Influence of cataract surgery on the diabetic eye: a prospective study

The aims of treating patients with asthma are to relieve symptoms, to prevent symptoms and exacerbations, and to prevent long-term deterioration in lung function. It is the role of medical practitioners to inform the patient what asthma is, and to develop a plan to achieve the aims for the individual, recognizing that asthma is frequently a chronic, lifelong disease. Most patients can be diagnosed, assessed for severity and causes, and treated in primary care practices, however, sometimes help from an asthma clinic of a specialist is required. The most important management decision is to determine whether the patient needs inhaled corticosteroids; subsequently, decisions about dose, duration and method of delivery of treatment can be tailored to the individual depending on the preferences and social conditions of the patient. The aim of this article is to present the latest strategies for the management of asthma and the simplest methods for their implementation. Important new strategies include careful assessment of the severity; immediate introduction of a plan that is tailored of the individual and aimed at the possible reversing of the disease; detailed instructions for management of exacerbations and the combined use of inhaled corticosteroids with a long-acting bronchodilator. It is becoming clear that these strategies obviate dependence on oral corticosteroids in newly diagnosed asthmatic patients. Furthermore, relatively low doses of inhaled corticosteroids can be used to maintain good control if used in conjunction with other therapies. The role of newly developed antagonists to leukotrienes is not yet known but it may well be useful in mild asthma and in special forms of the disease, such as those sensitive to aspirin. In the future, the most important strategy will be to prevent the disease.     

Pharmacologic therapy of asthma during pregnancy

Asthma is a common, potentially serious medical complication during pregnancy. Optimal clinical and pharmacologic management is necessary to mitigate maternal and fetal complications. Mild asthma may be managed in most cases with inhaled beta 2-mimetics. Anti-inflammatory therapy is recommended for the treatment of moderate and severe asthma. Based on limited human experience, beclomethasone is currently the recommended inhaled corticosteroid during pregnancy. However, other inhaled corticosteroids may have advantages compared to beclomethasone because of reduced systemic absorption, which may adversely affect intrauterine growth. Based upon theoretic considerations, theophylline is now considered a secondary therapy, but data demonstrating the superiority of inhaled corticosteroids versus theophylline during pregnancy are lacking.     

Treatment of brain cysticercosis

There are some concerns about the long-term effects of inhaled corticosteroids in children. Various steps can be taken to minimise the risks of treatment. The nurse has a crucial role in improving patients' and parents' understanding of asthma and its treatment.     

Acute asthma in adults

Acute asthma can be defined as first appearance of asthma or as a rapid deterioration of the asthmatic's habitual condition which can develop into a life-threatening condition. The severity of an attack and the effect of treatment has to be evaluated with the aid of peak flow measurements. The patient's self-treatment consists of increasing the dose of inhaled beta-2-receptor agonist and eventually doubling the dose of inhaled steroids. First-line treatment in hospital is high-dose inhaled nebulized beta-2-receptor agonist and oral corticosteroids. Ipratropium bromide and theophylline infusions may be added if necessary.     

High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group

Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 1. General principles

The safety of long-term inhaled corticosteroid therapy at commonly prescribed doses is an issue of growing concern to physicians and international regulatory bodies. This is so because long-term use of these drugs has become the mainstay of chronic asthma management and their introduction now is widely recommended in official treatment guidelines at the 'mild persistent' stage of asthma, where regular daily therapy is first begun. In addition to more frequent use of inhaled corticosteroids, there is a further trend to use higher doses of existing inhaler therapies and to use the newer and more potent compounds that have recently become available. At the same time as these developments have been taking place, there has not been a concurrent move to a more rigorous examination of the safety profile of these inhaled corticosteroid treatments - especially to assess their effects on the hypothalamic-pituitary-adrenal (HPA) axis. Most safety data with respect to HPA axis effects have been derived from testing methods that are limited in their ability to detect HPA system impairment and, more seriously, that can give the impression of functional integrity in the HPA axis when there may be moderate (or even greater) impairment. In this first part of a two-part review of the HPA axis effects of inhaled corticosteroids and of how these effects should be assessed, we examine the currently used and the currently available testing methodologies and also review the present state of knowledge concerning the structure and function of the HPA axis and the effects of its suppression. It is clear that there are state-of-the-art tests to assess in a discriminating manner the safety profile of inhaled corticosteroids. These tests have been insufficiently employed, including during the drug development process, yet they are readily available, relatively inexpensive and can detect adrenal suppression before the appearance of clinical effects. In part 2 of this review we examine what can be learned about the effects of inhaled corticosteroid therapy on the HPA axis from the limited amount of reliable published information from clinical and pharmacological studies describing their use and safety.     

