Herbal Drug EPs 7630 versus Amoxicillin in Patients with Uncomplicated Acute Bacterial Rhinosinusitis: A Randomized, Open-Label Study.

OBJECTIVE: Previous investigations suggest the use of extract from the root of Pelargonium sidoides (EPs 7630) for the therapy of uncomplicated acute upper airway inflammations, due to its strong antimicrobial and immunomodulatory effect. We aimed to compare clinical efficacy, safety and bactericidal effect of EPs 7630 and amoxicillin monotherapy in treatment of patients with mild to moderate acute bacterial rhinosinusitis (ABRS). METHODS: Fifty ABRS patients were divided into two groups by randomization. Group 1 (n = 25) received EPs 7630 tablets, 3 × 20 mg/day per os for 10 days. Group 2 (n = 25) received amoxicillin tablets 3 × 500 mg/day per os, for 10 days. We assessed total symptom score (TSS), individual symptom scores for each symptom (nasal obstruction, rhinorrhea, postnasal drip, facial pain/pressure, loss of the sense of smell), endoscopic findings, including total endoscopic score (TES) and individual endoscopic signs (mucosal edema, mucopurulent secretion), before and after treatment. Samples of discharge taken from the middle meatus of all patients were cultivated for bacteria before and after therapy. RESULTS: Higher absolute improvement after treatment was found for TSS, nasal obstruction, facial pain/pressure, impaired sense of smell, TES, mucosal edema and mucopurulent secretion in EPs 7630 group compared to amoxicillin group (P < .001 for all parameters). However, there were no differences in absolute improvement of rhinorrhea score and postnasal drip score between groups (P = .248; P = .679, respectively). Fewer types of bacteria grew on culture from middle meatal samples in EPs 7630 group compared to amoxicillin group. There were no reported adverse events from patients from either group. CONCLUSION: Our results demonstrated better clinical and antimicrobial efficacy of EPs 7630 than amoxicillin. EPs 7630 was shown as a potent agent and good alternative to antibiotic treatment of uncomplicated ABRS.

Nasal and bronchial response to exercise in children with seasonal allergic rhinitis out of the pollen season.

BACKGROUND: Allergic rhinitis is a type I allergic disease of the nasal mucosa, and is characterized by paroxysmal sneezing, watery rhinorrhea, and nasal blockage. In seasonal allergic rhinitis subjects, even subthreshold allergen doses have been found to cause inflammatory cell infiltration in the nasal mucosa. This study aimed to investigate the presence of nasal obstructions and symptoms in seasonal allergic rhinitis subjects by assessing an exercise challenge test (ECT) outside of the pollen season. METHODS: Twenty patients and 20 healthy children who were admitted to the Osmangazi University Medical School Pediatric Allergy Clinic were included in the study in a pollen free season. The total nasal airflow and visual analog scale (for rhinorrhea, nasal congestion, sneezing, and itching) and pulmonary function tests were evaluated before and after each ECT. The nasal airflow and resistance changes were evaluated with anterior rhinomanometry. RESULTS: Eight patients and one healthy child had nasal obstructions after the ECT. There was a significant difference in the exercise-induced nasal obstructions between the 2 groups (p = 0.02). Eighteen children with exposure to tobacco smoke in the patient and control groups had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25% to 75% (FEF25-75 ) values than the children without exposure to tobacco smoke. CONCLUSION: The prevalence of exercise-induced nasal obstruction in children with seasonal rhinitis out of the pollen season is 40%. We showed that minimal persistent inflammation and nasal symptoms can also be diagnosed in rhinitis children in a symptom-free period.

A comparative pilot study of symptom improvement before and after phototherapy in Korean patients with perennial allergic rhinitis.

Although allergic rhinitis is not life threatening, it significantly influences the quality of a patient's life. This study is intended to evaluate the safety and efficacy of phototherapy with low-level energy of a 650 nm laser irradiation system in perennial allergic rhinitis patients. This clinical trial was an open-label, single-center study with 42 perennial allergic rhinitis subjects. Following laser irradiation in the nasal cavity with a laser irradiation system, the efficacy at weeks 1 through 4 was determined. The symptoms were scored with four parameters (nasal obstruction, rhinorrhea, sneezing and itching) before and after illumination of the laser, and the total score was recorded. A survey of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was conducted by patients before and after treatment. Following treatment, significant improvement in the clinical symptoms of nasal obstruction (P < 0.001), rhinorrhea (P = 0.005), sneezing (P = 0.001) and itching (P = 0.003) was reported by 68% of perennial allergic rhinitis patients. The overall RQLQ scores significantly improved by 45% from the baseline with the treatment after 4 weeks. These results indicate that phototherapy is an effective modality for treating perennial allergic rhinitis and is another option in the steroid-free management of immune-mediated mucosal diseases.

