Corticosteroid Maintenance Therapy Research Articles

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.

Unmasking sarcoidosis following surgery for Cushing disease.

ABSTRACTWe present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease.

Postoperative weight gain during the first year after kidney, liver, heart, and lung transplant: a prospective study.

Studies of all types of organ transplant recipients have suggested that weight gain, expressed as an increase in body mass index (BMI), after transplant is common. To describe weight gain during the first year after transplant and to determine risk factors associated with weight gain with particular attention to type of transplant. A prospective study of 502 consecutive organ transplant recipients (261 kidney, 73 liver, 29 heart, 139 lung) to identify patterns of BMI change. Measurements were made during regular outpatient clinical visits at 2, 6, and 12 months after transplant. Data were retrieved from patients' charts and correlated with maintenance corticosteroid doses. Overall, mean BMI (SD; range) was 23.9 (4.5; 13.6-44.1) at 2 months and increased to 25.4 (4.0; 13.0-42.2) by the end of the first postoperative year. BMI levels organized by World Health Organization categories showed a trend toward overweight/obesity in kidney (53.4%), liver (51.5%), heart (51.7%), and lung (33.1%) patients by 12 months after transplant. BMI changed significantly (P= .05) for all organ types and between all assessment points, except in kidney recipients. Maintenance corticosteroid doses were not a predictor of BMI at 12 months after transplant for most patients. Weight gain was common among patients undergoing kidney, liver, heart, and lung transplant; however, many showed BMI values close to normality at the end of the first year after transplant. In most cases, increased BMI levels were related to obesity before transplant and not to maintenance corticosteroid therapy.

Factors Associated with Major Cardiovascular Events in Patients with Systemic Necrotizing Vasculitides: Results of a Longterm Followup Study

Systemic necrotizing vasculitides (SNV) are associated with more frequent subclinical atherosclerosis, suggesting that SNV might be associated with a higher risk of major cardiovascular events (MCVE). We aimed to identify factors predictive of MCVE in patients with SNV. Patients in remission from SNV were assessed for CV risk factors and subclinical atherosclerosis. MCVE was defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, and/or death from CV causes. MCVE-free survival curves were compared using the log-rank test. Forty-two patients were followed for 7.1±2.6 years. Eight patients (18.9%) had MCVE. The respective 5- and 10-year MCVE rates were 9.5% and 26.8%. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)-defined high-risk status [hazard ratio (HR) 5.02 (95% CI: 1.17-27.4), p=0.03], BMI>30 kg/m2 [HR 4.84 (95% CI: 1.46-116), p=0.02], and plaque detection in the abdominal aorta (p=0.01) were significantly associated with MCVE. SNV characteristics, corticosteroid maintenance therapy, and C-reactive protein>5 mg/l were not associated with MCVE. Plaque in the aorta was significantly associated with high-risk status (p<0.001), while BMI and high-risk status were independent variables. Thus, a BMI>30 kg/m2 and/or a high-risk status were strongly associated with MCVE (p=0.004). Carotid intima-media thickness (IMT) identified patients with early MCVE and was correlated with the time to MCVE (r2=0.68, p=0.01). These results suggest that factors associated with a higher MCVE risk in patients with SNV are NCEP/ATP III-defined high-risk status and BMI>30 kg/m2. Carotid IMT could help identify patients with SNV at risk of early MCVE.

FRI0343 Factors associated with major cardiovascular events in patients with primary systemic necrotizing vasculitides: results of a longitudinal long-term follow-up study

BackgroundPrimary systemic necrotizing vasculitides (SNV) were shown to be associated with more frequent subclinical atherosclerosis, independently of cardiovascular (CV) risk factors and C-reactive protein (CRP) level, suggesting that SNV might...

