Maintenance Inhaled Corticosteroids Research Articles

Protocol for the INFORM ASTHMA Trial: Budesonide-formoterol reliever in adults with asthma on maintenance inhaled corticosteroid

BackgroundInternational asthma guidelines recommend inhaled corticosteroid (ICS)/formoterol in preference to short-acting beta2-agonist (SABA) reliever-based regimens as reliever therapy in adults and adolescents of all asthma severities. A major limitation to this recommendation is the absence of randomised controlled trial (RCT) efficacy and safety data for this approach in patients who continue to use maintenance ICS. The anti-inflammatory effect of ICS/formoterol reliever therapy on airway inflammation is also not well characterised.ObjectiveTo determine the anti-inflammatory effect, efficacy and safety of budesonide-formoterol reliever therapyversusterbutaline reliever therapy in adults with asthma on maintenance ICS therapy. Fractional exhaled nitric oxide (FeNO) will specifically be examined to determine the time-course and magnitude of anti-inflammatory effect.MethodsA 26-week, open-label, parallel-group, 2-arm, phase IV, two-sided superiority RCT will recruit 180 adults aged 16–75 with a clinical diagnosis of asthma using reliever only therapy, or SABA reliever therapy with maintenance ICS at baseline, and with baseline FeNO at screening ≥25 ppb. Enrolled participants will be allocated to maintenance budesonide with the dose based on their baseline treatment step and randomised 1:1 to either budesonide-formoterol or terbutaline reliever therapy. All participants will perform at home FeNO measurements at regular intervals for the first 12 weeks of the study. The primary outcome is FeNO at 26 weeks. Key secondary outcomes include FeNO time-course, asthma exacerbations, asthma control and spirometry.ConclusionThis will be the first RCT comparing ICS-formoterolversusSABA reliever therapy in patients who use maintenance ICS therapy.

Mortality of COVID-19 is associated with comorbidity in patients with chronic obstructive pulmonary disease

Background The aim of this study was to compare the outcome of coronavirus disease 2019 (COVID-19) in hospitalised patients with chronic obstructive pulmonary disease (COPD) with the outcome in matched COVID-19 patients without COPD. Methods Sixty-three COPD patients hospitalised for acute COVID-19 from March through August 2020 were retrospectively identified and 63 hospitalised COVID-19 patients without COPD were selected and matched for age, gender and month of hospital admission. Results COPD patients had a higher rate of comorbidities, especially cardiovascular disease, and a trend towards a higher 30-day mortality than control patients (35% vs. 22%). In the COPD group, high Charlson comorbidity index (p = 0.03) and previous cerebrovascular disease (p = 0.04) were associated with 30-day mortality in univariate analysis. Inhaled corticosteroids maintenance therapy was not associated with lower mortality. Conclusion COPD patients hospitalised for acute COVID-19 disease had significantly more comorbidities and a high risk of severe outcome and death within 30 days. Comorbidity, especially cardiovascular diseases, was associated with mortality among COPD patients.

The cost-effectiveness of as-needed budesonide-formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in Canada

BackgroundThe Global Initiative for Asthma recommends the use of as-needed low-dose inhaled corticosteroid (ICS)-formoterol as a preferred controller therapy for patients with mild asthma. These recommendations were based, in part, on evidence from the SYGMA 1 and 2 studies of as-needed budesonide-formoterol. This analysis aimed to compare the cost-effectiveness of as-needed budesonide-formoterol to low-dose maintenance ICS plus as-needed short-acting β2-agonist (SABA) in patients with mild asthma.MethodsA Markov cohort model was designed that included three possible health states (non-exacerbation, severe exacerbation, and death) to compare as-needed budesonide-formoterol 200–6 μg to twice-daily budesonide 200 μg maintenance therapy (low-dose ICS) plus as-needed terbutaline 0.5 mg (SABA). The deterministic base-case analysis used severe exacerbation, adverse event (AE), and healthcare resource use data from SYGMA 2, and was conducted from a Canadian public payer perspective with a 50-year time horizon, and a discount rate of 1.5% per annum. Moderate exacerbation was modelled on data from SYGMA 1 in sensitivity analyses. Utility values were derived from SYGMA 2 quality of life data. All-cause- and asthma-related mortality rates and costs (reported in 2019 Canadian dollars) were based on published data, using Canada-specific values where available. One-way deterministic sensitivity, probabilistic sensitivity, and eight scenario analyses were conducted to examine the robustness of the results.ResultsAs-needed budesonide-formoterol was the dominant treatment option in the base-case analysis, providing incremental cost savings of $9882 per patient and quality-adjusted life year (QALY) gains of 0.002 versus low-dose maintenance ICS plus as-needed SABA over a 50-year time horizon. Using a willingness-to-pay threshold of $50,000/QALY ($100,000/QALY), as-needed budesonide-formoterol had a 94% (95%) probability of being cost-effective compared with maintenance ICS plus as-needed SABA. Cost-saving was mostly driven by lower overall medication and AE-related costs. As-needed budesonide-formoterol remained the dominant treatment in sensitivity and scenario analyses.ConclusionsAs-needed budesonide-formoterol is a cost-saving option for the treatment of mild asthma from the perspective of the Canadian public payer compared with low-dose maintenance ICS plus as-needed SABA.