Petasol butenoate complex (Ze 339) relieves allergic rhinitis-induced nasal obstruction more effectively than desloratadine.

BACKGROUND: Allergic rhinitis symptoms of itching, sneezing, rhinorrhea, and nasal obstruction significantly decrease patients' quality of life. Compared with histamine and leukotriene receptor antagonists, the petasol butenoate complex Ze 339 displays pharmacologically distinct properties. In vitro it inhibits the biosynthesis of leukotrienes and mediator release from activated eosinophils. OBJECTIVE: This study aimed to assess the efficacy and mode of action of Ze 339, desloratadine, and placebo on allergic rhinitis symptoms, nasal airflow, and local mediator levels after unilateral nasal allergen provocation. METHODS: In this double-blind, randomized, crossover study 18 subjects with allergic rhinitis to grass pollen received Ze 339, desloratadine, and placebo for 5 days before nasal allergen challenge with grass pollen extract. Rhinomanometry, symptom assessment, and local inflammatory mediator measurement were performed during the 24 hours after allergen challenge. RESULTS: With Ze 339, the patient's time to recovery (5.4 ± 1.6 hours) from nasal obstruction after allergen challenge (time for return to 90% of baseline value ± SEM) was significantly shorter than with placebo (9.1 ± 2.3 hours, P = .035) and desloratadine (10.7 ± 2.5 hours, P = .022). Likewise, Ze 339's standardized symptom assessment for nasal obstruction (3.2 ± 1.3 hours) showed significantly faster relief (time for return to baseline value ± SEM compared with placebo, 8.3 ± 2.4 hours; P = .027) and desloratadine (4.5 ± 1.2 hours, P = .030). One interesting finding was that Ze 339 significantly reduced IL-8 and leukotriene B(4) levels in nasal secretions before challenge. CONCLUSION: When compared with desloratadine and placebo, Ze 339 shows better efficacy in relieving nasal obstruction symptoms and inhibiting critical components of the chemokine network and as such represents a novel symptomatic and possible prophylactic treatment for allergic rhinitis.

[The atypical course of subperiosteal abscess of the orbital wall].

The authors describe a clinical case of malformation of intranasal structures of the lateral wall and the middle turbinated bone of the nose (bullous middle turbinated bone, lateral position of the middle turbinated bone, hypertrophy of ethmoidal bulla and uncinate process) in combination with expressed deformation of the nasal septum. These malformations were responsible for the development of acute hemisinusitis complicated by subperiosteal abscess of the superomedial orbital wall. Conjunctival chemosis was impossible to remove by traditional medicamental therapy and surgical intervention. Hirudotherapy produced the well-apparent anti-odematous, anti-inflammatory, anti-coagulative, and thrombolytic effects that resulted in reduced conjunctival oedema and marked positive dynamics of the state of the eyeball. Subcutaneous administration of anticoagulants was used to prevent thrombosis of orbital veins and cerebral venous sinuses.

Acupuncture for nasal congestion: a prospective, randomized, double-blind, placebo-controlled clinical pilot study.

BACKGROUND: Nasal congestion is one of the most common complaints dealt with in otorhinolaryngology. Side effects of decongestants are frequently seen in patients with chronic nasal congestion. This leads to an increasing demand of alternative treatments such as acupuncture. Future studies on acupuncture should aim at objectifying effects by both physical measuring and double blinding. Therefore, we were interested in whether these effects can potentially be measured as increase in nasal airflow (NAF) in ventus ("wind") disease of traditional Chinese medicine (TCM). METHODS: Twenty-four patients with a history of nasal congestion due to hypertrophic inferior turbinates or chronic sinusitis without polyposis were additionally diagnosed according to the Heidelberg model of TCM. They were asked to score the severity of their nasal congestion on a visual analog scale (VAS). The acupuncturist was blinded according to the Heidelberg blinding assay. NAF was measured by using active anterior rhinomanometry (ARM). Specific verum acupoints according to the Chinese medical diagnosis were tested against nonspecific control acupoints. VAS and NAF were scored and measured before and 15 and 30 minutes after acupuncture. RESULTS: Control acupuncture showed a significant improvement in VAS and a deterioration of NAF. Verum acupuncture showed highly significant improvements in VAS and NAF. In addition, verum acupuncture improved NAF and VAS significantly over time. CONCLUSION: Our control and verum acupoints fulfill the condition of a control and verum treatment, respectively. Measuring NAF by RRM and scoring VAS are possible and reflect acupuncture effects in vivo.

