Long-term Asthma Control Research Articles

Tools to assess (and achieve?) long-term asthma control

Assessment tools are needed to monitor asthma control and to detect exacerbations before the alteration of functional parameters and the occurrence of symptoms. The ability to effectively monitor asthma control would enable clinicians to increase corticosteroid dose or to stop corticosteroid tapering before symptoms occur. As a few severe exacerbations are expected per year in treated patients, these tools must be suitable for long-term use. They must also be reproducible, acceptable to patients and be non-invasive. Tools currently available to assess asthma control include assessment of: clinical parameters (e.g. nocturnal awakenings; bronchodilator intake; symptom scores); lung function (e.g. peak expiratory flow and forced expiratory volume in 1 s); subjective parameters of asthma control (e.g. asthma control questionnaire (ACQ)); bronchial hyper-responsiveness; eosinophilia in induced sputum; and exhaled nitric oxide (NO) concentration. Clinical symptoms, lung function and the ACQ have proved to be inadequate markers of asthma control, as changes in these parameters occur at the same time as symptom manifestation. By contrast, sputum eosinophilia and exhaled NO concentrations are truly predictive of asthma exacerbations; monitoring these parameters are useful in preventing exacerbations from occurring in the first instance. They also assess, and help to achieve asthma control in the long term.

Ketotifen alone or as additional medication for long-term control of asthma and wheeze in children.

Ketotifen is an antihistamine which may be used to treat asthma. Since administering inhaled therapy to younger children can be difficult, an oral agent such as ketotifen offers potential advantages. The objective of this review is to determine, whether ketotifen alone or in combination with other co-interventions results in better control of asthma in children with asthma and/or wheezing and examine its safety profile. We searched the Cochrane Airways Group register of trials (based on MEDLINE, EMBASE, CINAHL and handsearched respiratory journals) and reference lists of articles. The latest search was carried out in October 2002. Clinical studies had to be randomised-controlled and double-blinded, comparing oral ketotifen with placebo in children with asthma and/or wheeze for at least eight weeks at a dose not less than one mg daily. Two reviewers independently performed selection of trials, quality assessment and data extraction; a third reviewer was included in the consensus process if necessary. A total of 26 relevant studies involving 1826 participants were included in this review. Children's age ranged from 4 months to 18 years and ketotifen was given between 10 and 32 weeks. The proportion of children able to reduce or stop their bronchodilator use within 12 to 16 weeks of treatment was significantly higher in the ketotifen group (relative risk 2.39, 95% CI 1.64 to 3.48) based on four trials; this result was statistically significant in a subgroup of two trials with well described and adequate method of blinding. Statistically significant beneficial effects of ketotifen were also observed in the following secondary outcomes: efficacy evaluated by physician (10 trials) and parents/patients (7 trials), asthma symptom score (4 trials), asthma exacerbations (2 trials), and reduction in use of oral steroids (4 trials). However, sub-group analyses of trials with well described and adequate method of blinding was only significant for the outcome asthma symptom score and non-significant for the remaining secondary outcomes. Reported side effects were more frequent in the ketotifen group (sedation: 21%, weight gain: 27%) than in the placebo group (sedation: 12%, weight gain: 17%). Evidence from randomised controlled trials indicates that ketotifen alone or in combination with other co-interventions improves control of asthma and wheezing in children with mild and moderate asthma. However due to the high proportion of children with atopy in some trials the results cannot necessarily be generalised to all asthmatic children. The benefit is obtained at the cost of minor side effects, namely sedation and weight gain. The validity of this conclusion is limited by the low reported, methodological quality of included trials.

