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Biomedical subjects

N Mygind

Publications and source records attributed to N Mygind.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nasal inhalation of budesonide from a spacer in children with perennial rhinitis and asthma.

The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak inspiratory flow (P < 0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.

Administration, Inhalation↗
PubMed1998

IL-8 and the activation of eosinophils and neutrophils following nasal allergen challenge.

BACKGROUND: A growing body of evidence suggests that proinflammatory cytokines play a role in allergic inflammation by attracting and activating inflammatory cells. In this study, we have investigated the relationship between interleukin-8 (IL-8) in nasal lavage fluid and the local activation of eosinophils and neutrophils following nasal allergen challenge of allergic patients. METHODS: Nasal challenges were performed with grass pollen extract in 14 allergic patients and 5 nonallergic controls. Nasal lavage fluid was collected repeatedly for 10 h, and the levels of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were used as markers of eosinophil and neutrophil activation, respectively. The levels of these molecules were compared with that of IL-8 in nasal lavage fluid. RESULTS: Allergen challenge of allergic patients produced a significant late-phase increase in the levels of ECP and MPO. Furthermore, the level of MPO showed a highly significant correlation with the level of IL-8 in lavage fluid (r = 0.8, p< 0.0001), whereas there was no significant relationship between the levels of ECP and IL-8. CONCLUSION: Interestingly, our findings suggest that both eosinophils and neutrophils are activated following nasal allergen challenge. In addition, our results are consistent with the hypothesis that IL-8 acts as a chemoattractant/activator of neutrophils during the late phase of the allergic inflammation. In contrast, we were not able to demonstrate any significant relationship between the level of IL-8 in lavage fluid and the activation of eosinophils.

Adult↗
PubMed1998

Mechanisms of airflow limitation in the nose and lungs.

The main differences in the anatomies of the upper and lower airways are the vascular characteristics and bony surroundings of the upper airways compared with the smooth muscle component and the loose-lying situation of the lower airways. Both allergic asthma and rhinitis involve a similar process of mucosal inflammation in response to allergen exposure, characterized by inflammatory cell infiltration and local release of mediators. In addition, both the upper and lower airways are under similar influences from local neuronal reflexes, exercise, posture and cyclic variations. Challenge tests have been able to demonstrate the roles of the various influences and components in the inflammatory processes of asthma and allergic rhinitis. A particular difference in the response in asthma compared with rhinitis is the degree of non-specific hyperresponsiveness, which is a characteristic of the late response or response to repeated or prolonged exposure to allergen. Responsiveness of the bronchial mucosa in asthma patients is approximately 50 times that of normal (non-allergic or non-asthmatic) subjects, whereas that of the nasal mucosa in allergic rhinitis is only 2-8 times that of control subjects. The inflammatory process involved in hyperresponsiveness is similar in both conditions, involving increased infiltration of eosinophils and subsequent increased mediator release. The greater degree of hyperresponsiveness seen in asthma appears to be a consequence of the anatomical differences between the upper vs the lower airways. Evidence is presented for the contribution of increased airway wall thickness to the hyperresponsiveness in asthma, together with other possible factors, such as decoupling of responder tissue from surrounding tissue, increased smooth muscle contractility, and smooth muscle hypertrophy.

Allergens↗
PubMed1998

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season.

BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls. RESULTS: During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001-P<0.05). Significant differences were seen between the steroid groups and the placebo group for all parameters (P<0.001-P<0.05). Higher eosinophil count (P<0.05), serum EPO (P<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001). CONCLUSIONS: Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.

Acute-Phase Proteins↗
PubMed1998

Experimentally induced nasal hypersecretion does not reduce the efficacy of intranasal levocabastine.

In allergic rhinitis, a nasal H1-antihistamine spray seems to be well suited for usage on an as-needed basis, because it has a quick onset of action, and many patients prefer to take medicine only when they have symptoms. It is a prerequisite, however, that nasal hypersecretion during a rhinitis episode does not significantly reduce the efficacy of intranasal treatment by washing away the drug before it reaches the H1-histamine receptors. In order to investigate this problem, we have induced nasal hypersecretion with a methacholine challenge in one experiment and in four experiments we have washed the nasal cavities 0.5 min. before, 5 min. before, 0.5 min. after and 5 min. after intranasal use of the H1-antagonist, levocabastine. The symptom response to a subsequent histamine challenge was used as the effect parameter. Levocabastine reduced the number of histamine-induced sneezes with 81% (p < 0.0001) and the secretion weight with 62% (p < 0.001) compared with placebo. Neither methacholine-induced hypersecretion nor washing the nose with saline reduced the efficacy of the antihistamine spray. We conclude that experimentally induced nasal hypersecretion does not reduce the efficacy of the antihistamine spray, and probably the same applies to rhinorrhea during an acute episode of allergic rhinitis.

