Recent advances in corticosteroids for the treatment of asthma

The currently available therapy for asthma is highly effective and is able to control the disease in the majority of patients. There are two types of treatments for asthma: rapid relief of symptoms, used as needed and long-term control, used on a regular basis. Rapid relief is provided by short-acting beta2-agonists and anticholinergics. The control of asthma is achieved by treatment with inhaled corticosteroids (ICS), theophylline, long acting beta2-agonists and antileukotrienes. Beta2-agonists and corticosteroids dominate asthma therapy, with over 65% of the market share. Corticosteroids are the most effective drugs available to clinicians for the control of inflammation in patients with asthma. ICS have revolutionized the treatment of asthma and are now the first-line treatment for chronic asthma in all ages.     

Improving drug therapy for patients with asthma-part 2: Use of antiasthma medications

OBJECTIVES: To describe the use of antiasthma drugs among the study patients and to evaluate whether therapeutic outcomes monitoring (TOM) is associated with improved quality of drug therapy. DESIGN: Prospective, controlled, multicenter study. Consumption of antiasthma medications was measured as the number of defined daily doses (DDDs) purchased. Data were collected from the pharmacies' computer systems for a period beginning 6 months before the start of the study (period 1) and during its first and second half-years (periods 2 and 3). Treatment changes for TOM patients were classified on the basis of drug regimens at periods 1 and 3. SETTING: Community pharmacies in Denmark (16 intervention, 15 control). PATIENTS: Five hundred patients with asthma aged 16 to 60 years who were being treated in primary health care; this study used data from 350 patients from this sample. INTERVENTION: TOM. MAIN OUTCOME MEASURES: Changes in the use of individual drugs and changes in therapeutic patterns--distribution of purchased drugs; proportion of corticosteroid users; frequency of drug regimens used; treatment changes for TOM patients. RESULTS: TOM patients' consumption of beta2-agonists decreased by 12% overall from period 1 through period 3, while control patients' consumption of these medications decreased by only 1%. TOM patients' use of inhaled corticosteroids increased by more than 50% compared with 9% among controls. In both groups, about one-half of all purchased DDDs were for inhaled beta2-agonists. The proportion of inhaled corticosteroids increased from 27% to 42% of total DDDs for the TOM group and remained constant for controls. Of patients using beta2-agonists, 68% also used inhaled steroids initially in both the TOM and control groups. The proportion of inhaled steroid users in the TOM group increased to 84%, and to 70% among controls. The most common regimen was inhaled short-acting beta2-agonists and corticosteroids in combination, and the second most common regimen was monotherapy with short-acting beta2-agonists. With time, the regimens changed more toward consensus guidelines among TOM patients. Changes in drug therapy totaled 451, averaging 2.4 changes per TOM patient. The largest number of changes (49%) involved inhaled corticosteroids. CONCLUSION: Changes in medication use among TOM patients were toward improved asthma treatment. Our results show that community pharmacists, physicians, and patients, working together, can improve prescribing, solve drug therapy problems, and improve outcomes for patients with moderate-to-severe asthma.     

Cost-effectiveness of including salmeterol in asthma therapy in a primary care setting in Japan

To discuss and estimate the clinical and economic benefits obtained during combination therapy with inhaled corticosteroids (ICS) plus salmeterol (SLM) for Japanese patients with asthma on the basis of the Global Initiative for Asthma (GINA) Guidelines. Fifty-four cases aged>16 years with either moderate persistent asthma (step 3) or severe persistent asthma (step 4) were assessed in a retrospective survey. Participants must have been a patient at the author's clinic continuously from June 2001 and been users of SLM for more than one year. Signed informed consent was obtained. Both clinical and economic components of SLM use in asthma therapy over the past two years were evaluated. Cost analyses revealed that SLM use significantly reduced medical costs of leukotriene receptor antagonist and short-acting inhaled beta(2)-agonists. Moreover, clinical outcomes (e.g. symptom-free day) were significantly improved after initiation of SLM. Sensitivity analyses confirmed that use of SLM is cost-effective. Combination therapy with inhaled corticosteroids and SLM on the basis of GINA guidelines appears to be efficacious and cost effective for the treatment of moderate or severe persistent asthma in Japanese patients.     