Omalizumab is effective in the long-term control of severe allergic asthma

Previous reports show that addition of omalizumab to standard therapy reduces asthma exacerbations and simultaneously decreases use of inhaled corticosteroids (ICSs) and rescue medication in patients with allergic asthma. To determine the effect of omalizumab on long-term disease control in patients with severe allergic asthma. The present study concerns the 24-week, double-blind extension phase to a previous 28-week core study in which patients received subcutaneous omalizumab or matching placebo (at least 0.016 mg/kg/IgE [IU/mL] every 4 weeks) for 16 weeks in addition to their existing ICS therapy (beclomethasone dipropionate [BDP]; steroid-stable phase), followed by a 12-week phase in which controlled attempts were made to gradually reduce ICS therapy (steroid-reduction phase). During the extension phase patients were maintained on randomized treatment (omalizumab or placebo) and the lowest sustainable dose of BDP. The use of other asthma medications was permitted during the extension phase. Investigators were also allowed to switch patients from BDP to other ICS medications if considered necessary. A total of 460 patients (omalizumab, n = 245; placebo, n = 215) entered the extension phase. Overall, omalizumab-treated patients experienced significantly fewer exacerbations vs placebo during the extension phase (0.60 and 0.83 exacerbations per patient, respectively; P = 0.023), despite a sustained significant reduction in their use of ICS (mean BDP equivalent dose: omalizumab, 227 microg/d; placebo, 335 microg/d; P < 0.001). Treatment with omalizumab was well tolerated and the incidence of adverse events was similar in both treatment groups. These results indicate that omalizumab is effective in the long-term control of severe allergic asthma.

Effect of Practitioner Education on Adherence to Asthma Treatment Guidelines

To determine whether a letter-based intervention program submitted to prescribers and pharmacists would improve drug therapy in users of high-dose beta(2)-agonists (HDBs). Retrospective drug utilization review. The intervention group consisted of 135 asthmatic patients (identified through ICD-9-CM codes) in the Connecticut Medicaid Program who submitted >1 claim per month for short-acting beta(2)-agonists (over a 6-mo period). Patient-specific intervention packets were mailed to the patients' prescribers and pharmacists, and their use of long-term control agents and healthcare utilization was evaluated over 6 months. These variables were compared with a comparison group (n = 510) of asthmatics drawn from the same Medicaid program who were not considered to be high-dose users of short-acting beta(2)-agonists at baseline. Prior to the intervention, the intervention group used fewer long-term asthma control agents as compared with the comparison group (58% vs. 96%; p < 0.001); there was no significant difference after the intervention program (65% vs. 71%; p = 0.169). The acquisition of spacers was greater in the intervention group than in the control group after the intervention (7% vs. 2%; p = 0.007). At the end of the 6-month intervention period, 46% of patients in the intervention group were no longer HDB users (p < 0.001). The higher frequency of prescriber office visits in the intervention group than the comparison group before the intervention (0.46 +/- 0.82 vs. 0.25 +/- 0.66; p < 0.001) was not evident after the intervention program (0.24 +/- 0.63 vs. 0.18 +/- 0.60; p = 0.283). This intervention program had modest impact on improving the use of long-term control agents and reducing prescriber office visits.

Evaluation of efficacy and safety of flunisolide hydrofluoroalkane for the treatment of asthma

Background: Inhaled corticosteroids are currently recommended as first-line therapy for the long-term control and management of persistent asthma. Flunisolide hydrofluoroalkane (HFA) is a new formulation of the corticosteroid flunisolide that is delivered by a metered-dose inhaler containing an HFA propellant. HFA replaces the chlorofluorocarbon (CFC) propellant of the previous formulation, producing aerosols of smaller average particle size. Objective: This article reviews the physical and pharmacologic properties, deposition profile, and potential clinical benefits of flunisolide HFA for the treatment of asthma. Methods: Data included in this review were found via MEDLINE (search term, flunisolide HFA). Results: Flunisolide HFA has a mass median aerodynamic diameter (MMAD) of 1.2 μm, smaller than the 3.8 μm MMAD of the CFC formulation. Compared with flunisolide CFC, more of each flunisolide HFA dose reaches the lungs and less is deposited in the oropharynx. In addition, scintigraphic studies have found that the extra-fine particle size of flunisolide HFA gives it better access to small airways. In short- and long-term clinical studies, flunisolide HFA has been found to significantly increase pulmonary function relative to placebo. Although not statistically superior to the previous CFC formulation, flunisolide HFA exhibited small improvements in secondary efficacy measures, such as as-needed albuterol use and asthma symptoms, relative to flunisolide CFC. Furthermore, research suggests that the new HFA formulation has a low risk of systemic corticosteroid effects (eg, hypothalamic-pituitary-adrenal axis suppression, growth inhibition in children). Also, lower levels of oropharyngeal deposition, such as those seen with flunisolide HFA, are associated with lower incidence of local effects (eg, candidiasis). Conclusion: Flunisolide HFA offers effective asthma control with a high level of tolerability in an extra-fine particle formulation that distributes corticosteroid to all areas of the lung, including small airways.

