily beclomethasone dipropionate 200 μg or budesonide 200 μg. At entry and 3 and 6 months age appropriate lung function (FEV1, Tptef:Te), respiratory symptoms, quality of life of children and carers, growth and sexual maturation, bone mass and bone turnover, and health care costs were assessed.

Results

Drop out rate was 8% (7 of 86). No significant differences were found in FEV1 or Tptef:Te at 6 months. Respiratory symptoms and health‐related quality of life of children and carers improved equally in both groups. No significant differences were found in growth rates or in bone mass. In the ICS group markers of bone turnover (Pyd:Cr) fell (271 vs 237 nmol/mmol) in contrast to a rise in those on β2 alone (255 vs 319 nmol/mmol) P < 0.05. Combined health care costs were higher in the ICS group.

Conclusions

The low drop out rate provided evidence that the protocol was practical and acceptable. In order to confirm these results, and using the same study design, power estimates indicated that 260 children would need to be randomized.
Dietary factors associated with physician‐diagnosed asthma and allergic rhinitis in teenagers: analyses of the first Nutrition and Health Survey in Taiwan
Authors: Huang S.‐L. , Lin K.‐C. , Pan W.‐H.
Published: March 2003

The occurrence of asthma and allergy are related to lifestyle factors, and dietary pattern may be one of the contributing factors.

To examine the possible association between dietary intake and the prevalence of asthma and allergic rhinitis in teenagers.

In a population‐based cross‐sectional survey, the relationship was sought between food frequency and physician‐diagnosed asthma and allergic rhinitis in 1166 adolescents aged 13–17.

The prevalence was 4.0% for asthma and 12.4% for rhinitis. Living in an urbanized area was a significant predictor of asthma and rhinitis. In univariate analysis, higher frequencies of oily fish, butcher's meat, liver and deep‐fried foods were associated with asthma. Relevant food frequency variables were dichotomized at the 75th percentile for multivariate logistic regression analysis, which included adjustment for two levels of urbanization. Asthma was associated with intakes of liver (OR = 2.32, 95%CI 1.11–4.80), deep‐fried foods (OR = 2.13, 95%CI 1.06–4.30) and butcher's meat (OR 1.84, 95%CI 0.89–3.80). In a similar analysis, allergic rhinitis was associated with liver (OR = 1.67, 95%CI 1.06–2.63). No protective effect was demonstrated for any of the food items examined.

Protein‐rich and fat‐rich foods of animal origin were associated with a higher prevalence of asthma in teenagers.
Purification and characterization of the main allergen of Plantago lanceolata pollen, Pla l 1
Authors: Calabozo B. , Barber D. , Polo F.
Published: March 2003

English plantain (Plantago lanceolata) pollen is an important cause of pollinosis in the temperate regions of North America, Australia and Europe. However, very little is known about its allergen composition.

The aim of this study was to identify plantain allergens, and to isolate and characterize a major allergen.

Allergens were identified by immunoblotting with individual allergic patients' sera. Isolation of the major allergen was achieved by sequential reverse‐phase and size‐exclusion HPLC. Allergenic characterization was performed by ELISA and immunoblotting after SDS‐PAGE with sera from plantain‐allergic patients. N‐terminal amino acid sequence was established by Edman degradation.

Allergograms showed that 13 out of the 14 sera assayed had IgE to a group of proteins with a molecular weight in the range of 16–20 kd, that turned out to be different isoforms or variants of the major allergen Pla l l. Eighteen amino acid residues from the N‐terminal end of one of the isoforms, and 10 of three others, were sequenced, and a partial sequence identity with Ole e 1 was found. Prevalence of specific IgE to purified Pla l 1 in plantain allergic patients was 86%, and represents about 80% of the total IgE‐binding capacity of the plantain extract.

