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Biomedical subjects

N Mygind

Publications and source records attributed to N Mygind.

At least 19 recordsLinked to original sources
PubMed1999

Histamine and tryptase in nasal lavage fluid after allergen challenge: effect of 1 week of pretreatment with intranasal azelastine or systemic cetirizine.

BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine the effect of intranasal azelastine or systemic cetirizine (both potent antihistamines) on the allergen-induced release of mast-cell mediators from the human nasal mucosa in vivo. METHODS: Patients allergic to birch pollen (n = 11) and control subjects not allergic to birch pollen (n = 5) were included in a randomized, double-blind, placebo-controlled, 3-way crossover study outside the pollen season. Each subject was treated with azelastine nasal spray 0.14 mg per nostril twice daily, cetirizine tablets 10 mg every day, or placebo for 1 week using a double-dummy design. At the end of each treatment period, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing and a significant increase in the levels of histamine and tryptase. The challenge of subjects not allergic to pollen produced no such response. Azelastine and cetirizine significantly reduced allergen-induced sneezing and the associated increase in histamine and tryptase levels. No significant differences were found between the azelastine and cetirizine treatments. CONCLUSION: Pretreatment with azelastine or cetirizine inhibits the allergen-induced release of mast-cell mediators from the human nasal mucosa. Our results are consistent with the hypothesis that both antihistamines reduce mediator release from nasal mucosa mast cells in vivo. However, further studies are necessary to test this hypothesis.

Administration, Intranasal↗
PubMed1999

Advances in the medical treatment of nasal polyps.

The objectives of the medical management of nasal polyposis are to eliminate or reduce the size of polyps, re-establish nasal breathing, reduce symptoms of rhinitis, restore the sense of smell and prevent the recurrence of nasal polyps. Corticosteroids have a proven therapeutic effect on the symptoms of nasal polyposis and may reduce one of the underlying causes of polyps, inflammation. The efficacy of topical corticosteroids such as beclomethasone dipropionate nasal spray and betamethasone nasal drops in reducing polyp size and rhinitis symptoms has been demonstrated in several randomized, placebo-controlled trials. Flunisolide and budesonide have also been shown to delay the recurrence of polyps after surgery. Topical corticosteroids can be used as long-term therapy either alone in mild cases, or combined with systemic corticosteroids and/or surgery in severe cases. Most patients will respond well to topical corticosteroid treatment of their nasal polyposis; consequently, the requirement for repetitive nasal surgery will be reduced.

Administration, Intranasal↗
PubMed1998

Effect of nasal inflammation and of intranasal anti-inflammatory treatment on bronchial asthma.

It is logical to look upon the nose and the bronchi as integrated parts of one 'united airway' and we would like to advance the hypothesis that optimal management of airway disease, caused by inhaled allergens, may necessitate control of inflammation in all parts of the airways. Nasal inflammation can aggravate asthma symptoms, and there is a rationale for giving intranasal anti-inflammatory treatment to patients with asthma. (i) Inhaled allergens are predominantly deposited in the nose, whether a patient suffers from rhinitis, asthma or both. (ii) Antigen presentation consequently takes place in the nose, and the response of the airway immune system is thus initiated in the nasal mucous membrane. (iii) Antigen presentation in the nose may possibly induce cell recruitment and activation not only in the nasal mucosa but also in the lower airways. (iv) Suppression of nasal inflammation may therefore be necessary for optimal management of asthma.

Administration, Inhalation↗
PubMed1998

Histamine and tryptase in nasal lavage fluid following challenge with methacholine and allergen.

BACKGROUND: The level of histamine in nasal lavage fluid has been used as an index of mast cell/basophil activation in a number of studies. Obviously, such an index can only be valid if changes in the secretory activity of nasal glands do not affect the level of histamine in lavage fluid (i.e. hypersecretion, without a simultaneous activation of mast cells/basophils in the nasal mucosa, must not increase the level of histamine). OBJECTIVES: To asses the effect of nasal hypersecretion on histamine levels in lavage fluid. METHODS: Nasal challenges were performed with methacholine and allergen in grass pollen-allergic patients and non-allergic controls. Nasal lavage fluid was collected before and repeatedly for nine hours after nasal challenge, and the level of histamine was compared with that of a specific mast cell-derived enzyme, tryptase. In addition, the effect of methacholine on basophils was examined in vitro. RESULTS: Allergen challenge of allergic patients produced sneezing and a significant increase in histamine and tryptase levels, whereas challenge of non-allergic subjects produced no such response. Interestingly, challenge with methacholine also induced a significant increase in histamine levels. This increase was seen in both allergic and non-allergic subjects and it was not associated with any sneezing or increase in tryptase levels, indicating that mast cells were not activated. Furthermore, stimulation of basophils with methacholine did not induce any histamine release in vitro. CONCLUSIONS: Apparently, there exists a pool of histamine in the human nose that can be transferred to lavage fluid during glandular hypersecretion. The source of this histamine is yet to be identified. As the level of histamine seems to be affected by the secretory activity of nasal glands, we question the use of this single mediator as an index of mast cell/basophil activation in nasal lavage studies.

Administration, Intranasal↗
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↗