Comparison of the efficacy and safety of nebulized beclometasone dipropionate and budesonide in severe persistent childhood asthma

Inhaled steroids are recommended for long-term control of asthma, but their use may be limited in young children because of difficulties in using the associated inhaler device. The use of nebulizers may help to overcome this issue, without compromising therapeutic efficacy or safety. This 14-week, multicentre, randomized, controlled, open-label, parallel-group study compared the efficacy and safety of nebulized corticosteroids in paediatric patients (aged 6 months to 6 years) with severe persistent asthma. Beclometasone dipropionate (BDP) 800 μg day −1 suspension for nebulization and budesonide (BUD) 750 μg day −1 given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters. The primary efficacy endpoint was the number of patients who did not experience any major exacerbation, this being 40·4% and 51·7% in the BDP and BUD groups respectively in the ITT population ( P=0·28), and the mean number of global exacerbations (major plus minor) decreased respectively by −37.5% in the BDP group and −23.3% in the BUD group. Both treatments were also associated with marked reductions in the number of nights with wheezing and the number of days of oral steroid use. Moreover, the two treatment groups had a similar adverse-event incidence and profile. Only 11 adverse events were reported, and no serious adverse events were related to treatment. Urinary cortisol and the time course of height and weight were unaffected by both treatments, and BDP was confirmed to have a neutral effect on bone metabolism. In conclusion, this study demonstrates that both BDP 800 μg day −1 suspension for nebulization and BUD 750 μg day −1 administered by nebulization are effective, with an acceptable safety profile, for treatment of severe persistent asthma in infants and young children.

Use of long-term asthma controller medications before and after a hospitalization or emergency department visit

Use of long-term asthma controller medications before and after a hospitalization or emergency department visit

Inhaled corticosteroids in childhood asthma: long-term effects on growth and adrenocortical function.

Inhaled corticosteroids (ICS) are the most potent of all the available inhaled treatments, and are effective medications for long-term control of asthma. However, their use in children is limited by the risk of systemic adverse effects. Although results reported in the literature on the adverse effects of ICS are conflicting and often restricted to a small number of cases with a limited follow-up, most of them show an early decrease in growth velocity without significant influence on final adult height. Partial adrenal suppression has also been demonstrated in children treated with ICS for more than 2 months. Only children with mild persistent, moderate, or severe asthma not controlled by non-corticosteroid drugs should be treated with ICS for long periods. The dose of ICS must be individually adjusted to minimize the possible adverse effects on growth, and all children with asthma receiving long-term treatment with ICS must be regularly evaluated for growth impairment, which may necessitate dose reduction or drug replacement.

The whole story: treatment outcomes with SymbicortS

Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physic an education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort is more cost-effective than treatment with budesonide alone.

The role of inflammation and anti-inflammatory medication in asthma

Asthma is a chronic inflammatory disease of the airways involving a wide range of cells and mediators. First-line therapy of persistent asthma involves the use of inhaled corticosteroids to control the underlying inflammation ofthe airways. Inhaled β 2-agonists are also widely used in asthma therapy and are the most effective bronchodilators currently available. The short-acting β 2-agonists are now used on an as-needed basis for rapid relief of symptoms. In recent years, long-acting inhaled β 2-agonists have had an increasing role in the management of asthma, particularly in patients with moderate to severe asthma. This class of drug has a long duration of action and is recommended as add-on treatment to inhaled corticosteroids in the long-term control of asthma. New therapies have been added to asthma therapy as our understanding of the pathogenesis of asthma has increased. The use of multiple therapies necessitates a clear understanding of the mode of action of the drugs and any potential interaction or overlap of effect. For many people asthma is associated with complex therapy; thus treatment developments that simplify asthma treatment are an important step forward in asthma management.