A study into efficacy of omalizumab therapy in patients with severe persistent allergic asthma at a tertiary referral centre for asthma in Ireland

Asthma is a chronic airway disease characterized by airway inflammation, bronchial hyperresponsiveness and airflow obstruction. Patients with persistent symptoms despite maximum standard treatment as per Global Initiative of Asthma guidelines are considered to have severe persistent asthma. Omalizumab is a recombinant humanized monoclonal antibody licenced for use as an add-on therapy in these patients. To assess the clinical benefit amongst responders to omalizumab therapy at a tertiary referral centre. This was a retrospective audit assessing the effect of omalizumab therapy on asthma control, frequency of exacerbation and hospitalization rates over 6 months before and after therapy. The study included 30 responders (14 females). There was a reduction in exacerbation and hospitalization rates following initiation of omalizumab, 73 and 91%, respectively (P-value < 0.0001). The number of exacerbations decreased from 3.48 ± 2.20 to 0.93 ± 0.83 and the mean number of admissions decreased from 1.07 ± 1.1 to 0.1 ± 0.40 over the study duration (P < 0.001). There was 73% reduction in the weekly need for rescue salbutamol therapy with mean of 30.33 ± 6.49 puffs to 8.23 ± 1.51 puffs after omalizumab therapy (P < 0.0001). Seventy-nine per cent of patients were able to reduce their maintenance oral corticosteroid therapy. Overall, responders to omalizumab therapy are less likely to experience an asthma exacerbation and hospitalization. They were also more likely to reduce maintenance corticosteroid therapy and the need for rescue reliever therapy. These data suggest that omalizumab has proven effective in improving health outcomes for a cohort of carefully selected patients with severe allergic asthma in Ireland.

Obesity-Associated Severe Asthma Represents a Distinct Clinical Phenotype: Analysis of the British Thoracic Society Difficult Asthma Registry Patient Cohort According to BMI

Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airway inflammation. However, the role of obesity in severe asthma remains unclear. Thus, our objective was to explore the association between obesity (defied by BMI) and severe asthma. Data from the British Thoracic Society Difficult Asthma Registry were used to compare patient demographics, disease characteristics, and health-care utilization among three BMI categories (normal weight: 18.5-24.99; overweight: 25-29.99; obese: 30) in a well-characterized group of adults with severe asthma. The study population consisted of 666 patients with severe asthma; the group had a median BMI of 29.8 (interquartile range, 22.5-34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% vs 40.4% and 34.5% in the overweight and normal-weight groups, respectively), steroid burst therapy, and short-acting b 2 -agonist use per day. Significant differences were seen with gastroesophageal reflux disease (53.9% vs 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor use. Bone density scores were higher in the obese group, while pulmonary function testing revealed a reduced FVC and elevated carbon monoxide transfer coefficient. Serum IgE levels decreased with increasing BMI and the obese group was more likely to report eczema, but less likely to have a history of nasal polyps. Patients with severe asthma display particular characteristics according to BMI that support the view that obesity-associated severe asthma may represent a distinct clinical phenotype.

De novo acute hepatitis B in myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody-related microscopic polyangiitis treated with corticosteroids.

An 82-year-old female was referred to our hospital because of low-grade fever, anemia, and rapidly progressive nephritic syndrome. Her laboratory data showed mild proteinuria, mild renal failure, and the presence of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody. A skin biopsy specimen taken from the erythematous purpura revealed neutrophilic infiltration around the blood vessels with fibrinoid changes in the vessel walls. A renal biopsy specimen revealed segmental necrotizing glomerulonephritis with fibro-cellular crescent formation without deposits of immunoglobulin or complement components, indicating microscopic polyangiitis. The use of corticosteroid treatment, including intravenous methylprednisolone, improved renal failure. After 4years with low-dose maintenance corticosteroid therapy, she developed de novo acute hepatitis B, and entecavir was remarkably effective, showing a rapid recovery from liver dysfunction with jaundice. To prevent hepatitis B virus (HBV) reactivation and de novo acute hepatitis B induced by immunosuppressive or cytotoxic therapy, including corticosteroids alone, the measurement of HBV-related serological markers needs to be performed prior to the initiation of such therapy, even in renal diseases.

An Elderly Man with Syncytial Giant Cell Hepatitis Successfully Treated by Immunosuppressants

Here, we report an elderly man with acute-on-chronic hepatitis accompanied by massive ascites. He showed elevated serum transaminase and anti-nuclear antibody (ANA) levels. Liver biopsy showed diffuse multinucleated giant hepatocytes with interface hepatitis, and he recovered with administration of azathioprine in addition to corticosteroids. Follow-up liver biopsy after recovery showed improvement of hepatic inflammation and reduction of giant hepatocyte formation. The patient is receiving low-dose corticosteroid maintenance therapy and he has remained healthy for 8 years to date. Active immunosuppressive treatment may be beneficial in patients with adult syncitial giant cell hepatitis (AGCH).

