bluuebunny/crossref_metadata_2025 huggingface dataset:
The long‐term effects of capsaicin aqueous spray on the nasal mucosa
Authors: Blom  , Severijnen  , Van Rijswijk  , Mulder  , Gerth Van Wijk  , Fokkens
Published: March 2003

Background

Capsaicin has been shown previously to reduce nasal complaints in patients with a non‐allergic non‐infectious perennial rhinitis. Proposed pathophysiological mechanisms for non‐allergic non‐infectious perennial rhinitis include a chronic inflammatory disorder of an antigenic or neurogenic nature as well as the possibility of a functional neuronal disorder. We hypothesized that the beneficial effect of capsaicin might be the result of a down‐regulation of inflammation (by a reduction of inflammatory cells) or through modulation of neural tissue density.

Methods

Patients were treated with either a placebo or capsaicin spray solution delivering 0.15 mg of capsaicin per nostril once every second or third day for a total of seven treatments. Both sides were treated each visit. Biopsies were taken before and 2 weeks, 3 months and 9 months after the treatment period. Immunohistochemical staining of the biopsy specimen was performed to ascertain the effect of treatment on immunocompetent cell densities (quantitative) and neural tissue densities (semi‐quantitative) in the nasal mucosa.

Results

Nasal complaints were significantly reduced in the capsaicin‐treated group. The number of CD1+, CD25+, CD3+, CD68+, BMK13+, IgE+, tryptase+, and chymase+ cells did not significantly differ between capsaicin and placebo group. No significant differences between both groups were found in pan‐neurogenic staining of nasal mucosa using neurofilament and synaptophysine.

Conclusion

Capsaicin aqueous nasal spray has previously been shown to reduce nasal complaints without affecting cellular homeostasis or overall neurogenic staining up to 9 months after treatment. Immunocompetent cells are not involved in non‐allergic non‐infectious perennial rhinitis.
Vascular adhesion molecules in nocturnal asthma: a possible role for VCAM‐1 in ongoing airway wall inflammation
Authors: Ten Hacken  , Postma  , Bosma  , Drok  , Rutgers  , Kraan  , Timens
Published: March 2003

Background

Increased airway inflammation at night is thought to be one of the underlying mechanisms in nocturnal asthma. Vascular adhesion molecules may be important for the recruitment of inflammatory cells in the process of asthmatic airway inflammation.

Objective

To determine the possible role of vascular adhesion molecules in increased airway inflammation at night in subjects with nocturnal asthma.

Methods

Bronchial biopsies were obtained at 16.00 h and 04.00 h from 13 healthy controls, 15 asthmatic patients with PEF variation ≤ 15% and 10 asthmatic patients with PEF variation > 15%. Biopsies were snap‐frozen and double‐immunostained for CD31 in combination with P‐selectin, E‐selectin, ICAM‐1 or VCAM‐1.

Results

No significant day–night differences in expression of adhesion molecules were found in any of the three groups. The percentage of VCAM‐1 positive vessels in biopsies of asthmatic patients was higher than in biopsies of healthy controls: 5.8 vs 2.5% (P < 0.05) at 16.00 h and 11 vs 0% (P < 0.05) at 04.00 h. In asthma, VCAM‐1 expression was correlated with the number of EG2 positive cells: at 16.00 h (rho = 0.57, P < 0.01) as well as at 04.00 h (rho = 0.64, P < 0.01). Moreover, VCAM‐1 expression was correlated with the number of CD25 positive cells at 16.00 h (rho = 0.43, P < 0.05) and at 04.00 h (rho = 0.41, P < 0.05).

Conclusion

Increased nocturnal airway obstruction in asthma is not associated with an increased nocturnal expression of vascular E‐selectin, P‐selectin, ICAM‐1 or VCAM‐1. The relationship between vascular VCAM‐1 expression and sub‐mucosal EG2 and CD25 positive cells, both at 16.00 h and 04.00 h, suggests a role for VCAM‐1 in the ongoing airway wall inflammation of asthma.
Prediction of sensitization to inhalant allergens in childhood: evaluating family history, atopic dermatitis and sensitization to food allergens
Authors: Kulig  , Bergmann  , Niggemann  , Burow  , Wahn  ,   THE MAS STUDY GROUP
Published: March 2003

Background

A family history of atopy is a poor predictor of sensitization to inhalant allergens and allergic disease during childhood. We recently identified early sensitization to food allergens, especially hen's egg, as a valuable predictor of subsequent sensitization to inhalant allergens.

Objective

(1) Whether prediction will be improved by in vitro allergy tests at 1 year of age in combination with family history and medical history data. (2) Comparison with the capacities of in vitro tests to predict sensitization to aeroallergens.

Methods

Of an observational birth cohort study (MAS) 49 children who were sensitized to inhalant allergens at 5 years of age and 116 non‐sensitized controls were included in the present study. For the prediction of sensitization to inhalant allergens the following prognostic factors were evaluated: atopic family history (FH), atopic dermatitis (AD) during the first year of life, two in vitro allergy tests for specific IgE to common food allergens at 1 year of age (fx5 [Pharmacia] and single allergen specific tests (sIgE) for four allergens) and ‘high’ total serum IgE, defined by three different cut off points.