Up-regulation of ACE2, the SARS-CoV-2 receptor, in asthmatics on maintenance inhaled corticosteroids

BackgroundThe first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics.MethodsLarge airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS−), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays.ResultsAs a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS− or ICS+.ConclusionAirway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.

Clinician perspectives on a culturally adapted patient decision aid concerning maintenance therapy for asthma

Background and Objective Patients with persistent asthma often show poor adherence to inhaled corticosteroids (ICS). Shared decision-making can improve adherence rates in this population. Patient decision aids (PDAs) are tools to facilitate shared decision-making. To date, only one PDA, developed in a Canadian French-speaking population, exists for patients considering ICS maintenance therapy. This PDA has been culturally adapted in this study to contextualize to the needs of multi-ethnic Asian patients in Singapore. This study explored the views of local clinicians on the content, design and implementation of this newly-adapted PDA. Methods 24 clinicians, who were purposively sampled from polyclinics and a tertiary institution, were interviewed on the content, design and implementation of the PDA. The interviews were audio-recorded, transcribed and analyzed via thematic analysis. Results Clinicians generally accepted the design of the PDA. They suggested for the target users to be patients on Step 2 of GINA guidelines and the number of options to be reduced from four to two (do nothing or start inhaled corticosteroids). Moreover, they supported including a list of values for patients to select from given that Asian patients often do not articulate their values readily. The addition of more visual aids, the production of multilingual Asian editions and the involvement of nurses to administer the PDA was also suggested. Conclusion The PDA was culturally-adapted with local clinicians’ perspectives to target multi-ethnic Asian patients with persistent asthma (Step 2 GINA guidelines). The main changes include a list of values and addition of visual aids.

Hospital admission rate in children and adolescents with mild persistent asthma.

The health and financial burden of mild-persistent asthma has been poorly investigated. Our aim was to compare the rate of hospital admissions that have occurred during the preceding year between children and adolescents with current mild-persistent (MP) and moderate-severe (MS) asthma. We screened children and adolescents with asthma at eight outpatient clinics. The inclusion criteria were asthma diagnosis, age from 6 to 18 years and follow-up with a physician during the preceding 6 months. Subjects answered standardized questionnaires and underwent spirometry. We enrolled 220 MP and 102 MS asthmatic subjects. The proportion of subjects with HA during the preceding year was similar between MP and MS asthma groups (7% vs. 7%; p = .89). Symptoms score and the financial values spent by the family in the care of asthma were lower in MP asthma as compared with MS asthma group (asthma control questionnaire score 0.7 [0.3-1.0) vs. 2.0 [1.1-2.5]; p < .01) (asthma expenses in USD 13 [2-43] vs. 28 [10-83]; p < .01). The frequency of subjects using inhaled corticosteroids maintenance therapy was lower in the MP asthma group as compared with the MS asthma group (54% vs. 100%; p < .01). We conclude that the frequency of hospital admissions that have occurred during the preceding year was similar between subjects with current MP and MS asthma. Symptoms score and the financial values spent by the family in the care of asthma were lower in the MP asthma group.

