Nasal provocation challenge. The Committee on Upper Airway Allergy.
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Allergens↗
Biomedical subjects
H M Druce
Publications and source records attributed to H M Druce.
The effects of an H1-receptor antagonist, terfenadine, on histamine-induced microcirculatory changes and vasopermeability in nasal mucosa.
We used a nonsedating, selective histamine H1-receptor antagonist, terfenadine, to investigate the effects of antihistamines on the microcirculatory changes and vascular permeability induced by topical histamine provocation challenge. We assessed the former by the laser-Doppler measurement of blood flow, volume, and red blood cell speed, and the latter by analysis of albumin/total protein ratios in nasal lavages. Terfenadine reduced the mean symptom score and permeability changes (p less than 0.05) induced by histamine in a dose-related manner. Terfenadine had no effect on blood flow or other microcirculatory parameters. We propose that vascular effects of histamine in the nasal mucosa are not mediated uniquely through the H1 receptor.
Adult↗
Adjuncts to medical management of sinusitis.
The basic principles of sinusitis therapy are to treat any infection present, facilitate drainage, and promote drainage both during and after treatment to prevent recurrence. Adjunctive measures promoting ciliary function and drainage through the sinus ostia include the following nonpharmacologic measures: steam, astringents, inhalations, saline, and hot, dry air. Pharmacologic measures include decongestants, topical corticosteroids for chronic sinusitis, mucoevacuants, and analgesics. Antihistamines are indicated for acute sinusitis only when a patient with concomitant allergies is symptomatic during the allergy season or after infection has been ruled out as the primary cause of sinusitis. Sinusitis may be associated with asthma, and some patients do not respond optimally to asthma therapy until their sinusitis is diagnosed and treated.
Administration, Topical↗
Multicenter placebo-controlled study of nedocromil sodium 1% nasal solution in ragweed seasonal allergic rhinitis.
An 8-week double-blind study was carried out in 177 ragweed patients with seasonal allergic rhinitis to compare nedocromil sodium 1% nasal solution (Tilarin, QID, Fisons plc) and placebo. Symptoms of rhinitis were significantly reduced by nedocromil sodium during the peak 3-week pollen season (P = .001 for diary summary score) and the active treatment was rated effective by 74% of patients.
Administration, Inhalation↗
Measurement of multiple microcirculatory parameters in human nasal mucosa using laser-Doppler velocimetry.
LDV has been modified to measure four microcirculatory responses in human nasal mucosa. Resting nasal blood flow was measured in 115 observations in 23 nonatopic subjects and 111 observations in 21 atopic subjects with allergic nasal disease. Other parameters measured concurrently were the number density of moving red blood cells (RBC), mean RBC speed, and flow pulsatility. Challenges with aerosolized buffered saline or water had no significant effect on any parameter. By contrast, nasal application of alpha-adrenergic agonists, oxymetazoline and phenylephrine, produced significant dose-dependent reductions in flow without any significant change in RBC number density. These results suggest a selective alpha-agonist effect on resistance vessels but not on capacitance vessels. Topical cholinergic stimulation with methacholine selectively reduced the RBC number density without affecting other parameters. These modifications of LDV may prove useful in analyzing nasal responses to provocation and determining the sites of action of vasoactive agents on the microcirculation.
Adult↗
The pathophysiology of rhinitis. II. Assessment of the sources of protein in histamine-induced nasal secretions.
Nasal provocation tests were performed on nine atopic and 15 nonatopic subjects in order to assess the sources of protein in histamine-induced secretions and to examine the bilateral secretory response to unilaterally applied topical histamine (the nasonasal reflex). Nasal lavages were assayed for the following proteins: albumin, total protein, secretory IgA (sIgA), nonsecretory IgA (serum IgA), and total IgA. Histamine stimulation produced a profound ipsilateral protein secretion enriched in the serum proteins albumin and nonsecretory IgA. Histamine also produced a smaller contralateral protein secretion (about 15% as large as the ipsilateral response) which contained disproportionately elevated concentrations of the glandular protein sIgA. Topical pretreatment with chlorpheniramine (an H-1 antihistamine) completely abrogated the ipsilateral nasal secretory response to histamine. Nasal pretreatment with atropine (a muscarinic antagonist) had no significant effect on ipsilateral nasal secretion and did not alter the capacity of histamine to stimulate contralateral secretions (the nasonasal reflex). Histamine therefore stimulates secretion by both a direct action that increases plasma protein extravasation and by an indirect reflex mechanism that stimulates glandular secretion.
