Histamine In Nasal Secretions Research Articles

Nasal sodium cromoglycate (Lomusol) modulates the early phase reaction of mild to moderate persistent allergic rhinitis in patients mono-sensitized to house dust mite: A preliminary study

We evaluated the clinical improvement of patients with mild to moderate persistent allergic rhinitis (AR) due to mono-sensitization to house dust mite (HDM) allergen, by sodium cromoglycate nasal spray (Lomusol 4%). Lomusol was used as a single agent treatment, and its anti-inflammatory effects, in the early phase reaction were evaluated. Herein we showed that Lomusol significantly improved the subjective nasal symptom scores especially nasal obstruction. This was associated with significant and specific reduction in neutrophils influx in nasal cytology but had no effect on other cell types. This selective anti-inflammatory effect on nasal cytology was associated with significant reduction in the levels of platelet activating factor (PAF) and histamine in nasal secretions but had no effect on PGD2, LTC4 or CysLt levels. Lomusol was also able to induce significant reduction in eosinophil cationic protein (ECP) levels in nasal secretions without altering the percentage of eosinophil influx in nasal cytology. Taken collectively, we showed the first evidence that nasal sodium cromoglycate possesses a selective inhibition on neutrophil recruitment into nasal cytology in the early phase reaction of AR patients mono-sensitized to HDM. This may be attributed to the ability of Lomusol to significantly reduce the amount of PAF recovered in nasal secretion. These results were associated with significant improvement in subjective symptom scores especially nasal obstruction that may in addition, be due to the ability of Lomusol to down-regulate eosinophil degranulation activity as well.

The effect of intranasal carbon dioxide on the acute response to nasal challenge with allergen

Intranasal carbon dioxide (CO(2)) was shown to reduce symptoms of seasonal allergic rhinitis (SAR). This study was designed to evaluate the effect of CO(2) on nasal allergen challenge. We conducted a randomized, controlled, crossover trial in 12 subjects with SAR outside their pollen season. Thirty minutes after a 20-second exposure to CO(2) or no exposure, subjects underwent a unilateral, localized, nasal allergen challenge. Filter paper disks were placed on the nasal septum to deliver a sham challenge followed by 2 increasing doses of either grass or ragweed allergen. Secretions were collected from both sides of the septum to evaluate the nasonasal reflex and were assayed for histamine. Nasal and eye symptoms were recorded. The primary outcome measure was the contralateral, reflex, secretory response to allergen as measured by secretion weights. Secondary outcome measures included ipsilateral nasal secretion weights, nasal and eye symptoms, levels of histamine in nasal secretions, and eosinophils in nasal scrapings. Subjects reported a transient burning sensation during exposure to CO(2). Compared with no treatment, active treatment resulted in a significant reduction in sneezes (p = 0.05), contralateral secretion weights (p = 0.04), and bilateral runny nose symptoms (p = 0.01). Ipsilateral secretion weights were numerically reduced. Histamine levels in ipsilateral nasal secretions increased significantly when the subjects received sham treatment but did not increase after pretreatment with CO(2). Treatment with nasal CO(2) resulted in partial reduction of the acute response to allergen challenge. Reflex responses were reduced, supporting an effect on neuronal mechanisms, which predict usefulness in the treatment of allergic rhinitis. Registered with the U.S. National Institutes of Health clinicaltrials.gov. Identifier: NCT00618410.

The role of histamine in allergic disease: re-appraisal of its inflammatory potential.