Cost considerations of therapeutic options for children with asthma

Asthma is a prevalent health condition in children, with economic implications for the individual and their family, as well as for societies with nationalized healthcare. Pharmaceutical cost is the main driver of healthcare expenditure in asthma. Existent explicit guidelines are meant to guide asthma management across all age groups, but they are failing. Pharmacologic management of asthma consists of a stepwise treatment approach to achieve symptom control. Various studies suggest a significant number of medical practitioners are prescribing inhaled corticosteroids (ICS) and ICS/long-acting beta agonist (LABA) combination inhalers inappropriately, including prescribing high doses of ICS without specialist consultation. ICS/LABA combination inhalers should only be used in persistent asthmatics, which account for approximately 5% of all children with asthma. Despite this, there is an increase in prescribing rates of ICS/LABA combination inhalers in the context of a decrease in the prevalence of asthma. Furthermore, there is inappropriate prescribing of ICS/LABA combination inhalers in children under 5 years of age, and initiation of relatively more expensive ICS/LABA combination inhalers in patients who have not previously been prescribed ICS. There is evidence to suggest that cost is a significant barrier to asthma management, especially for the more expensive ICS/LABA combination inhalers. Hence, prescribing cost-effective asthma medications appropriately is one of the most important strategies in reducing the morbidity and mortality associated with asthma. It is incumbent on every medical practitioner to not prescribe expensive medications if not indicated, both for the sake of the patient and for society.     

Second-line controller therapy for persistent asthma uncontrolled on inhaled corticosteroids: the step 3 dilemma

The asthma syndrome is characterised by airway inflammation with associated bronchial hyperresponsiveness (BHR) and reversible airflow obstruction. Therapy has benefited from an enhanced understanding of the pathophysiology of asthma and the resulting guidelines that emphasise the pivotal role of anti-inflammatory inhaled corticosteroids (ICS) as first-line therapy. Most patients with mild-to-moderate asthma can be adequately controlled on low-to-medium dosages of ICS alone. For patients with moderate-to-severe asthma who are not adequately controlled by ICS, it is unclear which medication should be added on. The two principal drugs under consideration are long-acting beta(2)-agonists (LABAs) and leukotriene antagonists (LTAs). Although both LABAs and LTAs are both effective at improving lung function, reducing symptoms and decreasing exacerbations, important differences exist that may determine the selection of one over the other in particular circumstances. LABAs and LTAs are equally effective at reducing exacerbations and improving symptoms and quality of life when used as add-on therapy. LABAs tend to be more effective bronchodilators than LTAs. Although LABAs stabilise the airway smooth muscle, they do not affect the underlying inflammatory process. Their long-term use also leads to subsensitivity of response to both LABAs and short-acting beta(2)-agonists (SABAs). The subsensitivity of response to SABAs is more pronounced in the presence of acute bronchoconstriction, which could be relevant during an acute attack. When combined with an ICS, LTAs provide additive non-steroidal anti-inflammatory properties and alleviate associated BHR, but do not induce subsensitivity of response. Not only is the efficacy of LTAs maintained over time, but also they do not affect the response to SABAs as reliever therapy. LTAs also have beneficial effects in patients who have concomitant allergic rhinitis, thus treating the unified airway. The choice between LABA and LTA as add-on therapy will therefore be determined by the needs of the individual patient in terms of providing anti-inflammatory versus bronchodilatory control. For patients with poor lung function where bronchodilatation is required, then an LABA would seem to be a logical choice. For the patient whose lung function is less impaired, with evidence of ongoing BHR where bronchoprotection is needed (e.g. exercise, allergen, cold air), or when there is concomitant allergic rhinitis, then an LTA would be more suitable.     

Long-acting beta2-agonists or leukotriene receptor antagonists as add-on therapy to inhaled corticosteroids for the treatment of persistent asthma

It is well accepted that the combination of inhaled corticosteroids (ICSs) and long-acting beta2-agonists (LABAs) is effective in achieving asthma control, as it treats both components of asthma pathophysiology, namely inflammation and smooth muscle dysfunction of the airways. Leukotriene receptor antagonists (LTRAs) can also be used as add-ons to ICS therapy in patients whose asthma is not controlled by ICSs alone. The purpose of this review is to compare the effectiveness of ICSs plus LABAs with that of ICSs plus LTRAs for the treatment of persistent asthma that is not controlled by ICSs alone. Several studies have shown that, in comparison with an ICS plus an LTRA, the addition of an LABA to ICS therapy provides greater improvements in pulmonary function and overall control of asthma as measured by use of rescue medication and the number of exacerbations of the asthma, symptom-free days and symptom-free nights. The greater improvements in pulmonary function observed with an ICS plus the LABA, salmeterol, occurred within the first week of treatment (at first treatment assessment), and remained significantly greater than those achieved with an ICS plus an LTRA over the duration of the treatment. Moreover, the salmeterol-fluticasone propionate combination (SFC) produces consistently greater improvements in pulmonary lung function and control of asthma than does the addition of an LTRA to fluticasone propionate. In addition, SFC is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with asthma that is uncontrolled by ICSs alone. Important cost savings can be made with SFC in clinical practice compared with other combinations of ICSs plus salmeterol or ICSs plus LTRAs.     

