Inhaled Corticosteroids In Patients Research Articles

Inhaled budesonide and pulmonary sarcoidosis revisited.

Results of a few controlled clinical studies have been reported with inhaled corticosteroids (ICS) in patients with pulmonary sarcoidosis. Some evidence of efficacy has been observed, but mainly with the ICS budesonide (BUD). These clinically important and statistically significant results are restricted to maintenance therapy with BUD after induction of treatment with systemic corticosteroids for a few weeks or months. Positive results have also been described in patients with relapses after earlier treatment with oral corticosteroids. A possible explanation for BUD's efficacy in patients with parenchymal lesions could be that inhaled BUD is rapidly absorbed into systemic circulation, creating plasma peaks which result in systemic anti-inflammatory activity in both peripheral airways and lung tissue. At airway level this steroid activity is furthermore prolonged because a BUD fraction is intracellularly, reversibly transformed into lipophilic BUD-oleate. These mechanisms have been proposed to explain the theoretically unexpected similar efficacy of BUD compared with more lipophilic ICSs in patients with asthma and COPD. In this review we summarize the results of clinical studies with ICSs in patients with pulmonary sarcoidosis. It is obvious that current ICSs, including BUD, cannot generally be recommended as such for treatment of sarcoidosis. However, using BUD as a model substance further pharmacologic and kinetic studies could possibly define a kinetic profile giving optimal partitioning between airway and systemic activity with less adverse systemic risks. Such a substance could replace or reduce oral corticosteroids in the treatment of airway and pulmonary parenchymal diseases.

Comparing the Efficacy of Inhaled Corticosteroid (ICS) Treatment in COPD Patients Based on Blood Eosinophilia: A Clinical Trial Study

Background: Inhaled corticosteroids (ICSs) have been widely used in the maintenance therapy of chronic obstructive pulmonary disease (COPD). Eosinophilic airway inflammation is a recognized inflammatory endotype in COPD. Nevertheless, the benefits and risks of ICS treatment remain controversial. Objectives: Therefore, in this study, we determine the frequency of eosinophilia in COPD patients and compare the effects of ICSs in patients with and without eosinophilia referring to the lung clinics of Zahedan University of Medical Sciences. Methods: In this study, 58 COPD patients were examined. Peripheral blood smears (PBS) were collected from all patients, and they were randomly divided into 2 groups. First, a 6-minute walking test (6MWT) was performed on all patients. Thereafter, two groups of patients received standard treatment with the Symbicort spray for 3 months. They were followed for this period, and the 6MWT was performed again at the end of the 3 months. Results: The mean results of the 6MWT test before and after intervention in the eosinophilia-positive group were 164.02 meters and 192.11 meters, respectively. Therefore, there was a significant difference in patient activity levels before and after ICSs (P = 0.017). In the eosinophilia-negative group, there was a significant difference in patient activity levels based on the 6MWT test before and after taking ICSs (P < 0.001). However, there was no difference in activity levels between the two groups before and after the intervention (P = 0.68 and P = 0.36). Conclusions: Our finding showed that treatment with inhaled β2-agonists plus corticosteroids did not affect the response to this treatment in subjects' groups with and without eosinophilia compared to the pre-treatment conditions.

Assessment of primary care provider and pharmacist knowledge, comfort, and barriers to appropriate inhaled corticosteroid use in chronic obstructive pulmonary disease

AbstractPharmacotherapeutic management of chronic obstructive pulmonary disease (COPD) primarily involves the use of inhaled bronchodilators and inhaled corticosteroids (ICS). Mounting evidence in recent years suggests ICSs should be reserved for a limited COPD population. This study set out to understand primary care pharmacist and primary care provider comfort, barriers, and knowledge regarding appropriate ICS use in COPD. A cross‐sectional, survey‐based study was conducted. The survey was shared with primary care providers and primary care pharmacists at two healthcare organizations in Southeastern Wisconsin. Descriptive statistics were employed to summarize the survey results. The primary outcome was level of comfort, as reported using a 7‐point Likert scale of participants with five statements related to managing ICSs in patients with COPD. Secondary outcomes were level of agreeance, as reported using a 7‐point Likert scale of participants to the existence of seven different barriers to successfully executing ICS de‐escalation. Escalation in patients with COPD who qualify and percentage of participants who correctly answered a select‐all‐that‐apply knowledge‐check question regarding appropriate patient factors for ICS de‐escalation. Participants were most uncomfortable with creating a tapering schedule for ICS de‐escalation. Most participants agreed that many barriers exist to executing appropriate ICS de‐escalations. Twenty percent of all participants answered the knowledge‐check question completely correctly. The study's findings suggest the surveyed primary care providers and pharmacists are uncomfortable with several aspects of COPD management. There are many barriers that prevent clinicians from de‐escalating ICSs in appropriate patients. Clinicians may have knowledge gaps regarding what factors make patients appropriate for ICS de‐escalation.

