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G K Scadding

Publications and source records attributed to G K Scadding.

At least 19 recordsLinked to original sources
PubMed2002

Effects of non-steroidal anti-inflammatory drugs on cyclo-oxygenase and lipoxygenase activity in whole blood from aspirin-sensitive asthmatics vs healthy donors.

1. Cyclo-oxygenase (COX) and lipoxygenase (LO) share a common substrate, arachidonic acid. Aspirin and related drugs inhibit COX activity. In a subset of patients with asthma aspirin induces clinical symptoms associated with increased levels of certain LO products, a phenomenon known as aspirin-sensitive asthma. The pharmacological pathways regulating such responses are not known. 2. Here COX-1 and LO activity were measured respectively by the formation of thromboxane B(2) (TXB(2)) or leukotrienes (LT) C(4), D(4) and E(4) in whole blood stimulated with A23187. COX-2 activity was measured by the formation of prostaglandin E(2) (PGE(2)) in blood stimulated with lipopolysaccharide (LPS) for 18 h. 3. No differences in the levels of COX-1, COX-2 or LO products or the potency of drugs were found in blood from aspirin sensitive vs aspirin tolerant patients. Aspirin, indomethacin and nimesulide inhibited COX-1 activity, without altering LO activity. Indomethacin, nimesulide and the COX-2 selective inhibitor DFP [5,5-dimethyl-3-(2-isopropoxy)-4-(4-methanesulfonylphenyl)-2(5H)-furanone] inhibited COX-2 activity. NO-aspirin, like aspirin inhibited COX-1 activity in blood from both groups. However, NO-aspirin also reduced LO activity in the blood from both patient groups. Sodium salicylate was an ineffective inhibitor of COX-1, COX-2 or LO activity in blood from both aspirin-sensitive and tolerant patients. 4. Thus, when COX activity in the blood of aspirin-sensitive asthmatics is blocked there is no associated increase in LO products. Moreover, NO-aspirin, unlike other NSAIDs tested, inhibited LO activity in the blood from both aspirin sensitive and aspirin tolerant individuals. This suggests that NO-aspirin may be better tolerated than aspirin by aspirin-sensitive asthmatics.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Paradoxical low nasal nitric oxide in nasal polyposis.

BACKGROUND: Nitric oxide (NO) is synthesized in the respiratory tract. Three isoforms of NO synthase have been described in man, with the inducible form related to inflammatory disease. In the paranasal sinuses constitutive production of nitric oxide has been demonstrated, with levels of 20-25 p.p.m. being found in sinus puncture. Nasal polyposis is a chronic inflammatory condition in which inducible nitric oxide synthase (iNOS) expression is elevated in nasal polyp epithelium. OBJECTIVES: 1. Measurement of upper airway nitric oxide in nasal polyposis patients compared with those with allergic rhinitis, and with normal controls. 2. To assess the effect of polyp treatment on nasal NO levels. METHODS: NO levels (parts per billion) were measured in nasal and pulmonary exhaled air using a LR 2000 Logan Sinclair nitric oxide gas analyser. This utilizes the chemiluminescence principle. Eighty-two patients were studied: 44 with rhinitis, but without polyps, and 38 with nasal polyps. NO levels were compared with those of 20 normal controls. In 23 further polyp patients, levels were measured pre- and post-treatment and the changes were compared with alterations in polyp size, as assessed by rigid nasendoscopy. RESULTS: Nasal NO levels were significantly lower (Kruskal-Wallis, P = 0.000, chi2 = 27.5, d.f. = 3) in patients with polyps than those found in uncomplicated allergic rhinitis. NO levels were correlated directly with extent of polyposis as graded by the Lund-McKay index. Successful treatment, with reduction in polyp volume, was associated with a rise in NO levels (P = 0.042). CONCLUSION: NO levels are low in nasal polyposis, despite high levels of iNOS, possibly related to blockage of the ostiomeatal complex and failure of NO generated constitutively in the sinuses to reach the nasal airway. A rise in the NO levels is seen with successful polyp treatment, and is proportional to the reduction in endoscopically assessed polyp size, suggesting that with both medical and surgical therapy, the ostiomeatal complex obstruction is decreasing. We propose the following scenario. Nasal NO levels are the result of two processes: inducible NO production by inflamed nasal mucosa plus constitutive sinus mucosal production, detectable in normals. In uncomplicated allergic rhinitis with patent sinus ostia NO levels tend to be elevated, but when inflammation is sufficient to obstruct sinus ostia (as in nasal polyps), NO levels fall because sinus NO makes the major contribution.