Involvement of peroxynitrite in pollen-induced nasal blockage in guinea pigs.

Nitric oxide (NO) has been implicated in early and late phase nasal blockage in a Japanese cedar pollen-induced experimental allergic rhinitis guinea pig model. In this study, we investigated the role of peroxynitrite, which is formed by a rapid reaction of NO with superoxide anion, in the antigen-induced biphasic nasal blockage. Sensitized guinea pigs were repeatedly challenged by pollen inhalation once every week. The peroxynitrite scavenger, ebselen (30 mg/kg), or the xanthine oxidase inhibitor, allopurinol (50 mg/kg), was intraperitoneally administered 30 min before the antigen challenge. The late phase nasal blockage induced 4 h after the challenge was largely suppressed by ebselen (57% inhibition; P<0.05) and allopurinol (47% inhibition; P<0.05), but neither ebselen nor allopurinol influenced the early phase response. On the other hand, the intranasal instillation of peroxynitrite (10(-3) and 10(-2) M, 10 microl/nostril) caused a remarkable dose-dependent nasal blockage in the sensitized guinea pig. These results suggest that peroxynitrite plays a major role in the late phase nasal blockage induced by the antigen challenge in sensitized guinea pigs.

Different mechanisms between thromboxane A2- and leukotriene D4-induced nasal blockage in guinea pigs.

Although thromboxane (TX)A2 is involved in allergic rhinitis, the mechanisms inducing nasal blockage have not been elucidated. We evaluated the roles of nasal mucosal vascular changes following intranasal instillation of the TXA2 analog U-46619 or leukotriene (LT)D4 to induce nasal blockage in a guinea pig model of allergic rhinitis. Both U-46619- and LTD4-induced nasal blockages in sensitized animals were swiftly and completely suppressed by a vasoconstrictor, naphazoline. The nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester relieved LTD4-induced nasal blockage, but not U-46619-induced nasal blockage. Although both agonists produced vasodilatation of nasal mucosa in vivo, LTD4 caused vasodilatation while U-46619 caused vasoconstriction in vitro. Both LTD4- and U-46619-induced nasal blockages in vivo should depend on vasodilatation of nasal mucosa. LTD4-induced nasal blockage is induced by direct vasodilatation via nitric oxide. In contrast, U-46619-induced nasal blockage may be associated with contraction of a certain vein that should exist at the exit of capacitance vessels, leading to congestion of the nasal mucosa.

Valoración de la inflamación nasal / Evaluation of nasal inflammation

En la reacción de hipersensibilidad inmediata, el alérgenose une a su anticuerpo específico tipo IgE, unido a su vez a los receptores de alta afinidad para la IgE (FccRI) de las células efectoras, fundamentalmente mastocitos y basófilos. El entrecruzamiento de estas moléculas de F ccRI tras la unión de antígenos polivalentes a la IgE, activa a estas células produciéndóse tres respuestas biológicas: exocitosis del contenido preformado de sus gránulos, sintetización de mediadores lipídicos y secreción de citoquinas. Los mediadores de la inflamación son en último termino, las sustancias responsables de la sintomatología clínica. Pueden dividirse en general en mediadores preformados (aminas biógenas y macromoléculas de los gránulos) y mediadores de nueva síntesis (mediadores lípidicos y citoquinas)

In the reaction of immediate hypersensibility to alergene is joined to itsspecific type IgE antibody, also united to the high afflnity receptors for IgE (FccI) of the effecters cells fundamentally mastocites and basophiles. The interbreeding of these molecules Fcc to RI, after the union ofpolyvalent antigenes to IgE, active these cells, producing three biologic responses: excitosis of the preformed content of its granules, synthesization of lipidic mediators and citoquine secretion. The inflammation mediators are in last term, substances responsible of the clinic symptomatology. They can be divided generally in preformed mediators (biogene amines and macromolecules ofthe granules) and ofnew synthese mediators (lipidic and citoquine mediators)

Biofeedback training of nasal muscles using internal and external surface electromyography of the nose.