Results

The combination of medical history data and laboratory tests resulted in the best predictive discrimination. The positive predictive values (PPV) were higher if sensitization to food was detected by single allergen specific tests (PPV: 66%/75%/100% corresponding to the three evaluated risk groups) than by the qualitative fx5 (PPV: 46%/65%/100%). The negative predictive values were equal for both tests (69 and 92% for the two low risk groups). High total serum IgE had low predictive capacity.

Conclusion

During infancy the prediction of sensitization to inhalant allergens should be based on medical history data and allergy tests determining sensitization to food allergens. The in vitro tests improve the predictive discrimination, but the individual risk profile of the child must be considered for a reliable and valid prediction.
Approaches and issues in defining asthma and associated phenotypes map to chromosome susceptibility areas in large Minnesota families
Authors: Blumenthal  , Rich  , King  , Weber  ,   THE COLLABORATIVE STUDY FOR THE GENETICS OF ASTHMA (CSGA)
Published: March 2003

Evidence for linkage of asthma and its associated phenotypes with susceptibility genes on chromosome 12 has been demonstrated in one group of Minnesota families. The evidence is strong in affected sib pairs and weakens in analysis of the large pedigrees. A second group of families provided little evidence for such linkage. A discrepancy has been demonstrated in different families. This may be due to several factors, including genetic heterogeneity and gene–gene, or gene–environmental interaction effects as well as the statistical power of the sample population used.
Rapid symptom relief in rhinitis
Authors: Bousquet J.
Published: March 2003

In some patients, symptoms of allergic rhinitis can be severe and therefore rapid relief is required. There are many treatment options for allergic rhinitis but histamine H1 blockers and topical corticosteroids represent the first‐line treatment. Although the latter drugs are usually very effective on nasal symptoms, their onset of action is around 24 h. Thus drugs that are more rapidly effective are of interest.

 Recently 400 French specialists (in Allergy, ENT and Pneumology) met together to define the criteria for selecting a drug for the treatment of rhinitis. Twelve criteria were proposed and rapid onset of action (less than 24 h) was among the foremost designated criteria.

 In the first trial, a comparison of mizolastine (10 mg once daily [od]) with cetirizine (10 mg od) and placebo was carried out in the management of seasonal allergic rhino‐conjunctivitis (SAR) with special focus on onset of action. A total of 375 patients were included in this European multicentric, randomized, parallel group and placebo‐controlled study. By comparison to placebo, both cetirizine and mizolastine reduced significantly nasal and ocular symptoms during the 28‐day follow‐up trial. The percentage of responders ranged from 40% in the placebo group to 55% in the mizolastine group and 53% in the cetirizine group. Both active drugs were effective from the first intake with a rapid onset within 2 h. However, mizolastine was more rapidly and more profoundly effective than cetirizine during the first 12 h.

 A second trial included 257 patients suffering from perennial allergic rhino‐conjunctivitis (PAR) in a 4‐week double‐blind placebo‐controlled multicentric study. During the study, patients recorded, using a diary card, ocular and nasal symptoms, including nasal blockage. The mean values of nasal score between day 1, 14 and 28 in the mizolastine group were statistically significantly lower than those in the placebo group. The mean values of ocular score showed a statistical difference in recordings between day 1 and day 14 in favour of the mizolastine group.

 Mizolastine was an effective drug both in SAR and PAR with a rapid onset of action. Mizolastine relieved symptoms more effectively than cetirizine (SAR) and placebo (SAR and PAR) at the beginning of treatment.
Eotaxin levels and eosinophils in guinea pig broncho‐alveolar lavage fluid are increased at the onset of a viral respiratory infection
Authors: Scheerens J. , Folkerts G. , Van Der Linde H. , Sterk P. J. , Conroy D. M. , Williams T. J. , Nijkamp F. P.
Published: March 2003

In previous studies we found that guinea pigs demonstrate an increase in airway reactivity and eosinophil numbers 4 days after a respiratory infection with parainfluenza‐3 (PI3) virus. Clinical data support the possible involvement of eosinophils in virus‐induced airway hyperresponsiveness. Eotaxin, a newly discovered chemokine, could be involved in eosinophil migration to the airways. In this study, eosinophil numbers were counted in blood and bronchoalveolar lavage (BAL) fluid and related with eotaxin concentrations in BAL fluid 1, 2, 3, and 4 days after intratracheal PI3 virus administration. On day 1, blood eosinophils increased by more than 200% (P < 0.01). The number of eosinophils were only slightly enhanced from day 2 to day 4 (40%–70%). BAL fluid eosinophils were not increased on day 1 but were significantly elevated on day 2 (180%) and remained high on days 3–4 (>300%, P < 0.05). This increase in lung eosinophils correlated well with eotaxin levels measured in BAL fluid. There was no significant increase in eotaxin on day 1 following PI3 infection; however, on days 2–4 eotaxin levels in BAL fluid were significantly elevated (four–sixfold increase) when compared with medium inoculated controls. Eotaxin appears to play an important role in eosinophil accumulation in guinea pig lung following PI3 infection.
Betamethasone prevents virus‐induced airway inflammation but not airway hyperresponsiveness in guinea pigs
Authors: Leusink‐Muis A. , Ten Broeke R. , Folkerts G. , DE Clerck F. , Nijkamp F.P.
Published: March 2003