Effects of Inhaled Corticosteroids on the Innate Immunological Response to Pseudomonas aeruginosa Infection in Patients with COPD.

Inhaled corticosteroids (ICS) use is associated with an increased risk of Pseudomonas aeruginosa (PA) infection in patients with COPD. We aimed to evaluate the effects of ICS on alveolar macrophages in response to PA in COPD patients with and without baseline ICS treatment (COPD and COPD + ICS, respectively) as well as smoker and nonsmoker controls. To do so, cells were infected with PA and cotreated with budesonide (BUD) or fluticasone propionate (FLU). The analysis of NF-κB and c-jun activity revealed a significant increase in both factors in response to PA cotreated with BUD/FLU in smokers but not in COPD or COPD + ICS patients when compared with PA infection alone. The expression of Toll-like receptor 2 (TLR2) and the transcription factor c-jun were induced upon PA infection in nonsmokers only. Moreover, in the smoker and COPD groups, there was a significant increase in TLR2 and a decrease in c-jun expression when treated with BUD/FLU after PA infection, which were not observed in COPD + ICS patients. Therefore, the chronic use of ICS seemingly makes the macrophages tolerant to BUD/FLU stimulation compared with those from patients not treated with ICS, promoting an impaired recognition of PA and activity of alveolar macrophages in terms of altered expression of TLR2 and cytokine production, which could explain the increased risk of PA infection in COPD patients under ICS treatment.

Comparison of Risk of Pneumonia Caused by Fluticasone Propionate versus Budesonide in Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study

IntroductionInhaled corticosteroids (ICSs) play an important role in lowering the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD). However, ICSs are known to increase the risk of pneumonia. Moreover, previous studies have shown that the incidence rate of pneumonia varies depending on the type of ICS. In this study, the risk of pneumonia according to the type of ICS was investigated in a population-based cohort.MethodsA retrospective cohort study was conducted using claims data of the entire population from the Korean National Health Insurance Service. Patients who were newly diagnosed with COPD and prescribed fluticasone propionate or budesonide were enrolled as study subjects. Cumulative doses of ICSs were classified into categorical variables to analyze the risk of pneumonia within identical ICS doses.ResultsA total of 47,473 subjects were identified and allocated as 14,518 fluticasone propionate and 14,518 budesonide users through 1:1 propensity score matching. Fluticasone propionate users were more likely to develop pneumonia than budesonide users (14.22% vs 10.66%, p<0.0001). The incidence rate per 100,000 person-years was 2,914.77 for fluticasone propionate users and 2,102.90 for budesonide users. The hazard ratio (HR) of pneumonia in fluticasone propionate compared to budesonide was 1.34 (95% CI 1.26–1.43, p<0.0001). The risk of pneumonia for fluticasone propionate compared to budesonide increased with higher ICS cumulative doses: 1.06 (0.93–1.21), 1.41 (1.19–1.66), 1.41 (1.23–1.63), and 1.49 (1.33–1.66) from the lowest to highest quartiles, respectively.ConclusionICS types and doses need to be carefully considered during treatment with ICSs in patients with COPD.

Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD.

Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.

Discontinuation of inhaled corticosteroids in patients with controlled asthma: The DISCO (Discontinuation of Inhaled Steroid in Controlled asthmatics Over 6 months) study