The cost-effectiveness of as-needed budesonide/formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in the UK

BackgroundAs-needed budesonide/formoterol is effective in patients with mild asthma for whom low-dose inhaled corticosteroid (ICS) maintenance therapy is appropriate. We assessed the cost-effectiveness of this regimen versus maintenance low-dose ICS plus as-needed short-acting β2-agonist (SABA). MethodsA probabilistic Markov cohort model was developed that simulated time within/outside severe asthma exacerbations, conducted from a UK NHS perspective with a 70-year time horizon. Clinical efficacy inputs were derived from the SYGMA 2 trial. Patients with mild asthma eligible for low-dose maintenance ICS therapy received as-needed budesonide/formoterol 200/6 μg or twice-daily budesonide 200 μg maintenance therapy plus as-needed terbutaline 0.5 mg. A severe exacerbation was defined as worsening asthma requiring systemic corticosteroid use alone/in combination with an emergency department visit, or hospitalisation for acute asthma. Utility values were derived from SYGMA 2 EQ-5D-5L data, and all-cause- and asthma-related mortality, reduction in utility of an exacerbation, and costs were based on published data. The base-case analysis discount rate was 3.5%. Model robustness was evaluated with one-way sensitivity, probabilistic sensitivity, and two scenario analyses. ResultsOn average, as-needed budesonide/formoterol was associated with a £292.99 cost saving and quality-adjusted life year (QALY) gains of 0.001 versus ICS + SABA. At a willingness-to-pay of £20,000/QALY, as-needed budesonide/formoterol had >85% probability of being cost-effective versus ICS + SABA. Key drivers were budesonide/formoterol and budesonide maintenance annual exacerbation rates, mean daily budesonide/formoterol inhalations, and costs and outcomes discount rates. ConclusionsFrom a UK healthcare payer perspective, as-needed budesonide/formoterol is a cost-effective option for the treatment of mild asthma versus regular ICS.

Inhaled Corticosteroid Therapy in Adult Asthma. Time for a New Therapeutic Dose Terminology.

The Global Initiative for Asthma guidelines use the traditional terminology of "low," "medium," and "high" doses of inhaled corticosteroids (ICS) to define daily maintenance doses of 100 to 250 μg, >250 to 500 μg, and >500 μg, respectively, of fluticasone propionate or equivalent for adults with asthma. This concise clinical review proposes that this terminology is not evidence based and that prescribing practice based on this terminology may lead to the use of inappropriately excessive doses of ICS. Specifically, the ICS dose that achieves 80-90% of the maximum obtainable benefit is currently classified as a low dose, with the description of two higher dose levels of medium and high, which are associated with significant risk of systemic adverse effects. Asthma guidelines and clinician prescribing practice need to be modified in accordance with the currently available evidence of the dose-response relationship of ICS in adult asthma. We propose a reclassification of ICS doses based on a "standard daily dose," which is defined as 200-250 μg of fluticasone propionate or equivalent, representing the dose at which approximately 80-90% of the maximum achievable therapeutic benefit of ICS is obtained in adult asthma across the spectrum of severity. It is recommended that ICS treatment be started at these standard doses, which then represent the doses at which maintenance ICS are prescribed at step 2 and within ICS/long-acting β-agonist combination therapy at step 3. The opportunity is available to prescribe higher doses within ICS/long-acting β-agonist maintenance therapy in accordance with the stepwise approach to asthma treatment at step 4.

Effects of tiotropium + olodaterol versus tiotropium or placebo by COPD disease severity and previous treatment history in the OTEMTO® studies.

BackgroundAs lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest. OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease. Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.MethodsFour subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline. Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score. Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.ResultsIn all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy. Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup. Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.ConclusionsThese data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.Trial registrationClinicalTrials.gov: NCT01964352 and NCT02006732.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users.

Long-acting muscarinic antagonists: a potential add-on therapy in the treatment of asthma?

Asthma is a chronic inflammatory disorder of the airways that is a major global burden on both individuals and healthcare systems. Despite guideline-directed treatment, a significant proportion of patients with asthma do not achieve control. This review focuses on the potential use of long-acting anticholinergics as bronchodilators in the treatment of asthma, with results published from clinical trials of glycopyrrolate, umeclidinium and tiotropium. The tiotropium clinical trial programme is the most advanced, with data available from a number of phase II and III studies of tiotropium as an add-on to inhaled corticosteroid maintenance therapy, with or without a long-acting β2-agonist, in patients across asthma severities. Recent studies using the Respimat Soft Mist inhaler have identified 5 µg once daily as the preferred dosing regimen, which has shown promising results in adults, adolescents and children with asthma. Tiotropium Respimat has recently been incorporated into the Global Initiative for Asthma 2015 treatment strategy as a recommended alternative therapy at steps 4 and 5 in adult patients with a history of exacerbations. The increasing availability of evidence from ongoing and future clinical trials will be beneficial in determining where long-acting anticholinergic agents fit in future treatment guidelines across a variety of patient populations and disease severities.