Difficult asthma

Asthma is usually easy to manage, but approximately 5% of patients are not controlled even on high doses of inhaled corticosteroids. It is important to assess these patients carefully in order to identify whether there are any correctable factors that may contribute to their poor control. It is critical to make a diagnosis of asthma and to exclude other airway diseases, particularly chronic obstructive pulmonary disease (COPD), and vocal cord dysfunction ("pseudo-asthma"). Poor adherence to therapy, particularly inhaled corticosteroids, is a common reason for a poor response. There may be unidentified exacerbating factors, including unrecognized allergens, occupational sensitizers, dietary additives, drugs, gastro-oesophageal reflux, upper airway disease, or other systemic diseases, that need to be identified and avoided or treated. Psychological factors may be important in some patients, but it is difficult to know whether these are causal or secondary to troublesome disease. Some patients have instability of their asthma, with resistant nocturnal asthma, premenstrual exacerbations or chaotic and unpredictable instability (brittle asthma). A few patients are completely resistant to corticosteroids, but more patients are relatively resistant and require relatively high doses of corticosteroids to control their symptoms (steroid-dependent). Some patients develop progressive loss of lung function, as in patients with COPD. Management of patients with difficult asthma should be supervised by a respiratory specialist and should involve careful assessment to confirm a diagnosis of asthma, identification and treatment of exacerbating factors, particularly allergens, and recording of peak expiratory flow patterns. A period of hospital admission may be the best way to assess and manage these patients. Treatment involves optimizing corticosteroids therapy, assessing additional controllers such as long-acting inhaled or subcutaneous beta2-agonists or subcutaneous, theophylline and antileukotrienes. In some patients, the use of immunosuppressive treatments may reduce steroid requirements, although these treatments are rarely effective and have side-effects. In the future, the nonsteroid anti-inflammatory treatments now in development may be useful in these patients.     

Comparison of inhaled corticosteroids

OBJECTIVE: To review the comparative studies evaluating both efficacy and safety of inhaled corticosteroids in the management of asthma. Specifically, comparative clinical trials are evaluated that allow clinicians to determine relative potencies of the various inhaled corticosteroids. METHODS: A critical review was performed of the published clinical trials, either as articles or abstracts, comparing the clinical efficacy or systemic activity of inhaled corticosteroids. No a priori criteria were applied, as this was not a meta-analysis. FINDINGS: In vitro measures of antiinflammatory activity of corticosteroids consistently demonstrate potency differences among the various corticosteroids. Traditionally, these in vitro measures have been used to develop new corticosteroids with greater topical activity. While no accepted direct measure of antiasthmatic antiinflammatory activity exists, clinical trials using surrogate measures (e.g., forced expiratory volume in 1 second, peak expiratory flow, bronchial hyperresponsiveness, symptom control) indicate that in vitro measures provide a relatively accurate assessment of antiasthmatic potency. The relative antiinflammatory potency of the inhaled corticosteroids is in the following rank order. flunisolide = triamcinolone acetonide < beclomethasone dipropionate = budesonide < fluticasone. Studies of systemic activity appear to confirm this relative order of potency. Currently, no evidence exists for greater efficacy for any of the inhaled corticosteroids when administered in their relative equipotent dosages. The preponderance of current data suggests that when administered in equipotent antiinflammatory doses as a metered-dose inhaler plus spacer or as their respective dry-powder inhaler, the existing inhaled corticosteroids have similar risks of producing systemic effects. CONCLUSIONS: Delivery systems can significantly affect both topical and systemic activity of inhaled corticosteroids. More direct comparative studies between agents are required to firmly establish comparative topical to systemic activity ratios. The preponderance of evidence suggests that the agents are not equipotent on a microgram basis.     

Accuracy of asthma treatment in schoolchildren in NSW, Australia

Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.     

Nedocromil sodium (Tilade)

Nedocromil sodium is a well-tolerated antiasthmatic agent for initial therapy in patients with mild or moderate asthma not well controlled with inhaled beta-2 agonists and/or where methylxanthines are indicated. Like cromolyn sodium, nedocromil sodium offers a potential alternative to inhaled corticosteroids as maintenance therapy in patients with mild or moderate asthma not adequately controlled by bronchodilators. Furthermore, cromolyn sodium and nedocromil sodium may also reduce the usage of corticosteroids and provide some additional symptom control in patients whose asthma is not suitably controlled by optimal doses of inhaled corticosteroids. Both nedocromil sodium and cromolyn sodium are more efficacious than placebo for controlling of asthma, however, few studies have compared the effectiveness of cromolyn versus nedocromil at this time. Further experience and comparison studies of nedocromil sodium with cromolyn sodium in children are required before the role of nedocromil sodium as maintenance treatment in young asthmatic patients can be defined.     