The most relevant allergen from P.lanceolata pollen, Pla l 1, has been purified and characterized. This contributes to a greater knowledge of the allergen composition of this important weed, and clears the way for the standardization of plantain allergen products in terms of major allergen content.
Increased concentration of fecal α1‐antitrypsin is associated with cow's milk allergy in infants with atopic eczema
Authors: Majamaa H. , Aittoniemi J. , Miettinen A.
Published: March 2003

Background The use of fecal α1‐antitrypsin in the monitoring of intestinal inflammation in infants with atopic eczema and food allergy was evaluated.

Methods The study material comprised 26 atopic infants with confirmed food allergy. Fecal samples were collected before an elimination diet and 3 months later for the determination of α1‐antitrypsin.

Results Nine (35%) of the 26 patients demonstrated an increased fecal concentration of α1‐antitrypsin (median 3 mg/g; range 2.8–6.4 mg/g). In all nine patients (100%) the oral cow's milk challenge was positive as opposed to only six (35%) in those with normal α1‐antitrypsin concentration (P = 0.0024). No further connections between α1‐antitrypsin and other food allergies were detected. As a result of an adequate elimination diet, the fecal concentration of α1‐antitrypsin was normalized in seven patients, with a favourable clinical response in atopic eczema in six and no improvement in one patient.

Conclusions Our results indicate that serial determinations of fecal α1‐antitrypsin provide a useful non‐invasive tool for the detection and follow‐up of intestinal inflammation in a certain group of atopic infants with cow's milk allergy and severe inflammation of the gut.
Antigen‐specific IgE and IgA antibodies in bronchoalveolar lavage fluid are associated with stronger antigen‐induced late phase reactions
Authors: Stokes Peebles R. , Hamilton R. G. , Lichtenstein L. M. , Schlosberg M. , Liu M. C. , Proud D. , Togias A.
Published: March 2003

The mechanism(s) leading to the development of late phase allergic reactions is (are) unknown. Previous studies have indicated that a relationship between serum IgE and the late phase exists.

To explore the relationships between allergen‐specific immunoglobulins in bronchoalveolar lavage (BAL) fluids and the magnitude of airflow limitation during the late phase response to inhaled allergen.

Ragweed‐specific IgE, IgA, secretory IgA (sIgA) and IgG were measured in BAL fluid and in the serum 1–5 weeks before whole lung antigen challenge with ragweed extract, in 16 ragweed allergic asthmatics. In addition, BAL and serum eosinophil cationic protein (ECP) and BAL fibrinogen levels were determined and BAL cells counted and differentiated. The latter procedures were repeated in a second BAL performed 24 h after the end of the ragweed challenge. After the challenge, lung function was monitored hourly for 8 h, to record the magnitude of airflow limitation.

Ragweed‐specific immunoglobulins were detected in 25% to 37.5% of BAL samples. Compared to the subjects with undetectable BAL fluid ragweed‐specific IgE levels at baseline, those with detectable antibodies had stronger late phase reactions as determined by the nadir of FEV1 between hours 4 and 8 after the ragweed inhalation challenge (P = 0.0007). Allergen‐induced changes in BAL ECP and fibrinogen levels were also higher in those subjects with detectable ragweed‐specific IgE in baseline fluids (P = 0.03 and P = 0.005, respectively). Significant relationships between BAL antigen‐specific IgA, serum ragweed‐specific IgE and IgA and the late phase reaction were also found.

The results of this study point towards the possibility that allergen‐specific IgE and IgA may be independently involved in the pathogenesis of the late phase reaction. This notion merits further exploration.
Citrus red mite (Panonychus citri) may be an important allergen in the development of asthma among exposed children
Authors: Kim Y.‐K. , Park H.‐S. , Kim H.‐Y. , Jee Y.‐K. , Son J.‐W. , Bae J.‐M. , Lee M.‐H. , Cho S.‐H. , Min K.‐U. , Kim Y.‐Y.
Published: March 2003

BackgroundRecent investigations have demonstrated that spider mites are important allergens in the development of asthma in fruit‐cultivating farmers.

