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  • 1
    Electronic Resource
    Electronic Resource
    Nasal challenge studies with bradykinin: influence upon mediator generation (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have shown that nasal allergen provocation leads to dose-dependent increases of inflammatory mediators, e.g. histamtne, kinins, LTC4 and PGD2 in nasal lavages. To investigte further the interaction of these mediators, a titration study with intranasal bradykinin (Bk) application (maximal dose 100 nmol/nostril) and consecutive lavage were performed in eight grass-pollen-allergic patients out of season, and five controls. The nasal lavages were analysed for albumin, N-α-tosyl-l-arginine methyl ester (TAME) esterase activity, histamine, 9α,11β-PGF2, and LTC4. The clinical reactions were mesured with a subjective symptom score. A dose-dependent elevation of albumin was found which was significantly higher in patients with allergic and non-allergic rhinitis compared with normal volunteers. TAME-eslerase activity also increased in relation to the dosage of Bk given without significant difference between the various groups. No influence on histamine, LTC4 and 9α,11β-PGF2, release (PGD2 metabolite) was seen. Short-lasting clinical symptoms like irritation, sneezing, and obstruction were noticed after the two highest Bk dosages (10 and 100 nmol). We conclude that intransally applied Bk induces a dose-dependent plasma leakage into the nasal cavity, which is significantly higher in patients with seasonal allergic rhinitis out of season compared to normals. Bk does not seem to affect the mast cell since hisiamine, LTC4 and 9αl lβ-PGF2 levels do not alter. The ability to induce relevant symptoms of rhinitis provides strong support for the hypothesis that kinins may be important mediators of inflammatory disorders of the upper airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1991.tb01682.x
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  • 2
    Electronic Resource
    Electronic Resource
    Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 22 (1992), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mucosal exudation of almost unfiltered plasma proteins, plasma-derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine-induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double-blind, randomized, cross-over and placebo-controlled study with pretreatment with a single dose oxymetazoline chloride (5 μg or 50 μg; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30-min intervals during this period. The concentrations of two exudative indices, N-alpha-tosyl-l-arginine methyl ester (TAME)-esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique.Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine-induced plasma exudation. It is concluded that histamine-induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical α-adrenoreceptor-mediated vasoconstriction. It is further suggested that the antiblockage effect of oxymetazoline can be utilized in nasal research without interfering with the exudative indices which appear on the mucosal surface as a quantitative reflection of the airway tisue involvement in inflammatory processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1992.tb03103.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of bβ-endorphin on nasal allergic inflammation (2002)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background πβ-endorphin is a derivative of pro-opiomelanocortin. Cells of the immune system can also synthesize and secrete β-endorphin. Its concentration is increased during the allergic reaction and during stress. Increased reactivity during psychological stress of allergic subjects is also well known.Objective Is β-endorphin one physiological link between stress and an exacerbation of the allergic reaction?Methods First, intranasal β-endorphin challenges with subsequent lavages to determine histamine and albumin levels and measurements of nasal flow and resistance in dose-response and time course experiments were performed. Secondly, we examined whether β-endorphin pre-treatment increased the antigen-induced release of histamine and albumin in nasal lavages and the clinical symptoms.Results Exogenous β-endorphin (100 pM−10 µM/mL) induced a dose-dependent increase in nasal symptoms in asymptomatic allergic subjects with rhinitis (n = 14) as well as in non-allergic controls (n = 10), but did not release any mediators into nasal secretion. However, comparing the antigen-evoked release of mediators into nasal secretions with that of a β-endorphin pre-treated antigen challenge we could note a significant enhancement of human serum albumin influx (P 〈 0.05) and histamine liberation (P 〈 0.05) 10 min after antigen challenge compared with the allergen challenge alone, with also a correlation with the more pronounced decrease in nasal flow (P 〈 0.05).Conclusion These results suggest that β-endorphin-induced increase in nasal congestion is mediated through direct neuroendocrine receptor activation independent of mast cell activation and that during the allergic reaction there is a β-endorphin/mast cell interaction that enhances the mediator response to nasal allergen challenge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2002.01284.x