In this study the effect of betamethasone was investigated in guinea pigs that demonstrate airway inflammation and airway hyperresponsiveness after a viral respiratory tract infection with parainfluenza‐3 (PI3) virus. Guinea pigs were pretreated with saline or betamethasone 8 mg/kg intraperitoneally twice a day for five consecutive days, starting on day 0 and ending on day 4. On day 1, the guinea pigs were inoculated with either control solution (medium) or PI3 virus. On day 5, airway responsiveness was measured. Furthermore, a blood sample was taken, lungs were lavaged, blood leucocytes were counted, and bronchoalveolar lavage (BAL) cells were counted and differentiated. Accordingly, the activity of the bronchoalveolar cells was measured by lucigenin‐amplified chemiluminescence. In virus‐infected guinea pigs the total bronchoalveolar cell number was increased by 44% compared with medium‐treated guinea pigs. This was mainly due to the increase in macrophages (70%, P < 0.05) and eosinophils (344%, P < 0.001). The increase in both total and differential (macrophages and eosinophils) cell numbers in virus‐infected guinea pigs was completely abolished in animals treated with betamethasone. Moreover, betamethasone prevented the decrease in number of blood leucocytes in virus‐infected guinea pigs. In contrast, betamethasone did not prevent the increase in airway responsiveness to both histamine (>200%) and methacholine (>100%) after the virus infection. In conclusion, betamethasone treatment prevents virus‐induced airway inflammation but not airway hyperresponsiveness in guinea pigs.
Genetics of allergy and bronchial hyperresponsiveness
Authors: Howard T. D. , Wiesch D. G. , Koppelman G. H. , Postma D. S. , Meyers D. A. , Bleecker E. R.
Published: March 2003

Allergy and asthma are closely related complex diseases caused by a combination of both genetic and environmental influences. Two common genetic approaches, candidate gene studies and genome‐wide screens, have been used to localize and evaluate potential genetic factors that confer susceptibility or modify the phenotype of these diseases. Four genome screens suggest multiple chromosomal locations likely to contain asthma and allergy genes and many potential candidate genes exist in these regions. These screens were performed in six different populations and identified many common susceptibility regions as well as novel regions for each population. Ideally, these genes may point towards key biological pathways that will eventually serve as targets for therapeutic agents.
Association between mast cell chymase genotype and atopic eczema: comparison between patients with atopic eczema alone and those with atopic eczema and atopic respiratory disease
Authors: TANAKA  , SUGIURA  , UEHARA  , SATO  , HASHIMOTO‐TAMAOKI  , FURUYAMA
Published: March 2003

Background

It has remained unclear whether genetic background of patients with atopic eczema (AE) alone is identical to that of patients with both AE and atopic respiratory disease.

Objective

We aimed to assess whether there is a genetic difference between these two groups of AE patients.

Method

We determined the genotype with regard to an allelic polymorphism in the gene for mast cell chymase (MCC; a serine protease secreted from mast cells) in 169 AE patients.

Results

MCC genotype was significantly associated with pure AE patients who did not have a predisposition to atopic respiratory disease and whose serum IgE concentration was < 500 IU/mL. The distribution of MCC genotypes also differed significantly between the latter patients and those AE patients with bronchial asthma and a serum IgE concentration of > 2000 IU/mL.

Conclusion

These results suggest that pure AE is associated with genetic variants of MCC, and that the genetic basis of pure AE differs from that of AE associated with atopic asthma.
IFN‐γ is only partially restored by co‐stimulation with IL‐12, IL‐2, IL‐15, IL‐18 or engagement of CD28
Authors: Jung  , Witzak  , Dieckhoff  , Zachmann  , Heidrich  , Aversa  , Neumann
Published: March 2003

Background

Although it is well established that T cells derived from patients with atopic diseases produce low levels of interferon‐gamma (IFN‐γ), the mechanisms responsible for this phenomenon are poorly understood.

Objectives

To elucidate whether IFN‐γ production may be restored by co‐stimulatory molecules known to increase IFN‐γ production in vitro. Further, to investigate whether deficient IFN‐γ production is associated with disease activity.

Methods

Purified peripheral T cells obtained from patients with severe atopic dermatitis (AD), individuals with a history but no symptoms of AD and healthy control subjects were activated with anti‐CD3 MoAbs in the presence or absence of anti‐CD28 MoAbs, interleukin (IL‐) 12, IL‐2, IL‐15 or IL‐18. IFN‐γ production was determined at the single cell level by flow cytometry, as well as by ELISA.

Results

Activated T cells from patients with severe AD produced less IFN‐γ than T cells from healthy control individuals. IL‐12 or engagement of CD28 enhanced IFN‐γ production in both healthy and atopic T cells. However, absolute values of IFN‐γ were still different. IL‐2, IL‐15 and IL‐18 did not restore IFN‐γ production. T cells from individuals with a history of AD produced more IFN‐γ than those from subjects with severe AD, but less than T cells from healthy individuals. Atopic T cells expressed regular levels of CD3, CD28 and Stat4, the main signal transducer and activator of transcription for IL‐12. IL‐4, IL‐10 and TGF‐β production by T cells were not different between healthy and atopic individuals.

