Nasal Pool Research Articles

Nasal treatment with a microemulsion reduces allergen challenge-induced symptoms and signs of allergic rhinitis

Conclusions. Intranasal microemulsion treatment can attenuate allergen challenge-induced nasal symptoms and plasma exudation in allergic rhinitis. We hypothesize that the mechanism of action involves modification of the allergen–mucosa interaction. The present observation suggests a novel principle for prevention in allergic rhinitis. Objective. To evaluate a specific microemulsion as a treatment for allergic rhinitis in an acute allergen challenge model. Patients and methods. Patients with allergic rhinitis were examined out of the pollen season. Treatment with a single dose of a specific microemulsion was given in a single-blind, placebo-controlled, and crossover design using a nasal pool device. Nasal allergen challenges were carried out and symptoms of allergic rhinitis were scored. Furthermore, nasal lavages were performed and levels of the plasma protein α2-macroglobulin were measured as an index of exudative inflammation. Results. The allergen challenges produced significant increases in nasal symptoms (p=0.007) and in nasal lavage fluid levels of α2-macroglobulin (p=0.008). The challenge-induced symptoms as well as the plasma exudation were attenuated by treatment with the microemulsion (p=0.016 and 0.012, respectively, compared with placebo).

Nasal provocation test in the diagnosis of natural rubber latex allergy

Natural rubber latex (NRL) allergy in workers using rubber gloves has been an occupational health problem for the last 10 years. In the case of the occupational agents, clinical history may be far from conclusive; hence, appropriate provocation should be carried out. The objective was to evaluate the usefulness of the nasal challenge test in the diagnosis of allergic rhinitis in subjects occupationally exposed to NRL. A single-blind, placebo-controlled study was conducted in 16 nurses with respiratory symptoms (bronchial asthma and/or rhinitis) related to NRL exposure as well as positive skin prick test (SPT) response to NRL. The controls were nine nurses with asthma and/or perennial rhinitis unrelated to NRL exposure; six atopic patients not occupationally exposed to NRL, with asthma and/or perennial rhinitis; and six healthy subjects. All the controls had negative results of SPT with NRL. Patients with a history of anaphylaxis or positive results of RAST to NRL were not considered in the study. The "nasal pool" technique was used to evaluate the cellular response and changes in protein level and ECP concentration in nasal washings after topical provocation with allergen or placebo. A significant increase was noted in eosinophil and basophil number, albumin/total protein ratio, and ECP level only in NRL SPT-positive patients subjected to nasal challenge with NRL. Neither bronchial nor systemic reactions were found after the nasal provocation with NRL. The nasal challenge test appears to be useful for diagnosing occupational rhinitis in NRL-sensitized patients.

Nasal mucosal endorgan hyperresponsiveness.

Nonspecific hyperresponsiveness of the upper and lower airways is a well-known characteristic of different inflammatory airway diseases but the underlying mechanisms have not yet been satisfactorily explained. In attempts to elucidate the relation of hyperresponsiveness to disease pathophysiology we have particularly examined the possibility that different airway endorgans may alter their function in allergic airway disease. The nose, in contrast to the bronchi, is an accessible part of the airways where in vivo studies of airway mucosal processes can be carried out in humans under controlled conditions. Different endorgans can be defined in the airway mucosa: subepithelial microvessels, epithelium, glands, and sensory nerves. Techniques may be applied further in the nose to determine selectively the responses/function of these endorgans. Topical challenge with methacholine will induce a glandular secretory response, and topical capsaicin activates sensory c-fibers and induces nasal smart. Topical histamine induces extravasation of plasma from the subepithelial microvessels. The plasma exudate first floods the lamina propria and then moves up between epithelial cells into the airway lumen. This occurs without any changes in the ultrastructure or barrier function of the epithelium. We have therefore forwarded the view of mucosal exudation of bulk plasma as a physiological airway tissue response with primarily a defense function. Since the exudation is specific to inflammation, we have also suggested mucosal exudation as a major inflammatory response among airway endorgan functions. Using a "nasal pool" device for concomitant provocation with histamine and lavage of the nasal mucosa we have assessed exudative responses by analyzing the levels of plasma proteins (e.g., albumin alpha 2-macroglobulin) in the returned lavage fluids. A secretory hyperresponsiveness occurs in both experimental and seasonal allergic rhinitis. This type of nasal hyperreactivity may develop already 30 minutes after allergen challenge. It is attenuated by topical steroids and oral antihistamines. We have demonstrated that exudative hyperresponsiveness develops in both seasonal allergic rhinitis and common cold, indicating significant changes of this important microvascular response in these diseases. An attractive hypothesis to explain airway hyperresponsiveness has been increased mucosal absorption permeability due to epithelial damage, possibly secondary to the release of eosinophil products. However, neither nonspecific nor specific endorgan hyperresponsiveness in allergic airways may be explained by epithelial fragility or damage since nasal absorption permeability (measured with 51CR-EDTA and dDAVP) was decreased or unchanged in our studies of allergic and virus-induced rhinitis, respectively. Thus, the absorption barrier of the airway mucosa may become functionally tighter in chronic eosinophilic inflammation.