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  • 4
    Electronic Resource
    Electronic Resource
    Changes in non-specific nasal reactivity and eosinophil influx and activation after allergen challenge (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 20 (1990), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been suggested that the eosinophilic granulocyte plays a crucial role in the genesis of increased reactivity of the airways. In order to characterize changes in non-specific reactivity in the upper airways following a nasal allergen challenge further 16 subjects with strictly seasonal allergic rhinitis were studied. They were challenged with allergen outside the relevant pollen season and monitored at intervals for a period of 24 hr for nasal symptoms, changes in nasal reactivity, eosinophil influx and activation, and markers of inflammation. The same challenge sequence without an initial allergen challenge was used as a control. A symptom score technique was used to record nasal symptoms and methacholine challenges were used to monitor changes in non-specific reactivity. A nasal lavage was made prior to each methacholine challenge to monitor the influx of cells, specifically eosinophils, and to determine changes in the levels of eosinophil cationic protein (ECP) and TAME-esterase activity. Cells from the mucosal surface were also collected with a Rhinobrush® prior to the allergen challenge as well as at the 24-hr follow up. The allergen challenge induced a five-fold increase in non-specific nasal reactivity, as measured by the methacholine challenges, at the 2-hr follow up from 0·051 ml ± 0·012 (mean ± s.e.m.) to 0·255 ± 0·062 (P 〈 0·01) and a significant increase was also noted at all observation points, whereas no increases could be observed in the control setting. With a similar timing the allergen challenge also induced an increase in the proportion of eosinophils on the mucosal surface from an initial 0·8 ± 0·4% to 6·2 ± 2·1% of the cells as early as 2 hrs later (P 〈 0·05). A significant correlation was foundbetween the levels ofECP and eosinophils in the lavage fluid (r= 0·64, P 〈 0·001) and between the levels of ECP and TAME esterase (r= 0·43, P 〈 0·01). No correlations were, however, disclosed between the increases in non-specific nasal reactivity and the number of eosinophils (regardless of the cell-harvesting technique) or ECP levels at any of the observed time points. It is therefore suggested that the allergen-induced change in non-specific nasal reactivity is a complex phenomenon rather than just the recruitment and activation of eosinophilic granulocytes in the nasal cavity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1990.tb03147.x
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  • 5
    Electronic Resource
    Electronic Resource
    Substance P is generated in vivo following nasal challenge of allergic individuals with bradykinin (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 27 (1997), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Bradykinin, a potent inflammatory mediator, is released during allergic and non-allergic rhinitis and asthma in man. Nasal bradykinin challenge induces a dose-dependent plasma leakage into the nasal cavity and relevant symptoms of rhinitis.Objective We now report on substance P generation during nasal bradykinin challenge in vivo.Methods The effect ot locally applied bradykinin on substance P generation was studied in nine individuals, allergic to grass pollen and six non-allergic controls. In the allergies TAME-esterase activity, histamine and substance P concentrations were measured in nasal lavages and correlated to the clinical symptoms.Results Substance P concentrations in nasal lavages increased in a dose-dependent fashion during nasal bradykinin challenge in both groups. In the allergic group Substance P-increases correlated with the production of TAME-esterase activity (r= 0.9. P 〈 0.05) whereas these allergic individuals did not produce any histamine increases. The generation of substance P and the increase of TAME-esterase activity was associated with the onset of clinical symptoms. Correlation of oedema and hypersecretion to substance P were signiticant by linear regression analysis (r = 0.88, P 〈 0.005 and r= 0.89. P 〈 0.02, respectively). Bradykinin induced irritations like burning and itching were shortterm and rare. Serial dilutions of nasal washes produced Substance P-RIA displacement curves that paralleled the standard curve and recovery of standard substance P that was added to nasal washes was 76 ± 4% (mean ± sem), n= 8.Conclusion Bradykinin induces in vivo a dose-dependent plasma leakage into the nasal cavity without affecting mast cells, but stimulates nerve endings resulting in the release of the neuropeptide substance P.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1997.tb01178.x
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  • 6
    Electronic Resource
    Electronic Resource
    Tryptase in nasal lavage fluid after local allergen challenge: Relationship to histamine levels and TAME-esterase activity (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 46 (1991), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P 〈 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1991.tb04362.x
