Dermal blood flow after local challenges with allergen, histamine, bradykinin and compound 48/80

Blood flow was determined in weal and flare reactions and in late dermal reactions after skin-prick tests with allergen, histamine, bradykinin and compound 48/80 in pollen-allergic subjects. Local blood flow was measured with laser Doppler flowmetry intermittently for up to 48 hr at three distances from the prick centre (2 mm; weal, 15 mm; flare and 30 mm). Continuous recordings were also made in the weal area after challenge with bradykinn and compound 48/80. The size of the induced weal and flare area of all the substances and the late phase after allergen was determined using digitized planimetry. Furthermore, simultaneous determinations of local dermal temperature and blood flow in the weal and flare site were performed intermittently for 6 hr after allergen and histamine challenges. There was a dose-dependent and distance-related increase in blood flow for all the substances tested. The blood flow in the 2-mm registrations had normalized 20 min after bradykinin, 1.5-2 hr after histamine and 3 hr after compound 48/80, while allergen induced a continuous increase in blood flow for more than 24 hr. The area of the weal and flare reaction was dose related for all substances, and a similar dose-dependent increase was noted for the observed dermal late-phase reactions present after allergen. The local temperature after challenge with allergen and histamine was also increased in a distance-dependent manner. These studies suggest that laser Doppler flowmetry is a sensitive and reproducible method to quantify blood flow changes occurring after skin-prick tests. Different putative mediators or mast cell stimulating substances produce various response profiles, all of which differ from those observed after allergen. Temperature measurements after skin-prick tests seem to follow the observed changes in blood flow as measured with laser Doppler flowmetry, which may be why both techniques might reflect changes in capillary blood flow.     

Blood flow in histamine- and allergen-induced weal and flare responses, effects of an H1 antagonist, α-adrenoceptor agonist and a topical glucocorticoid

Allergen has previously been shown to induce a continuous increase in local dermal blood flow after a prick test in allergic subjects, whereas histamine induced, initially, similar peak increases in blood flow of much shorter duration. Blood flow changes induced by histamine and allergen have now been evaluated (i) after pretreatment with a local corticosteroid cream, clobetasole-17-propionate; (ii) after oral administration of the H1-antihistamine loratadine; and (iii) after oral pretreatment with the alpha 1-adrenoceptor agonist pseudoephedrine. Blinded placebo-controlled designs were used in the substudies. Laser doppler flowmetry was used for non-invasive recording of changes in local blood flow intermittently for 24 h after the topical corticosteroid, 6 h for the substudies on loratadine and pseudoephedrine. The size of the immediate weal and flare reactions, as well as late phase reactions, were also determined. Pretreatment with clobetasole-17-propionate cream on the skin for 1 week prior to prick tests did not affect the blood flow response elicited by histamine or allergen, in either the initial part (up to 1 h) or the protracted 24 h determinations. The size of the weal and flare reactions decreased. Loratadine and pseudoephedrine did not reduce the initial allergen-induced increase in blood flow, while lower blood flow compared with placebo pretreatment was noted for the protracted (1-6 h) determinations. Blood flow changes after histamine were unaffected. The histamine-induced weal and flare was inhibited by loratadine more effectively than the corresponding allergen-induced reaction. The weal and flare reactions after histamine and allergen were not changed after pseudoephedrine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wheal-and-flare reactions induced by allergen and histamine: evaluation of blood flow with laser Doppler flowmetry