Administration, Intranasal↗
PubMed1997

A time-dose study of the effect of topical ipratropium bromide on methacholine-induced rhinorrhoea in patients with perennial non-allergic rhinitis.

Intranasal application of the anticholinergic drug, ipratropium bromide, is used for the treatment of watery rhinorrhoea. We have performed a time-dose study of ipratropium bromide in patients with perennial non-allergic rhinitis, using rhinorrhoea, induced by nasal methacholine challenge, as a laboratory model. Two doses of ipratropium bromide, 40 microg and 80 microg, delivered from a pressurized aerosol, were both very effective, reducing the volume of methacholine-induced secretion by 85 to 95%. The maximum effect lasted for at least 4 h and then slowly diminished. A significant effect was demonstrable for 12 h with 40 microg and for 18 h with 80 microg ipratropium bromide. These results from a laboratory challenge study indicate that the presently used frequency of ipratropium bromide, namely four times daily, may not be necessary in many patients. Perhaps once in the morning, followed by an as-needed medication, will be a better way to use intranasal ipratropium bromide in perennial non-allergic rhinitis.

Administration, Intranasal↗
PubMed1997

Effect of corticosteroids on nasal blockage in rhinitis measured by objective methods.

This paper gives an overview of placebo-controlled studies of the effect of corticosteroid treatment on nasal blockage, based on objective measurements of nasal airway patency. A few studies of perennial rhinitis have indicated that pretreatment with an intranasal corticosteroid has a moderate effect on nasal hyperresponsiveness, measured as the histamine-induced increase of nasal blockage. Whereas the effect on allergen-induced early-phase symptoms is variable, the effect on the late-phase blockage is almost complete. In seasonal allergic rhinitis, a few studies have shown an effect of intranasal steroids on nasal airway resistance, nasal peak flow and on acoustic rhinometry, but there are no reports on the effect in adults with perennial rhinitis. In children with perennial disease, intranasal treatment results in increased nasal patency and, in one study, also in reduced mouth breathing and in an increased threshold for exercise-induced bronchoconstriction. In patients with nasal polyposis, intranasal steroids have an effect on nasal airway resistance and on nasal peak flow both before and after polypectomy. There is convincing evidence that intranasal corticosteroids provide a better effect than antihistamine on nasal blockage. Amazingly, there does not appear to be any report on the effect of systemic corticosteroid treatment on nasal airway patency, and it is therefore difficult to recommend this treatment in a rational dosage. In conclusion, there is a fairly good documentation in support of the efficacy of intranasal steroid treatment on nasal airway patency in rhinitis. An objective measurement of nasal airway patency ought to be the routine in controlled rhinitis trials.

Adrenal Cortex Hormones↗
PubMed1997

Common cold and high-dose ipratropium bromide: use of anticholinergic medication as an indicator of reflex-mediated hypersecretion.

UNLABELLED: It was our aim to study the role played by parasympathetic reflexes for the amount and physical characteristics of nasal discharge during a common cold, and to define the maximum anti-rhinorrhoea effect obtainable with anticholinergic medication. Fifty adults with naturally acquired colds were treated with a very high dose of the topically active cholinoceptor-antagonists ipratropium bromide in a randomized, double-blind, placebo-controlled study of parallel groups. A dosage of 400 micrograms was given 4 times daily for 3 days, using a specially manufactured high-dosed pressurized aerosol. This treatment resulted in a 56% reduction in the number of nose blowings (p < 0.01) and a 58% reduction in the weight of blown secretions (p < 0.01). Assessment of the "pourability" of the nasal discharge indicated that ipratropium bromide mainly reduces the watery secretions but not the mucopurulent secretions. The high dose of ipratropium bromide caused nose- and mouth-dryness in a considerable number of the patients. IN CONCLUSION: (1) during the first days of a common cold about 60% of the nasal discharge is a reflex-mediated product from nasal glands; (2) this type of secretion is predominantly watery; and (3) ipratropium bromide can reduce watery rhinorrhoea in the common cold, but a lower dose is required in order to avoid side effects.