Impact of montelukast on symptoms in mild-to-moderate persistent asthma and exercise-induced asthma: results of the ASTHMA survey. Adding Singulair Treatment to Handle symptoms in Mild to moderate Asthmatics

A nation-wide survey was undertaken in Belgium among general practitioners (GPs) to evaluate the impact of the leukotriene receptor antagonist (LTRA) montelukast on the control of asthma symptoms, after at least 4 weeks of treatment. Patients from 6 years of age were eligible if they were suffering from mild-to-moderate persistent asthma which was still symptomatic despite inhaled corticosteroids (ICS) treatment, or from exercise-induced asthma. Patient general satisfaction was evaluated by recording the willingness to continue the treatment. A total of 1360 GPs took part in the study and more than 11000 patients were included in the survey. Of the included patients, 85% were receiving inhaled corticosteroids, 60% of whom were also on long-acting beta2-agonists (LABA). However, despite the use of daily controller medication, 92% of the patients still reported limitation of activities, 49% difficulties with sleep and 45% early morning awakening due to asthma. Moreover, 78% of the patients used rescue medication more than twice a week. At the end of the survey, 90% of the patients expressed their willingness to continue montelukast therapy. Of the patients having symptoms at the start of the study, 87% reported amelioration in sleep while on montelukast therapy, 80% less frequent early morning awakening, 85% better ability to perform daily activities and 77% decreased need for rescue medication.     

Advances in asthma and COPD treatment: combination therapy with inhaled corticosteroids and long-acting beta 2-agonists

Asthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone, thereby addressing two processes fundamental to asthma: bronchoconstriction and inflammation. Superior control--including a reduction in severe exacerbations--of asthma and COPD by ICS/LABA combination therapy has been demonstrated. Results from clinical studies suggest additive and potentially synergistic effects when the two agents are used in combination. No new safety-related issues have been identified with ICS/LABA compared with the monocomponents. The exact mechanisms for the enhanced efficacy of ICS/LABA combinations are under investigation but likely include drug interactions at the receptor level and interwoven signalling pathways, which may result in improved function of 2- adrenoceptors and steroid receptors. Data from preclinical studies provide evidence of additive, compensatory, complementary and synergistic effects of ICS and LABA in the control of inflammation and airway and lung remodelling. These effects may contribute to the improved efficacy seen when treating asthma and COPD with ICS/LABA combinations in clinical studies. Two ICS/LABA combination products are available: budesonide/formoterol (Symbicort) and salmeterol/fluticasone propionate (SeretideTM). An ICS/LABA combination in a single inhaler represent safe, effective and convenient treatment options for the management of patients with asthma and COPD. Clinical results also suggest that adjustable dosing with budesonide/formoterol provides better asthma control than fixed dosing. Further elucidation of the underlying mechanisms responsible for this superior disease control is needed.     

Combination therapy in asthma--fixed or variable dosing in different patients?

The introduction of combination products, for the coadministration of an inhaled corticosteroid (ICS) with a long-acting beta2-agonist in a single inhaler, has greatly simplified asthma therapy. The two combination inhalers currently available, Symbicort (budesonide/formoterol in a single inhaler) and Seretide (salmeterol/fluticasone), comply with Step 3 of international guidelines that recommend the addition of a long-acting beta2-agonist to ICS in patients who are inadequately controlled on ICS alone. Importantly, combination inhalers ensure that patients cannot neglect their ICS maintenance therapy in favour of the long-acting beta2-agonist--which may improve adherence and overall asthma control. In vitro experiments suggest that ICS and long-acting beta2-agonists may interact beneficially when they are administered via one inhaler. The efficacy and tolerability of budesonide/formoterol and salmeterol/fluticasone have been demonstrated. There are currently two approaches for treating asthma using combination therapy--fixed and adjustable dosing. Fixed dosing with budesonide/formoterol or salmeterol/fluticasone provides effective asthma control in line with guideline goals. However, given the inherent variability of asthma, there is increasing evidence that adjusting the dose of ICS according to fluctuations in symptoms is beneficial. Findings from a series of studies comparing fixed and adjustable symptom-guided dosing regimens demonstrate that adjustable dosing may improve asthma control at an overall lower steroid dose. Ultimately, if adjustable dosing proves to be an effective treatment option, it may be possible to use budesonide/formoterol for both maintenance therapy and symptom relief, thereby overcoming the need for a separate reliever inhaler. This is because formoterol has a more rapid onset and greater dose-related effects than salmeterol in salmeterol/fluticasone. Given that all patients are different, with different disease severities and treatment preferences, both fixed and adjustable dosing strategies are likely to be important in the long-term management of asthma. It is possible that different treatment options will be used for different patients, depending on their disease severity, personality and ability to adhere to therapy.     