Conclusion

IFN‐γ deficiency in atopic T cells is not due to a lack of responsiveness to CD28, IL‐12, IL‐2, IL‐15 or IL‐18. T cell‐derived cytokines able to antagonize IFN‐γ do not contribute to decreased IFN‐γ production. The extent of IFN‐γ deficiency seems to be dependent on disease activity.
IgE and T‐cell responses to high‐molecular weight allergens from bee venom
Authors: Kettner  , Henry  , Hughes  , Corradin  , Spertini
Published: March 2003

Background

Bee venom contains multiple allergens with a wide distribution of molecular weight. In contrast with conventional bee venom desensitization, peptide or recombinant allergen immunotherapy may have to take into account patients' individual patterns of humoral or cellular response.

Objective

To study immunoglobulin (Ig)E and T‐cell responses to high‐molecular weight bee venom allergens ≥ 50 kDa.

Methods

Bee venom proteins were separated by size exclusion chromatography and fractions were characterized by one and two‐dimensional gel electrophoresis. IgE antibody binding to bee venom fractions was analysed by immunoblotting and T‐cell responses by proliferation assay.

Results

Among 38 bee venom‐hypersensitive patients, IgE recognition pattern of bee venom allergens varied greatly. IgE bound mainly to phospholipase A2 and furthermore to several proteins ≥ 50 kDa (50, 54, 69, 84 and 94 kDa). N‐terminal sequences of these proteins showed no homology with known proteins. In addition, peripheral mononuclear cells from patients as well as from nonatopic donors strongly proliferated in response to those proteins.

Conclusions

Although present in low amounts, high‐molecular weight allergens from bee venom elicit strong IgE and T‐cell responses, and may need to be considered as clinically relevant. Therefore, the development of peptide or recombinant protein‐based immunotherapy for bee venom allergy may require careful characterization of such allergens.
Increased levels of IL‐5 positive peripheral blood eosinophils and lymphocytes in mild asthmatics after allergen inhalation provocation
Authors: HALLDÉN  , HELLMAN  , GRÖNNEBERG  , LUNDAHL
Published: March 2003

Background

In allergic inflammation eosinophils and TH2‐like lymphocytes are supposed to be the major effector cells and considered to contribute as cellular source of the key cytokine interleukin (IL)‐5.

Objective

The purpose of this study was to enable detection of IL‐5 containing leucocytes and to investigate whether the number of these cells in the blood circulation differed between healthy and asthmatics before and after allergen provocation.

Methods

The distribution of intracellular IL‐5 in human peripheral blood eosinophils (PBE) and lymphocytes (PBL) has been investigated using fixation and cell membrane permeabilization with octyl‐glucopyranoside, the FOG‐method, and flow cytometry. The intracellular staining was performed on leucocytes without any prior purification and in vitro stimulation. The specificity of IL‐5 binding to intracellular compartment of both PBE and PBL was confirmed by complete inhibition with human recombinant IL‐5.

Results

Preformed intracellular IL‐5 was detected in the main population of PBE (> 70%) in both healthy individuals and asymptomatic patients. Moreover, preformed intracellular IL‐5 was also detected in 4.8% and 2.4% of PBL from healthy individuals and asymptomatic patients, respectively. There was a correlation between the absolute number of PBE and IL‐5 positive PBE. In patients with pollen‐related asthma, the number of IL‐5 positive PBE and PBL increased significantly 24 h after an allergen inhalation provocation (P < 0.05). In the healthy control group no differences regarding IL‐5 positive PBE and PBL were obtained pre‐ and post‐allergen challenge.

Conclusions

In patients with mild allergic asthma, but not in healthy individuals, allergen provocation induces an increased absolute number of IL‐5 positive PBE and PBL. The reason for the relatively high number of IL‐5 positive PBL is unclear, but a plausible explanation might be that other lymphocyte subsets besides CD4+ TH2 can produce IL‐5. However, enumeration of IL‐5 positive leucocytes may be used as an activity marker and also be a useful tool in monitoring the inflammation in asthma.
Cord blood leucocytes/basophils produce and release sulfidoleucotrienes in response to allergen stimulation
Authors: Szépfalusi  , Todoran  , Elsässer  , Jagdt  , Wank  , Urbanek
Published: March 2003

Background

Leucocyte‐derived sulfidoleucotrienes (SLT) from children and adults can be detected in vitro in response to specific allergen stimulation, a mechanism thought to require the presence of allergen‐specific immunoglobulin (Ig)E antibodies on the surface of basophils. It is unknown whether this mechanism is functional in cord blood basophils.

Objective

We studied the in vitro SLT‐release of leucocytes in response to allergen and anti‐IgE stimulation in term newborns and children with allergic diseases.

Methods

Cord blood from randomly selected term newborns were analysed for total IgE‐antibodies and in vitro SLT‐release in response to allergen and anti‐IgE stimulation. Children from an allergy outpatient clinic were used as the control group. The Cellular Allergen Stimulation Test (CAST) was used as read‐out system. Allergen stimulation was performed with an allergen‐mix containing 21 nutritive and inhalant allergens.

Results

Peripheral blood leucocytes/basophils derived from allergic children (n = 56; median SLT release 1049 pg/mL) were more responsive to anti‐IgE stimulation as cord blood leucocytes/basophils (n = 104; median 419 pg/mL P < 0.0001). In response to stimulation with an allergen‐mix, the two groups did not differ significantly from each other. Only SLT‐releasability in response to anti‐IgE showed a correlation with cord blood IgE.