BackgroundAlthough inhaled corticosteroids (ICSs) are the recommended first-line therapy for asthma, determining whether to continue or discontinue ICS treatment in patients with mild asthma remains challenging for clinicians. Several studies have revealed that patients with mild-persistent asthma maintained a well-controlled state after ICS withdrawal. However, the long-term outcomes of ICS withdrawal have not yet been determined. ObjectiveTo determine the possible clinical outcomes of the discontinuation of ICS in patients with well-controlled mild asthma. MethodsWe investigated the clinical outcomes of discontinuing ICSs in patients with well-controlled mild asthma and compared the time to loss of control (LOC) between patients who stopped ICS treatment (ICS withdrawal group, IWG) and those who continued treatment for 3 years (continuous ICS group, CIG). ResultsA significant difference in the time to LOC was observed between the IWG and CIG (hazard ratio, 2.56; 95% confidence interval, 1.52-4.33; P < .001). Increasing fractional exhaled nitric oxide levels (P = 0.008) and sputum eosinophil counts (%) (P = 0.015) revealed a weak but significant association with LOC risk in the CIG. The sputum eosinophil counts (P = 0.039) and serum total immunoglobulin E levels (P = 0.014) were significantly higher in the LOC group than in the non-LOC group of the CIG. ConclusionOur results suggest that the maintenance of ICS treatment may help keep patients’ asthma under control. Furthermore, patients with LOC had significantly higher sputum eosinophil counts in the CIG than those in the non-LOC group. Therefore, continuous ICS use by patients with mild, well-controlled asthma could be associated with good clinical outcomes. Trial RegistrationClinicalTrials.gov Identifier: KCT0002234.

Treatment of COPD Groups GOLD A and B with Inhaled Corticosteroids in the COSYCONET Cohort - Determinants and Consequences.

BackgroundIn COPD patients of GOLD groups A and B, a high degree of treatment with inhaled corticosteroids (ICS) has been reported, which is regarded as overtreatment according to GOLD recommendations. We investigated which factors predict ICS use and which relationship it has to clinical and functional outcomes, or healthcare costs.MethodsWe used pooled data from visits 1 and 3 of the COSYCONET cohort (n=2741, n=2053, interval 1.5 years) including patients categorized as GOLD grades 1–4 and GOLD group A or B at both visits (n=1080). Comparisons were performed using ANOVA, and regression analyses using propensity matching and inverse probability weighting to adjust for differences between ICS groups. These were defined as having ICS at both visits (always) vs no ICS at both visits (never). Measures were divided into predictors of ICS treatment and outcomes.ResultsAmong 1080 patients, 608 patients were eligible for ICS groups (n=297 never, n=311 always). Prior to matching, patients with ICS showed significantly (p<0.05 each) impaired lung function, symptoms and exacerbation history. After matching, the outcomes generic quality of life and CO diffusing capacity were increased in ICS patients (p<0.05 each). Moreover, costs for respiratory medication, but not total health care costs, were significantly elevated in the ICS group by 780€ per year.ConclusionICS therapy in COPD GOLD A/B patients can have small positive and negative effects on clinical outcomes and health care costs, indicating that the clinical evaluation of ICS over-therapy in COPD requires a multi-dimensional approach.

Respiratory medication used in COPD patients from seven Latin American countries: the LASSYC study.

BackgroundLimited information is available regarding medication use in COPD patients from Latin America. This study evaluated the type of medication used and the adherence to different inhaled treatments in stable COPD patients from the Latin American region.MethodsThis was an observational, cross-sectional, multinational, and multicenter study in COPD patients attended by specialist doctors from seven Latin American countries. Adherence to inhaled therapy was assessed using the Test of Adherence to Inhalers (TAI) questionnaire. The type of medication was assessed as: short-acting β-agonist (SABA) or short-acting muscarinic antagonist (SAMA) only, long-acting muscarinic antagonist (LAMA), long-acting β-agonist (LABA), LABA/LAMA, inhaled corticosteroid (ICS), ICS/LABA, ICS/LAMA/LABA, or other.ResultsIn total, 795 patients were included (59.6% male), with a mean age of 69.5±8.7 years and post-bronchodilator FEV1 of 50.0%±18.6%. The ICS/LAMA/LABA (32.9%) and ICS/LABA (27.7%) combinations were the most common medications used, followed by LABA/LAMA (11.3%), SABA or SAMA (7.9%), LABA (6.4%), LAMA (5.8%), and ICS (4.3%). The types of medication most commonly used in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 category were ICS/LABA (A: 32.7%; B: 19.8%; C: 25.7%; D: 28.2%) and ICS/LAMA/LABA (A: 17.3%; B: 30.2%; C: 33%; D: 41.1%). The use of long-acting bronchodilators showed the highest adherence (good or high adherence >50%) according to the TAI questionnaire.ConclusionCOPD management in specialist practice in Latin America does not follow the current guideline recommendations and there is an overuse of ICSs in patients with COPD from this region. Treatment regimens including the use of long-acting bronchodilators are associated with the highest adherence.