The whole story: treatment outcomes with Symbicort®

Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort® (budesonide and formoterol in a single inhaler), atreatmentthat provides better control of asthma compared with budesonide alone.While the prescribing costs of Symbicort® were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physician education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations.Treatment with Symbicort® is more cost-effective than treatment with budesonide alone.

Combination therapy with inhaled long-acting beta2-agonists and inhaled corticosteroids: a paradigm shift in asthma management.

Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of drugs with different mechanisms of action that are commonly used to provide effective long-term control of persistent asthma. Scientific and clinical data support the complementary mechanisms of action of the inhaled corticosteroids and the long-acting beta2-agonists in achieving a superior level of asthma control. In addition, evidence supports significant reductions in exacerbations and effective control of airway inflammation with an inhaled corticosteroid and a long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or combinations of other therapeutic agents with an inhaled corticosteroid. Finally, there are distinct economic advantages to combining an inhaled corticosteroid and a long-acting beta2-agonist in the treatment of asthma relative to other treatment regimens.

Fluticasone propionate favoured for long-term asthma control

Fluticasone propionate favoured for long-term asthma control

Fluticasone propionate favoured for long-term asthma control

Fluticasone propionate favoured for long-term asthma control

Using Case Management to Increase Antiinflammatory Medication Use Among a Managed Care Population with Asthma

The National Heart, Lung, and Blood Institute (NHLBI) recommends the regular use of antiinflammatory medications to achieve and maintain control of persistent asthma, while recommending that quick-relief beta2-agonist medications should be used to treat acute symptoms and exacerbations. Despite these suggestions, the overuse of short-acting quick-relief medications and underuse of long-acting antiinflammatory medications persists. ConnectiCare, Inc., a regional managed care company, used pharmacy claims data to identify members who had been dispensed a total of three or more beta2-agonist prescriptions for three consecutive months in a 12-month period. These members had also not been prescribed an inhaled corticosteroid, cromolyn sodium, or nedocromil during the same three consecutive months. An intensive case management intervention was developed that included multiple contacts from a nurse case manager to provide education and information about asthma control and the guidelines. Twenty-eight percent (n = 40) were purposively chosen to receive the intensive multiple-contact intervention and the remainder received a standard, single-contact intervention. After adjusting for the effects of age, gender, and pre-intervention medication use, ConnectiCare members who received the intensive intervention were 4.3 times more likely to increase the number of antiinflammatory medication prescriptions dispensed than those who received a standard intervention (p < 0.001). This study suggests that the use of intensive case management for persons identified as inappropriate users of asthma medication may result in medication changes that achieve the long-term control of asthma.

Safety of antileukotriene agents in asthma management

This article presents information on the safety of zafirlukast, montelukast, and zileuton, three antileukotrienes (anti-LTs) approved in the United States for the prophylaxis and treatment of asthma. After reading this article, readers should have an understanding both of the general safety of anti-LTs and their specific adverse effects. Relevant and appropriate controlled clinical studies on the safety of anti-LTs in asthma were used. Only literature in the English language was reviewed. Material was taken from academic/scholarly journals and appropriate reviews. Antiasthma agents, including corticosteroids, beta2-agonists, and methylxanthines, may be categorized into two classes: those used for the long-term control and prevention of persistent asthma and those used for the prompt relief of acute symptoms and exacerbations of the disease. Although most agents are safe and well tolerated when used properly, adverse effects may occur with use at higher dose levels. The anti-LTs, including zafirlukast, montelukast, and zileuton, are the first new pharmacologic class in the therapeutic armamentarium for asthma management to be approved in the United States in the past 20 years. Both zafirlukast and montelukast carry pregnancy category B classification whereas zileuton carries pregnancy category C classification. The most common adverse effects observed in clinical trials were headache, pharyngitis, abdominal pain, dyspepsia, and cough. The results of clinical trials and real-world experience indicate that these agents are generally safe and well tolerated, with an incidence of adverse effects comparable with placebo.