Reduced airway absorption in seasonal allergic rhinitis.

The common notion that increased mucosal absorption characterizes allergic and inflamed airways is poorly supported by physiologic in vivo data. We have now examined whether the airway mucosa of patients with seasonal allergic rhinitis develop a change in absorption during their active disease period. Twelve patients with birch pollen rhinitis were examined twice, prior to and late into a Swedish birch pollen season. Ten healthy subjects were examined once. A nasal pool device was used to fill the unilateral nasal cavity with fluid containing 1-deamino-8-D-arginine vasopressin (desmopressin, 20 micrograms/ml) as absorption tracer. The peptide tracer solution was removed after 15 min, and absorption was determined by analysis of the peptide in the 24-h urine sample. Nasal absorption did not differ between healthy subjects and symptom-free patients outside the season. After 3 wk of symptom-producing seasonal allergic rhinitis, absorption of the peptide across the nasal mucosa was less (p < 0.05) than outside the season. These data indicate that hyperresponsiveness and disease progression in seasonal allergic rhinitis are not due to a compromise of the mucosal barrier that would permit increased absorption of mucosally deposited solutes. The reduced absorption may in part reflect the ability of the airway epithelium in vivo to maintain and potentially improve its barrier function by efficient epithelial restitution processes.

The "nasal pool"-device for challenge and lavage of the nasal mucosa in children: histamine-induced plasma exudation responses.

The accessibility of the nasal airway allows important examination of the airway mucosa in health and disease. However, the current methods for nasal challenge and lavage in children suffer from several shortcomings. In the present study, we have assessed the utility of a recently developed "nasal pool"-device in 7-9 year old children, and explored the ability of the nasal mucosa of these school-children to mount a plasma exudation response (lumenal entry of bulk plasma). Isotonic saline was instilled and maintained (1 min) as a "pool" in the unilateral nasal cavity. Recovery of the "pool" (lavage fluids) was determined. Concomitant challenge and lavage was then performed by exposing the nasal mucosa to a "pool" of isotonic saline and histamine (40-400 micrograms/ml) for 2 min. "Pool" fluids were analysed for alpha 2-macroglobulin as an index of microvascular-epithelial exudation of bulk plasma. The school-children successfully managed to carry out nasal lavages as well as concomitant histamine challenges and lavages with the "nasal pool"-device. The recovery of the nasal lavage fluids was almost quantitative (> 85%) and thus well reproducible. Histamine produced significant exudation of bulk plasma (alpha 2-macroglobulin). We suggest that the "nasal pool"-device is well suited for challenge and lavage of the nasal airway mucosa in children above 6 years of age, and conclude that lumenal entry of multipotent humoural protein-systems may be an important first line respiratory defence mechanism in children.

Effects of two weeks of topical budesonide treatment on microvascular exudative responsiveness in healthy human nasal airways

Extravasation and luminal entry of plasma (mucosal exudation) is not only a key feature of airway inflammation in rhinitis and asthma but also a major first-line respiratory defence mechanism. Topical steroids are effective antiexudative agents in disease but, so far, little is known about the direct effects of these drugs on the responsiveness of the microcirculation in human airways. In this study, the effects of prolonged budesonide treatment on histamine-induced mucosal exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were carried out before and late in the treatment periods. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. Histamine produced concentration-dependent mucosal exudation of plasma before as well as after treatment with either placebo or budesonide. The topical steroid treatment only marginally (1.8 fold) decreased the response to the low concentration histamine (40 microg x mL(-1)) and, although it was significantly (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant mucosal exudation of plasma in the budesonide group. If the present observations are extrapolated to inflammatory conditions, the antiexudative effects of topical steroids in rhinitis (and asthma) may reflect only a small degree of microvascular antipermeability effects. We suggest that topical steroid treatment may not impede mucosal exudation responses when called for in acute human airway defence reactions.