Administration, Inhalation↗
PubMed1996

The rationale for use of topical corticosteroids in allergic rhinitis.

The rationale for using topical corticosteroids in the treatment of allergic rhinitis is that high drug concentrations can be achieved at receptor sites in the nasal mucosa, with minimal risk of systemic adverse effects. Topical corticosteroids have been demonstrated to reduce the number of Langerhans' cells (or their markers) in the nasal mucosa, and this is thought to attenuate antigen presentation. T lymphocytes have been identified as being significant in orchestrating the immune-inflammatory response, particularly the TH2 cells, which represent an important target for topical corticosteroids. TH2 cell-evoked mast cells and basophils are the sole producers of histamine, a mediator of major importance for rhinitis symptoms. Several studies have shown that the increased number of mast cells and basophils in the epithelium following antigen challenge/exposure, are markedly reduced by topical corticosteroids. Furthermore, the number of eosinophils, an important morphological marker of allergic rhinitis, can be profoundly reduced by treatment with topical corticosteroids. The rationale for topical treatment is strengthened by evidence of inhibition of cytokine release from surface epithelial cells, resulting in reduced recruitment and activation of mast cells, basophils, and eosinophils, which may be attributed to the high drug concentration achieved in epithelial cells. Ongoing inflammation in the mucous membrane is indicated by entry of plasma into the nasal lumen which subsides with the anti-inflammatory efficacy of topical corticosteroids. In contrast to antihistamine therapy, which has little effect on nasal blockage, pretreatment with topical corticosteroids results in almost complete attenuation of late-phase symptoms including nasal blockage, and moderate efficacy in early phase symptoms. Clearly, the spectrum of anti-inflammatory activity afforded by topical corticosteroid therapy is of clinical significance in reducing the three major symptoms of allergic rhinitis- sneezing, watery rhinorrhoea and nasal blockage.

Administration, Intranasal↗
PubMed1996

Challenge tests in nose and bronchi: pharmacological modulation of rhinitis and asthma.

In order to study the pathophysiology of allergic airway disease and its response to pharmacotherapy, allergic and non-allergic provocation challenge techniques can be employed. Lower airway challenge has been used widely, but the use of nasal challenge is becoming more widespread as its advantages are realized. New measurement techniques are also being used (e.g. acoustic rhinometry), along with more classical methods such as spirometry, peak airflow rate and symptom scores, to determine the response to challenge. In the lungs, allergen challenge produces a biphasic response, which is less clearly defined in the nose. Topical histamine challenge closely resembles the effects of an allergic reaction and acts by stimulating sensory nerve endings. Methacholine is also often used for nasal challenge (often in addition to histamine), due to its effects on glandular sensitivity. Exercise induces bronchoconstriction in asthmatics and can be imitated by inhalation of cold, dry air. Cold air induces glandular hypersecretion and nasal discharge in normal subjects, which is increased in severity in rhinitic patients. Drug effect investigations using antihistamines have shown that histamine is important in producing the symptom of sneezing, whereas nasal blockage is due to vasodilatation rather than plasma exudation and oedema. Beta 2-agonists reduce allergen-induced symptoms by stabilizing mast cells, whereas cholinoceptor antagonists reduce watery nasal secretion. Increased responsiveness of sensory nerves and nasal glands is a characteristic clinical feature of asthma and rhinitis, which is responsible for the symptomatology. These effects can be reduced by topical corticosteroids.

Asthma↗
PubMed1996

Effects of corticosteroid therapy in non-allergic rhinosinusitis.

Corticosteroids have a multifactorial effect initiated by their binding to a specific cytoplasmic glucocorticoid receptor. At the cellular level there is a reduction in the number of antigen-presenting cells, in the number and activation and T cells, in the number of epithelial mast cells, and in the number and activation of eosinophils. Steroids have a proven effect on symptoms and signs in non-allergic rhinosinusitis with eosinophilia and in nasal polyposis. Topically applied drugs, studied in many controlled trials, reduce rhinitis symptoms, improved nasal breathing, reduce the size of polyps and their recurrence, but have a poor effect on the sense of smell and no direct effect on sinus pathology. Systemic steroids, less well studied, appear to have an effect on all types of symptoms and pathology, the sense of smell included. A short course of systemic steroids is as effective as polypectomy with a snare. Individualized management of nasal polyposis and non-allergic rhinosinusitis with eosinophilia may consist of long-term topical steroids, short-term systemic steroids, or surgery, in various combinations.