Adult↗
PubMed2002

High levels of nitric oxide synthase activity are associated with nasal polyp tissue from aspirin-sensitive asthmatics.

The pathogenesis of aspirin intolerance remains unclear. Inducible nitric oxide synthase (iNOS) expression is upregulated in nasal polyp epithelium, implying a role for nitric oxide (NO) in its formation. We decided to compare iNOS activity in polyp tissue from patients with and without aspirin intolerance. Nasal polyp tissue was collected from 15 patients undergoing routine nasal polypectomy. These patients were classified into three groups: Group A comprised patients with nasal polyps without asthma; Group B contained patients with nasal polyps and asthma; and Group C comprised patients with nasal polyps, asthma and aspirin sensitivity. All subjects in Group C had a history of aspirin-induced reaction and a confirmatory intranasal challenge with lysine-aspirin. NOS activity was measured by the ability of tissue homogenates to convert 3,4-L-arginine to L-citrulline in an L-N(G)-nitro-L-arginine-inhibitable fashion. The iNOS activity (picomoles) in polyp tissue from the 3 groups was: A, 248.72+/-220.79; B, 23.71+/-41.06; and C, 549.71+/-132.11. Thus, nasal polyps from patients with Samter's triad had a significantly higher iNOS activity (p = 0.004; one-way ANOVA). This finding does not correlate simply with disease severity or with the occurrence of asthma and could indicate another important facet of aspirin-induced airways disease.

Adult↗
PubMed2001

An open audit of montelukast, a leukotriene receptor antagonist, in nasal polyposis associated with asthma.

BACKGROUND: Nasal polyposis occurs frequently in patients with intrinsic asthma, especially in those who are aspirin sensitive. It can be difficult to treat effectively, even with surgery and regular topical intranasal corticosteroids many patients are still symptomatic. OBJECTIVE: To investigate the response to montelukast, a leukotriene D4 receptor antagonist, as an add-on therapy to topical and inhaled corticosteroids in patients, both aspirin sensitive (AS) and aspirin tolerant (AT), with nasal polyposis and asthma. METHODS: Nasal polyposis symptoms were assessed by visual analogue scales; nasal polyps were assessed by nasendoscopy and via the measurement of nasal volumes by acoustic rhinometry. The nasal airway was assessed by nasal inspiratory peakflow (NIPF). Asthma was monitored using symptom scores and peak expiratory flow measurements. Aspirin sensitivity was assessed by history together with intranasal lysine aspirin challenge. Upper and lower airway nitric oxide measurements were made before and during treatment. RESULTS: Clinical subjective improvement in nasal polyposis occurred in 64% AT (P < 0.01), patients and 50% AS patients (P > 0.05); asthma improvement in 87% AT and 61% AS patients (P < 0.05 for both). Objective changes in peak flow occurred only in AT patients (P < 0.05). Acoustic rhinometry, nasal inspiratory peak flow and nitric oxide levels did not change significantly in any group, however, correlations were seen between nitric oxide levels and polyp scores and between nitric oxide levels and acoustic rhinometry changes. Improvement on montelukast therapy was not associated with any of the following variables: age, sex, skin prick test positivity, disease duration or aspirin sensitivity. (P > 0.05 for all). CONCLUSION: The findings are consistent with a subgroup of nasal polyps/asthma patients in whom leukotriene receptor antagonists are effective. This is not related to aspirin sensitivity. Further placebo-controlled studies need to be undertaken.

Acetates↗
PubMed2001

Corticosteroids in the treatment of pediatric allergic rhinitis.