Safety and tolerability of once-daily tiotropium Respimat® add-on to at least inhaled corticosteroid maintenance therapy in adolescent patients with moderate or severe symptomatic asthma

Background: Once-daily tiotropium Respimat® add-on to at least ICS has demonstrated efficacy, safety and tolerability in adult patients across severities of asthma. We assess the safety and tolerability of once-daily tiotropium Respimat® in adolescent patients aged 12 – 17 years with moderate or severe symptomatic asthma.

Posterior Pharyngeal Candidiasis in the Absence of Clinically Overt Oral Involvement: A Cross-Sectional Study

Although oropharyngeal candidiasis is associated with inhaled corticosteroid (ICS) usage, there is sparse data on the prevalence of posterior pharyngeal candidiasis in those without any detectable oral candidiasis on clinical examination. We systematically investigated the relationship between oral candidiasis on clinical examination and the presence of posterior pharyngeal candidiasis at bronchoscopy. We conducted a cross-sectional study on a convenience sample of 100 patients undergoing bronchoscopy at our institution. Patients were assessed for symptoms of and risk factors for candida infection and had an examination of their oropharynx for evidence of candidiasis before bronchoscopy. They subsequently had a detailed assessment for posterior candidiasis at bronchoscopy. We performed a posteriori subgroup analysis, which focused solely on those patients on ICS maintenance therapy. Median age was 54.7 (27-84) years, and 55 patients were male; 47% of patients were on ICS, and 20% of this cohort received recent oral corticosteroids. Twenty-eight percent of this convenience sample had posterior pharyngeal candidiasis; however, only 10.7% (3/28) of these patients had clinically detectable oral candidiasis on clinical examination before bronchoscopy. Factors that were independently associated with the presence of pharyngeal candidiasis at bronchoscopy were OR (95% CI) ICS usage 6.9 (2.5-19.2), particularly fluticasone usage 6.8 (2.62-17.9) and the presence of dysphonia 3.2 (1.3-8.0). In the subgroup analysis of ICS usage, posterior pharyngeal candidiasis was correlated with the presence of dysphonia but was not independently associated with fluticasone or budesonide dosage. This study demonstrates that posterior pharyngeal candidiasis in the absence of clinically overt oral candidiasis is frequent amongst ICS users. A history of ICS use, particularly fluticasone usage, as well as the presence of dysphonia are associated with posterior pharyngeal candidiasis at bronchoscopy, even in the absence of clinically overt oral involvement.

Should we Substitute Intermittent for Maintenance Inhaled Corticosteroids in Patients with Persistent Asthma? A Systematic Review and Meta-Analysis

Background: Although guidelines recommend maintenance inhaled corticosteroids (ICS) in mild persistent asthma, most patients use, and many physicians prescribe, intermittent ICS. Objective: To compare the efficacy and safety of maintenance versus intermittent ICS in children and adults with persistent asthma and to explore potential effect modifiers attributable to either strategy. Methods: We searched the literature using: the Cochrane airways group specialized register of trials and ClinicalTrials.gov website until October 2012. All randomized controlled trials, at least of four-week duration, comparing maintenance and intermittent ICS initiated at the onset of exacerbations. The primary efficacy and safety outcomes were the risk of patients with exacerbations requiring rescue oral corticosteroids and serious adverse events, respectively. Secondary outcomes included exacerbations, asthma control, lung function, airway inflammation, withdrawals, and adverse events. Results: Six (4 pediatric; 2 adult) trials involving 1211 patients with mild persistent asthma met the eligibility criteria; they lasted 12-52 weeks. There was no statistically significant group difference in the risk of patients with exacerbations requiring rescue oral corticosteroids (RR 1.07; 95% CI 0.87, 1.32). The response magnitude was not influenced by age, asthma severity, step-up protocol, and intervention duration. Maintenance ICS was superior to intermittent ICS in several indicators of symptoms, s2-agonist use, lung function, and airway inflammation. There was no group difference in the risk of patients with serious adverse events (RR=0.82; 95% CI 0.33, 2.03). In children, maintenance ICS was associated with less linear growth (MD=0.41 95% CI 0.13, 0.69) over 44-52 weeks. Conclusions: In children and adults with persistent asthma, maintenance and intermittent ICS strategies did not significantly differ in the risk of patients experiencing exacerbations requiring rescue oral corticosteroids and severe adverse events; however the wide confidence interval precludes equivalence. Maintenance ICS was superior to intermittent ICS in several indicators of lung function, airway inflammation, asthma control and reliever use. The paucity of trials prevents firm conclusions.