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  • 7
    Electronic Resource
    Electronic Resource
    Tryptase in nasal lavage fluid after local allergen challenge: Relationship to histamine levels and TAME-esterase activity (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 46 (1991), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P 〈 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1991.tb04225.x
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  • 8
    Electronic Resource
    Electronic Resource
    Mediator release is altered in immunotherapy-treated patients: a 4-ear study (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 51 (1996), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In recent years, it has been possible to demonstrate mediator release into the nasal secretion after nasal allergen challenge in patients with allergic rhinitis. Using the nasal provocation model, we determined whether the mediator release was altered in immunotherapy-treated patients. Seventeen grass-pollen-allergic patients were examined under controlled, reproducible conditions. Serial challenges with increasing doses of grass pollen produced increasing numbers of clinical symptoms and release of mediators such as kinins, TAME-esterase activity, and histamine. Ten patients received a semidepot perennial grass-pollen extract for 4 years. Seven patients served as controls and did not receive immunotherapy during the observation period. Data from the group of patients receiving immunotherapy over the first year already showed a partially significant decline in the maximal mediator release after nasal allergen challenges compared to the results of pretreated challenges, whereas controls did not show any significant changes. Nasal allergen challenges after termination of 4 years' immunotherapy significantly modified the mediator release compared to pretreatment values (TAME-esterase activity P〈0.05, kinins P〈0.01, and histamine P〈0.01). Decrease of mediator release paralleled the symptom-medication scores and quantitative skin prick test. Finally, we could demonstrate a significant correlation between specific IgG increase and mediator decrease in the treated group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1996.tb00025.x
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  • 9
    Electronic Resource
    Electronic Resource
    Contralateral differences among biomarkers determined by a modified nasal lavage technique after unilateral antigen challenge (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 50 (1995), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The concentration of biomarkers from vessels and inflammatory cells in nasal lavage fluid reflects the degree of hyperresponsiveness in patients with allergic rhinitis. The lavage has usually been performed of both nasal cavities together after prewashings and administration of decongestants. To improve the technique, we introduced a modification involving lavage of the nasal cavities separately without any prewashings or decongestants. We challenged 20 rhinitic subjects sensitive to timothy unilaterally with timothy extract. In nasal lavages performed before, immediately after, and 6 h after the challenge, we determined the concentrations of albumin, histamine, bradykinin, TAME (TV-α-tosyl-L-arginine methyl ester)-esterase, and leukotriene C4 (LTC4). In eight subjects, the procedure was repeated 1 and 2 weeks later. After the challenge, albumin, bradykinin, TAME-esterase, and LTC4 in the nasal lavage fluid increased on the ipsilateral side but not on the Contralateral side. Histamine did not increase after antigen challenge. After 6 h, the biomarkers were not increased. The concentrations of biomarkers did not differ between sides before the challenge and not between visits. Thus, the modified nasal lavage technique is reliable and improved compared to previous methods because it involves reproducible determinations of different biomarkers, and it is simple and easy to perform.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1995.tb01153.x
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  • 10
    Electronic Resource
    Electronic Resource
    Kinin generation following methacholine nasal airway challenge of non-allergic subjects (1992)
    Springer
    European archives of oto-rhino-laryngology and head & neck 249 (1992), S. 318-321 
    Details
    ISSN: 1434-4726
    Keywords: Chronic non-allergic rhinitis ; Kinins ; Methacholine challenge ; Muscarinic receptor stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following nasal challenges with the muscarinic neurotransmitter methacholine in 14 patients with chronic non-allergic rhinitis, kinin generation was induced. This occurrence was inhibited by pretreatment with anticholinergic agents (ipratropium bromide) and by an overdose of neurotransmitter, indicating that a muscarinic receptor is stimulating the liberation of kinin. These observations suggest that patients with chronic non-allergic rhinitis exhibit cholinergic neurotransmitter-induced kinin generation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179380
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