Studiesofallergicdiseases,inparticularasthma,rhinitisand urticaria, have suggested that histamine, a biogenicamine synthesized and stored mainly in mast cells andbasophils, plays a prominent role in the pathophysiol-ogy of these diseases (1–3). Several immunologic andnonimmunologic stimuli, such as allergen, immunoglo-bulin (Ig)E, cytokines (interleukin (IL)-1, IL-3, IL-8,GM-CSF), substance P, complement C3a and C5a,platelet-activating factor (PAF), hyperosmolarity, phy-sical stimuli (vibration, heat, cold), etc., induce therelease of histamine from mast cells and basophils,following which it diffuses rapidly into the surroundingtissues and exerts its effects, before being metabolismand excreted in the urine (4).In experimental asthma induced by allergen orexercise challenge, it has been demonstrated that thelevels of histamine are increased in the circulation andimplicated in bronchoconstriction (5–7). Studies ofsymptomatic asthmatics have also demonstrated thathistamine levels are significantly increased in thebronchoalveolar lavage (BAL) of these individuals,compared with histamine levels in BAL of asympto-matic asthmatics (8,9). Similarly, allergen challenge inpatients with allergic rhinitis significantly increases thelevels of histamine in nasal secretions of theseindividuals (10–12), implicating a role for this mediatorin the pathophysiology of allergic rhinitis. Indeed, nasalchallenge with histamine has been shown to inducenasal blockage, sneezing and rhinorrhoea (13,14), likelyas a result of sensory nerve stimulation in the nasalmucosa (15). In patients with cold urticaria, challengewith ice-water leads to a rapid rise in plasma histamineconcentration within 2 min, which peaks at 5 min andreturns to baseline values by 15–30 min (16).Investigations of patients with chronic urticaria havealso indicated that histamine is a central mediator inthis allergic condition, with increased levels detectedboth in the lesions and normal skin of patients withurticaria, compared with skin of healthy individuals(17–19). Furthermore, the responsiveness of skin tohistamine is also increased in patients with urticaria(19).Apart from the classical activities of histamine, thereis an increasing body of evidence that histamine alsoelicits pro-inflammatory and immune-modulatoryeffects, whichmight be of pathophysiological relevance.The findings of histamine receptors expressed on avarietyof immuneandnonimmunecellssuggesta muchwider and more critical role of this mediator in allergicdisease, than is considered presently. Consequently, it islikely that antihistamines have a wider impact onallergic inflammation, and that effects on immune cellswhich have been linked to nonreceptor mediatedpathways so far, may actually be receptor-dependent.This review aims to give an overview on a currentlyemerging new understanding of the role of histamine inallergic disease.

Bilateral increases in histamine after unilateral nasal allergen challenge.

Studying the inflammatory response that follows the early response to nasal challenge with antigen provides a better understanding of allergic rhinitis than just studying the immediate (early) response. Nine allergic volunteers were challenged unilaterally with antigen-containing discs, and bilateral changes in physiologic responses as well as in the concentration of histamine in nasal secretions were measured for 11 h. We found significant immediate increases in symptoms, sneezes, ipsilateral nasal airway resistance, and ipsilateral histamine in the early phase response. Two-thirds of the allergen-challenged volunteers showed increases in physiologic parameters or histamine in the hours after allergen challenge. The pooled data of all subjects exhibited significant increases in bilateral nasal airway resistance and in ipsilateral and contralateral histamine, hours after unilateral provocation. These responses differed significantly from control subjects. In another group of 11 volunteers challenged ipsilaterally with antigen, the number of basophils increased both on the side of challenge and on the contralateral side. The magnitude of the increase on the ipsilateral side correlated with the increase on the contralateral side (r(s) = 0.72). The basophils are the most likely source of the contralateral increase in histamine as they are on the ipsilateral side. Although the mechanisms underlying this contralateral increase in basophils and histamine are not known, we speculate that delayed, neurogenic responses play a contributory role.

Acoustic rhinometry in the study of the acute nasal allergic response.

Acoustic rhinometry is a recently developed method for the objective assessment of nasal patency. In this study, acoustic rhinometry was used to measure changes in nasal cavity dimensions in the immediate response to nasal allergen challenge in eight pollen-sensitive subjects. Acoustic rhinometric changes were compared with subjective symptoms, as well as histamine in nasal secretions, cytology of nasal mucosal scrapings, and changes in olfactory function. A significantly greater decrease in nasal airway caliber occurred following allergen challenge as compared to buffer diluent challenge in the same individuals (70% +/- 7% versus 22% +/- 5%). During an allergic response, a strong correlation was found between the minimum cross-sectional area and the volume of the nasal cavity measured by acoustic rhinometry (r = .9). However, no correlation was observed between nasal airway caliber and concomitant subjective congestion reported by the subjects. A modest decrease in olfactory function was seen following allergen challenge (3.1 +/- 1.4 fewer odors identified correctly out of 20; p = .08). However, the alterations of olfactory function did not correlate with changes in nasal patency. The results presented in this study demonstrate that acoustic rhinometry has great potential as a reproducible method for the objective assessment of nasal obstruction occurring in nasal allergen challenge studies.

Eosinophil cationic protein in the nasal secretions of patients with mite allergic rhinitis.

In 25 patients with mite nasal allergy and 13 healthy control subjects, levels of eosinophil cationic protein (ECP) and histamine in nasal secretions were examined before and after challenge with mite extract. The ECP level was found to be significantly higher in the washings taken 30 minutes after challenge compared with the washings taken before challenge (P < .05). ECP levels measured both before and after mite extract challenge were found to be significantly higher in the patients than in the controls (P < .01). These facts suggest that the ECP affects the nasal mucosa by causing injury to ciliated cells and by acceleration of the processes of modification and inhibition of the allergic reaction.