Psychosocial Outcomes Are Related to Asthma Control and Quality of Life in Pregnant Women with Asthma

Background. Little is known about the psychosocial impact and perceived teratogenic (fetal harm due to medication) risks of asthma treatment (inhaled/oral corticosteroids and β-agonist) during pregnancy. Aims. To assess the perception of asthma control, quality of life (QoL), and perceived risks of therapy in pregnant women with asthma. Methods. Pregnant women with asthma (n = 125) were recruited between 12 and 20 weeks gestation. QoL (generic: Short Form-12 Health Survey v1, and asthma specific: Asthma Quality of Life Questionnaire-Marks (AQLQ-M)) and psychological variables were assessed using the Perceived Control of Asthma Questionnaire (PCAQ), the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Women’s perceptions of the teratogenic risks of asthma therapy were also assessed and analyzed for adherence to maintenance inhaled corticosteroids (ICSs), poor asthma control, and QoL. Results. Women reported good QoL (median AQLQ-M total score/maximum score = 0.88/10), moderate ability to deal with asthma symptoms (mean PCAQ score = 42.6/55), positive beliefs about their asthma and low anxiety (median STAI score = 26.7/80). Perceived teratogenic risks for asthma drugs were excessive and class dependent. Women perceived there was a 42% teratogenic risk for oral corticosteroid, a 12% risk for ICSs, and a 5% risk with short-acting β-agonist. Illness beliefs, emotional response to illness (p = .030), age ≥ 30 years (p = .046), and maintenance ICS use (p = .045) were significantly associated with uncontrolled asthma, while maintenance ICS use (p = .023), illness beliefs, consequences (p = .044), timeline (p = .016), and emotional response (p = .015) and anxiety (p ≤ .0001) were significantly associated with reduced QoL. Conclusions. In pregnancy, women with asthma experience good QoL but overestimate teratogenic risks of asthma medication. Maintenance ICS use, illness beliefs, and anxiety are associated with impaired QoL and asthma control.

Growth deceleration of children on inhaled corticosteroids is compensated for after the first 12 months of treatment

Timing and duration of linear growth suppression in children on long-term inhaled corticosteroids (ICS) are not entirely clear; we undertook a "pragmatic" study to determine growth of asthmatic children on long-term ICS managed by a flexible dosing step-down approach. Standard deviation scores of height (HSDS), height velocity (HVSDS), and body mass index (BMISDS) of pre-pubertal asthmatic children on maintenance therapy with either budesonide (BUD) or fluticasone propionate (FP) were calculated in a prospective open-label non-randomized study. Outcomes were recorded at initiation of ICS, 6, 12, 24, and 36 months, as applicable, and 6 months after ICS treatment discontinuation. Three hundred twenty-two children on BUD and 319 on FP were enrolled after the completion of 6-month treatment. The median (range) daily dose at initiation was 400 mcg (400-1,200) and 200 mcg (200-500), the final maintenance 200 mcg (200-400) and 100 mcg (100-200), respectively. In the first 6-12 months, a decrease in HSDS of approximately 18% below baseline values was noted (P < 0.01) that was restored to almost baseline average levels by 24 months, and slightly increased to above baseline during the third year. HVSDS showed a linear increase in both treatment arms (P < 0.01). No differences were found between the two treatment arms regarding HSDS, HVSDS, and BMISDS at any time point over the course of the study. In conclusion, growth deceleration of asthmatic children on maintenance ICS is compensated for after the first 12 months of treatment. This effect does not differ between BUD and FP treatment, despite some variation in the pattern of linear growth.