BACKGROUND: The purpose of this paper is to describe the outcome of biofeedback training of nasal muscles in cases of nasal valve stenosis and collapse. The present study was performed to investigate the best way of using surface electromyography (sEMG) in biofeedback training of muscles involved in nasal valve function. In the present study, we present the way of biofeedback training of these muscles introducing the intranasal placement of sEMG electrodes and a home exercise program. METHODS: A nonrandomized pilot study of patients presenting with symptoms of obstructed nasal breathing was conducted. All selected patients (n = 15) demonstrated nasal valve stenosis with a positive Cottle maneuver and clinically evident nasal valve collapse. Follow-up ranged from 9 to 12 months. Treatment included surface and intranasal EMG biofeedback-assisted specific strategies for nasal muscle education and a home exercise program of specific nasal movements. RESULTS: All patients exhibited variable subjective improvement. In 86.66% (n = 13), the improvement was proved objectively and there was no need for operation. In 13.33% (n = 2), an endonasal operation was recommended. CONCLUSION: Relieve of obstructed nasal breathing after nasal valve stenosis and/or collapse can be achieved with biofeedback training of nasal muscles and a home exercise program as described. It helps a significant cohort of patients with symptoms of obstructed nasal breathing to avoid surgical intervention.

Effect of oral immunotherapy on nasal blockage in experimental allergic rhinitis.

We previously reported that when Japanese cedar pollen was prophylactically p.o. administered before a sensitization stage in a guinea-pig model of allergic rhinitis, pollen-induced nasal blockage was suppressed. In this study, we evaluated whether the oral immunotherapy is also effective when the pollen extract was administered starting from the day when the nasal blockage was clearly induced and whether the effectiveness continued after cessation of the immunotherapy. Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the extract was orally administered twice a week until the 30th challenge. At the 11th challenge, the oral immunotherapy showed inhibition of the biphasic nasal blockage. The effectiveness was consistently observed during the immunotherapy until the 30th challenge. Furthermore, the increased nasal responsiveness to intranasal application of leukotriene D4 was markedly suppressed by the immunotherapy. Interestingly, even after cessation of the therapy, inhibition of the nasal blockage was sustained for more than 2 months. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. In conclusion, Oral immunotherapy may be clinically useful for allergic nasal blockage. Mechanisms underlying the effectiveness may be associated with the hyporesponsiveness of the nasal mucosa to released mediators.

Effect of intranasal triamcinolone acetonide on bronchial hyper-responsiveness in children with seasonal allergic rhinitis and comparison of perceptional nasal obstruction with acoustic rhinometric assessment.

OBJECTIVE: Many patients with allergic rhinitis (AR) have bronchial hyper-responsiveness (BHR), and seasonal variation of BHR has been demonstrated in these patients. We aimed to investigate how BHR in children with seasonal AR is modified by triamcinolone acetonide aqueous nasal spray (TANS) therapy during the pollen season. A secondary aim was to assess the efficacy of TANS on nasal congestion by acoustic rhinometry and symptom scores. METHODS: A total of 34 children aged 7-18 years with grass pollen-induced AR and 18 age and sex-matched healthy controls were included in study. The patients were divided into the following two subgroups: 22 patients who had AR only; and 12 patients who had AR and asthma. All of them had a baseline BHR (PC20FEV1 methacholine < 8mg/ml). All patients received 220 microg TANS once daily for 4 weeks following a 1-week run-in period. Nasal patency was measured by acoustic rhinometry and patients recorded their nasal obstruction scores in a diary. RESULTS: There was no significant difference at baseline pulmonary function test parameters between the patients and the healthy control children. None of the control subjects had BHR. Asthmatic children with AR had significantly reduced baseline PC20FEV1 when compared with the AR only group [mean +/- S.E.M., (1.60 +/- 0.57 mg/ml versus 2.93 +/- 0.42 mg/ml, P = 0.021)]. The mean PC20FEV1 values increased slightly at the end of treatment in both group (from 1.60 +/- 0.57 mg/ml to 3.25 +/- 1.11 and from 2.93 +/- 0.42 mg/ml to 3.93 +/- 1.41 mg/ml), but the change was not statistically significant. TANS produced substantial symptomatic recovery in nasal obstruction according to patients' daily diary assessments, and significantly improved all objective acoustic rhinometry parameters. CONCLUSIONS: Once-daily intranasal TANS 220 microg effectively controlled nasal obstruction in children with seasonal AR according to subjective and objective assessments, and blocked the increase in BHR to methacholine after high-load natural pollen exposure. There was no correlation between patients' own subjective assessment of nasal obstruction and objective acoustic rhinometric assessment.