Dermal blood flow was evaluated after skin prick test with histamine and allergen in six patients with seasonal allergic rhinitis. Blood flow was registered continuously for 60 minutes after the test procedure with laser doppler flowmetry, which allows noninvasive measurements. Blood flow was measured close to the skin test in the wheal obtained, and at a greater distance from the prick in the flare reaction. Tests were performed with preloaded skin test needles with histamine and the appropriate allergen freeze-dried on the point of the lancet, as well as with the appropriate negative control. The prick test procedure, by itself, induced a transient increase in blood flow that was normalized again after 9 minutes for the closest measurement. Histamine induced a rapid increase in blood flow in both the flare and wheal reaction that was normalized after about 45 minutes. The increase was significantly higher in the flare compared to the wheal for the time points from 6 1/2 to 13 minutes. Allergen induced a similar increase in blood flow. However, the increase was not noticeable until 2 1/2 minutes after the allergen application and was not completely abolished within 60 minutes. Furthermore, the difference between the flare and wheal reaction, with the higher values for the flare reaction, was present for a longer period of time than for the equivalent histamine measurements. In conclusion, laser doppler flowmetry appears useful for continuous evaluation of vascular changes induced at skin prick tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Allergen-induced hyperreactivity is not a feature of dermal immediate allergic reactions—in contrast to reactions of airways mucosa

Allergen challenges of airway mucosa are commonly followed by an increased sensitivity to rechallenge with allergen. In the lower airways this phenomenon has been associated with the late phase of allergic airway reactions, which in turn has been suggested as a link between anaphylaxis and continuous allergic airway disease. The aim of the present investigation was to explore further the phenomenon of allergen-induced hyperreactivity and to see whether it was possible to induce such a reaction in the skin. Twenty-six patients with seasonal allergic rhinitis due to birch and/or grass pollens were studied in the pollen-free winter months. Nine of these patients had previously demonstrated an increased reactivity following allergen challenge in the nose, and nine of the patients had cutaneous allergen-induced late-phase reactions to the allergen tested. Skin-prick tests were performed with pollen allergen, histamine, and a negative control. The areas of the weal-and-flare reactions were measured 15 min after the tests were set. Any late-phase reactions were recorded 6 hr after the skin challenge. The subjects were re-tested with allergen and histamine 24 hr after the initial prick test within the area of the corresponding weal from the previous day. In contrast to previous challenges of human airway mucosa. where the same time interval was used, we found no increased responsiveness to rechallenge as compared with the initial allergen challenge. This was true, even if only the subgroups with previously demonstrated nasal allergen-induced hyperreactivity. or cutaneous late-phase reaction were evaluated. It is. therefore, suggested that allergen-induced hyperreactivity as a feature of allergic airway mucosa may be related to changes in the epithelial barrier function.     

Influence of bronchial allergen challenge on histamine release by human basophils

BACKGROUND: Basophils can be primed by cytokines such as interleukin (IL) -3, IL-5 or granulocyte macrophage-colony stimulating factor (GM-CSF). It has been described that the concentrations of these cytokines are enhanced at sites of allergic inflammation as well as systemic in allergic asthma. OBJECTIVE: To investigate the priming status of basophils as detected by thapsigargin-induced histamine release during bronchial allergen challenge. METHODS: Ten subjects allergic to house dust mite were challenged via an aerosol delivery system. Spontaneous leucocyte histamine release as well as histamine release induced by various stimuli was measured in vitro at several time points. In addition, lung function parameters, serum IL-5 and blood eosinophil counts were evaluated. RESULTS: We found no effect of bronchial allergen challenge upon spontaneous leucocyte histamine release, nor upon histamine release induced by anti-immunoglobulin (Ig) E, house dust mite extract, C5a, fMLP, IL-3, PMA+ thapsigargin or IL-3+ thapsigargin. However, the priming status of basophils as measured by thapsigargin-induced histamine release was enhanced at 24 h after bronchial allergen challenge. Analysis of the individual data showed a heterogeneous initial response (30 min, 6 h) followed by a predominant increase at 24 h after allergen challenge. This increase in the thapsigargin-induced histamine release correlated with the increase in serum IL-5 levels at 24 h after allergen challenge. CONCLUSION: The priming status of human basophils as measured by thapsigargin-induced histamine release is enhanced 24 h after allergen challenge.     

Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC₂₀ histamine after 24 h. When the group was divided into three subgroups according to baseline PC₂₀ histamine, a significant decrease in PC₂₀ histamine was found only in patients with relatively high baseline PC₂₀ histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC₂₀ and allergen-induced PC₂₀ histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC₂₀ histamine; no further decrease in mean PC₂₀ histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC₂₀ values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.     