ObjectiveThe aim of this study was to evaluate the sensitization rate to the citrus red mite (Panonychus citri) in children living in rural areas, and to determine the allergenic cross‐reactivity with other mites.

MethodsA total of 7254 children (ages 7–15 years) living in rural areas were enrolled, and each subject was evaluated by a questionnaire and a skin prick test. Allergenic cross‐reactivity was evaluated by ELISA inhibition tests.

ResultsThe most common sensitizing allergens were house dust mites, followed by citrus red mite and cockroach. High serum‐specific IgE bindings to the citrus red mite were detected in 21 of 100 randomly selected subjects. The prevalence of asthma was higher among those with positive skin responses to the citrus red mite than with negative skin responses to this mite. ELISA inhibition tests showed that IgE bindings to this mite were minimally inhibited with additions of domestic mites.

ConclusionSpider mites such as the citrus red mite may be important outdoor allergens among children living in rural areas, and spider mite‐derived allergens have unique allergenic determinants compared with domestic mites.
Temporal relationship between air pollution and hospital admissions for asthmatic children in Hong Kong
Authors: Wong G. W. K. , Ko F. W. S. , Lau T. S. , Li S. T. , Hui D. , Pang S. W. , Leung R. , Fok T. F. , Lai C. K. W.
Published: March 2003

Background Many epidemiological studies have shown positive association between respiratory health and current levels of outdoor air pollution in Europe and America.

Objective The aim of this study was to investigate the association between air pollution and the number of childhood admissions for asthma in Hong Kong.

Methods Daily counts of childhood admission for asthma to a large teaching Hospital were obtained from the computerized database for the period 1993–1994. A Poisson regression allowing for seasonal patterns and meteorological conditions was used to assess the associations between the number of Hospital admissions and the three pollutants: nitrogen dioxide, sulphur dioxide and inhalable particles (measured as PM10, particles < 10 µm in aerodynamic diameter).

Results A total of 1217 children under 15 years of age were admitted for asthma during the study period. The calculated annual hospitalization rates were 283 and 178 per 100 000 for boys and girls, respectively. The mean PM10, NO2 and SO2 levels were 44.1 µg/m3, 43.3 µg/m3, and 12.2 µg/m3, respectively. Daily admission for asthma increased significantly with increasing ambient level of nitrogen dioxide (relative risk (RR) = 1.08 per 10 µg/m3 increase), sulphur dioxide (RR = 1.06) and inhalable particles (RR = 1.03). No association was found between hospital admission and humidity, temperature or atmospheric pressure.

Conclusion This is the first daily time series study of childhood admissions for asthma and air pollution in Hong Kong. The results support that current levels of air pollution contribute to the respiratory morbidity in asthmatic children in Hong Kong.
Safety of a specific COX‐2 inhibitor in aspirin‐induced asthma
Authors: Szczeklik A. , Nizankowska E. , Bochenek G. , Nagraba K. , Mejza F. , Swierczynska M.
Published: March 2003

In a subset of patients with asthma, aspirin and several other non‐steroidal anti‐inflammatory drugs (NSAID) that inhibit simultaneously cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2) precipitate dangerous asthmatic attacks.

We tested the hypothesis that in patients with aspirin‐induced asthma the attacks are triggered by inhibition of COX‐1 and not COX‐2.

In twelve asthmatic patients (seven men, five women, average age 39 years) oral aspirin challenge precipitated symptoms of bronchial obstruction with fall in FEV1 > 20%, and a rise in urinary leukotriene E4 (LTE4) excretion; also in five patients the stable metabolite of PGD2, 9α11βPGF2, increased in urine. The patients then entered a double‐blind, placebo‐controlled, cross‐over study in which they received either placebo or rofecoxib in increasing doses 1.5–25.0 mg for 5 consecutive days, separated by a 1‐week wash‐out period. No patient on rofecoxib developed dyspnoea or fall in FEV1 > 20%; mean urinary LTE4 and 9α11βPGF2 urinary levels, measured on each study day for 6 h post‐dosing, remained unchanged. Two patients on placebo experienced moderate dyspnoea without alterations in urinary metabolites excretion. At least 2 weeks after completion of the study, all patients received on an open basis 25 mg rofecoxib without any adverse effects.