Canine model of nasal congestion and allergic rhinitis.

The ragweed- and histamine-induced decreases in nasal patency in cohorts of ragweed-sensitized and nonsensitized dogs were assessed. The volume of nasal airways (V(NA)) was assessed by acoustic rhinometry and resistance to airflow (R(NA)) by anterior rhinomanometry. Histamine delivered to the nasal passages of five dogs caused a rapid and prolonged increase in R(NA) (0.75 +/- 0.26 to 3.56 +/- 0.50 cmH(2)O. l(-1). min), an effect that was reversed by intranasal delivery of aerosolized phenylephrine. Ragweed challenge in five ragweed-sensitized dogs increased R(NA) from 0.16 +/- 0.02 to 0.53 +/- 0.07 cmH(2)O. l(-1). min and decreased V(NA) from 12.5 +/- 1.9 to 3.9 +/- 0.3 cm(3), whereas administration of saline aerosol neither increased R(NA) nor decreased V(NA). Prior administration of d-pseudoephedrine (30 mg po) attenuated the ragweed-induced increase in R(NA) and decrease in V(NA). Ragweed challenge changed neither R(NA) nor V(NA) in four nonsensitized dogs. Mediator-induced nasal congestion and allergen-induced allergic rhinitis in ragweed-sensitized dogs, which exhibit symptoms similar to human disease, can be used in the evaluation of safety and efficacy of antiallergic activity of potential drugs.

Acquired nasal hyperresponsiveness aggravates antigen-induced rhinitis in the guinea pig.

Whether a state of nasal hyperresponsiveness influences antigen-induced biphasic nasal blockage and sneezing were examined using a guinea pig model of allergic rhinitis. Sensitized animals were challenged with an antigen, Japanese cedar pollen, once every week. Before the 13th challenge, the animals were randomly divided into 2 groups, and then the 13th challenge was performed (Groups A-0 and B-0). The 14th challenge was done on day 2 (Group A-2) and on day 7 (Group B-7) after the 13th challenge, on which nasal hyperresponsiveness was present and absent, respectively. Biphasic nasal blockage and sneezing after the challenge in Group A-2 were more severe than those in Group A-0, while those of Group B-7 were almost the same as those of Group B-0. An anti-histaminic, mepyramine, inhibited sneezing but not the biphasic nasal blockage in Group B-7. A cysteinyl leukotriene (CysLT) antagonist, pranlukast, suppressed the late nasal blockage but not the early blockage and sneezing in Group B-7. In contrast, in Group A-2, mepyramine significantly attenuated not only sneezing but also the early nasal blockage. Pranlukast significantly inhibited both nasal blockage and sneezing in Group A-2. In conclusion, nasal hyperresponsiveness aggravated the antigen-induced nasal responses, to which histamine and CysLTs considerably contributed.

Effect of oral antigen administration on nasal blockage in experimental allergic rhinitis in guinea pigs.

OBJECTIVE AND DESIGN: We evaluated the effectiveness of oral treatment with Japanese cedar pollen on experimental allergic rhinitis in guinea pigs. SUBJECTS: Male Hartley guinea pigs. TREATMENT: From 16 days before the first sensitisation, 1 and 100 mg/time/animal pollen suspension was orally administered twice weekly. Animals were then sensitised and repeatedly challenged with the pollen. METHOD: Guinea pigs were sensitised by intranasal instillation of cedar pollen extracts adsorbed onto Al(OH)3 at a dose of 0.3 microg pollen protein/0.3 mg Al(OH)3/3 microl/nostril twice a day for 7 days. Then the animal was challenged by inhalation with cedar pollen (1.8 mg/nostril) once every week. We evaluated the effects of the oral treatment with antigen on: 1) sneezing frequency, 2) nasal blockage after antigen challenge, 3) nasal hyperresponsiveness to histamine and leukotriene D4, and 4) titres of anaphylactic antibodies. RESULTS: During the course of the high dose administration, several animals died from a possible cytotoxicity, whereas the low dose caused no discernible change. The oral administration of the pollen at both the doses significantly inhibited nasal blockage, and the hyperresponsiveness to the stimuli was also strongly suppressed by the oral treatment. Inhibitory effectiveness did not differ substantially between the 1 and 100 mg/animal-treated groups. In contrast, neither sneezing frequency nor the increasing level of anaphylactic antibodies was influenced by the oral administration. CONCLUSIONS: In this study, we found that the pollen-induced nasal blockage and hyperresponsiveness were suppressed by the oral administration of the pollen in the sensitised guinea pig.