Conclusions

Sulfidoleucotriene‐release of cord blood basophils is functional in response to allergens. It appears possible that cord blood basophils are armed with allergen‐specific IgE‐antibodies though not detectable in serum. Therefore, cord blood SLT‐release may indirectly reflect prenatal priming with allergens with subsequent production of allergen‐specific IgE.
VEGF levels in asthmatic airways do not correlate with plasma extravasation
Authors: Demoly  , Maly  , Mautino  , Grad  , Gougat  , Sahla  , Godard  , Bousquet
Published: March 2003

Background

Vascular permeability/vascular endothelial growth factor (VEGF) is a multifunctional cytokine which plays a role in chronic inflammation and angiogenesis. Its expression in bronchoalveolar lavage (BAL) has not been determined although VEGF may be relevant to the pathophysiology of asthma in which oedema is an important feature.

Methods

We studied VEGF, albumin and IgA immunoreactive levels in the BAL fluids obtained from 27 chronic stable asthmatics, nine untreated chronic bronchitis patients and 15 control subjects.

Results

BAL fluid levels of VEGF and VEGF normalized to IgA were not significantly different in any patient group. Both asthmatic steroid‐ and non‐steroid‐treated groups had significantly lower albumin levels in their BAL fluids explaining most of the 179% increased VEGF normalized to albumin ratios in non‐steroid treated asthmatics. Moreover, VEGF and albumin markers correlated in control subjects (r = 0.73, P = 0.006) and in chronic bronchitics (r = 0.75, P = 0.03, Spearman test), but not in asthmatics. VEGF was inversely correlated with asthma severity (GINA/NHLBI scores) in non‐steroid treated asthmatics (τ = − 0.52, P = 0.009, Kendall test).

Conclusions

Thus, the potential role of VEGF in asthma requires further studies on bronchial biopsies and induced sputum.
Immunocytochemical localization of cyclo‐oxygenase isoforms in cultured human airway structural cells
Authors: PETKOVA  , PANG  , RANGE  , HOLLAND  , KNOX
Published: March 2003

Background

Cyclo‐oxygenase (COX) exists as two isoforms, COX‐1, the constitutive isoform, and COX‐2, which is inducible by cytokines or inflammatory stimuli and may participate in airway inflammation.

Objective

To determine the basal distribution of COX isoforms, and their regulation by interleukin‐1 beta (IL‐1β), bradykinin (BK) and dexamethasone (Dex) in cultured airway structural cells.

Methods

We measured COX‐1 and COX‐2 in cultured human airway smooth muscle (HASM) cells, MRC5 fibroblasts and normal human epithelial cells (NHBE) using immunocytochemical analysis.

Results

The majority of all types of untreated cultured cells expressed COX‐1 (75% of HASM, 75% of MRC5 fibroblasts and 72% of NHBE cells). Fibroblasts and smooth muscle cells showed low constitutive COX‐2 expression (2 and 8%, respectively) but this was higher in NHBE cells (28%). IL‐1β (24 h incubation) or BK (4 h incubation) had no effect on COX‐1 expression in any of the cells studied. In contrast, there was a two‐ and 1.5‐fold rise in the percentage of NHBE cells expressing COX‐2; a 7.5‐ and sixfold rise in the percentage of HASM cells expressing COX‐2 and a 33.5‐ and 20.5‐fold increase in the percentage of fibroblasts expressing COX‐2 after IL‐1β or BK treatment, respectively. Pretreatment with dexamethasone abolished IL‐1β‐ and BK‐stimulated COX‐2 induction in all cells studied.

Conclusion

COX‐1 is expressed constitutively in human airway fibroblasts, smooth muscle and epithelial cells but epithelial cells also show constitutive expression of COX‐2. Both IL‐1β and BK induced COX‐2 expression in all cells studied and this induction was blocked by dexamethasone. Immunocytochemical techniques can be successfully used to detect the distribution of COX isoforms in cell cultures.
Mucosal immunity in extrinsic allergic alveolitis: salivary immunoglobulins and antibody against inhaled avian antigens among pigeon breeders
Authors: McSHARRY  , MacLEOD  , McGREGOR  , SPEEKENBRINK  , SRIRAM  , BOYD  , BOYD
Published: March 2003

Background

Inhaled antigens from pigeons can cause extrinsic allergic alveolitis (EAA); a model disease of pulmonary inflammation. Among pigeon breeders, serum antibody and sensitized lymphocytes specific for these antigens have been described primarily, but not always, with disease. Antibody activity within the lung may have a closer association with disease, however, sampling by alveolar lavage at bronchoscopy is impractical for screening, therefore we used saliva to quantify the mucosal antibody response.

Objective

To establish: (a) if antibody activity against inhaled avian antigens was detectable in the saliva of pigeon breeders, (b) if the distribution of saliva antibody and total immunoglobulin levels were quantitatively or qualitatively different from serum, and (c) whether the hypersensitivity symptoms of EAA were associated more with the mucosal or the systemic humoral immune response.

Measures

Saliva and serum total and avian antigen‐specific IgG, IgA (IgA1 and IgA2) antibody activity in 87 pigeon breeders and 24 control subjects with no avian exposure. Albumin levels were used as a protein reference and cotinine levels confirmed smoking status. Specific hypersensitivity symptoms and various exposure indices to pigeons were established by interview.