Plasma histamine changes during provoked bronchospasm in asthmatic patients

Seven patients with bronchial asthma underwent bronchial inhalation challenge with aerosolized allergen extracts and methacholine. Simultaneously, venous blood samples were collected and histamine was measured. Each patient was challenged on successive days with an allergen extract to which he had no skin-sensitizing antibody (skin test-negative allergen), followed by methacholine and skin test-positive allergen. Bronchospasm was not induced by inhalation of skin test-negative allergens but was observed in all patients after methacholine and in the majority of patients after skin test-positive allergens. No changes in plasma histamine were detected after challenges with methacholine and skin test-negative allergens. After challenge with skin test-positive allergens, significant rises in plasma histamine were detected in 5 of 7 patients. Plasma histamine was elevated within the first 5 min after inhalation of aerosolized allergen, and elevations persisted as long as 30 min. These studies showing that histamine increases significantly in the plasma during allergen-induced asthma in man suggest that histamine should be considered as at least one of the mediators of bronchospasm in allergic asthma. Bronchospasm induced by the cholinergic drug methacholine, unlike allergen-induced bronchospasm, is not associated with changes in plasma histamine.     

The effect of an increase in inhaled allergen dose after terfenadine on the occurrence and magnitude of the late asthmatic response

We have attempted to use a potent and selective histamine H1-receptor antagonist terfenadine to allow a larger dose of allergen to be administered to previous single early responders to investigate if an increased dose of allergen could induce a late asthmatic response. Pre-treatment with 180 mg of terfenadine enabled a geometric mean increase in allergen dose of 4.12-fold to be inhaled by eight atopic subjects with mild asthma, who initially were classified as single early responders, with maximal fall in FEV1 3-8 hr after allergen challenge (Lmax) of less than 15% from baseline value. The magnitude of early asthmatic response was similar to that obtained on the control day when allergen challenge was performed in the absence of terfenadine. Two subjects were converted to dual responders with Lmax of 23.1 and 24.3%, which occurred with a 32- and 65-fold increase in allergen dose respectively, and a 6- and 4.9-fold decrease in non-specific airways responsiveness measured as the cumulative provocative concentration of methacholine that caused a 20% fall in FEV1 from baseline. The remaining six subjects failed to achieve an Lmax of greater than 10% even with a 1.29-2.66-fold increase in allergen dose. For the group as a whole an increase in allergen dose was associated with an increase in overall bronchoconstrictor response 3-8 hr after challenge. These results indicate that it is possible to induce a late asthmatic response in a subject who previously demonstrated only an early response by increasing the dose of allergen inhaled.     

Comparison of allergen-induced late inflammatory reactions in the nose and in the skin in house dust mite-allergic patients with or without asthma

BACKGROUND: It remains to be established which factors contribute to the occurrence of asthma in allergic individuals. We hypothesized that differences in the late allergic inflammatory reaction to allergen between asthmatic and non-asthmatic house dust mite-allergic individuals might contribute to the difference in the clinical presentation of allergy. AIM: To compare allergen-induced changes in parameters for cellular inflammation during the phase of the late allergic reaction in the skin and nose, in house dust mite-allergic individuals with or without asthma. MATERIAL AND METHODS: Nasal and dermal allergen challenges with house dust mite (Dermatophagoides pteronyssinus) extract were performed in 52 house dust mite-allergic individuals, of whom 26 had mild to moderate persistent asthma and 26 had perennial rhinitis without current or past asthmatic symptoms. Serial nasal lavage samples were analyzed for the presence of inflammatory cells (eosinophils and neutrophils) and soluble markers associated with cellular inflammation [interleukin-5 (IL-5), interleukin-8 (IL-8), eosinophil cationic protein (ECP) and myeloperoxidase (MPO)]. Macroscopic late phase skin reactions were studied after intracutaneous skin tests with house dust mite extract. RESULTS: Fixed dose nasal allergen provocation elicited a similar degree of immediate allergic reaction as judged by plasma protein exudation and histamine concentrations in asthma and non-asthmatic rhinitis. Subsequently, no differences between groups were found during the phase of the late allergic reaction (4-24 h) in inflammatory cell influx, plasma protein leakage, ECP or MPO. Likewise, there were no differences in levels of chemotactic cytokines IL-5 and IL-8. In agreement with the results of nasal challenge, the late skin reaction after dermal challenge with a fixed allergen dose and after an allergen dose 10,000 times above the skin threshold for an early skin reaction did not differ between the groups. CONCLUSION: House dust mite-allergic patients with or without asthma have very similar late allergic inflammatory reactions in the skin and in the nose after allergen challenge. Hence, it is unlikely that the occurrence of pulmonary symptoms in asthma is explained by a general tendency of asthmatics to have an enhanced late allergic cellular inflammatory response. Nasal and dermal allergen provocations are adequate models to study allergen-induced inflammation but probably lack the pivotal link which is essential for the development of asthma.     