Comparison of the Bronchodilator Effect of Inhaled Short- and Long-Acting beta(2)-Agonists in Children with Bronchial Asthma: A Randomised Trial

OBJECTIVE: This study compared the bronchodilator effects of short-acting (salbutamol and procaterol) and long-acting (salmeterol and formoterol) beta(2)-agonists in children with bronchial asthma. PATIENTS: Twenty-seven (18 male, 9 female) children with bronchial asthma were enrolled in the study. Drugs were administered randomly in the morning for 5 days as follows: 1 single dose of two short-acting beta(2)-agonists, salbutamol 200microg and procaterol 20microg, and two long-acting beta(2)-agonists salmeterol 50microg and formoterol 24microg, and placebo. RESULTS: All beta(2)-agonists demonstrated a significantly higher bronchodilator effect than that observed with placebo. This effect appeared to be due to the forced expiratory flows. Formoterol produced a higher bronchodilator effect than salbutamol, and salmeterol showed a bronchodilator effect comparable with salbutamol at 30 minutes but higher than salbutamol after 3 hours. CONCLUSION: Our study confirmed the efficacy of the bronchodilator effects of the beta(2)-agonists. Salmeterol and formoterol, in particular, produced an improvement in respiratory function with a significant increase in forced expiratory flows in children with bronchial asthma.     

Pediatric asthma controller therapy

The treatment of children with asthma has historically relied upon expert opinion using data extrapolated from adult studies. Over the past few years, landmark studies have been completed providing healthcare professionals with evidence on which a reasonable approach can be made for children suffering from this common and serious disease. Asthmatic phenotype in children, unlike adults, tends to differ according to age, which must be taken into account as well as triggers, severity, and level of control. The care of the child with asthma is complex, but accumulating data have demonstrated that we are on the right path for optimizing control while reducing the burden of side effects. The newest Global Initiative for Asthma (GINA) guidelines, as well as recent updates from the landmark CAMP (Childhood Asthma Management Program) study and information from the PACT (Pediatric Asthma Control Trial) and budesonide/formoterol controller and reliever studies, along with recent comparisons of higher dose inhaled corticosteroids (ICS), and ICS/long-acting β(2)-adrenoceptor agonist (LABA) combination and leukotriene receptor antagonist (LTRA) therapies in children have clarified a few of the big questions in pediatric asthma. For children with asthma aged 5 years and older, the CAMP trial demonstrated that regular use of ICS reduces the frequency of symptoms; however, height was adversely affected and there is no evidence for altering the natural history of asthma. In patients aged 6 years and over whose asthma is uncontrolled on ICS alone, combination therapy with ICS and a LABA has been recently compared with the use of higher dose ICS and the addition of an LTRA in pediatric patients. The addition of a LABA statistically will be of most benefit; however, some children will have optimal control with doubling the baseline dose of ICS or addition of an LTRA. Use of budesonide/formoterol as a controller and reliever therapy extends the time to first exacerbation versus contemporary use of this medication in patients aged 4 years and older. Ciclesonide, a newer ICS, has demonstrated acceptable efficacy but has the added benefit of not affecting growth. Certainly, with mounting evidence, the care-map in pediatric asthma control is becoming clearer.     