Adult↗
Hypersensitivity reactions to human seminal plasma.
A rare but serious allergic reaction has been described. Human seminal plasma hypersensitivity predominantly occurs in young women possibly as a result of altered immune status involving the reproductive organs. The patients generally have a history of atopy and, in typical cases, immunologic tests corroborate a reaginic humoral mechanism. Fortunately, there is considerable evidence that selected patients can be successfully treated with selective immunotherapy. Alternatively, the application of topical cromolyn holds promise for successful prevention of symptoms.
Adult↗
Pathophysiology of rhinitis. 1. Assessment of the sources of protein in methacholine-induced nasal secretions.
Nasal provocation tests with normal saline and methacholine (MC) were performed in 25 atopic and 27 nonatopic subjects in an effort to assess the sources of protein in induced airway secretions. Nasal lavages obtained at baseline and after provocation were analyzed for albumin, total protein, secretory IgA (sIgA), and total IgA. Compared with baseline levels or saline provocation, MC provocation increased the secretion of albumin (p less than 0.025), total protein (p less than 0.001), sIgA (p less than 0.025), and total IgA (p less than 0.025), but did not significantly affect the relative proportions of albumin-to-total protein (albumin percent) or sIgA-to-total IgA (sIgA/total IgA ratio). Nasal pretreatment with atropine significantly inhibited MC-induced secretion of all 4 proteins, again without affecting the albumin percent or the sIgA/total IgA ratio. Because MC is known to stimulate atropine-inhibitable secretion of glandular products, these data suggest that sIgA and albumin may accompany glandular secretions. Immunohistochemical analyses of nasal turbinates confirmed that secretory component was found only on serous cells within submucous glands. Thus, it appears that cholinergic stimulation may regulate sIgA secretion and thereby participate in local nasal (and possibly respiratory tract) immunity.
Adolescent↗
Measurement of nasal mucosal blood flow.
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Humans↗
Nasal provocation challenge--strategies for experimental design.
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Airway Obstruction↗
Nasal physiology.
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Autonomic Nervous System↗
Cholinergic nasal hyperreactivity in atopic subjects.
Increased nasal secretions are a fundamental component of allergic rhinitis. In order to analyze various parameters of nasal secretions, a relatively nontraumatic method for collecting nasal secretions was required. A small, flexible rubber catheter connected to a vacuum and inserted 4 cm into the nose proved to be an efficient method for recovering secretions produced from a series of nasal washes. An average of 67% of the washings were recovered and analyzed for protein content. Topical methacholine (5 to 100 mg) stimulated a dose-related increase in the amount of protein secreted with atopic patients demonstrating significantly more responsiveness than nonatopic patients (29.9 times the prechallenge production of protein for atopic patients and 4.8 times for nonatopic patients). Pretreatment with atropine (10 micrograms) reduced the effects of methacholine in atopic subjects, indicating that the secretory activity was in response to muscarinic receptor stimulation. Therefore, in addition to the array of autonomic abnormalities already recognized in atopic patients, these subjects are also hyperresponsive to nasal cholinergic stimulation.
Adolescent↗
Response of nasal blood flow to neurohormones as measured by laser-Doppler velocimetry.
Laser-Doppler velocimetry (LDV) has been adapted to measure nasal blood flow (NBF) in the mucosa of human volunteers. Resting NBF was 42.4 +/- 2.1 ml X 100 g-1 X min-1 in 19 nonatopic subjects and 37.9 +/- 1.7 ml X 100 g-1 X min-1 in 24 atopic subjects. Topical saline, but not water, reduced ipsilateral NBF by 15.4 +/- 6.6% (n = 22) without affecting contralateral NBF. Administration of 60 microgram of oxymetazoline reduced NBF by 26.5% (n = 28), whereas 120 microgram resulted in a 54.3% reduction. Phenylephrine produced a dose-related reduction in NBF with an ID50 (dose producing 50% reduction) of 1,456 microgram. Methacholine (0.006 to 12 mg) had no significant effect on NBF when studied alone or after oxymetazoline pretreatment. Therefore, LDV can be employed to monitor NBF, which has been found to be sensitive to alpha-adrenergic, but not cholinergic, stimulation.
Adolescent↗
Brompheniramine maleate: a double-blind, placebo-controlled comparison with terfenadine for symptoms of allergic rhinitis.