Exudative hyperresponsiveness of the airway microcirculation in seasonal allergic rhinitis.

Summary Background Mucosal exudation of plasma is a non‐injurious, physiological response of the airway microcirculation to different inflammatory processes. The exudative response is similar in the nose and bronchi and exudation occurs in both allergic asthma and rhinitis. The educative response is a specific end‐organ function of the mucosal microcirculation that may be altered in airway diseases. Objective This study examines the hypothesis of altered responsiveness of the superficial airway microcirculation to vascular permeability‐increasing challenges in sustained allergic inflammation. Methods Fourteen patients with birch‐pollen induced allergic rhinitis were studied for 7 weeks during a Swedish birch‐pollen season. Nasal symptoms (itching, sneezing. blockage, and discharge) were recorded and the occurrence of pollen was determined. The plasma exudation response was examined by topical histamine challenges at the end (May) and well out of (December) the season. Challenge and lavage were carried out concomitantly using a‘nasal pool’ ‐device. The unilateral nasal cavity was filled for consecutive 10 minute periods with saline and two concentrations of histamine (80μg/ mL and 400μg/mL). The lavage fluid levels of different‐sized plasma proteins (albumin‐66 000 D. fibrinogen‐340000 D, and α 2‐macroglobulin‐725000D) were determined. Results The pollen season was mild resulting in only minor nasal symptoms. Histamine produced exudation of all plasma proteins across the microvascular epithelial barriers with particularly strong correlation between the levels of albumin and α 2‐macroglobulin (r =0.98; P< 0.001). The exudative response to histamine was concentration‐dependent (P<0.05) and, furthermore, it was significantly greater late into the season compared with outside the pollen season (albumin: P < 0.05. tibrinogen: P<0.05. α 2‐macroglobulin: P<0.01). Conclusion We conclude that histamine produced concentration‐dependent nasal airway exudation of bulk plasma in subjects with seasonal rhinitis and that this response is abnormally great during the pollen season. Whether angiogenesis or increased responsiveness of the mierovascular endothelium may explain this phenomenon now remains unknown. We suggest that a mierovascular exudative hyperresponsiveness may characterize allergic airway disease.

Allergen challenge-induced entry of α 2-macroglobulin and tryptase into human nasal and bronchial airways

Background: Microvascular-epithelial exudation of bulk plasma may characterize inflammatory airway diseases. This study compares the acute allergen challenge–induced mast cell and exudative responses in nasal and bronchial airways. The focus is on α 2-macroglobulin as an index of luminal entry of plasma exudates. Methods: Separate nasal and bronchial allergen challenges were carried out outside the pollen season in eight patients with pollen-induced seasonal allergic rhinitis. The levels of different-sized plasma proteins (albumin molecular weight, 66,000 d and α 2-macroglobulin molecular weight, 725,000 d) and tryptase were determined in pre- and postchallenge nasal lavage and bronchoalveolar lavage (BAL) fluids. Diluent and increasing doses of allergen were sprayed into the right nasal cavity, and each challenge was followed by a nasal lavage (volume, 15 ml) with a “nasal pool” device (recovery, >80%). Endobronchial allergen challenge (individual doses) and BAL (volume, 2 × 25 ml) were performed in a lobe bronchus through a fiberoptic bronchoscope (recovery, 30%). Saline challenge and BAL were carried out in the contralateral lung as control. Results: The levels of albumin, α 2-macroglobulin, and tryptase increased dose-dependently in postchallenge nasal lavage fluids ( p < 0.05) and correlated to nasal symptoms. In particular, albumin and α 2-macroglobulin correlated ( r = 0.98, p < 0.001). Both α 2-macroglobulin and tryptase, but not albumin, were increased in BAL fluids from the allergen-challenged side ( p < 0.05). Conclusion: Local allergen challenge causes luminal entry of tryptase and α 2-macroglobulin in the nose and bronchi of patients with allergy. We suggest that mast cell and plasma exudation responses may be similar in human nasal and bronchial airways and that albumin levels (in BAL fluids) may not well reflect the exudation process in bronchial airways. (J A LLERGY C LIN I MMUNOL 1995;96:239-46.)