Medications prescribed to asthmatic children: an historical cohort study comparing clinical practice with NIH recommendations

Purpose — NIH guidelines recommend maintenance treatment of persistent moderate or severe childhood asthma with preventive anti‐inflammatory medication (inhaled corticosteroids, cromolyn or nedocromil). The objective was to determine if the NIH guidelines for the treatment of childhood asthma were implemented by examining the prevalence of prescribing preventive medication. Methods — This was a non‐concurrent cohort study of 311 children (aged 2 to 19 years) who were treated for asthma between January and December 1994 by nine Medicaid managed care plans in the northeastern USA. Results — Preventive medications were prescribed at least once to 61.1% of the children with moderate or severe asthma and to 27.1% of the children with mild asthma. Logistic regression analyses indicated prescribing preventive medication was associated with moderate or severe asthma (aOR 5.34, 95% CI 3.22 – 8.83) and age 5 to 19 years (aOR 2.11, 95% CI 1.19 – 3.72). Prescribing preventive medication was also associated with a prior emergency department visit (aOR 2.27, 95% CI 1.24 – 4.16), after adjusting for age. Conclusions — Prescribing preventive medications is related to sentinel clinical events and the NIH recommendations are not routinely implemented for all children with moderate or severe asthma during this study period. Copyright © 2000 John Wiley & Sons, Ltd.     

Clinical characteristics,treatment patterns,disease burden,and persistence/adherence in patients with asthma initiating inhaled triple therapy: real-world evidence from Japan

Abstract

Objectives: To help optimize triple therapy use, treatment patterns and disease burden were investigated in patients in Japan with persistent asthma who initiated multi-inhaler triple therapy (inhaled corticosteroid/long-acting β₂-agonist/long-acting muscarinic antagonist; ICS/LABA/LAMA).

Methods: This retrospective, observational cohort study using health insurance claims data included adults with persistent asthma who initiated triple therapy in 2016. Patients who were prescribed ICS/LABA in 2016 were included as an ICS/LABA-matched cohort. Patients were stratified into those with asthma only and those with asthma and chronic obstructive pulmonary disease (COPD) codes (asthma-COPD overlap [ACO]). Patient data from 1-year prior to 1 year post index date were analyzed.

Results: For patients with asthma only in the triple therapy and ICS/LABA cohorts, baseline demographics were similar. A higher proportion of the triple-therapy cohort than the ICS/LABA cohort was receiving high-dose ICS at index (68.2% and 27.6%, respectively), and had experienced an exacerbation in the last year (64.0% and 29.4%, respectively). The proportion of patients with asthma only who developed any exacerbation was lower in the year following initiation of triple therapy compared with the year prior to initiation of triple therapy (45.8% vs 64.0%, respectively). For asthma only patients receiving triple therapy, the mean (standard deviation) proportion of days covered and medication possession ratio was 0.51 (0.36) and 0.86 (0.16), respectively. Similar trends were seen in patients with ACO in the triple-therapy and ICS/LABA cohorts.

Conclusion: Evidence from this study may serve as a reference for the use of inhaled triple therapy for asthma.     

Improving asthma control in patients suboptimally controlled on inhaled steroids and long-acting beta2-agonists: addition of montelukast in an open-label pilot study

BACKGROUND: Airway inflammation and symptoms often persist in asthma patients despite treatment with inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA). It is hypothesized that the leukotriene receptor antagonist montelukast, treating a pathway of inflammation distinct from that of ICS, might confer additional benefit. OBJECTIVE: To evaluate the efficacy of montelukast in improving asthma control in patients symptomatic on a fixed-association (FA) medium dose of ICS and LABA. METHODS: A 2-month, open-label, real-life observational study was undertaken by 131 Belgian pulmonologists. Patients (> or = 15 years old) suffering from persistent asthma (pre-bronchodilator FEV1 > or = 60% of predicted value) and insufficiently controlled on a FA therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as add-on therapy. Asthma control was assessed by the standardized Juniper asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with montelukast. Global evaluation of therapy was made both by the patients and physicians. RESULTS: A total of 313 patients were eligible for analysis. Forty-nine per cent received inhaled fluticasone/salmeterol and the rest budesonide/formoterol. Mean ACQ score decreased significantly on montelukast (13.9 +/- 5.1 at baseline versus 7.4 +/- 4.7 on montelukast, p < 0.001), with a significant improvement in all individual symptom scores (p < 0.001) and in pre-bronchodilator FEV1 score (from 2.2 +/- 1.5 to 1.6 +/- 1.4; p < 0.001). Parallel to these results, 78.6% of the patients reported a global improvement of their asthma. The same proportion of improvement was observed in the global evaluation made by the physicians (kappa = 0.66). CONCLUSION: This pilot study suggests that addition of montelukast in patients symptomatic on a FA of ICS and LABA may result in significant improvements in asthma control. A randomised, placebo-controlled clinical trial seems warranted.     