Results

Absolute levels and relative proportions (vs albumin) of IgG, IgA and IgA1 in saliva, and IgG in serum, were significantly higher in pigeon breeders compared with controls, suggesting mucosal inflammation. Avian antigen‐specific antibody of all isotypes was readily demonstrable in saliva (predominantly IgA) and serum (predominantly IgG) from pigeon breeders, and there were no significant titres in controls. The levels of IgG antibody in saliva and in serum correlated significantly (r = 0.52, P < 0.001), and both correlated with the raised immunoglobulin levels. In both saliva and serum the IgG rather than the IgA antibody activity was associated with symptoms of EAA.

Conclusions

Antibody activity in saliva and serum, representing the mucosal and systemic responses, respectively, were both strongly stimulated by inhaled antigens. The IgG antibody titres of saliva and serum correlated significantly and were a useful index of inflammation, as measured by the raised total immunoglobulin levels, and symptoms. This suggests that IgG antibody in serum may reflect clinical and immunological sensitization of the lung mucosa. Collecting saliva is noninvasive, and saliva antibody measurement is a convenient method for monitoring EAA, especially in children, and will facilitate sampling for example in epidemiological studies of antibody prevalence.
Subtribe‐specific monoclonal antibodies to Lolium perenne
Authors: LOVBORG  , BAKER  , TAYLOR  , YIN  , TOVEY
Published: March 2003

Background and objectives

The ability to measure personal exposure to airborne grass pollen is important in the understanding of allergic diseases. Visual identification is time consuming and it is difficult to distinguish between many grass pollens morphologically. Although grass pollens share common allergenic determinants, we attempted to produce monoclonal antibodies that would distinguish between species, tribes and subfamilies of grasses which would allow immunodetection of pollens.

Methods

Monoclonal antibodies raised against Lolium perenne were screened for specificity against an extended panel of grass pollen extracts using standard ELISA techniques and a novel particle blotting assay using whole pollen grains.

Results

Antibodies showing specificity ranging from subfamily to part‐tribe specificity were raised. The most specific monoclonal antibodies (numbers 4, 13 and 17) had reactivity to Lolium perenne and Festuca elatior but displayed little cross‐reactivity to Phalaris arundinaceae and the rest of the Poeae tribe when tested by ELISA and no detectable cross‐reaction when tested with particle blotting.

Conclusion

Monoclonal antibodies that are functionally specific to only two grasses can be produced and used to discriminate between related grass species.
Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5′‐monophosphate‐induced bronchoconstriction in patients with COPD
Authors: Rutgers  , Koëter  , Van Der Mark  , Postma
Published: March 2003

Background

Inhalation of adenosine 5′‐monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP‐induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1‐receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP.

Objective

To investigate the mechanism of AMP‐induced bronchoconstriction in COPD.

Methods

We performed a randomized, double‐blind, placebo‐controlled, crossover trial. Forty‐four nonatopic hyperresponsive smokers with COPD (mean age ± sd: 60 ± 7 years, FEV1 61 ± 12% of predicted and FEV1/VC 51 ± 8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 μg of inhaled ipratropium bromide, or placebo.

Results

GM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P < 0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P < 0.0001).

Conclusion

These findings indicate that histamine release is important in the pathophysiology of AMP‐induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.
Amalgam allergy associated with exacerbation of aspirin‐intolerant asthma
Authors: Yoshida  , Mikami  , Nakagawa  , Hasegawa  , Onuma  , Ishizaki  , Shoji  , Amayasu
Published: March 2003

Background

Aspirin‐intolerant asthma can be induced not only by acidic analgesics (including acetylsalicylic acid), which effectively inhibit cyclo‐oxygenase, but also by cross‐reactivity with paraben, and other chemical additives.

Objective

We examined whether amalgam allergy is involved in the pathogenesis of a aspirin‐intolerant asthma.

Methods

We present the first case of aspirin‐intolerant asthma that improved after the removal of dental amalgam. In addition, we performed both the methacholine provocation testing and sulpyrine provocation testing before and after the removal of dental amalgam.

Results

In addition, the methacholine concentration causing a 20% fall in FEV1 in provocation tests rose significantly, though hypersensitivity to analgesics evaluated with sulpyrine provocation testing did not decrease. These results suggest that amalgam sensitization is involved in bronchial hyperresponsiveness in aspirin‐intolerant asthma.

Conclusion

Sensitivity to amalgam may cause exacerbation of aspirin‐intolerant asthma in some patients. To the best of our knowledge, this is the first case report of amalgam allergy associated with aspirin‐intolerant asthma.
The contribution of ‘holiday deaths’ to seasonal variations in asthma mortality in England and Wales
Authors: Nichols  , Hansell  , Strachan
Published: March 2003

Background

In younger age groups there is a summer peak in asthma deaths, but whether this is due to social or environmental factors is not known. One suggested social factor is a summer holiday away from home during which there may be a lack of compliance with medication or greater difficulty in getting medical help. In older age groups there is a winter peak in asthma deaths.

Objective

To study the contribution of ‘holiday deaths’ to seasonal variations in asthma mortality in England and Wales.