One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide

Inhaled corticosteroids have become a mainstay in the management of chronic asthma. Their use had been considered safe, although some degree of adrenal suppression has been demonstrated after 2 and 4 weeks of treatment with either 400 microg x day(-1) of beclomethasone dipropionate or budesonide. To weigh the benefits and risks of long-term treatment, 12 children with moderately severe asthma were assessed in a follow-up study on budesonide 200 microg b.i.d. After 1 yr, the nocturnal cortisol production was significantly reduced by 19%, but no greater compared to 2 and 4 weeks of treatment. Growth and growth hormone levels were normal. Lung function tests were significantly better, not only versus baseline values but also versus 2 and 4 weeks of treatment. We conclude that systemic effects of inhaled corticosteroids in conventionally low doses do not accumulate with length of treatment, whilst lung function parameters will continue to improve. Therefore, inhaled corticosteroids once started in asthmatic children not controlled on other medications should be continued, but their use should be carefully considered and the minimal dose required to control the asthma employed.     

Asthma treatment during pregnancy. What can be safely taken?

'Safe' pharmacological therapy for gestational asthma is defined as therapy during which the apparent risks of the drug appear to be lower than the maternal and potential fetal risks of uncontrolled asthma that could result if the drug were not used. Major malformations occur in 2 to 4% of all newborns, 1% of which can be attributed to medication in general. Information regarding the effects of drugs administered during pregnancy may come from animal studies, human case reports, and prospective cohort studies. Based on a review of the available information, it is recommended that mild asthma during pregnancy be managed with inhaled beta 2-agonists, as required; step therapy for moderate asthma would include inhaled sodium cromoglycate (cromolyn sodium), inhaled beclomethasone dipropionate and oral theophylline. Severe gestational asthma should be treated with oral corticosteroids at the lowest effective dosage. The pharmacological management of acute asthma during pregnancy should include nebulised beta 2-agonists and ipratropium bromide, and intravenous methylprednisolone. Intravenous aminophylline would not generally be recommended, unless the patient requires hospitalisation. Optimal medical practice medico-legal considerations demand that the patient's informed consent be obtained for that recommended gestational management programme.     

Pharmacological management of asthma

Asthma management is changing, and there are many potential new drugs undergoing early and late phase trials. Nonetheless, it is unlikely that any dramatic alterations in therapy will occur within the next 3 years. The asthma treatment paradigm has altered over the past 10 or so years, with the emphasis on symptom relief from short acting beta agonists giving way to preventive treatment of underlying airway inflammation with inhaled corticosteroids. More recently, long acting beta agonists have been demonstrated to reduce the need for increasing doses of inhaled steroids in patients with poorly controlled asthma. This article reviews these trends.     

Fluid-bed microencapsulation of ascorbic acid

Epidemiological studies suggest the prevalence of asthma is increasing, though some remain sceptical as to the magnitude or indeed the presence of an increase. However, despite improved diagnosis and the availability of the potent drugs now available there remains considerable respiratory morbidity associated with asthma. It is clear from a number of studies that failure to deliver drugs to the lungs when using inhaler devices is a factor contributing to this high level of morbidity. Failure of drug delivery may result from the prescribing of inappropriate devices, failure to use devices appropriately or failure to comply with a treatment regimen. For most of the currently available forms of asthma therapy there are significant advantages to be gained from administering them in aerosol form. The benefits to be derived from administering these drugs as an aerosol include a rapid onset of action for drugs such as beta-agonists and a low incidence of systemic effects from drugs such as beta-agonists and corticosteroids. Over the past 25 years our understanding of the nature of asthma has changed. Though this has been reflected in the emphasis on inhaled corticosteroid therapy in recent guidelines, it has not been reflected in the range of inhaler devices available. Manufacturers continue to place drugs such as corticosteroids in the same devices as short acting beta-agonists even though the requirements for these different drug classes are very different. It is likely that this contributes to suboptimal therapeutic responses with inhaled corticosteroids. However, the variability associated with current delivery systems is relatively small compared with the variability introduced by poor compliance. There is no work currently available to indicate how the use of cheap disposable devises which do not incorporate any form of positive feedback influence compliance with inhaled steroids. Optimising aerosolised drug delivery in childhood involves consideration of the class of drugs, the particular drug within a class but more importantly, the age and abilities of the child. Devices must be selected to suit a particular child's needs and abilities. Devices utilising tidal breathing are generally used such as spacing chambers or, less commonly these days, nebulisers. A screaming or struggling child, or failure to use a closely fitting mask, reduces drug delivery to the lungs enormously. Failure to respond to inhaled therapy in early childhood may be attributable to failure of drug delivery. Drug delivery in early childhood using current devices remains more an art than a science.     