Fixed-Dose combination of the inhaled corticosteroid and long-acting beta2-agonist therapy in adults with persistent asthma

Introduction: Asthma is a respiratory condition characterized by airway inflammation, airflow obstruction, and bronchial hyperresponsiveness. The standard treatment of asthma comprises inhaled corticosteroid and beta₂-agonist. Inhaled short-acting-beta₂-agonists have been used as rescue medication for exacerbation. However, long-acting-beta₂-agonists (LABA) used as monotherapy for asthma had been reported for having a safety concern. Consequently, it had been recommended as an add-on treatment to inhaled corticosteroid (ICS) in moderate to severe persistent asthma. The fixed-dose combination (FDC) of ICS and LABA has been approved since the year 2000. Evidences revealed using the combination of these medications is more effective in asthma control.

Areas covered: The rational and phase III onward randomized-controlled studies were reviewed. Sources of evidences were from studies published in Medline until November 2015.

Expert opinion: There are six FDC inhaler regimens approved worldwide. The significant synergistic effects of ICS and LABA in one device are well evidenced. A FDC reduces the daily dosage of ICS and asthma exacerbation. It is safe to use regularly as controller. The efficacy of each individual combination on asthma treatment is generally similar. Clinical experience, ease of use, cost and side effects of medication would guide the clinician’s preferences.     

Impact of Montelukast on Symptoms in Mild-to-Moderate Persistent Asthma and Exercise-Induced Asthma: Results of the ASTHMA Survey

Summary

A nation-wide survey was undertaken in Belgium among general practitioners (GPs) to evaluate the impact of the leukotriene receptor antagonist (LTRA) montelukast on the control of asthma symptoms, after at least 4 weeks of treatment. Patients from 6 years of age were eligible if they were suffering from mild-to-moderate persistent asthma which was still symptomatic despite inhaled corticosteroids (ICS) treatment, or from exercise-induced asthma. Patient general satisfaction was evaluated by recording the willingness to continue the treatment. A total of 1360?GPs took part in the study and more than 11 000 patients were included in the survey.

Of the included patients, 85% were receiving inhaled corticosteroids, 60% of whom were also on long-acting β2-agonists (LABA). However, despite the use of daily controller medication, 92% of the patients still reported limitation of activities, 49% difficulties with sleep and 45% early morning awakening due to asthma. Moreover, 78% of the patients used rescue medication more than twice a week.

At the end of the survey, 90% of the patients expressed their willingness to continue montelukast therapy. Of the patients having symptoms at the start of the study, 87% reported amelioration in sleep while on montelukast therapy, 80% less frequent early morning awakening, 85% better ability to perform daily activities and 77% decreased need for rescue medication.     

Treatment of childhood asthma: how do the available options compare?

The National Asthma Council of Australia suggests that "the aim of preventive therapy should be to enable patients to enjoy a normal life (comparable with that of non-asthmatic children), with the least amount of medication and at minimal risk of adverse events. The level of maintenance therapy should be determined by symptom control and lung function in the interval periods." The British Thoracic Society/Scottish Intercollegiate Guidelines Network states that the aims of the pharmacological treatment of asthma should be to control symptoms, prevent exacerbations and achieve the best possible lung function with minimal adverse effects. We have used the current published international guidelines to highlight the international differences in management recommendations, and compared the possible pharmacological options with a focus on the above ideals. Cromones have been used for many years in childhood asthma. Most evidence suggests they now have little role. Regarding inhaled corticosteroids (ICS), beclomethasone and budesonide are essentially similar in their efficacy. Fluticasone propionate is equally as effective at one-half the equivalent dose of budesonide or beclomethasone. Adverse effects are rare in dosages <400 microg/day of budesonide and beclomethasone or <200 microg/day of fluticasone propionate, but may occur in individual patients. Relevant clinical adverse effects are rare and pharmacological systemic effects are less noticeable with budesonide and fluticasone propionate than with beclomethasone, but data are conflicting. Long-acting beta2-adrenoceptor agonists (beta2-agonists) are recommended once low-dose ICS have failed to control symptoms. The main pharmacological difference between the agents is that formoterol is a full beta2-adrenergic agonist, whereas salmeterol is a partial agonist at the beta2-adrenoceptor and has a unique pharmacological action. The main clinical distinction between these two agents is that their onset of bronchodilation differs. Bronchodilation begins at about 3 minutes after inhalation of formoterol, which is similar to the short-acting agents, whereas salmeterol has a much slower onset of action at about 15-30 minutes. The many in vitro differences between the two drugs are probably not clinically relevant. There are no comparative pediatric data on the leukotriene modifiers to make clear recommendations.