Administration, Topical↗
PubMed1996

Comparison between the effect of ipratropium bromide as a pressurized aerosol and as an aqueous pump spray on methacholine-induced rhinorrhoea.

Topical application of the anti-cholinergic drug ipratropium bromide is used for the treatment of rhinorrhoea. As the commercially-available pressurized aerosols are now largely being replaced by aqueous pump sprays, not containing CFC gases, we have compared these two types of sprays in a time-effect study of 20 normal persons, using the secretory response to nasal methacholine challenge as the effect parameter. Pre-treatment has been given as a single dose of 80 mg of ipratropium bromide, and 24 mg methacholine was used for challenge. The pressurized aerosol reduces rhinorrhoea with 60% (p < 0.05) and the effect lasts for at least 8 h. The corresponding value for the aqueous pump spray is 40% (p < 0.05) and the effect lasts for less than 4 h. The differences between the two sprays is significant 30 min, 1, 2 and 4 h after medication (p < 0.05). This finding is unexpected and we cannot offer a satisfactory explanation. The result indicates that changes in dosing and dose-frequency of ipratropium bromide may be necessary when patients are transferred from a pressurized spray to an aqueous pump spray.

Administration, Intranasal↗
PubMed1995

Progress in the drug management of allergic rhinitis.

The diagnosis of allergic rhinitis is based on the case history, rhinoscopy and allergy testing. Therapy consists of allergen avoidance, pharmacotherapy, immunotherapy and/or surgery. This review deals only with pharmacotherapy, since there has been significant progress in this area. The first advance was the introduction of topical nasal steroids in the mid-1970s and the second the introduction of the second generation of H1 antihistamines in the early 1980s. The task for future developments is to optimize therapy by rational and combined use of available drugs, especially the steroid sprays and non-sedating antihistamines. A systematic approach to the choice of drug for the treatment of rhinitis is presented.

Administration, Intranasal↗
PubMed1994

Budesonide powder administration for the treatment of grass-pollen-induced allergic rhinitis.

The new dry-powder inhaler system, Turbuhaler, has proved to be equivalent to metered-dose inhalers when used in the nose, and the objective of this study was to investigate the efficacy, dose-response effects, and safety of budesonide powder given in the morning during the grass pollen season to patients with grass-pollen-induced allergic rhinitis. Of 190 randomized patients, 186 were treated and 180 completed this double-blind study, which comprised a 4-week treatment period, preceded by a 1-week run-in period. The patients were randomized to three parallel treatment groups: budesonide 400 micrograms, budesonide 200 micrograms, or placebo once in the morning. Assessment of efficacy, by comparing changes in mean scores of nasal symptoms from run-in to treatment, showed a statistically significant effect for all symptoms with active treatments, as compared with placebo. The mean reduction of symptom severity was more pronounced in the 400-micrograms group than in the 200-micrograms group, and this difference was statistically significant for runny nose (P < 0.02) and combined nasal symptoms (P < 0.02). Nasal peak-inspiratory flow improved significantly in both budesonide-treated groups, as compared with placebo (P < 0.01 and P < 0.01). During the treatment period, patients on active treatment showed, on average, a reduction of all nasal symptoms, whereas the placebo-treated patients, on average, showed an increase of nasal symptoms. Approximately 40% in the high-dose group felt total control of rhinitis symptoms, as compared with 26% in the low-dose group. There was no difference between budesonide- and placebo-treated groups in side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

Early and late nasal symptom response to allergen challenge. The effect of pretreatment with a glucocorticosteroid spray.

We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment with the glucocorticosteroid budesonide (200 micrograms twice daily) for 14 d and with placebo in a double-blind, cross-over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose-blowings, and of a sustained nasal blockage. These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72% reduction; P < 0.01), a moderate effect on discharge (37% reduction; P < 0.01), and a slight effect on blockage (17% reduction of nasal inspiratory peak flow rate; P < 0.02). The degree of inhibition of the rechallenge response was similar to the effect on the initial early response. The effect on the late response was very pronounced for all symptoms and signs (97% reduction of sneezes, 76% reduction of nose-blowings, 96% reduction of blockage; P < 0.01). In conclusion, we found it difficult in the individual subject to identify a well-defined late symptom response by criteria similar to those employed to characterize the late response in the bronchi. The effect of budesonide was more marked on sneezing than on blockage, and the drug was considerably more effective on the late response than on the early response.

Administration, Topical↗