This was a double-blind, randomized, placebo-controlled, multicenter, parallel study comparing the effectiveness, at recommended doses, of an extended-release formulation of brompheniramine maleate and terfenadine in the treatment of allergic rhinitis. Subjects with symptoms of seasonal and/or perennial allergic rhinitis received brompheniramine 12 mg (n = 106), 8 mg (n = 105), terfenadine 60 mg (n = 106), or placebo (n = 53) twice daily for 14 days. On treatment days 3, 7, and 14, symptom severity ratings (i.e., rhinorrhea, sneezing, nasal congestion, itchy nose, eyes or throat, excessive tearing, postnasal drip) were completed by the physician; subjects and physicians each completed a global efficacy evaluation. Brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05) on the physicians' global: brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. On the subjects' global evaluation, brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05); brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. In general, brompheniramine 8 mg was comparable to terfenadine. On days 3 and 7, the total symptom and total nasal symptom severity scores for subjects receiving brompheniramine 12 mg were significantly more improved than for placebo (p < 0.05); terfenadine was not different from placebo; brompheniramine 12 mg was significantly better than terfenadine on day 7 (p < 0.05) for reducing total symptom severity and on days 3, 7, and 14 for reducing total nasal symptom severity. Adverse experiences were reported by 155 (41.9%) of the 370 subjects enrolled in the study. The overall rate of adverse experiences in the brompheniramine 12 mg treatment group (57.5%) was significantly greater (p < 0.05) than for brompheniramine 8 mg (38.1%), terfenadine (31.1%), and placebo (39.6%). In conclusion, an extended-release formulation of brompheniramine 12 mg or 8 mg bid alleviates allergic rhinitis symptoms and brompheniramine 12 mg provides significantly better relief of these symptoms than terfenadine 60 mg bid.
Administration, Oral↗
Anticholinergic properties of brompheniramine, chlorpheniramine, and atropine in human nasal mucosa in vitro.
Brompheniramine and chlorpheniramine have anticholinergic activities, but the relative potency of these effects has not been well defined. The anticholinergic properties of brompheniramine, chlorpheniramine, and atropine were assessed in an in vitro model of human nasal mucosal glandular secretion. Methacholine was used as a cholinergic agonist to stimulate glandular secretion of 7F10-mucin. These drugs (0.01-1000 microM) or vehicle (saline) were added to explant cultures with and without 100 microM methacholine. 7F10-mucin concentrations were measured in culture supernatants after 2-hour incubations. The effective dose reducing methacholine-induced secretion (ED50) was determined. ED50 was 0.25 microM for atropine, 4.10 microM for brompheniramine, and 4.63 microM for chlorpheniramine. None of the anticholinergic drugs changed spontaneous glandular exocytosis. Brompheniramine and chlorpheniramine are equipotent anticholinergic agents in human nasal mucosa in vitro. Atropine was 16 to 19 times more potent.
Atropine↗
The use of ultrasound as an imaging technique in the diagnosis of sinusitis.
In recent years the high prevalence of chronic sinusitis has been noted in association with bronchial asthma, perennial rhinitis, aspirin sensitivity and on its own. Diagnosis conventionally requires use of radiographs, especially to detect ethmoid and sphenoid sinus disease. To limit radiation exposure, alternative diagnostic tests have been sought. The currently available tests will be reviewed and their advantages and disadvantages will be discussed. One imaging technique, that of A-mode ultrasound, has appeared as a promising adjunct to plain radiographs for diagnosis of maxillary and frontal sinus disease. The data utilizing ultrasound has been mixed and needs to be interpreted with care. This data will be reviewed and guidelines will be presented on the current use of the technique. Data obtained in the author's laboratory comparing the use of A-mode ultrasound and mucosal thickening as seen on plain radiographs will be presented. Further studies using the technique are suggested to better define patients who may be followed on a serial basis. Ultrasound is one of a number of new imaging techniques that are being applied to paranasal sinus disease. Early studies from Europe showed considerable promise, and instruments have been actively marketed in the U.S. before there has been much published experience here. The data are as yet incomplete, and the precise role of ultrasound either as a screening test or as a tool to monitor progress in chronic sinusitis is as yet undetermined.
Chronic Disease↗
Chronic rhinitis.
Chronic rhinitis may present as a syndrome of multiple symptoms or as a single symptom such as rhinorrhea, sneezing, or nasal obstruction. In patients whose symptoms do not conform to "classic" presentations of syndromes such as allergic rhinitis, a detailed differential diagnosis should be considered, to exclude anatomic, allergic, or systemic disease. If necessary, an imaging test of the sinuses should be obtained. Treatment depends on pathophysiology and can be prophylactic or symptomatic. A variety of nonpharmacologic measures are described which may prove helpful in reducing the severity of symptoms.
Chronic Disease↗