NSAID that inhibit COX‐1, but not COX‐2, trigger asthmatic attacks in patients with asthma and aspirin intolerance. Rofecoxib can be administered to patients with aspirin‐induced asthma.
Der p 1 and Der p 2 induce less severe late asthmatic responses than native Dermatophagoides pteronyssinus extract after a similar early asthmatic response
Authors: Van Der Veen M. J. , Jansen H. M. , Aalberse R. C. , Van Der Zee J. S.
Published: March 2003

Background The models for exposure to house dust in research and clinical practice are selected with respect to their role in IgE‐mediated immediate hypersensitivity. The use of isolated major allergens instead of complex allergen extracts is becoming increasingly popular as it offers some important advantages for quantitative measures in diagnosis and research.

Objective To compare house dust mite extract and isolated mite major allergens with respect to their ability to induce early and late asthmatic responses and bronchial hyperreactivity.

Methods Bronchial responses to house dust mite (HDM, Dermatophagoides pteronyssinus) extract and isolated major allergens from HDM (Der p 1 and Der p 2) were compared in a double‐blind, randomized, cross‐over study in 20 patients with mild to moderate asthma who were allergic to HDM. Allergen was titrated to a standardized early asthmatic response. Bronchial hyper‐responsiveness to histamine (PC20histamine) was determined before and after allergen inhalation to assess allergen‐induced bronchial hyper‐responsiveness and IL‐5 was measured in serum. In addition, the allergens were applied in intracutaneous skin tests and activation of basophil leucocytes and proliferation of peripheral blood mononuclear cells was tested in vitro.

Results After a similar early asthmatic response (mean Δforced expiratory volume in 1 s (FEV1),max−29.4 (SD 7.2) vs. −33.1 (8.6) %; mean difference 3.6 (95% CI −0.9 to 8.2) %), the late asthmatic response (mean ΔFEV1,max−45.9 (21.9) vs. −32.7 (22.3) %; mean difference 13.2 (3.8–22.3) %), the degree of allergen‐induced bronchial hyper‐responsiveness (mean ΔPC20histamine, 1.8 (1.0) vs. 1.2 (0.9) doubling dose; mean difference 0.6 (0.2–1.1) doubling dose) and serum IL‐5 at 6 h were found to be significantly higher after bronchial challenge with HDM extract than after challenge with an isolated HDM major allergen. Likewise, there was an increased late skin reaction with HDM compared with isolated major allergen after a similar early skin reaction.

Conclusion Constituents of HDM extract, other than Der p 1 or Der p 2, with no significant influence on the IgE‐mediated early asthmatic response contribute significantly to the allergen‐induced late asthmatic response and bronchial hyper‐reactivity.
Importance of inflammatory and immune components in a mouse model of airway reactivity to toluene diisocyanate (TDI)
Authors: Matheson J. M. , Lange R. W. , Lemus R. , Karol M. H. , Luster M. I.
Published: March 2003

Background Nearly 9 million individuals are exposed to agents in the workplace associated with asthma, and isocyanates represent the most common cause of occupationally induced asthma.

Objectives Nonetheless, the immunological mechanisms responsible for isocyanate‐induced asthma are not clear. A murine model for toluene diisocyanate (TDI) asthma is described and employed to examine inflammatory and immune components that may be involved in the disease.

Methods Groups (n = 6) of C57BL/6J and athymic mice were sensitized by subcutaneous injection (20 µl on day 1, 5 µl on days 4 and 11), and 7 days later challenged by inhalation (100 p.p.b., days 20, 22 and 24) with TDI. Twenty‐four hours following the last challenge the tracheae and lungs were examined for histological changes as well as for the expression of Th1, Th2 and pro‐inflammatory cytokines. Mice were also examined for airway reactivity to methacholine challenge and for specific and total IgE and IgG antibodies.