Bronchial allergen challenge in subjects with low levels of allergic sensitization to indoor allergens

BACKGROUND: Low skin reactivity to common inhalant allergens is frequently found in asymptomatic individuals as well as in patients with respiratory complaints. However, most studies on bronchial allergen challenge concern patients with high levels of allergic sensitization. The present study was directed to bronchial reactions after allergen challenge in subjects with low skin reactivity to Dermatophagoides pteronyssinus or cat dander. METHODS: Titrated intracutaneous skin tests, skin prick tests, specific IgE assays, histamine release on washed leukocytes, and bronchial histamine and allergen-challenge tests were performed in 20 subjects with an intracutaneous skin test threshold for cat dander (Felis domesticus) or D. pteronyssinus above 0.1 BU/ml (mean wheal diameter in skin prick test with 10000 BU/ml: 4.4mm). Ten of the 20 patients had specific IgE below the detection limit in at least one of the three IgE assays which were done. Fifteen patients had a specific IgE level below 2 kU/I in all three tests. As a positive control group, the same parameters were studied in seven moderately sensitized patients with an intracutaneous skin test threshold below 0.1 BU/ml (mean wheal diameter with 10000 BU/ml: 7.2mm). RESULTS: The 20 subjects with low levels of allergic sensitization had an early decrease in FEV1 of 8.6% (P<0.01) and a mean late decrease of 6.3% (P<0.05). There was a trend for decrease in PC20 histamine 24h after allergen challenge (-0.4 doubling doses, P=0.09). CONCLUSIONS: In this group of subjects with low levels of allergic sensitization, a statistically significant early and late decrease in FEV1 was found. However, the decrease in lung function was small and unnoticed by most patients. The increase in nonspecific bronchial hyperresponsiveness after bronchial allergen challenge did not reach statistical significance in the study group. The results indicate that allergen exposure in patients with low levels of allergic sensitization may lead to airways changes in the absence of acute symptoms.     

Nasal mucosal blood flow after intranasal allergen challenge

The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated.     

Nasal response to a single antigen challenge in patients with allergic rhinitis — inflammatory cell recruitment persists up to 48 hours

BACKGROUND: Allergen challenge in some patients with respiratory allergy is followed by an early and a late reaction. OBJECTIVE: To evaluate the duration of mediator release and inflammatory cell recruitment during the late antigen-induced nasal response. METHODS: Eight patients with seasonal allergic rhinitis due to grass pollen underwent local challenge with the relevant allergen, a non-relevant allergen (Parietaria judaica), and nebulized saline solution. Nasal lavages were performed at baseline and 6, 24, 48, 72 h after challenge. Eosinophil cationic protein (ECP), leukotriene C4 (LTC4), leukotriene B4 (LTB4) myeloperoxidase (MPO) and prostaglandin D2 (PGD2) levels were radioimmunoassayed and histamine concentration was measured by an automated fluorometric method. RESULTS: Nasal challenge with the relevant antigen induced a response 6 h after stimulation, which subsided within 24 h. Eosinophilia, observed in the nasal lavages collected from 6 to 24 h after this challenge, was accompanied by ECP release. Neutrophilia were found in the nasal lavages collected from 6 to 24 h after challenge. The increase in neutrophil number correlated with MPO levels and LTB4 concentrations, but not with the intensity of nasal obstruction. Antigen challenge also induced significant recruitment of mononuclear cells 48 h after provocation. The challenge significantly raised histamine, but not PGD2, levels in the nasal lavages collected 6 h after provocation. A trend towards an increase in LTC4 levels in the nasal lavages collected 6 h after specific antigen challenge was also found. Nasal challenge with a non-relevant allergen or with saline solution did not cause either inflammatory cell recruitment or mediator release. CONCLUSION: Nasal challenge with the relevant antigen can induce a late response characterized by local accumulation of eosinophils, neutrophils and mononuclear cells persisting for 48 h and accompanied by release of ECP, MPO, LTB4 and histamine. These results indicate that a single antigen challenge in patients with allergic rhinitis causes prolonged inflammatory alterations which may contribute to the development of airway hyperreactivity.     