Updates on the use of inhaled corticosteroids in asthma

The purpose of this review is to compare and contrast the newer inhaled corticosteroid (ICS) ciclesonide with older ICSs in terms of pharmacodynamic and pharmacokinetic properties and how these affect comparative efficacy. In addition, clinical dosing strategies for ICSs including as-needed use will be explored. Ciclesonide has demonstrated similar efficacy to that of fluticasone propionate and mometasone furoate in equipotent doses with a potentially improved therapeutic index. Once-daily administration of ICSs is generally not as effective as twice-daily. Continuous administration of ICSs does not change the natural history of asthma in either children or adults. Long-term administration of medium dose ICSs does not increase the risk of cataracts or osteopenia in children and young adults. Studies of as-needed ICSs in mild persistent asthma in adults and children have demonstrated mixed results, with some showing equal efficacy to continuous therapy and others showing superiority of continuous therapy. Ciclesonide provides a newer ICS with favorable pharmacokinetics that may improve the therapeutic index, but assessment of its systemic effects such as growth await further studies. Continuous administration of ICSs in low to medium dose over many years is well tolerated. The use of as-needed ICSs in patients with mild persistent asthma is promising as a potential step-down therapy but awaits further studies.

Impact of asthma controller medications on medical and economic resource utilization in adult asthma patients

Objective:To compare asthma-related resource utilization, adherence and costs among adults prescribed asthma controller regimens.Research design and methods:Medical and pharmacy claims from a US managed-care claims database were used to identify adults (18–56 years) initiating asthma controller therapy. Patients had 2 years continuous enrollment and ≥1 medical claims for asthma (ICD9: 493.xx) (January 2004 – March 2009). Asthma exacerbations, short-acting β-agonist (SABA) fills, adherence (MPR ≥0.80) and asthma-related costs were assessed for 1 year after the initial asthma controller medication claim. Separate logistic and negative binomial regression models for monotherapy and combination therapy were developed to examine the impact of controller therapy on outcomes.Results:A total of 28 074 patients [inhaled corticosteroids (ICS) (26.3%), leukotriene modifiers (LM) (23.2%), ICS + long acting β-agonist (LABA) (48.5%), ICS + LM (2%)] were included. LM patients had lower odds of ≥6 SABA fills (ORadj = 0.83, 95% CI: 0.73–0.96) and lower rates of asthma exacerbations (RRadj = 0.82, 0.75–0.89) vs. ICS patients. Odds of ≥6 SABA fills were similar for ICS + LM vs. ICS + LABA (ORadj = 1.3, 0.96–1.76); the rate of asthma exacerbations was greater for ICS + LM compared with ICS + LABA (ORadj = 1.4, 1.2–1.6). The proportion adherent was greatest for LM (14.9%) and ICS + LABA (4.1%). LM patients had higher unadjusted pharmacy costs, but lower medical costs compared to ICS patients. For combination therapy, ICS + LM had higher unadjusted mean medical and pharmacy costs vs. ICS + LABA. Higher adjusted mean total costs in the post-index period were observed for LM vs. ICS patients ($837 vs. 684) and for ICS + LM vs. ICS + LABA patients ($1223 vs. 873).Conclusions:LM monotherapy was associated with lower medical costs but higher total costs resulting from greater treatment adherence. Conversely, higher costs for ICS + LM resulted from greater exacerbations compared to ICS + LABA despite similar adherence. Higher total costs with LM were due to drug costs. Precise utilization of the medications filled by patients could not be determined.