Adrenal Function Improves in Asthmatic Children on Inhaled Steroids: A Longitudinal Study

Background/Aims: Asthmatic children on long-term treatment with inhaled corticosteroids (ICS) may exhibit mild adrenal suppression. We aimed to test the hypothesis that baseline adrenal function of some asthmatic children might be lower than that of others and that this difference might be accentuated by ICS therapy. Methods: A low-dose Synacthen test was performed in 41 prepubertal asthmatic children placed on long-term inhaled budesonide (400 µg/day) prior to the onset of ICS treatment, 6 and 12 months later. Five children withdrew before the 6- and another 2 before the 12-month follow-up. Results: Low adrenal function was demonstrated in 4 children (9.8%) upon recruitment and in another 8 at the 6-month evaluation (22.2%). Adrenal function normalized in the aforementioned 4 children at the 6-month evaluation, while 6 (17.6%) exhibited suppressed adrenal function at the 12-month evaluation. Three of these patients had also exhibited adrenal suppression at the 6-month visit. A significant improvement in peak cortisol values from baseline to the 6- and 12-month evaluation (95% confidence intervals: –283.9 to –69.0 and –239.8 to –50.8, respectively) was evident when children with suppressed adrenal response at the second or third evaluation were excluded. Conclusions: In many asthmatic children, adrenal response improves on long-term ICS. The expected adrenal suppression of certain patients on maintenance ICS appears to constitute a separate phenomenon.

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Unscheduled healthcare resource use among asthma patients receiving low-dose inhaled corticosteroids maintenance treatment

This survey describes asthma control and unscheduled healthcare resource use (HCRU) among patients receiving low-dose inhaled corticosteroids (ICS) alone in five European countries and the USA. Physicians and patients completed forms collecting data on asthma symptoms, sudden increase in chest/respiratory symptoms, asthma-related HCRU, quality of life (QoL) and drug therapy. Fifty-seven per cent of patients on low-dose ICS alone had physician-rated moderate or severe asthma. Only 13% of patients receiving low-dose ICS alone achieved asthma control; 36% reported nocturnal wakening and 22% reported unscheduled healthcare services in the past year. Gender, symptom frequency, episodes of sudden increase in chest/respiratory symptoms and impaired QoL were all related to unscheduled healthcare resource utilisation. Many patients receiving low-dose ICS alone do not have adequate asthma control. Some patient characteristics were found to be significantly different, but not exclusive, between unscheduled healthcare resource users and non-users.

Effect of Corticosteroids on Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease

Periodic exacerbations of disease severity, which may lead to hospitalization, are a characteristic feature of asthma and chronic obstructive pulmonary disease (COPD), becoming more prevalent as disease severity increases. Oral corticosteroids increase the rate of resolution of these episodes in both diseases. Inhaled corticosteroids are much less effective at conventional doses and are not recommended as a primary treatment for exacerbations of either disease. Maintenance therapy with inhaled corticosteroids significantly reduces the chance that a further exacerbation will occur in asthma. In general, increasing doses of inhaled corticosteroids are more effective than placebo therapy in preventing exacerbations, at least until patients become persistently symptomatic and regular users of inhaled corticosteroid therapy. Thereafter, the gains from doubling the dose of inhaled corticosteroid maintenance therapy are modest and generally inferior to those that result from adding other antiinflammatory or bronchodilator agents to the treatment regime. The reduction in the incidence of exacerbations with inhaled corticosteroids, compared with placebo, ranges from 15 to 20% in COPD versus almost 50% in severe asthma. However, given the impact of exacerbations on overall quality of life in COPD, even this modest reduction is likely to be clinically important.

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

SUMMARYThe introduction of combination products, for the co-administration of an inhaled corticosteroid (ICS) with a long-acting β2-agonist in a single inhaler, has greatly simplified asthma therapy. The two combination inhalers currently available, Symbicort* (budesonide/formoterol in a single inhaler) and Seretidet (salmeterol/fluticasone), comply with Step 3 of international guidelines that recommend the addition of a long-acting β2-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 β2-agonist -which may improve adherence and overall asthma control. In vitro experiments suggest that ICS and long-acting β2-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.