Measurement of histamine in nasal lavage fluid: Comparison of a glass fiber-based fluorometric method with two radioimmunoassays

The determination of histamine in nasal secretions and nasal lavage fluid may be of importance to monitor activation of histamine containing cells in the nasal cavity. However, such studies have been besieged by controversy, specifically to findings of changes in histamine levels in relation to allergenic stimulation. This controversy may be due to the specificity and accuracy of the various methods used to determine histamine in the nasal fluid. We have therefore applied and compared three new methods to determine histamine in nasal lavage fluids obtained before and after allergen challenge in normal subjects and patients with allergic rhinitis. We used a fluorometric glass fiber-based histamine method (FHR) and two RIAs, I and II. The FHR (detection limit, 7.0 nmol) and the RIA II (detection limit, 0.2 nmol) are specific for histamine itself, whereas the RIA I (detection limit, 18.0 nmol) measures mainly methylhistamine and cross-reacts to some extent with histamine. The histamine levels in the nasal lavage fluids from the nasal challenges demonstrated histamine values between 100 and 2000 nmol/L of histamine with significantly higher levels in the postallergen challenges for the allergic subjects as compared to the normal control subjects. The FHR correlated well with the RIA I and RIA II methods with correlation coefficients of 0.77 to 0.88 (p less than 0.001), respectively. However, the RIA I (methylhistamine antibody) always demonstrated absolute histamine values 5% to 20% of values measured by the RIA II (at the level of cross-reactivity to histamine).(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains

Nasal challenges with pollen grains represent one of the techniques of provocation. However, the clinical criteria of positivity are not clearly established. Nasal challenges with increasing numbers of orchard-grass pollen grains were performed in 60 patients allergic to grass pollens and 20 normal subjects. Before any challenge, the nose was washed three times with saline and then lactose, and 50, 150, 450, 1350, and 4050 orchard-grass pollen grains were insufflated into the nostrils until a symptom score of 5 was reached. This score was mainly based on major symptoms of allergic rhinitis, for example, rhinorrhea, nasal obstruction, sneezes, and to a lesser extent, on minor symptoms, such as pruritus, conjunctivitis, and pharyngitis. Nasal secretions were obtained after each challenge by lavage. Histamine was titrated by a radioimmunoassay with a monoclonal antibody against acylated histamine. Prostaglandin D 2 (PGD 2) was assayed with an enzyme immunoassay with a polyclonal antibody against PGD 2 methoxamine. None of the normal subjects had a symptom score >2; 55 60 patients had a positive challenge. The release of PGD 2 was significantly ( p < 0.001, Kruskal-Wallis test) correlated with a symptom score of 5; 74.5% of patients had a significant release of PGD 2 in nasal secretions. In contrast, although 58.2% of patients had a release of histamine in nasal secretions when the challenge was positive, the correlation with symptom scores was not significant. PGD 2 in nasal secretions increased 3.7-fold after a positive nasal challenge. In a second experiment series, the number of grains required to elicit a positive challenge was tested in 40 patients who were challenged twice, and a significant ( p < 0.001, Kruskal-Wallis test) correlation was observed between the number of pollen grains required in both tests. The correlation between the threshold release of PGD 2 or histamine in nasal secretions was tested in 24 patients who were challenged twice, and there was a significant correlation between the numbers of pollen grains required in both tests. This study confirms the value of PGD 2 as a marker of nasal allergy and demonstrates that symptom scores can be used to assess the positivity of nasal challenges with pollen grains.

Mediators of immediate hypersensitivity in nasal secretions during natural colds and rhinovirus infection.

To test the hypothesis that viral respiratory infections cause symptoms by activating mucosal mast cells to release mediators active on vasculature and mucosal glands, the presence of histamine in nasal secretions was assessed during natural colds and rhinovirus infections. Secretions were collected either with saline washes of the nasal cavity or by forcibly blowing into a beaker, and histamine was assayed spectrofluorometrically. In blown secretions from uninfected subjects, large variations were seen between individuals (ranging from 3 +/- 2 to 59 +/- 32 ng/ml), and equally large variations were seen from day to day in given subjects. Infection with rhinovirus and with influenza A did not change these concentrations significantly. In general, both with blown nasal secretions and with nasal washes, histamine concentrations tended to be lower during infection. Concentration of another preformed mast cell mediator, TAME-esterase, also was not elevated during infection. Thus, these data do not support an hypothesis that mast cell activation occurs during rhinovirus infections.

Histamine in nasal secretions and serum may be elevated during viral respiratory tract infections.

This study investigated histamine concentration in nasal secretions from children who had viral respiratory tract infection. It demonstrated that (1) there may be appreciable histamine in nasal secretions during viral respiratory tract infection; (2) concentration of histamine in serum may be elevated at the same time; and (3) children with past medical or family history of atopy had more histamine in nasal secretions during viral infections than did nonatopic children.