The goal of treatment in pediatric allergic rhinitis is to provide effective prevention of or relief from allergic rhinitis symptoms as safely and effectively as possible. Removing or avoiding allergens is always advised; however, pharmacotherapy is often necessity. Pharmacologic options include systemic decongestants, which are associated with irritability and insomnia, particularly in children. Antihistamines are widely used; however, first-generation antihistamines are known to cause dry mouth and sedation. Oral corticosteroids are very effective but can have unwanted systemic effects. Over the past decade, intranasal corticosteroids have been shown to be the most effective form of pharmacologic treatment for allergic rhinitis. Data support the use of intranasal corticosteroids as first-line therapy over oral antihistamines; nonetheless, some clinicians have been reluctant to prescribe these agents, particularly for children, because of concerns for systemic effects. Overall, the newer corticosteroids, including mometasone furoate (MF), beclomethasone dipropionate, and budesonide have an improved risk-benefit ratio compared with older cortico-steroids and are now considered the drug of choice for pediatric allergic rhinitis. A good deal of evidence exists that confirms the lack of systemic effects from intranasal cortico-steroids. However, reports of decreased bone growth in children receiving intranasal budesonide short-term and beclomethasone dipropionate long-term have heightened concerns that some of these drugs may have systemic effects. A new intranasal corticosteroid, MF nasal spray, has been studied in children 3 to 12 years of age and has been shown to be effective. Intranasal MF is available with once-daily dosing, which has the potential to decrease systemic side effects.

Administration, Intranasal↗
PubMed2001

Non-allergic rhinitis: diagnosis and management.

Patients in the rhinitis clinic with negative skin prick tests present a challenge. Non-allergic rhinitis consists of a variety of conditions including infection, hormonal changes, drugs and autonomic dysfunction. There is also a range of systemic disorders to be considered. The pathogeneses of many of these are less well understood than that of allergic rhinitis, diagnosis and treatment pathways are also more complex. A detailed accurate history needs to be taken followed by relevant investigations which may include allergen challenge, because skin prick and RAST-negative allergic rhinitis is now recognised. Nitric oxide levels may prove helpful: elevated levels suggest inflammation, very low levels indicate the possibility of primary ciliary dyskinesia or cystic fibrosis. Treatment is of the underlying cause when found: for those without obvious pathology a trial of combined therapy with topical corticosteroids plus antihistamine or plus anti-cholinergic may be worth while. A complex inter-relationship between allergic and infectious rhinitis is becoming apparent.

Drug Hypersensitivity↗
PubMed2001

Topical corticosteroids in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial using fluticasone propionate aqueous nasal spray.

Chronic rhinosinusitis (CRS) is a recalcitrant inflammatory process which has a marked detrimental impact on quality of life. At the present there is no cure for this condition, measures are taken to stop progression, and provide symptomatic relief. Topical corticosteroids are commonly prescribed in the management of CRS, but few trials show effectiveness in clinical settings. We set up a randomized, double-blind, placebo-controlled trial to study the effectiveness of a topical corticosteroid agent--fluticasone propionate aqueous nasal spray (FPANS) in patients with CRS. We measured symptoms, diary card, and rigid endoscopy scores, acoustic rhinometry, middle meatal swabs, blood tests--CRP, ESR, WBC, and eosinophil count. Measurements were done at the start of the trial, at 8 weeks, and 16 weeks where possible. Twenty-two patients completed the trial, 9 received FPANS, and 13 had placebo. There was no difference between the 2 groups on all counts. When patients were considered as one group, there was an improvement in the diary card scores (p = 0.054), comparing baseline to 8 or 16 weeks. There was no evidence that the regular use of topical corticosteroid increased the risk of developing an infection. An important observation was that the topical corticosteroid did not precipitate acute sinusitis. There is compelling evidence that topical corticosteroids down-regulate cytokine expression, and it is likely that a larger, and longer multi-centre trial may prove their efficacy in CRS.

Administration, Intranasal↗
PubMed2000

Other anti-inflammatory uses of intranasal corticosteroids in upper respiratory inflammatory diseases.