Characterization of nasal obstruction in the allergic guinea pig using the forced oscillation method.

INTRODUCTION: This is the first report to evaluate changes in nasal resistance in a preclinical animal model using the forced oscillation method. METHODS: The method involves characterizing pressure-flow relationships of the respiratory system due to external oscillatory forces. RESULTS: First, we evaluated changes in nasal resistance using an established small-animal rhinometric technique. In these studies, aerosolized ovalbumin (3%) administered to the nasal cavity of ovalbumin-sensitized guinea pigs increased nasal resistance at 30 min by 99 +/- 14%. The histamine H1 antagonists, chlorpheniramine (1 mg/kg i.v.) and pyrilamine (1 mg/kg i.v.), blocked the increase in nasal resistance due to ovalbumin provocation (50 +/- 17% and 39 +/- 11% over baseline, respectively). The alpha-adrenergic agonist phenylpropanolamine (3 mg/ kg i.v.) had no effect on the nasal actions of ovalbumin. In separate studies, nasal resistance was measured at 2 Hz by forced oscillation and ovalbumin (3%) increased nasal resistance by 91 +/- 14%. Chlorpheniramine (1 mg/kg i.v.) significantly attenuated the increase in nasal resistance due to ovalbumin. Finally, changes in nasal resistance for each treatment group were evaluated at frequencies of 1 - 18 Hz. Area under the curve analysis demonstrated that chlorpheniramine blocked the nasal obstructive effect of ovalbumin. In contrast, a pharmacologically active dose of phenylpropanolamine (3 mg/kg i.v.) did not produce decongestant activity. DISCUSSION: The current data are inconsistent with the well-established clinical efficacy of alpha-adrenergic agonists as nasal decongestants. Consequently, we suggest that allergic nasal obstruction in the guinea pig may not be the best preclinical approach to assess the nasal decongestant activity of vasoconstrictor alpha-adrenergic agonists. Additionally, our studies demonstrate the utility of the forced oscillation technique in assessing changes in nasal resistance in small laboratory animals.

Nasal secretion in ragweed-sensitized dogs: effect of leukotriene synthesis inhibition.

Allergic rhinitis is an inflammatory disease associated with local leukotriene release during periods of symptoms. Zileuton, a leukotriene synthesis inhibitor, is known to inhibit the release of leukotriene B4. Because we previously showed that leukotriene B4 is a potent mediator of neutrophil-dependent nasal secretion, we investigated whether Zileuton inhibited allergen-induced nasal secretion. Using a newly developed method for isolating and superfusing a nasal segment, we examined the effect of Zileuton on nasal secretion and neutrophil recruitment in ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused time-dependent increases in the volume of airway fluid and the recruitment of neutrophils. Zileuton prevented ragweed-induced neutrophil recruitment and nasal secretion. These results indicate that leukotrienes are important mediators of allergy-induced nasal secretion in dogs. Future clinical studies in allergic patients will determine whether there is a therapeutic role for leukotriene synthesis inhibitors in modulating neutrophil recruitment and hypersecretion in the nose.

Value of acoustic rhinometry in environmental medicine.

It is a weak point of environmental medicine that health disturbances, e.g. functional affections of the upper respiratory tract, cannot be objectively judged by physicians resp. researchers. In this study, the validity of acoustic rhinometry, a method giving information on cross-sectional areas of the upper airways by means of ultrasound probing, was tested in 40 volunteers seven times during one year. Furthermore, using a simplified model of the nose the accuracy of this method to measure the minimal cross-sectional area (MCA) in the nose was tested. The measurements were extremely confounded by the mode of connection to the nose (e.g. selected adapter, direction of application) and by the MCA in the nasal cavity. Statistical analyses showed a good reproducibility of measurements repeated within minutes, but suggested an intrapersonal variability over the analyzed examination phases due to apparatus independent factors. However, this variability could not be explained by influencing and confounding factors obtained by questionnaire, medical history, and physical examination. The test model showed little to great errors (1.5 to 568.5%) between the actual and the measured MCA, depending on the diameter. It is concluded that the method of acoustic rhinometry has to be standardized before it's value for environmental medicine can finally be judged. Further studies are necessary that should focus among others on factors influencing the variability of MCA and the effect of MCA on the measurement of the area behind the MCA. So far, the use of acoustic rhinometry for the evaluation of nasal function cannot be recommended.