The therapeutic strategy for autoimmune pancreatitis is subject to the endoscopic features of the duodenal papilla.

Autoimmune pancreatitis (AIP) often presents with a swollen duodenal papilla, however, the clinical significance of the duodenal papilla in AIP has not been fully elucidated. Data have shown swollen duodenal papillae shaped like a pear and/or with a submucosal tumor having IgG4-bearing plasma cells. Immunohistopathology has potentially verified duodenal papillitis associated with AIP. FOXP3-positive lymphocytes are also recognized in AIP. AIP has shown spontaneous remission and relapse irrelevance to corticosteroid therapy. The results of a multivariate analysis revealed the absence of a swollen duodenal papilla as the only significant independent factor predictive of spontaneous remission in AIP cases. In addition, the results of another multivariate analysis revealed the presence of a swollen duodenal papilla and the presence of extrapancreatic lesions as the significant independent factors predictive of relapse in these cases. Results suggest that the lack of a swollen duodenal papilla is a predictive factor for spontaneous remission, and thus negates the need to administer corticosteroids in those AIP patients. In contrast, a swollen duodenal papilla and the presence of extrapancreatic lesions are risk factors for relapse, and those AIP patients are candidates for maintenance corticosteroid therapy to reduce relapse. Therefore, the therapeutic strategy such as the indication for corticosteroid administration is subject to the endoscopic features of the duodenal papilla.

Treatment of Patients with Autoimmune Cytopenia and Progressive CLL Using Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP).

Abstract 4410 BACKGROUNDAutoimmune cytopenia occurs in 5%-10% of patients with CLL. Treatment for patients with both autoimmune cytopenia and progressive CLL is challenging due to poor tolerance of myelosuppression, and the risk of exacerbation of autoimmune cytopenia by purine analogues. METHODSWe identified 20 patients from our CLL database of approximately 3000 patients who were treated with a chemoimmunotherapy regimen of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) for both autoimmune cytopenia and progressive CLL from January 2000-December 2008 at Mayo Clinic Rochester. RESULTSAutoimmune cytopenia responded in 19 patients (14 CR and 5 PR) with a median time to progression (TTP) of 13.6 months (range 5 – 29). Five patients remain in sustained remission at last follow up (range 15 – 30 months) and 4 patients have had recurrent autoimmune cytopenia requiring re-treatment. Six patients required maintenance corticosteroid therapy after completing R-CVP. Progressive CLL responded to treatment in 17 patients (9 CR/CCR, 8 PR by NCI-WG 1996 criteria) with a median TTP of 6.3 months (range 1-40 months). Fourteen patients have required additional treatment for progressive CLL at a median of 5.4 months (range 4-22 months). Five patients have not required additional treatment for either CLL or autoimmune cytopenia at 15 -30 months after completing treatment. R-CVP treatment toxicity included 3 patients with grade 3-4 infections, 2 with grade 1 peripheral neuropathy, and one with grade 3 drug-induced pneumonitis. No patient required blood cell transfusions after the completion of cycle 1 of therapy. CONCLUSIONSAlthough R-CVP is an effective and tolerable therapy for patients with simultaneous autoimmune cytopenia and progressive CLL requiring therapy, the duration of response is suboptimal. Clinical trials testing alternative treatment strategies are needed for this patient population. Disclosures:Zent:Genentech, Bayer, Genzyme, Novartis: Research Funding. Shanafelt:Cephalon: Research Funding; Celgene: Research Funding; Polyphenon Pharma : Research Funding; Hospira: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Bayer Health Care Pharmaceuticals: Research Funding. Kay:Biogenc-Idec, Celgene, Genentech, genmab: Membership on an entity's Board of Directors or advisory committees; Genentech, Celgene, Hospira, Polyphenon Pharma, Sanofi-Aventis: Research Funding.