Topical corticosteroids are an effective treatment for nasal polyposis and other conditions associated with rhinitis. There is evidence that asthma, otitis media with effusion, and acute sinusitis may all benefit from such therapy. Fluticasone propionate (FP) drops have been shown to reduce polyp size, and to improve nasal inspiratory flow, while avoiding the side-effects of, for example, topical betamethasone therapy. In small children with allergic rhinitis, fluticasone propionate aqueous nasal spray (FPANS) has been shown to be significantly more effective than ketotifen in relieving night and daytime symptoms, and nasal blockage. There is also preliminary evidence of efficacy in obstructive sleep apnoea and acute sinusitis. The advent of FP, with its low propensity to cause systemic side-effects, makes it possible to use topical corticosteroid therapy safely for prolonged periods to treat many inflammatory diseases of the upper respiratory tract.

Administration, Intranasal↗
PubMed2000

Patient and physician perspectives on the impact and management of perennial and seasonal allergic rhinitis.

Patient and physician perspectives on the impact and management of perennial (PAR) and seasonal allergic rhinitis (SAR) were studied. In all, 2139 subjects were questioned about their medical conditions, severity and frequency of symptoms and satisfaction with treatment. A group of general practitioners (GPs) were also invited to discuss their experiences in the management of rhinitis. In this UK survey, allergic rhinitis was more common than asthma, hypertension, skin rashes, eczema and diabetes. The prevalence of SAR and PAR was 15% and 2%, respectively. Sneezing and runny nose were the most common symptoms and GPs were the main contact for advice and treatment (54% of patients). Symptoms were well-controlled in 32% of patients. Allergic rhinitis affected work, home and social life in 29%, 34% and 30% of patients, respectively. The GPs considered PAR to be more difficult to treat than SAR, and GP and patient level of satisfaction in the treatment of PAR was low. This suggests that education of patients and physicians on the benefits of allergen avoidance, and the selective use of the highly effective therapies available on prescription could improve the level of satisfaction with therapy. Adherence to current guidelines on the management of rhinitis could lead to an effective, structured treatment plan for patients.

Adolescent↗
PubMed1999

Management of rhinosinusitis in children.

The authors provide definitions for the different forms of pediatric rhinosinusitis, with an enumeration of the main symptoms and signs. They also provide the indications for CT scan examination and microbiological investigations. In addition, they emphasize the importance of concomitant systemic disease, such as allergy and immunological disorders. The adequate medical management, which is mandatory before any surgery, is considered and discussed, and the indications for surgery are provided.

Child↗
PubMed1999

Cellular infiltration and cytokine mRNA expression in perennial allergic rhinitis.

BACKGROUND: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2-type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast-cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T-cell and eosinophil infiltration of the nasal mucosa, local Th2-type cytokine expression, and increased numbers of nasal epithelial mast cells. METHODS: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA-expressing cells. RESULTS: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase-positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)-5 were higher (P=0.01) and the numbers of cells expressing IL-2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL-4 or interferon-gamma between the groups. CONCLUSIONS: Perennial allergic rhinitis is characterized by mast-cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T-cell cytokine production in favour of enhanced IL-5 and reduced IL-2 expression.

Adult↗
PubMed1999

Inflammatory cell populations and cytokine mRNA expression in the nasal mucosa in aspirin-sensitive rhinitis.

Aspirin-sensitive rhinitis is characterized by severe perennial nasal congestion and discharge. The study questioned whether this disease, like immunoglobulin E-mediated rhinitis, might be associated with local recruitment and activation of T-lymphocytes, mast cells and eosinophils with parallel increases in "T-helper2-type" cytokines. Nasal biopsies from 10 patients with aspirin-sensitive rhinitis and 12 healthy controls subjects were studied. Nasal mucosal sections were examined by immunohistochemistry in order to determine cell phenotypes and by in situ hybridization to detect cells expressing messenger ribonucleic acid (mRNA) for cytokines. In aspirin-sensitive rhinitis there were increases in total (CD3+) (p=0.05) and activated (CD25+) T-cells (p=0.007), total (major basic protein (MBP) positive) (p=0.004) and activated (monoclonal antibody which recognizes the cleaved form of eosinophil cationic protein (EG2) positive) eosinophils (p=0.003), tryptase+ mast cells (p=0.04) and CD68+ macrophages (p=0.002). Neutrophils and cells expressing human leukocyte antigen-DR were no different. Marked increases were observed in the numbers of interleukin (IL)-5 mRNA+ cells (p=0.004) in aspirin-sensitive patients, whereas lower numbers of IL-4 mRNA+ cells were observed, with a trend for a difference from controls (p=0.07). No differences were observed for either IL-2 or interferon-gamma. In conclusion, in aspirin-sensitive rhinitis there is intense inflammation of the nasal mucosa characterised by T-lymphocytes, eosinophils and mast cells. The predominance of macrophages and disproportionate increase in interleukin-5 compared to interleukin-4 messenger ribonucleic acid expression suggests that factors other than "allergic" mechanisms may be important in this disease.