Exercise-Induced Bronchoconstriction in Asthmatic Children

The aim of this article is to critically review the efficacy and safety data from randomized controlled trials (RCTs) using inhaled corticosteroids (ICSs), long- or short-acting beta(2)-adrenoceptor agonists (LABAs, SABAs), parasympatholytics and oral leukotriene receptor antagonists in the management of exercise-induced bronchoconstriction (EIB) in children with persistent asthma (EIA). The studies with sufficient information on patient characteristics and outcomes were chosen using a MEDLINE search. Results from the individual searches were combined and repeated. Studies were also found by reviewing the reference lists of the articles not included in this review. Studies focusing solely on individuals with asthma and other allergic co-morbidities (i.e. a degree of bronchial reversibility) were considered in this review. To make the paper evidence-based, the design and the quality of different studies were assessed employing the Sign criteria (evidence level [EL] and grades of recommendation [GR]). No additional statistical analyses were performed. Most of studies included paediatric patients with underlying EIA. We need to distinguish children with recurrent asthma symptoms in whom EIB is also present (patients with EIA) from asthmatic subjects whose symptoms appear only as a result of exercise (patients with EIB). Further controller treatment is indicated in patients with EIA and further reliever treatment in patients with EIB. ICSs are the first-choice controller drugs for EIA in children with persistent asthma (Sign grade of recommendation [GR]:A). In children with EIA without complete control with ICSs, SABAs (GR:A), leukotriene receptor antagonists (LTRAs) [GR:A] or LABAs (GR:A) may be added to gain control. Treatment with relievers such as SABAs (GR:A), parasympatholytics (GR:B) or, eventually, LABAs (GR:A), administered 10-15 minutes before exercise is the most preferable method of preventing EIB symptoms in children; however, not as monotherapy in children with EIA. The disadvantages and controversy relating to inhaled beta(2)-adrenoceptor agonist use lie in the development of tolerance to their effect when they are used on a regular basis, and the possibility of a resulting underuse of ICSs in patients with EIA. Researchers and guidelines recommend that if any patient requires treatment with a beta(2)-adrenoceptor agonist more than twice weekly, a low dose of ICSs should be administered. Inhaled parasympatholytics may be effective as preventive relievers in some children with EIB or EIA, especially among those with increased vagal activity. LTRAs have a well balanced efficacy-safety profile in preventing the occurrence of EIB symptoms in children. Compared with LABAs, LTRAs produce persistent attenuation of EIB and possess an additional effect with rescue SABA therapy in persistent asthmatic patients with EIA. A disadvantage of LTRAs is a non-response phenomenon. There are still insufficient data on the efficacy-safety profiles of ICS/LABA combination drugs in the treatment of EIA in children to recommend this treatment without caution. Safety profiles of inhaled SABAs, anticholinergics and montelukast in approved dosages seem sufficient enough to recommend use of these drugs in the prevention of EIB symptoms in children. Many researchers agree that treatment of EIA in children should always be individualized.

A safety review of long-acting beta2-agonists in patients with asthma.

Inhaled corticosteroids are the mainstay of asthma therapy; however, inhaled long-acting beta2-agonists (LABAs) are frequently used in the treatment of patients with asthma. LABAs are combined with high-dose inhaled corticosteroids (ICSs) for patients with severe persistent asthma, and they are combined with low-dose ICSs for patients older than 5 years with moderate persistent asthma. Recent safety concerns raised by data from the Salmeterol Multi-Center Research Trial (SMART) have indicated that use of LABAs in some populations may contribute to increased mortality. These concerns are warranted when LABAs are used as monotherapy in the treatment of patients with asthma in whom they may cause increased exacerbations, blunting of rescue-medication effect, and worsening symptoms. However, when used in combination with an ICS, they decrease both rescue-medication use and symptoms, increase lung function, and act as steroid-sparing agents.

Asthma rescue and allergy medication use among asthmatic children with prior allergy prescriptions who initiated asthma controller therapy

Asthma and allergic rhinitis are frequently comorbid conditions. Montelukast is effective in treating both diseases and may reduce total medication use among children with asthma and allergic rhinitis. To determine the differences in respiratory and allergy medication use and costs, as proxies for control, in pediatric patients with asthma and allergy who initiated asthma controller therapy. A 24-month, retrospective, pre-post cohort study using a pharmacy claims database of children (age < 16 years) with 2 or more consecutive asthma controller prescriptions and 1 or more allergy prescription (within 12 months before initial controller prescription). Children taking inhaled corticosteroids (ICSs) and montelukast were matched one to one based on age, days of prior allergic rhinitis therapy supply, duration of controller therapy, and propensity score. Differences in costs of rescue or acute asthma medications, prescription allergy medications, other respiratory medications, and the number of days of rescue or acute asthma medication use and allergy medication use were calculated. A total of 1,236 children were matched into ICS and montelukast groups (n = 618 each). Montelukast patients had a smaller cost increase overall compared with ICS patients (combined cost for rescue or acute asthma medications, allergy medications, and other respiratory medications: $5.55 vs $12.08, P < .001). Cost increase for rescue or acute asthma medications was significantly lower in the montelukast group ($0.94 vs $3.82, P = .003). The cost increase for allergy medications ($5.29 vs $10.06, P < .001) was also significantly lower in the montelukast group. Patients taking montelukast also had fewer days of therapy with asthma rescue medication and allergy medication compared with patients taking ICSs. Initiating therapy with montelukast was associated with better asthma and allergy control demonstrated via lower increase in use and costs of asthma rescue and allergy medications compared with initiating ICS therapy.