Methods

Routinely collected mortality statistics were used (all asthma deaths of persons dying in England and Wales, 1991–93 and 1995). Deaths occurring 40 miles or more from home were estimated using the District Health Authority in which the person was usually resident; the registration district of death; and the ‘transferability code’ (derived by the Office for National Statistics).

Results

There were 484 asthma deaths in people aged 0–34 years, and 6337 asthma deaths in people aged 35 years or more. Deaths estimated to occur 40 miles or more from home contributed little (16%) to the summer peak in asthma deaths age 0–34 years, and nothing to the winter peak in asthma deaths age 35 years or more.

Conclusions

Holidays away from home do not play an important part in explaining the seasonal variation of either young or old asthma deaths. Other social or environmental factors are more important.
Value of immunoglobulin E density in predicting nasal and bronchial response to inhaled allergens in rhinitic and asthmatic subjects with multiple sensitizations
Authors: Crimi E. , Voltolini S. , Minale P. , Falagiani P.
Published: March 2003

Background

In atopic subjects with multiple sensitizations to inhalant allergens the relationship between the specific serum immunoglobulin (Ig) E and the in vivo response to each allergen is not well established.

Objective

To investigate the relationship between the specific serum IgE expressed as amount (kU/L) or density (specific IgE/total IgE percentage) with the in vivo response to inhaled allergens in rhinitic and asthmatic subjects with multiple sensitization.

Methods

By means of Reverse Enzyme AllergoSorbent Test (REAST) the absolute values and the density of specific IgE for each sensitizing allergen was determined. Rhinitics (n = 12) underwent nasal and asthmatics (n = 11) bronchial allergen challenges with the two to three sensitizing allergens for a total of 33 nasal and 32 bronchial challenges. Correlations and degree of concordance between specific serum IgE and results of challenges were calculated.

Results

IgE density significantly correlated with nasal challenge score (rs = 0.72, P < 0.001), bronchial challenge score (rs = 0.56, P < 0.001) and late asthmatic response (rp = 0.53, P < 0.005). Among subjects with three sensitizations, comparison of values of IgE density with the results of challenges showed significant concordance in graduation (χ2 = 11.3, P < 0.005).

Conclusions

In subjects with multiple sensitizations, the nasal and bronchial response to the different sensitizing allergens may be predicted, at least in part, by the IgE density. A satisfactory agreement between graduation of the IgE density to the different allergens and the in vivo response to the same allergens has been found within subject.
Gaseous air pollution and atopy
Authors: Charpin  , Pascal  , Birnbaum  , Armengaud  , Sambuc  , Lanteaume  , Vervloet
Published: March 2003

Background

Photochemical air pollutants are commonly thought to be implicated in the gradual increase in the prevalence of atopy. However, no epidemiological data are available.

Methods

To clarify this issue, we performed a cross‐sectional epidemiological survey in 2604 primary school children, 10 and 11 years old, living in seven communities among which some have the highest photochemical exposure in France. The mean levels of the main gaseous air pollutants (SO2, NO2 and O3) were measured during a 2‐month period in 1993. The protocol included a standardized questionnaire, skin prick tests to common aeroallergens and in the atopic children, collection of a sample of mattress dust to measure group 1 mite allergens. Atopy was only defined on the basis of the skin prick tests.

Results

Percentage of positive skin tests and the number of positive skin tests were similar in the different communities looked at. The distribution of dust samples with a group 1 allergen level greater than 2 μg/g dust, was also similar. Logistic regression analysis including potential confounding factors, as well as the mean level of air pollutants, did not demonstrate any association between atopy and mean SO2, NO2 and O3 levels.

Conclusion

The increase in photochemical air pollutants is unlikely to be a major determinant for the recent increase in the prevalence of atopy.
Experimental models in asthma
Authors: Holgate S. T.
Published: March 2003

Histamine is an important mediator released from activated mast cells in acute bronchoconstriction provoked by allergen, exercise, hypertonic stimuli and inhaled adenosine. Histamine may also contribute to the allergen‐induced late asthmatic response probably following the recruitment and activation of basophils. H1‐receptor antagonists partially attenuate these responses but greater inhibition when these drugs are combined with cysteinyl LT1‐receptor antagonists indicative of an interaction between mast cell‐derived mediators. The combination of two or more selective mediator antagonists in the treatment of allergic disorders such as asthma offers a new therapeutic approach worthy of careful appraisal.
Assessment of urticaria and angio‐oedema
Authors: Friedmann P. S.
Published: March 2003

There are many types of urticaria and the principal form of assessment is by clinical history and examination. Urticarial weal formation involves acute, reversible vasodilatation and increased vascular permeability. If the process is deeper the more diffuse swelling is termed angio‐oedema. The major types of urticaria include allergic, physical and idiopathic forms. In allergic urticaria, IgE‐mediated degranulation of mast cells results in weals of short duration which typically respond well to antihistamines. Physical urticarias are induced by physical insults including pressure, scratch, cold, etc. The distribution and duration of individual weals may suggest the causal factor. Chronic idiopathic urticaria can be very variable, with individual weals lasting between 90 min and 24 hours. Longer‐lasting weals are less responsive to anti‐histamines and clearly involve other mediators. When long‐lasting weals fade leaving a bruised appearance urticarial vasculitis is present which may only respond to systemic corticosteroids. In a proportion of individuals with chronic idiopathic urticaria, auto‐antibodies are present with specificity for the high affinity receptor for IgE or sometimes, for IgE itself. In general laboratory tests for allergic factors or other assessments of general health are completely unhelpful.
Antihistamines: models to assess sedative properties, assessment of sedation, safety and other side‐effects
Authors: Hindmarch I. , Shamsi Z.
Published: March 2003