Topical dermal anaesthesia inhibits the flare but not the weal response to allergen and histamine in the skin-prick test

The effect of topical dermal anaesthesia on the immediate allergic skin reaction was evaluated in a double-blind, randomized, placebo-controlled study. Twenty-one patients with strictly seasonal allergic rhinitis, confirmed by a positive skin test for the respective pollen allergen, were studied in the pollen-free winter months. Skin-prick tests for one pollen allergen and histamine were performed after pre-treatment of the skin for 1 hr with an emulsion of lidocaine and prilocaine (EMLA®) and the equivalent vehicle on different test sites. The skin-prick tests were made with a preloaded standardized test needle (Phazet®). The area of the induced weal-and-flare reaction was measured and subsequently calculated with the help of a digitizer served by a microcomputer. The topical dermal anaesthesia induced a reduction of the flare response to histamine by 49% (P < 0.01) and allergen by 21% (P < 0.05). No reduction of the histamine- and allergen-induced weal response were noted. Our findings indicate that the treatment did not affect the allergen-induced release of inflammatory mediators and the vascular leakage induced by these mediators. However, this study seems to confirm earlier suggestions that the flare response is partly mediated through neural reflex activity as it was ameliorated by topical anaesthesia. Furthermore, from a clinical point of view, this study shows that it is possible to perform a valid skin test, without any associated itching and pain, if only the weal response is taken into account n i the evaluation of the skin-prick test.     

Mucosal blood flow in the human nose following local challenge with histamine

Nasal blood flow was measured using the 133Xe wash-out method in 10 non-allergic subjects and 13 asymptomatic hay fever patients. Determinations were made before and 15 min after challenge with diluent, 0.13 mg, 1.3 mg and 13 mg of histamine/nasal cavity. Nasal symptom scores were recorded. The nasal inspiratory peak flow was determined simultaneously in the hay fever patients. No differences in blood flow or symptom score recordings were found between the normal subjects and allergic patients under basal conditions or after histamine challenge. The nasal blood flow increased after challenge with the highest histamine dose. The increase was 34% (P less than 0.05) from baseline in normals and 47% (P less than 0.05) in allergics. There was a dose-dependent increase in nasal symptom scores following histamine challenge, again with no difference between normal and allergic subjects. The nasal peak flow decreased in a similar manner with a maximum decrease of 74% (P less than 0.001). The present study gives further support to the notion that histamine is not the only mediator involved in vascular reactions during allergic rhinitis.     

The late asthmatic response is associated with baseline allergen-specific proliferative responsiveness of peripheral T lymphocytes in vitro and serum interleukin-5