Treatment Persistence with Leukotriene Receptor Antagonists and Inhaled Corticosteroids

Background. Leukotriene receptor antagonists (LTRAs) and inhaled corticosteroids (ICSs) must be taken continuously to control persistent asthma. We compared the use of LTRAs and ICSs in patients with similar level of asthma control at treatment initiation with particular attention to treatment persistence. Methods. Two cohorts of 15 to 45 year old patients with asthma were selected from the Quebec Health Insurance Plan Database between January 1, 1998, and December 31, 2000. We first identified new users of LTRAs and from the remaining patients, we selected new users of ICSs. The ICS patients were then one-to-one matched to LTRA patients on the use of short-acting β2-agonists and oral corticosteroids in the year prior to the date of the first LTRA or ICS dispensation (index date). We compared compliance to initial therapies using Cox proportional hazards models. Results. Each of the LTRA and ICS cohorts included 2200 patients. Multivariate model showed that compliance was significantly better for LTRAs than for ICSs [adjusted rate ratio of treatment discontinuation (aRR), 0.46; 95% confidence interval (CI), 0.42–0.49]. If in both groups all medications filled were taken at the prescribed dose, the annual percent of days on therapy for LTRA users would have been twice that for ICS users (38% vs. 19%; p < 0.0001). Conclusion. The findings of this observational study indicate a far from optimal persistence to LTRAs and ICSs in asthmatic patients. The superior persistence to LTRAs might result in better effectiveness.

The impact of budesonide and other inhaled corticosteroid therapies in the management of asthma in children and adults

Background: Since the recognition that asthma is characterized by extensive inflammation of the airways, the use of inhaled corticosteroids (ICSs) as controller therapy has become central to successful disease management. As the prevalence of asthma increases worldwide, there is concern about increasing numbers of patients with untreated or undertreated asthma, which may lead to deterioration in disease control, with direct effects on morbidity and mortality rates. The costs attributed to asthma translate into a considerable economic burden, from the direct costs of medical treatment to the costs incurred through lost work or school days. International treatment guidelines currently recommend early intervention with ICS therapy to improve lung function and disease control. Objective: This article reviews the role of therapy with ICSs, particularly budesonide, in improving the management of asthma in patients of all ages and in reducing the economic and social burdens of this disease. Results: Randomized, controlled clinical studies confirm the efficacy of early intervention with ICSs in patients with mild persistent asthma. Regular use of an ICS can reduce the number of exacerbations and hospitalizations in patients of all ages and with all disease severities. Conclusions: Budesonide has a well-established efficacy and safety profile. Its once-daily dosing may contribute to improved adherence and cost-effectiveness.

Efficacy and safety of fluticasone propionate 250 μg administered once daily in patients with persistent asthma treated with or without inhaled corticosteroids

Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously. We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS). In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning. At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001). FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.

TNF-alpha dysregulation in asthma: relationship to ongoing corticosteroidtherapy.

Tumour necrosis factor-alpha (TNF-alpha) is a major proinflammatory cytokine that is thought to be important in the pathogenesis of asthma. However, alterations in systemic regulation of this cytokine in asthma have not been examined in the context of corticosteroid therapy. To examine the ability of peripheral blood mononuclear cells (PBMC) from three different groups of patients with asthma requiring varying amounts of inhaled corticosteroids (ICS) for clinical control, and to examine cells from age- and sex-matched nonasthmatic patients to produce TNF-alpha. All patients with asthma had a positive methacholine challenge test. 'High dose' ICS patients with asthma required ICS greater than or equal to 800 microg/day. 'Medium dose' patients with asthma were on less than or equal to 500 microg/day of ICS, whereas 'no ICS' patients with asthma had received no ICS for at least three months. Each patient with asthma was examined in parallel with an age- and sex-matched, nonasthmatic, nonatopic control subject. Cells were cultured (with or without the addition of potential stimulators phytohemagglutinin, lipopolysaccharide, formyl-methionine-leucine-phenylalanine or antihuman CD3), and TNF-alpha production was assessed by ELISA. PBMC from both high dose ICS (n=8) and no ICS (n=11) patients with asthma produced more than twice the amount of TNF-alpha than cells from matched nonasthmatic control patients (P<0.01) when cultured alone or in the presence of each stimulus (P<0.05). In contrast, there was no significant difference in TNF-alpha production between medium dose ICS patients with asthma and control patients. A group of asymptomatic atopic patients (n=6) did not have an increased level of TNF-alpha production. Increases in TNF-a production within the PBMC compartment can be observed in both patients with asthma receiving high dose ICS and in a group of patients with mild asthma receiving no ICS therapy, but not in patients with asthma receiving a medium dose of ICS or atopic patients.