These guidelines have been replaced by British Guideline on the Management of Asthma. A national clinical guideline. Superseded By 2012 Revision Of 2008 Guideline: British Guideline on the Management of Asthma. Thorax 2008 May; 63(Suppl 4): 1–121.

/pdf/british-guideline-on-the-management-of-asthma-a-national-3q1wreyszl.pdf

British guideline on the management of asthma: A national clinical guideline

From the Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor (M.P.-G.); and the Center for Allergy and Inflammation, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle (W.R.H.). Address reprint requests to Dr. Peters-Golden at the Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, 6301 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-5642, or at petersm@umich.edu.

Mechanisms of disease: Leukotrienes

Transdermal skin delivery: predictions for humans from in vivo, ex vivo and animal models.

It is preferred that topically administered drugs act either dermally or transdermally. For that reason they have to penetrate into the deeper skin layers or permeate the skin. The outermost layer of the human skin, the stratum corneum, is responsible for its barrier function. Most topically administered drugs do not have the ability to penetrate the stratum corneum. In these cases modulations of the skin penetration profiles of these drugs and skin barrier manipulations are necessary. A skin penetration enhancement can be achieved either chemically, physically or by use of appropriate formulations. Numerous chemical compounds have been evaluated for penetration-enhancing activity, and different modes of action have been identified for skin penetration enhancement. In addition to chemical methods, skin penetration of drugs can be improved by physical options such as iontophoresis and phonophoresis, as well as by combinations of both chemical and physical methods or by combinations of several physical methods. There are cases where skin penetration of the drug used in the formulation is not the aim of the topical administration. Penetration reducers can be used to prevent chemicals entering the systemic circulation. This article concentrates on the progress made mainly over the last decade by use of chemical penetration enhancers. The different action modes of these substances are explained, including the basic principles of the physical skin penetration enhancement techniques and examples for their application.

Overcoming the stratum corneum: the modulation of skin penetration. A review.

Background
Anti-leukotrienes (5-lipoxygenase inhibitors and leukotriene receptors antagonists) serve as alternative monotherapy to inhaled corticosteroids (ICS) in the management of recurrent and/or chronic asthma in adults and children.

Objectives
To determine the safety and efficacy of anti-leukotrienes compared to inhaled corticosteroids as monotherapy in adults and children with asthma and to provide better insight into the influence of patient and treatment characteristics on the magnitude of effects.

Search methods
We searched MEDLINE (1966 to Dec 2010), EMBASE (1980 to Dec 2010), CINAHL (1982 to Dec 2010), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (Dec 2010), abstract books, and reference lists of review articles and trials. We contacted colleagues and the international headquarters of anti-leukotrienes producers.

Selection criteria
We included randomised trials that compared anti-leukotrienes with inhaled corticosteroids as monotherapy for a minimum period of four weeks in patients with asthma aged two years and older.

Data collection and analysis
Two review authors independently assessed the methodological quality of trials and extracted data. The primary outcome was the number of patients with at least one exacerbation requiring systemic corticosteroids. Secondary outcomes included patients with at least one exacerbation requiring hospital admission, lung function tests, indices of chronic asthma control, adverse effects, withdrawal rates and biological inflammatory markers.

Main results
Sixty-five trials met the inclusion criteria for this review. Fifty-six trials (19 paediatric trials) contributed data (representing total of 10,005 adults and 3,333 children); 21 trials were of high methodological quality; 44 were published in full-text. All trials pertained to patients with mild or moderate persistent asthma. Trial durations varied from four to 52 weeks. The median dose of inhaled corticosteroids was quite homogeneous at 200 µg/day of microfine hydrofluoroalkane-propelled beclomethasone or equivalent (HFA-BDP eq). Patients treated with anti-leukotrienes were more likely to suffer an exacerbation requiring systemic corticosteroids (N = 6077 participants; risk ratio (RR) 1.51, 95% confidence interval (CI) 1.17, 1.96). For every 28 (95% CI 15 to 82) patients treated with anti-leukotrienes instead of inhaled corticosteroids, there was one additional patient with an exacerbation requiring rescue systemic corticosteroids. The magnitude of effect was significantly greater in patients with moderate compared with those with mild airway obstruction (RR 2.03, 95% CI 1.41, 2.91 versus RR 1.25, 95% CI 0.97, 1.61), but was not significantly influenced by age group (children representing 23% of the weight versus adults), anti-leukotriene used, duration of intervention, methodological quality, and funding source. Significant group differences favouring inhaled corticosteroids were noted in most secondary outcomes including patients with at least one exacerbation requiring hospital admission (N = 2715 participants; RR 3.33; 95% CI 1.02 to 10.94), the change from baseline FEV1 (N = 7128 participants; mean group difference (MD) 110 mL, 95% CI 140 to 80) as well as other lung function parameters, asthma symptoms, nocturnal awakenings, rescue medication use, symptom-free days, the quality of life, parents' and physicians' satisfaction. Anti-leukotriene therapy was associated with increased risk of withdrawals due to poor asthma control (N = 7669 participants; RR 2.56; 95% CI 2.01 to 3.27). For every thirty one (95% CI 22 to 47) patients treated with anti-leukotrienes instead of inhaled corticosteroids, there was one additional withdrawal due to poor control. Risk of side effects was not significantly different between both groups.