BACKGROUND: Increasing insights into the mechanism underlying the allergen-induced late asthmatic response (LAR) have been gained with implication of activated eosinophils and CD4+ T lymphocytes. However, the patient characteristics that indicate the individual capacity to develop a LAR are not well-defined. METHODS: In 22 subjects with mild to moderate house dust mite-allergic asthma, we investigated the relationship between the LAR and two other models of late-phase allergic inflammation, i.e. the allergen-specific proliferative response of peripheral blood T lymphocytes in vitro and the late cutaneous response. Non-specific bronchial responsiveness (PC20histamine), lung function (FEV1), peripheral blood eosinophil count, early phase allergic skin sensitivity, and levels of total and specific immunoglobulin E (IgE) were determined prior to bronchial allergen challenge. Serum levels of interleukin-5 (IL-5) were measured before and at several time points after allergen inhalation. RESULTS: A significant correlation was found between the magnitude of the LAR and the allergen-specific proliferative response of peripheral T lymphocytes (r = 0.44, P = 0.04) but not the late cutaneous response. Stepwise-multiple linear regression of the magnitude of the LAR on the parameters analysed at baseline, resulted in a model combining PC20 histamine, early phase allergic skin sensitivity, and the allergen-specific proliferative response of peripheral T lymphocytes (R2 = 0.84, P<0.001). No contribution of the late cutaneous response to the prediction of the LAR was found. Serum levels of IL-5 increased significantly at 6 h (P = 0.01) and 24 h (P = 0.003) after bronchial allergen challenge and correlated with the allergen-specific proliferative response of peripheral T lymphocytes in vitro (rho = 0.48, P = 0.02). CONCLUSIONS: The findings in this study point to a role of TH2-lymphocyte responses in the development of the allergen-induced LAR. In allergic asthmatic patients, allergen-specific responsiveness of peripheral T-lymphocytes in vitro may serve as a model to determine the individual capacity to develop a LAR after allergen inhalation.     

Nasal histamine release following hyperosmolar and allergen challenge

Allergic rhinitis is characterised by symptoms of sneezing, itching of the nose with watery secretions, and nasal obstruction. We have previously shown that patients can have the diagnosis of allergic rhinitis confirmed by nasal provocation tests and assessment of nasal inspiratory peak flow (NIPF) after specific allergen or hyperosmolar challenge. We now show that histamine is released into the nasal lavage fluid in response to such challenges. Saline lavage alone results in detectable histamine levels in the order of 5 ng/ml, but in the presence of allergen (HDM) there is a significant increase in histamine release in atopics but not in control subjects. With hyperosmolar challenge, atopics showed a biphasic response in that histamine release was increased with 1.8% and 3.6% saline but returned to baseline with 5.4% and 7.2% saline, then showing a further increase with 9.0% saline. This raises the possibility of two populations of responsive mast cells. Hyperosmolar challenge leads to symptoms of nasal itch and sneezing as well as histamine release in atopics but not in controls. This suggests that hyperosmolar challenge can be used as a simple diagnostic test for allergic rhinitis and may provide a model for nasal hyper-reactivity.     

The effect of anti‐allergic mattress encasings on house dust mite‐induced early‐ and late‐airway reactions in asthmatic patients. A double‐blind, placebo‐controlled study

BACKGROUND: Anti-allergic mattress encasing may provide clinical benefit in asthmatic patients. However, the effect of mattress encasings on allergen-specific parameters, such as bronchial reactions to house dust mite (HDM) challenge, is not clear. OBJECTIVE: To investigate the effect of anti-allergic mattress encasings on allergen sensitivity in patients with moderate to severe asthma. METHODS: Twenty-seven patients with asthma and HDM allergy were studied in a double-blind, placebo-controlled study. Concentrations of Dermatophagoides pteronyssinus (Der p 1) were measured in mattress dust before and after 1 year of treatment; bronchial histamine challenge, bronchial challenge with HDM and intradermal skin challenges with HDM were performed. The number of eosinophils in peripheral blood was assessed. RESULTS: In the active group, but not in the placebo group, there was a significant reduction in Der p 1 concentration in the dust collected from the mattresses after 1 year of treatment compared to before. There was a significant difference between the groups with respect to HDM-induced early-reaction (ER) in the airways and the number of blood eosinophils, which reflected an increase in ER and eosinophils in the placebo group without significant change in the active group. No significant improvement in PC20 histamine, late-reaction (LR) and skin tests was found in either groups. CONCLUSION: Our data suggest that encasings protect against a further increase in allergen sensitivity in asthmatic patients, so their use should be recommended.     