Beyond Our Pages

Beyond Our Pages

Benefits of high altitude allergen avoidance in atopic adolescents with moderate to severe asthma, over and above treatment with high dose inhaled steroids.

Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure. We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS. Eighteen atopic asthmatic adolescents (12-18 yr, 500-2000 microg ICS daily) with established house dust mite allergy, participated in a parallel-group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10-week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups. During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U-EPX), leukotriene E4 (U-LTE4) and 9alpha11beta prostaglandin F2 (U-9alpha11beta PGF2) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U-EPX (P < 0.05) and U-LTE4 (P < 0.05) were maintained. A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long-acting beta2-agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short-term, rigorous allergen avoidance can improve the long-term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.

What are the alternatives to increasing inhaled corticosteroids for the long term control of asthma?

The Global Initiative for Asthma (GINA) guidelines stated the therapeutic goals for the management of asthma and, through a stepwise approach to treatment, defined the various grades of asthma severity and the therapeutic options available to the clinician at each step. This article considers the options at step 3; the management of a patient with poorly controlled asthma who is already taking low-dose inhaled corticosteroids. Before considering a change in therapy, the clinician should rule out alternative diagnoses, confirm compliance with treatment, explore potential exacerbants in the patient's environment and, where possible, remove them. If a change in medication is necessary, the choice of drug will depend on the therapeutic goal that needs to be achieved. If the most important goal is the control of symptoms and optimisation of lung function, most studies support the addition of a long-acting beta(2)-agonist to low dose inhaled corticosteroids. If recurrent severe exacerbations are a major feature of the poor control, increasing the dosage of inhaled corticosteroids may be most effective. The addition of a leukotriene antagonist may be the best choice if exercise-induced symptoms are prominent or in the setting of aspirin-sensitive asthma. General recommendations supported by the findings of large therapeutic trials do not allow for significant variability in the individual response to a particular drug. Receptor polymorphisms have recently been discovered that may account for variability in the response to beta(2)-agonists and leukotriene receptor antagonists. However, until more is known about the reasons behind this variability, a therapeutic trial may be the most effective way of determining the best drug for an individual patient. One of the key developments in asthma over the past decade has been the acceptance of the concept of asthma as a chronic inflammatory disorder of the airways. However, the long term significance of this inflammation is not clear and the importance of control of inflammation beyond the suppression of symptoms, reduction of exacerbation frequency and the optimisation of lung function has not been established.

Body composition and growth in asthmatic children treated with inhaled steroids

Prolonged treatment with inhaled steroids is recommended for long-term control of asthma in children; however, it can interfere with growth and body composition. The aim of this study is to answer the question whether 6 months treatment with inhaled steroids causes body fat accumulation and growth velocity reduction. Hospital-based, open study of body composition [by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and skinfolds] and growth of 26 asthmatic children, treated for 6 months with inhaled steroids [budesonide (BUD) 400 microg/day (group 1) or fluticasone proprionate (FP) 200 microg/day (group 2)], sodium cromoglycate and beta2-agonist (salbutamol) compared with a control group of 16 asthmatic children treated only with sodium cromoglycate and beta2-agonist. On average, total and regional fat mass, adjusted for pubertal stage and gender, and growth velocity were similar in all three groups of patients and were not influenced by treatment (% mean change +/- 1 SD of fat mass during treatment in BUD 0.1 +/- 3.0%, FP -1.1 +/- 3%, and control -2.8 +/- 3.5%; ANOVA P > or = .05); however seven patients, two in group 1 (1 preschool child), three in group 2 (2 preschool children) and two in the control group (two prepubertal boys aged 8.5 and 9.5 year), during treatment, showed a growth velocity standard deviation score below the third percentile. A 6-month treatment with inhaled BUD and FP does not induce body fat accumulation; however, in a few preschool children the treatment was associated with growth velocity below the third percentile. Our results suggest the need for constant monitoring of growth in all asthmatic children on chronic treatment with inhaled steroids. Further studies devoted to the effects of inhaled steroids use in preschool children are needed.