Results TDI sensitization resulted in increased reactivity to methacholine challenge as well as a significant inflammatory response in the trachea and nares of wild‐type mice, but not in the athymic mice nor in the lungs of the C57BL/6J mice. Airway inflammation was characterized by inflammatory cell influx, goblet cell metaplasia and epithelial damage. Histological changes in the trachea were accompanied by increased mRNA expression of interleukin (IL)‐4, tumour necrosis factor α, lymphotoxin β, lymphotactin and Rantes, as well as TDI‐specific IgG antibodies and elevated levels of total IgE. IgE‐specific antibodies were not detected with this exposure regimen but were produced when the TDI concentrations were increased.

Conclusions These studies provide a unique murine model for occupational asthma that generates both inflammatory and immune mediators similar to those occurring in TDI‐induced asthma in humans.
Freezing of homogenized sputum samples for intermittent storage
Authors: Holz O. , Mücke M. , Zarza P. , Loppow D. , Jörres R. A. , Magnussen H.
Published: March 2003

Background Among the reasons that restrict the application of sputum induction in outpatient settings is the need for processing of samples within 2 h after induction.

Objective The aim of our study was to assess whether freezing is suitable for intermediate storage of sputum samples before processing.

Methods We compared differential cell counts between two sputum aliquots derived from the same sample. One aliquot was processed within 2 h after production and one, after it had been frozen under addition of dimethyl‐sulfoxid (DMSO) and stored up to 10 days at −20 °C. Thirty‐five samples were frozen immediately prior to preparation of cytospins, and 10 samples were frozen at an even earlier stage, directly after homogenization.

Results In both sets of experiments we observed a significant relationship between frozen and native samples regarding macrophages, neutrophils and eosinophils, as indicated by respective intraclass correlation coefficients of 0.96, 0.96, and 0.93 in the first, and of 0.92, 0.96 and 0.77 in the second experiments.

Conclusion Our results indicate that the freezing of sputum samples at different stages of processing does not alter sputum morphology to an extent that affects the results of differential cell counts.
Prevalence of immunoglobulin E for fungi in atopic children
Authors: Nolles G. , Hoekstra M. O. , Schouten J. P. , Gerritsen J. , Kauffman H. F.
Published: March 2003

Background The prevalence of sensitization to fungi in young atopic patients in relation to age and clinical importance is largely unknown.

Objective The aim of this study was to investigate the prevalence of sensitization to different fungi in atopic children in relation to age and other aeroallergens.

Methods A total of 137 atopic children (male 62%, female 38%; mean age 5 years and 9 months, range 5 months−14 years) were studied. Sera of all patients were routinely tested for total IgE and specific IgE against aeroallergens and milk. Positive sera were also tested for IgE against Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum and Penicillium chrysogenum, using the Pharmacia Enzyme CAP procedure.

Results In this study in atopic children total IgE showed a significant linear relation with age, whereas specific IgE against outdoor fungi, indoor fungi and house dust mite showed significant non‐linearity with age. Prevalence of specific IgE for Cladosporium ranked first, followed closely by Aspergillus and Alternaria. Calculation of the sensitization of indoor and outdoor fungi showed maximum prevalence at 7.8 years, followed by lower values at higher ages. A similar significant relation was also found for Alternaria, while this relation was not significant for the other individual fungi. Specific IgE for indoor and outdoor fungi was associated with the presence of specific IgE for aeroallergen and milk. We found that all children aged 4 years and older showed IgE for house dust mite that did not decline with increasing age.