Effect of seasonal allergic rhinitis on airway mucosal absorption of chromium-51 labelled EDTA.

Hyperpermeability of the airway mucosa is thought to be characteristic of allergic rhinitis and asthma. Nine subjects with seasonal rhinitis caused by birch pollen were studied and the nasal mucosal absorption of chromium-51 labelled EDTA was examined both in an asymptomatic period before the season and late into the season when significant allergic rhinitis symptoms were present. A nasal pool device was used to keep a concentration of the absorption tracer in contact with a larger part of the mucosa of the ipsilateral nasal cavity. Absorption was allowed for 15 minutes and measured as the radioactivity appearing in the 24 hour urine sample. The nasal absorption of 51Cr-EDTA in subjects with seasonal allergic rhinitis was less during active disease than before the season. An airway epithelial barrier that is subject to prolonged eosinophilic inflammation may not be disrupted but may rather increase its functional tightness.

125I-Albumin May Not Be Used as a Tracer of Absorption Across the Human Nasal Airway Barriers

This study set out to examine the effects of histamine on airway absorption of macromolecules. By employment of a novel "nasal pool" technique instillates containing 125I-albumin, with or without histamine, were kept for 15 min on human nasal mucosa. Unaffected by the presence of histamine, the instillations produced significant levels of plasma radioactivity, increasing for 60 min. However, gel-filtration data showed that only 30% of the plasma radioactivity was still bound to albumin. Incubation experiments indicated that radioiodine did not dissociate from albumin in nasal liquids nor in the blood. Further experiments involved oral ingestion of the entire nasal instillate. Prompt gastrointestinal absorption of radioactivity occurred, giving rise to plasma levels about two orders of magnitude higher than those recorded after the nasal applications. Moreover, only 25% of the plasma radioactivity was now bound to albumin. It must be considered unavoidable that a small portion (less than 1%) of the nasal instillate is swallowed. Hence, the plasma radioactivity detected in this study may largely reflect gastrointestinal break-down of 125I-albumin and subsequent absorption of radioiodine. We conclude that 125I-albumin may not be employed in studies addressing macromolecular absorption across the human nasal mucosa and that previous work and conclusions based on nasal absorption of 125I-albumin are invalid.

The‘nasal pool’device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions

A 'nasal pool' (NP) device, a compressible plastic container with an adapted nozzle, was used to perform a continuous 10-min nasal provocation and lavage. This novel technique brings known concentrations of agents into contact with a large and defined area of the nasal mucosal surface for extended periods of time. Simultaneously, the surface exudations/secretions of the same nasal mucosa are effectively sampled by the NP fluid. A concentration-response study of histamine (80, 400 and 2000 micrograms/ml) was performed in 12 normal subjects on three different occasions. Exudation of plasma albumin into the lavage fluid was measured to quantitate the histamine-induced airway inflammation. The effect of the dwell time on exudation was examined using histamine (400 micrograms/ml) instilled in the nasal cavity for time periods from 10 sec to 10 min. The time course of histamine-induced plasma exudation response was studied by exposing the mucosa to histamine (400 micrograms/ml) for 12 min, with the NP renewed every minute. Allergen-provocations were performed in subjects with hay fever and TAME-esterase activity in the returned lavage fluid was determined to indicate the degree of response. Histamine produced a concentration-dependent increase in albumin levels in the NP fluid; 123.3 +/- 25.6, 213.8 +/- 19.7 and 430.2 +/- 32.0 micrograms/ml (mean +/- s.e.m.), respectively. The time-course study demonstrated that plasma exudation into the lumen occurred promptly and that the exudation response reached a maximum after exposure to histamine for 6-10 min. The dwell-time experiments supported this finding. After 10 min the exudation appeared to decline despite the continued presence of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)