Adult↗
PubMed1999

Mizolastine is effective and well tolerated in long-term treatment of perennial allergic rhinoconjunctivitis. Riperex Study Group.

The aim of this study was to determine the long-term efficacy and safety of mizolastine, a new second-generation antihistamine with European approval, in the treatment of perennial allergic rhinoconjunctivitis. In this study, 141 patients were treated with once-daily mizolastine 10 mg or 15 mg in a 5-month open-label extension of a 1-month double-blind, placebo-controlled trial, which assessed once-daily mizolastine 10 mg. Mizolastine significantly reduced the nasal subscore (sneezing, rhinorrhoea, itch; end-baseline +/- SD, -2.5 +/- 6.3), nasal obstruction (-1.2 +/- 2.6) and rhinoscopy scores (-1.3 +/- 2.6), and improved ocular and total nasal scores after 6 months' treatment. Improvement was maintained for the duration of the study with no loss of drug efficacy. Adverse effects were mild with no specific effects associated with prolonged use. These results clearly demonstrate that mizolastine is effective and well tolerated in the long-term treatment of perennial allergic rhinoconjunctivitis. The significant clinical improvement in nasal blockade may reflect mizolastine's histamine/5-lipoxygenase dual inhibition.

Adult↗
PubMed1999

Clinical assessment of antihistamines in rhinitis.

The first line of treatment for allergic rhinitis must be identification and avoidance as far as possible of the relevant allergens. This is rarely completely successful and so pharmaceutical treatment is also needed. Antihistamines are effective in allergic rhinitis, which comprises approximately 80% of rhinitis found in children and 30% in adults. Antihistamines antagonize the effect of histamine at the H1 receptor and their major clinical effects are related to this. They are effective against rhinorrhoea, itch and sneezing but have little effect on nasal obstruction. Clinical trials show between 36% and 80% of patients experiencing good to excellent symptom relief (approximately twice that induced by placebo), in seasonal allergic rhinitis; between 55% and 86% of patients experience moderate to excellent symptom relief in perennial allergic rhinitis. Meta-analysis reveals that antihistamines are inferior to corticosteroids in allergic rhinitis therapy. Antihistamines are generally well tolerated, although serious cardiac dysrhythmias have occurred with terfenadine and astemizole. Their place in therapy is probably as sole agent in mild, intermittent rhinitis and in combination with topical corticosteroids in more severe disease not controlled by corticosteroids alone.

Arrhythmias, Cardiac↗
PubMed1998

Management of rhinosinusitis in children: consensus meeting, Brussels, Belgium, September 13, 1996.

OBJECTIVES: To (1) provide definitions for the different forms of pediatric rhinosinusitis, with an enumeration of the main symptoms and signs; (2) provide indications for microbiological, allergic, and immunologic assessment as well as for imaging studies; (3) suggest standard medical management with judicious use of antimicrobial agents; and (4) discuss indications for surgery. DATA SOURCES: Clinical studies and literature data relevant to the different topics of pediatric rhinosinusitis. CONCLUSIONS: Rhinosinusitis in children is a multifactorial disease in which the importance of several predisposing factors changes with increasing age. Continued study to obtain a better understanding of the disease and carefully controlled comparative evaluations of medical and surgical therapies are suggested.

Child, Preschool↗