Conclusions Sensitization to fungi is prevalent in childhood, with an age‐dependent distribution reaching maximum values at 7.7–7.8 years, followed by a decline for all fungal sensitization with increasing age. The importance and relative contribution of fungal sensitization to airway disease, compared with the other allergens, remains to be established.
Increased release of matrix metalloproteinase‐9 in the plasma of acute severe asthmatic patients
Authors: Belleguic C. , Corbel M. , Germain N. , Léna H. , Boichot E. , Delaval PH. , Lagente V.
Published: March 2003

Background Matrix metalloproteinases (MMPs) are likely to be relevant mediators of the extracellular matrix (ECM) degradation and airway remodelling.

Objective

We have compared the levels of MMPs, eotaxin and soluble interleukin 2 receptor (IL‐2R) in the plasma of healthy subjects, atopic patients and asthmatic patients.

Methods The asthmatic patients were separated into two groups, either well controlled on inhaled therapy or acute severe asthma. Patients with acute severe disease had all received systemic corticosteroids from 12 to 48 h before the blood was taken. Blood was recovered in EDTA tubes, incubated with either f MLP, PMA or vehicle for 10 min and centrifuged. MMP‐9, TIMP‐1, IL‐2R and eotaxin levels were measured in the plasma by ELISA. Moreover, the activity of MMPs was also evaluated by zymography.

Results An increased basal level of MMP‐9 and IL2‐R was observed in acute severe asthma. Following stimulation with f MLP and PMA there was an enhanced production of MMP‐9 in the plasma of all groups of patients. However, the MMP‐9 level was significantly enhanced in acute severe asthma, compared with the others. No difference was found for the TIMP‐1 level between the patients. The eotaxin level in plasma was found to be significantly lower in acute severe asthmatics compared with the others groups. Zymography technique showed a significant increased activity of MMP‐9 (92 kDa) but not MMP‐2 (66 kDa) in the plasma of patients with acute asthma.

Conclusion The increased in MMP‐9 production and activity observed in the present study suggests a process of extracellular matrix degradation in acute severe asthmatic patients and proposes MMP‐9 as a non‐invasive systemic marker of inflammation and airway remodelling in asthma.
Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm
Authors: Portengen L. , Sigsgaard T. , Omland Ø. , Hjort C. , Heederik D. , Doekes G.
Published: March 2003

Background Recent studies have shown that in several countries atopic sensitization to common allergens (common atopy) and atopic symptoms are markedly less prevalent in children living on a farm, compared with non‐farm children living in the same rural areas. Living conditions on farms may, however, vary largely between different countries. It is also not yet known whether the ‘protective’ effect of a farm environment can also be found in adults.

Materials and methods Common atopy and respiratory health were assessed by skin prick tests (SPT), questionnaire and measurement of bronchial hyper‐responsiveness (BHR) in the Sund Stald (SUS) study, a cohort study on respiratory health in Danish farming students and conscripts from the same rural areas as controls. Results of SPT were confirmed by IgE serology in all SPT+ subjects and a subset of SPT– subjects. Prevalences of common atopy, respiratory symptoms and bronchial hyper‐ responsiveness were compared for farmers and controls, and for those who had or had not lived on a farm in early childhood.

Results In multiple logistic regression analyses adjusting for ever smoking and a familial history of allergy, both being a farmer (ORs 0.62–0.75) and having had a farm childhood (ORs 0.55–0.75) appeared to contribute independently to a lower risk of sensitization to common allergens as assessed by SPT and IgE serology. A farm childhood was also inversely associated with high total IgE (OR 0.68), presence of respiratory symptoms (ORs 0.69–0.79) and BHR (OR 0.61) in these analyses. Direction and strength of the association between being a farmer and respiratory symptoms or BHR varied widely (ORs 0.69–1.28).