The role of budesonide/formoterol for maintenance and relief in the management of asthma

The aim of asthma management is to gain and maintain asthma control and reduce the risk of future exacerbations. However, despite the availability of effective therapies and national and international guidelines for their use, many patients remain inadequately controlled and continue to endure and accept a reduced quality of life. This review discusses current challenges in asthma management facing primary care physicians and provides insight into new treatment strategies developed to improve asthma control. A web-based literature review was undertaken with a focus on studies and reviews discussing asthma control and management with traditional therapies and new therapies, including a novel treatment approach using budesonide/formoterol maintenance and reliever therapy. One of the most common problems in long-term asthma control is poor adherence to inhaled corticosteroid (ICS) maintenance therapy, resulting in under-treatment of inflammation. Many patients tend to over-rely on short-acting β 2-agonist medication for quick relief of symptoms at the expense of ICS therapy, thus lowering anti-inflammatory protection and increasing the propensity for the development of severe and potentially life-threatening exacerbations. New simplified treatment strategies have been investigated with the aim of overcoming many of these primary care challenges, ultimately improving asthma control and reducing the future risk of exacerbations.

Autoimmune Pancreatitis Associated with Various Extrapancreatic Lesions during a Long-term Clinical Course Successfully Treated with Azathioprine and Corticosteroid Maintenance Therapy

Autoimmune pancreatitis (AIP) is often associated with systemic extrapancreatic lesions, and the concept of IgG4-related autoimmune disease has been proposed. We report a 62-year-old woman with AIP associated with various extrapancreatic lesions during a long-term clinical course. These extrapancreatic lesions occurred after the withdrawal of steroid therapy. Sclerosing sialadenitis occurred before AIP, whereas autoimmune sensorineural hearing loss, allergic purpura and endocapillary proliferative glomerulonephritis occurred after AIP. However, no relapse was observed for 5 years after the start of maintenance therapy with prednisolone and azathioprine.

Substitution of Aspartic Acid at Position 57 of the DQβ1 Affects Relapse of Autoimmune Pancreatitis

Although autoimmune pancreatitis (AIP) responds well to corticosteroid therapy, relapse during maintenance corticosteroid therapy or after the withdrawal of corticosteroid treatment is not uncommon. To date, the factors related to relapse of AIP have not been fully explored. To determine the clinical and genetic predictors relating to the relapse of AIP, we evaluated clinical factors, HLA polymorphisms, and the amino acid sequences in 40 patients with AIP. At a median follow-up period of 40 months (range, 12-67 months), relapse developed in 13 of 40 patients with AIP (33%), in whom complete remission was achieved with oral corticosteroid therapy. Among demographics, clinical characteristics in the initial diagnosis of AIP, we could not find any clinical predictor for relapse of AIP; however, in amino acid sequence analysis for relapse of AIP, the substitution of aspartic acid to nonaspartic acid at residue 57 of DQbeta1 showed a significant association with relapse of AIP (nonrelapse group, 29.6%; relapse group, 100%; P = .00003; odds ratio, 3.38; 95% confidence interval, 1.9-6.0). There was a significant difference in the timing of relapse of AIP, according to density of the nonaspartic acid residue at DQbeta1 57 (nonaspartic acid homozygosity: mean +/- SD, 6.7 +/- 4.2 months; nonaspartic acid heterozygosity: mean +/- SD, 33 +/- 11 months; P < .001). Substitution of aspartic acid to nonaspartic acid at DQbeta1 57 appears to represent a key genetic factor for relapse of AIP (ClinicalTrials.gov number, NCT00444444).

Two‐dose basiliximab compared with two‐dose daclizumab in renal transplantation: a clinical study

Addition of the interleukin-2 receptor (IL-2R) antagonists basiliximab or daclizumab to a calcineurin inhibitor-based regimen significantly reduces risk of acute rejection with a tolerability profile similar to a placebo. Use of a truncated two-dose regimen of daclizumab has been reported, but till date, there has been no controlled study of two-dose daclizumab vs. two-dose basiliximab. Deceased-donor renal transplant recipients were randomized to basiliximab (20 mg on days 0 and 4) or daclizumab (50 mg on days 1 and 14) with cyclosporine, mycophenolate mofetil and corticosteroids. Flow cytometry was used to calculate the proportion of CD25(+) T cells in peripheral blood. Thirty patients were randomized to basiliximab and 28 to daclizumab. There was one patient death in each group, with no other graft losses. By six months, the incidence of biopsy-proven acute rejection was 0% with basiliximab vs. 21.4% with daclizumab (p < 0.05). Three patients in the daclizumab group required OKT3 for steroid-resistant rejection. There were no between-group differences in the incidence of infection. The proportion of CD25(+) T cells declined markedly during the first two wk in both groups, but was significantly lower in the basiliximab group during weeks six to eight. Two doses of basiliximab are more effective than two 1 mg/kg doses of daclizumab in preventing acute rejection in de novo renal transplant patients receiving cyclosporine, mycophenolate mofetil and corticosteroid maintenance therapy. In patients receiving relatively low-level immunosuppression in order to minimize toxicity, basiliximab may be preferable to a truncated daclizumab regimen.