Effects of topical treatment with H1 and H2 antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis

Fifteen asymptomatic subjects with allergic rhinitis participated in a double-blind, randomized, crossover, placebo-controlled study. The subjects were pretreated intranasally with a single dose of a selective H1 receptor antagonist, levocabastine, and/or selective H2 receptor antagonist, ranitidine, prior to a nasal allergen challenge. The nasal symptoms obtained at the challenge were assessed using a scoring technique 15 min after the allergen exposure. The nasal airway resistance was determined twice prior to and once after the allergen challenge using anterior rhinomanometry. The nasal mucosal blood flow was determined before and 15 min after allergen challenge using the 133Xe wash-out technique. After pretreatment with the H1 antagonist there was a statistically significant reduction in the number of sneezes and rhinorrhea compared to pretreatment with placebo. Pretreatment with the H2 receptor significantly decreased the rhinorrhea but not the sneeze. The nasal blockage was unaffected by both the H1 and the H2 antagonists. Pretreatment with the H1 and/or the H2 antagonists inhibited the reduction in the nasal mucosal blood flow induced by the allergen challenge to a significant degree. The present findings suggest that topical treatment with the highly selective histamine antagonist, levocabastine, inhibits allergen-induced reflex-mediated symptoms. H1 and H2 receptors do not appear to be involved in the regulation of the tone of the capacitance vessels. This indicates that a more complex mechanism participates in the induction of nasal blockage than the direct effect of histamine on H1 and H2 receptors on the capacitance vessels of the nasal mucosa alone. Both H1 and H2 receptors are of importance for the regulation of nasal mucosal blood flow during the allergic reaction.     

Release of tryptase together with histamine during the immediate cutaneous response to allergen

Better in vivo techniques are needed for objective assessment of mast cell-dependent events. Tryptase, a neutral protease selectively concentrated in human mast cells, appears along with histamine in skin chamber fluid overlying sites of allergen challenge in sensitive human subjects. Maximal amounts of histamine were found 0 minutes to 30 minutes after challenge; maximal amounts of tryptase were found 30 minutes to 60 minutes after challenge. The later appearance of tryptase most likely reflects its slower diffusion through tissue after release of tryptase from cutaneous mast cells as a macromolecular complex with proteoglycan. The mean weight ratio of tryptase (134,000 molecular weight tetramer) to histamine (111 molecular weight) in chamber fluid after allergen challenge during a 1-hour time course was 4:1. Total amounts of tryptase and histamine recovered in the 0.3 ml chamber fluid samples after a 1-hour challenge averaged 95 ng and 26 ng, respectively. Tryptase levels in skin chamber fluid are an accurate indicator of mast cell activation.     

Immediate and late phase allergic cutaneous reactions are not inducers of unspecific or specific local hyperreactivity

The present study evaluates the possibility of allergen-induced unspecific and specific dermal hyperreactivity with special reference to the presence of late cutaneous reactions and allergen-induced nasal hyperreactivity. Twenty-six patients with strictly seasonal allergic rhinitis participated. All had a positive skin prick test for birch (Betula verrucosa) and/or timothy (Phleum pratense). Ten patients had previously displayed an allergen-induced nasal hyperreactivity and six patients a late cutaneous reaction. An initial skin prick test with a relevant pollen allergen was done in triplicate. The immediate skin reactions were recorded after 15 min and any late-phase reaction after 6 h. Twenty-four hours later the patients were retested. The same pollen allergen was sited in the first flare reaction from the previous day. A histamine prick test was sited in the weal as well as in the third reaction from day 1. A histamine control was also performed in a previously unaffected area. The allergen-induced weal reactions decreased significantly at rechallenge compared with the results from the previous day (P less than 0.05). The histamine tests resulted in similar skin reactions regardless of whether or not they were done on a previous allergen test site. This was true for both specific and unspecific reactions when the subgroups of patients with previously demonstrated allergen-induced nasal hyperreactivity or late-phase skin reactions were evaluated separately. These results indicate that allergen-induced hyperreactivity is not a general feature of allergic inflammation but is a phenomenon restricted to specific sites, such as the airway mucosa.