Conclusion The ‘anti‐atopy’ protective effect of a farm childhood could be confirmed in Danish farming students: prevalences of positive SPT, specific and total IgE, allergic symptoms and BHR were lower in those being born or raised on a farm. Past exposure to the farm environment in early childhood may therefore also contribute to a lower risk of atopic sensitization and disease at a later age.
Nasal air sampling used for the assessment of occupational allergen exposure and the efficacy of respiratory protection
Authors: Renström A. , Karlsson A.‐S. , Tovey E.
Published: March 2003

Background Occupational exposure to rodent allergens may cause laboratory animal allergy. Personal exposure to occupational allergens is measured by collecting airborne dust on filters using person‐carried pumps. This technique cannot be used to evaluate personal protective respiratory equipment. Recently developed intranasal air samplers collect inhaled particles by impaction on adhesive strips within the samplers.

Objective The aims were to compare rodent aeroallergen exposure assessment using nasal air samplers with personal air sampling, and to evaluate the efficacy of using respiratory protection during rodent work using nasal air samplers.

Methods Aeroallergen exposure was assessed during rodent work using both nasal air samplers and personal air samplers. The efficacy of respiratory protection (P2 facemasks and fresh‐air helmets) was studied in subject pairs working side by side, one person with protection, the other without. Right nostril samples were laminated with protein‐binding membrane and immunostained for rat urinary allergen‐containing particles. Left nostril samples and air samples were eluted in buffer and analysed in amplified ELISAs for rat (RUA) and mouse (MUA) urinary allergen content (detection limit 10 pg/mL). Allergen collection efficacy of the nasal air samplers was tested at high and low exposure levels and at different flow rates using static sampling.

Results P2 facemasks decreased the amount of inhaled allergen by about 90%, and very little allergen was inhaled using fresh‐air helmets. Allergen levels in air and nasal samples correlated well (rs was about 0.8 for both RUA and MUA). The number of RUA‐positive particles and nasal allergen levels measured in ELISA also correlated significantly (rs = 0.8). Collection efficacy of the nasal air sampler was better during high exposure (cleaning cages, median 73% of allergenic particles collected), than during low exposure (undisturbed room, 49% of particles).

Conclusion Nasal air sampling is a relevant and sensitive complement to personal air sampling and enables evaluation of personal respiratory protection equipment. Use of P2 facemasks and fresh‐air helmets may substantially reduce occupational exposure to inhaled allergens.
Cloning and expression of Blo t 1, a novel allergen from the dust mite Blomia tropicalis, homologous to cysteine proteases
Authors: Mora C. , Flores I. , Montealegre F. , Díaz A.
Published: March 2003

Background House dust mite allergens have been shown to be a very important stimulus in the causation of asthma and triggers for the exacerbation of symptoms. Therefore, characterization of mite‐derived allergens at the molecular level is an important step for the development of effective diagnostic and therapeutic approaches, as well as for epidemiological studies.

Objective To clone, express and characterize at the molecular level the cysteine protease from Blomia tropicalis (Bt).

Methods A full‐length cDNA encoding Blo t 1 was cloned from a Bt cDNA library using a PCR and RACE‐based strategy. The cDNA was PCR‐amplified, sequenced and subcloned into a prokaryotic expression vector. The allergenicity of the recombinant Blo t 1 was evaluated for IgE reactivity by Western blot.

Results Blo t 1 cDNA encodes a 221 amino acids polypeptide with an estimated molecular weight of 25 kDa. The recombinant protein is 35% identical to other mite cysteine proteases. Recombinant Blo t 1 (rBlo t 1) bound IgE from 62% of Bt skin test‐positive serum. Dermatophagoides pteronyssinus (Dp) skin test‐positive sera did not react with rBlo t 1, indicating the possible presence of unique IgE epitopes on the rBlo t 1 molecule. A three‐dimensional image of Blo t 1, constructed based on predicted analysis, showed conserved secondary and tertiary structure with other cysteine proteases.

Conclusion We report the cloning, expression and IgE reactivity of Blo t 1, a novel allergen from the domestic mite Blomia tropicalis (Bt), highly homologous to cysteine proteases. This putative cysteine protease, designated Blo t 1, may play a major role as an immunodominant allergen involved in dust mite‐specific IgE‐mediated hypersensitivity.