Body Weight Alterations Under Early Corticosteroid Withdrawal and Chronic Corticosteroid Therapy with Modern Immunosuppression

Weight gain is a known complication of corticosteroid maintenance therapy. The purpose of the present study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) with that observed under early (i.e., within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal-transplant recipients. Renal-transplant recipients who underwent early CSWD under four prospective, institutional review board-approved clinical trials were compared with a historic control group of patients receiving maintenance CCST. One hundred sixty-nine patients with early CSWD were compared with 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced weight gain because white CSWD patients demonstrated greater reductions in weight gain compared with African-American patients. Sex also influenced weight gain: women demonstrated a greater benefit from CSWD than did men. Corticosteroid rejection therapy in CSWD patients completely restored weight gain because these patients showed weight gains similar to the CCST group. Finally, pretransplant body mass index (BMI) also influenced weight gain because patients who were overweight (BMI 25-30) or obese (BMI>30) demonstrated a greater reduction in weight gain with CSWD than did patients of normal weight (BMI<25). Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites, and patients with high pretransplant BMI had greater reductions in weight gain with early CSWD.

A Prospective, Randomized, Multicenter, Double-Blind Study of Early Corticosteroid Cessation Versus Long-Term Maintenance of Corticosteroid Therapy With Tacrolimus and Mycophenolate Mofetil in Primary Renal Transplant Recipients: One Year Report

This report summarizes year 1 blinded data from a 5-year prospective, randomized (1:1, stratified by race and donor type), multicenter, double-blind study comparing treatment failure rates between early cessation of corticosteroid therapy and long-term corticosteroid maintenance therapy in 397 primary renal transplant recipients receiving tacrolimus and mycophenolate mofetil with antibody induction. Sixteen (4.1%) patients died or experienced graft loss during year 1 (9 deaths, 6 graft losses, and 1 death with a graft loss). Fifty-nine (15.3%) patients experienced rejection; 40 (10.4%) of these cases were biopsy-confirmed. Values for 10-year predictive risk of coronary heart disease (CHD) estimated from the Framingham Heart Study scores showed a shift from baseline toward a more favorable risk profile. Renal transplant recipients treated with a tacrolimus-based immunosuppressive regimen and either early cessation or maintenance of corticosteroid therapy experienced excellent patient and graft survival, low acute rejection rates, low rate of posttransplantation diabetes mellitus (9.0%), and improved CHD risk profile at 1 year posttransplantation.

Body Weight Alterations Under Early Corticosteroid Withdrawal and Chronic Corticosteroid Therapy With Modern Immunosuppression

Weight gain is a well-known complication of corticosteroid maintenance therapy. The purpose of our study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) to those observed under early corticosteroid withdrawal (CSWD) in renal transplant recipients. Methods Renal transplant recipients who underwent early CSWD in IRB-approved prospective trials were compared to a historical control group of patients receiving CCST who were matched for age, sex, and race. Results One hundred sixty-nine patients with early CSWD were compared to 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 12 months (5.52 kg vs 3.05 kg, P < .05) posttransplant. Caucasian CSWD patients demonstrated a greater reduction in weight gain with CSWD than African Americans (mean weight decrease 2.9 vs 1.9 kg/patient, P < .05). Patients who were overweight (body mass index [BMI] 25–30) or obese (BMI > 30) demonstrated a greater reduction in weight gain with CSWD at 1 year (mean reduction in weight gain with CSWD 5.3 kg/patient and 4.4 kg/patient) than did patients of normal weight (BMI < 25; 0.1 kg/patient, P < .01 and <.05 versus BMI < 25). Conclusions Early CSWD patients gain significantly less weight than CCST patients following transplantation. Marked variations in the effect of early CSWD on weight gain may be observed due to race and pretransplant BMI. Caucasians and overweight patients demonstrate greater benefits from CSWD than African Americans and patients with normal BMI.

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.