Are anti-oxidant and anti-inflammatory treatments effective in different subgroups of COPD? A hypothesis

The treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids or anti-oxidants is still under debate and the identification of sub-groups of COPD patients who may benefit from either anti-inflammatory or anti-oxidant treatment is needed. We re-analysed data from an earlier study of inhaled beclomethasone therapy in COPD (n = 28) and asthma (n = 28) patients in order to determine patient characteristics that predict a favourable inhaled steroid treatment effect. A higher bronchodilatory response, a faster decline of FEV1 prior to the treatment period and a lower Tiffeneau index were significantly related to more beneficial treatment effects. Increased smoking tended to be related to less steroid treatment benefits, though it was not statistically significant. In this paper these findings are presented in light of the available literature on anti-inflammatory and anti-oxidant COPD treatment. On this basis the hypothesis is presented that anti-oxidant treatment might be relatively more effective among those COPD patients who respond less well to inhaled steroids (low reversibility and heavy smoking).     

Asthma in the elderly: underperceived, underdiagnosed and undertreated; a community survey

Bronchial asthma is now increasingly recognized in the elderly and is associated with significant morbidity and mortality. The aims of this study were two-fold: first, to assess the prevalence and, second, to evaluate diagnostic awareness, therapeutic management and patient perception of bronchial asthma among elderly patients in the community. From the age-sex register of an urban general practice in NE England, 2004 patients aged > 65 years were eligible for inclusion. Response to an initial screening questionnaire on respiratory symptomatology was 68% (n = 1362). Of these, 869 patients had respiratory symptoms: 390 voluntarily agreed to be evaluated further including assessment of airway physiology. In this group 369/390 had obstructive spirometry and, of these, 95 patients fulfilled clinical and physiological criteria of bronchial asthma. Prevalence of asthma within this age cohort was minimally and rather crudely assigned at 4.5% (95/2004). Among the 95 patients so-defined patients with asthma [age 70 +/- 8 years (mean +/- SD), FEV1 = 0.96 +/- 0.41, 33 male, 75 life-long non-smokers], subjective awareness, perception and attribution of pulmonary symptoms were poor. Further, despite tangible evidence of reversible and significant airflow limitation, only 21 were receiving inhaled glucocorticoid therapy (median daily dose 400 micrograms). Asthma in the elderly remains poorly perceived, poorly recognized and suboptimally treated. These findings are particularly apposite in the light of current epidemiological trends in asthma mortality and morbidity in elderly age cohorts.     

Peptidoleukotriene receptor antagonists in asthma therapy]

Peptidoleukotrienes reproduce some of the functional and histological features of clinical asthma, such as potent bronchoconstriction, airway microvascular leakage, mucus hypersecretion, eosinophilic airway infiltration, in addition to inducing bronchial hypersensitivity. An important role for peptidoleukotrienes has been demonstrated in experimental challenge studies in asthmatic patients and in acute asthma attacks. Antagonists of peptidoleukotrienes can inhibit bronchoconstriction in response to inhaled allergen, exercise or inhaled cold air, and oral or inhaled aspirin. These compounds demonstrate beneficial effects in clinical studies with improvement in symptoms and lung function. Peptidoleukotriene antagonists may provide a new therapeutic approach for the treatment of asthma.     

Induction of germinal vesicle breakdown in a cell-free preparation from starfish oocytes

THE PERSISTENCE OF AIRWAY INFLAMMATION is believed to cause the mechanical changes and symptoms of asthma. After decades of research, a new class of medication has emerged that focuses on leukotrienes, mediators of inflammation. These substances are potent inducers of bronchoconstriction, increased vascular permeability and mucus production, and they potentiate the influx of inflammatory cells in the airways of patients with asthma. In this article the author reviews the development, mechanism of action, and clinical and toxic effects of the leukotriene synthesis inhibitors and receptor antagonists that are entering the North American market. These agents can decrease airway response to antigen, airway hyperresponsiveness and exercise-induced asthma. They are also effective inhibitors of ASA-induced symptoms. Although few published studies are available, the antileukotrienes seem almost as effective in the management of chronic asthma as low-dose inhaled corticosteroids, and their use permits a decrease in the frequency of use or dose of corticosteroids. Further evaluation and clinical experience will determine the position of targeted inhibition of the leukotriene pathway in the treatment of asthma.