Authors' conclusions
As monotherapy, inhaled corticosteroids display superior efficacy to anti-leukotrienes in adults and children with persistent asthma; the superiority is particularly marked in patients with moderate airway obstruction. On the basis of efficacy, the results support the current guidelines' recommendation that inhaled corticosteroids remain the preferred monotherapy.

Anti‐leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children

Prediction of skin penetration using artificial neural network (ANN) modeling.

Background Increased amounts of cysteinyl leukotrienes have been demonstrated in urine samples from asthmatic patients, particularly during exacerbations of asthma. Although the use of leukotriene receptor antagonists has been recommended in the treatment of chronic asthma, no guidelines are available regarding their use in the treatment of acute asthma. Objective To investigate the safety and effectiveness of a 4-mg tablet of oral montelukast in addition to short-acting β 2 -agonist bronchodilator as the initial treatment in mild to moderate asthma exacerbations in children between 2 and 5 years old. Methods Fifty-one patients who were experiencing mild to moderate asthma exacerbation were included in a randomized, double-blind, placebo-controlled, parallel-group study. Each patient received either a 4-mg tablet of montelukast or placebo in addition to inhaled salbutamol and were followed up for 4 hours. The pulmonary index score, respiratory rate, and pulse were determined at baseline and throughout 4 hours after administration. Results Compared with placebo, the pulmonary index scores and respiratory rates were significantly lower in the montelukast group starting at 90 minutes ( P = .01). This difference persisted at 120, 180, and 240 minutes of the study ( P = .008, P = .02, and P = .048, respectively). At the end of the first hour of treatment, oral steroid need was 20.8% and 38.5% in patients randomized to the montelukast and placebo groups, respectively ( P = .22). Hospitalization rates were not different between the 2 treatment groups. Conclusion A single 4-mg tablet of montelukast had the potential to provide additive clinical benefit in mild to moderate acute asthma in preschool-aged children when administered concomitantly with short-acting β 2 -agonist bronchodilators as the initial treatment.

Oral montelukast treatment of preschool-aged children with acute asthma

Evaluation of neuroprotective and anti-fatigue effects of sildenafil.

Insulin is a polypeptide drug and it is degraded by gastrointestinal enzymes, therefore, it cannot be used via oral route readily. There are only parenteral forms available in the market. The aim of this study was to investigate the effect of rectal and vaginal administration of various insulin gel formulations on the blood glucose level as alternative routes in rabbits. Chitosan gel (CH-gel) was used as a carrier; the penetration enhancing effect of sodium taurocholate and dimethyl-beta-cyclodextrin (DM-betaCD) was also investigated. CH-gel provided longer insulin release. The maximum decreasing effect on blood glucose level was observed with insulin-CH-gel containing 5% DM-betaCD. In conclusion, our results indicate that insulin may penetrate well through the rectal and vaginal mucosae from the CH-gel. DM-betaCD was also found to be a useful agent to enhance the penetration of insulin through rectal and vaginal membranes.

Rectal and vaginal administration of insulin–chitosan formulations: An experimental study in rabbits

The octanol/water partition coefficient (log K) is one of the most commonly used parameters in structure-activity relationships in many areas such as drug design (including pesticides), pharmacokinetics, anesthesiology, environmental sciences, toxicology, bioaccumulation and predicting skin permeability as a predictive parameter log K is generally determined using shake flask method, but the possibility of calculating log K using pH-metric titrations and half neutralization points is demonstrated in this study The potentiometric pH titration technique has been developed as an automatic technique for log K determination but it can be achieved by manual titrations This technique uses the pKa of the substance The pKa of the substance shifts pK'a when the titration is repeated in the presence of octanol log K value of the substance can be determined using pKa, pK'a values and relevant equation The aim of the study was to determine the log K values of a series of compounds using pH-metric titrations and to compare pH-metric log K determination results with the other methods The log K values of famotidine, naproxen, nizatidine, ranitidine and salicylic acid were determined using both shake flask method and potentiometric titrations Their log K values were also calculated theoretically using computer program and all results were compared The pH-metric log K values were found to be close to the shake flask method results This method was found to be useful for the determination of log K values as it provides a high degree of accuracy even in the presence of titratable impurities in the solution

Tuncer Degim

Papers

Prediction of skin penetration using artificial neural network (ANN) modeling.

Oral montelukast treatment of preschool-aged children with acute asthma

Evaluation of neuroprotective and anti-fatigue effects of sildenafil.

Rectal and vaginal administration of insulin–chitosan formulations: An experimental study in rabbits

pH-Metric log K calculations of famotidine, naproxen, nizatidine, ranitidine and salicylic acid.