Combined histamine H1 and H3 receptor blockade produces nasal decongestion in an experimental model of nasal congestion.

We studied the pharmacological actions of combined histamine H1/H3 receptor blockade on the increase in nasal airway resistance (NAR) and decrease in nasal cavity volume produced by nasal exposure to compound 48/80, a mast cell degranulator. In the anesthetized cat compound 48/80 (1%) produced a maximum increase in NAR of 9.1 +/- 0.7 cmH20.L/minute. The increase in NAR in animals pretreated with a combination of the H1 antagonist, chlorpheniramine (CTM; 0.8 mg/kg i.v.) and increasing doses of the H3 antagonist, thioperamide (THIO; 1.0, 3.0, and 10.0 mg/kg i.v.) were 6.1 +/- 2.1, 4.2 +/- 1.0 and 2.2 +/- 0.7 cmH20.L/minute, respectively. A second H3 antagonist, clobenpropit (CLOB; 0.03, 0.3, and 1.0 mg/kg i.v.) combined with CTM (0.8 mg/kg i.v.) also inhibited the nasal effects of compound 48/80. When the nonsedating H1 antihistamine, loratadine (3.0 mg/kg i.v.), was substituted for CTM, it also reduced nasal congestion when given in combination with THIO (10 mg/kg i.v.). In contrast, treatment with CTM (1.0 mg/kg i.v.) and the H2 antagonist, ranitidine (RAN; 1.0 mg/kg i.v.) were without activity. Loratadine, CTM, CLOB, RAN, or THIO administered alone were inactive. The alpha-adrenergic agonist, phenylpropanolamine (PPA; 1.0 mg/kg i.v.) demonstrated decongestant effects, but in contrast to H1/H3 blockade, PPA produced a significant hypertensive effect. Using acoustic rhinometry (AcR) we found that combined i.v. CTM (1.0 mg/kg) and THIO (10 mg/kg) and combined oral CTM (10 mg/kg) and THIO (30 mg/kg) blocked the decrease in nasal cavity volume produced by intranasal compound 48/80 (1%, 50 microL). We conclude that combined H1/H3 histamine receptor blockade enhances the efficacy of an H1 antagonist by conferring decongestant activity to the H1 antihistamine. We propose that the decongestant activity of combined H1/H3 blockade may provide a novel approach for the treatment of allergic nasal congestion without the hypertensive liability of current therapies.

Development of pollen-induced allergic rhinitis with early and late phase nasal blockage in guinea pigs.

OBJECTIVE AND DESIGN: Development of nasal blockage and sneezing during repeated inhalation challenges with Japanese cedar pollens was evaluated in guinea pigs. SUBJECTS: Male Hartley guinea pigs. TREATMENT: Guinea pigs were sensitized by intranasal instillation of cedar pollen extracts + Al(OH)3 2 times a day for 7 days. The animal was then forced to inhale the pollens for challenge, which was restrictively trapped in the upper airways, once a week. METHODS: Change of specific airway resistance (sRaw), sneezing frequency, and titers of anaphylactic antibodies in the serum were measured after each of the 30 challenges. RESULTS: At the first challenge, no obvious increase in sRaw was observed. However, the second and third challenges to the animals caused modest biphasic elevations of sRaw, with peaks at the first and the fourth to sixth hour. At the fourth to tenth challenges, marked elevations of sRaw were observed. However, with repetition of the inhalation challenge, the early and the late responses became almost indistinguishable because of partial overlapping as the responses expanded. All guinea pigs sneezed immediately after each pollen inhalation challenge. Apparent increases of both circulating gamma1 and IgE antibodies were seen after the seventh challenge. CONCLUSIONS: These results indicate that the experimental allergic rhinitis established in the present study can be a valuable model for analyzing the pathogenesis of the disease and developing new therapeutic drugs.