Behavioural changes are produced by any drug that enters the central nervous system. These psychoactive effects include changes in alertness, concentration, attention, memory, cognition, psychomotor accuracy, skilled performance and affect. Changes in psychological performance may affect the safety of both the individuals taking the drug and of those people coming into contact with them. The aims of psychopharmacological performance tests are to describe the nature, extent and severity of these changes and identify drugs without deleterious effects upon performance.  Use of traditional antihistamines has until recently been associated with a number of undesirable side‐effects, the most troublesome of which is sedation. There are two aspects to sedation. Firstly, an objectively determined one based on the results of psychometric tests from controlled trials and secondly, the subjects response to the administration of a drug. Although the second generation of antihistamines have a much more favourable therapeutic index, use of these agents has also been reported to cause varying degrees of sedation. As antihistamines are largely used by ambulant patients, a complete evaluation of sedation should be performed through standardized objective tests, shown to be sensitive to the central effects of antihistamines as well as reliable ratings of subjective experiences.  An extensive review of the literature has identified a number of tests which appear to be sensitive to the central effects of antihistamines. These include tests of psychomotor performance, sensori‐motor co‐ordination speed, information processing, sensory skills as well as physiological measures and subjective rating scales.  Using this battery of cognitive and psychomotor tests, it is evident that only a very limited number of antihistamines can claim to be virtually free of both objective and subjective sedative effects, although the second generation of antihistamines are generally less impairing than the original ones; when prescribed at their recommended doses.
Lack of behavioural toxicity of mizolastine: a review of the clinical pharmacology studies
Authors: Rosenzweig P. , Patat A.
Published: March 2003

First‐generation H1 antihistamines were associated with major sedative side‐effects which were heavily disruptive to young active and aged patients when performing everyday activities. Mizolastine is a potent and selective H1‐receptor antagonist which slowly penetrates into the brain and thus lacks the sedative effects of earlier antihistamines.

In this paper we present an overview of five clinical pharmacology studies which were carried out with a view to assessing mizolastine effects on psychomotor and skilled performances, and on cognitive functions in young and aged subjects.

The studies were all randomized, double‐blind, placebo and (with the exception of one) active‐drug controlled, cross‐over studies. A total of 76 young and 15 aged subjects were enrolled. Two studies evaluated mizolastine over a range of doses (5–45 mg), and three involved a single or multiple administrations of the therapeutic dose (10 mg/day). Comparators were first generation (clemastine, tripolidine) and second generation (terfenadine, cetirizine) antihistamines. Drug effects were evaluated through standardized psychometric and memory tests, and subjective self‐ratings (visual analogue scales). In two studies, driving performance was assessed using an actual driving test. Two studies investigated drug interaction with depressants of the central nervous system such as alcohol and lorazepam.

The results of the five reported studies were consistent in that mizolastine showed to be free from sedative effects when administered at the therapeutic dose. As with other newly developed antihistamines, some changes occurred at higher dose levels. At the therapeutic dose mizolastine did not alter driving performance and did not potentiate the depressant effects of alcohol and lorazepam.

Mizolastine was shown to be free from sedative effects that could affect the safe performance of everyday life activities in young and aged patients when administered at the therapeutic dose.
Spontaneous reporting of suspected adverse reactions to antihistamines: a national and international perspective
Authors: Routledge P. A. , Lindquist M. , Edwards I. R.
Published: March 2003

Twenty‐one sedative and five non‐sedating antihistamines are presently available on the UK market. Analysis of spontaneous reports of suspected adverse drug reactions was performed for those drugs with more than 90 reported reactions on the UK ADROIT database to the period ending 31 December 1997. Thus nine antihistamines, (four sedative antihistamines and five non‐sedating antihistamines) were included. For each of the four sedative agents (azatidine, chlorpheniramine, diphenhydramine and trimeprazine), reactions associated with the cardiovascular, gastrointestinal, central nervous systems, the skin, general and psychiatric reactions made up more than 70% of total reported reactions. For all four agents, fatal reactions constituted less than 2.5% of total reactions. For each of the five non‐sedating agents (acrivastine, astemizole, cetirizine, loratidine and terfenadine), reactions associated with the cardiovascular, gastrointestinal central nervous systems, the skin, general and psychiatric disorders together made up more than 75% of total reported reactions. For all five non‐sedating agents, fatal reactions constituted less than 1% of total reactions. However, there were 21 reports of fatality in association with terfenadine, 11 (52%) of which were either sudden deaths or those associated with a cardiac rate of rhythm reaction. Analysis of the WHO database for non‐sedating drugs showed a similar pattern, with terfenadine being associated with the highest frequency of reports of potentially serious arrhythmias and of sudden death and death related to disturbances of cardiac rate and rhythm combined. Despite the limitations of spontaneous reporting systems, comparison of the benefit–risk profiles of drugs using this data within a class of drugs can provide valuable information, and pharmacovigilance of antihistamines (and all other agents) using this and other means should continue for the lifetime of their use in humans.