Use Of High-dose Inhaled Corticosteroids Research Articles

Clinical characteristics and cytokine profiles of adult obese asthma with type2 inflammation

Obesity-related non-eosinophilic asthma has been identified as a phenotype of asthma. However, mepolizumab and omalizumab improve asthma control in severe asthma with obesity, implying that type-2 cytokines may be involved in the deterioration of control in obese asthma. Despite this, the clinical details of obese asthma with positive type-2 inflammation markers have not yet been reported. The objective of this study was to investigate the clinical characteristics of patients with obese asthma with positive type-2 inflammation markers. Adult obese asthmatic patients were enrolled and were classified into two groups: obese asthma with positive type-2 inflammation markers (T2) and obese asthma with negative type-2 inflammation markers (NT2), then data were compared. In total, 434 patients were enrolled (85% of patients were at GINA therapy step 4–5). The T2 group had a higher proportion of patients with persistent asthma since childhood and with allergic rhinitis. A higher percentage of patients used high-dose inhaled corticosteroids (ICS) and experienced acute exacerbations (annual exacerbation ratio ≥ 1) in the T2 group. Multivariate logistic regression analysis showed that the T2 group was independently associated with younger age, comorbidity of allergic rhinitis, persistent asthma since childhood, use of high-dose ICS, and acute exacerbation rate ≥ 1. Adipocytokine levels were similar between the groups. Collectively, obese asthma with positive type-2 inflammation markers is characterised by a higher percentage of persistent asthma since childhood and more severe asthma.

Inhaled Corticosteroids and Mycobacterial Infection in Patients with Chronic Airway Diseases: A Systematic Review and Meta-Analysis.

Inhaled corticosteroids (ICSs) have been widely used in chronic airway diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. However, whether ICS use causes mycobacterial infection is uncertain. Some conclusions of published studies were inconsistent. We aimed to investigate the association between the use of ICSs and mycobacterial infections in patients with chronic airway diseases. This review was registered on PROSPERO (CRD42021284607). We focused on examining the association between ICS use and mycobacterial infection (nontuberculous mycobacterial [NTM] infection as well as tuberculosis [TB]). We searched PubMed (MEDLINE), Sciencenet, Cochrane, and EMBASE databases for studies up to 2021 to retrieve articles. The enrollment conditions included gender, enrollment diagnosis and ICS use in chronic airway disease patients, and so on. Preclinical studies, review articles, editorials, reviews, conference abstracts, and book chapters were excluded. Methodologically, the study was assessed using the Newcastle Ottawa Scale, and Rev-man5 was used for statistical analysis. Ten studies (including 4 NTM and 6 TB articles) with 517,556 patients met the inclusion criteria and were included in this meta-analysis. From the NTM pooled analyses, ICS use was associated with increased odds of NTM infection in patients with chronic airway diseases (odds ratio [OR] = 3.93, 95% confidence interval [CI] 2.12-7.27), subgroup analysis showed that high-dose ICS use (OR = 2.27, 95% CI 2.08-2.48) and fluticasone use (OR = 2.42, 95% CI 2.23-2.63) were associated with increased odds of NTM infection risk in patients with chronic respiratory diseases. The TB pooled analyses showed a significant association between ICS use and risk of TB infection in patients with chronic respiratory diseases (OR = 2.01, 95% CI 1.23-3.29). Subgroup analysis showed that in chronic respiratory diseases, ICS use increased odds of TB infection in high-dose ICS use (OR = 1.70, 95% CI 1.56-1.86) and in COPD patients (OR = 1.45, 95% CI 1.29-1.63). Our meta-analysis indicated that ICS use may increase the odds of mycobacterial infection in chronic respiratory disease patients, and this conclusion is more applicable to patients with high dose of ICS or fluticasone in NTM infection subgroups. In addition, high-dose ICS use may have higher risk of TB infection in patients with chronic respiratory diseases, especially COPD. Therefore, we should be vigilant about the application of ICS use in chronic respiratory diseases to avoid infection.

Inhaled Corticosteroid Therapy in Bronchiectasis is Associated with All-Cause Mortality: A Prospective Cohort Study.

Background and ObjectivePrescribing inhaled corticosteroids (ICS) for bronchiectasis (BE) in the absence of obstructive lung disease is controversial. Studies investigating ICS therapy and impact on morbidity and mortality in BE are sparse.MethodsThis study comprises all patients with BE managed at respiratory outpatient clinics at two university hospitals in the Capital Region of Denmark 2014–2015. Baseline data were obtained from patient medical records, and patients were followed until April 2020.ResultsOut of 264 patients, 122 (46%) were prescribed ICS with no demographic differences between users/non-users of ICS. Among patients prescribed ICS, 21% did not have a concomitant diagnosis of asthma or COPD. Patients prescribed ICS had lower lung function (median FEV1 65.2 vs 80.9%pred, p<0.001) and a higher symptom burden in terms of cough (p 0.028), sputum production (p <0.001) and dyspnea (p <0.001). Pseudomonas-positive sputum cultures were more common in ICS-treated patients (6.5 vs 20%, p 0.010), as were previous severe exacerbations (41% vs 21%, p <0.001). In terms of mortality, high-dose ICS use was associated with increased mortality in multivariable Cox regression adjusted for age, sex, FEV1 and concomitant asthma/COPD (HR 4.93 [95% CI 1.73–14.0], p 0.003).ConclusionIn this cohort, close to one out of five patients with BE were prescribed ICS despite having no concomitant diagnosis of asthma or COPD. Overall, ICS treatment was associated with higher morbidity and mortality, though causation is difficult to establish.

Osteoporosis and fracture risk associated with inhaled corticosteroid use among Swedish COPD patients: the ARCTIC study.

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.

A Single Institution Retrospective Study of the Clinical Efficacy of Tiotropium Respimat in Never-Smoking Elderly Asthmatics with Irreversible Airflow Limitation.

In Japan, most asthma deaths occur among the elderly. We should improve the control of asthma in elderly patients to reduce the number of deaths due to asthma. This retrospective study aimed to evaluate the efficacy of tiotropium RespimatⓇ (Tio-Res) in symptomatic, never-smoking, elderly asthmatics with irreversible airflow limitation despite the use of high-dose inhaled corticosteroids (ICS) plus long-acting β2-adrenoceptor agonists (LABA). The Asthma Control Test™ (ACT), pulmonary function tests, morning and evening peak flow (mPEF, ePEF, respectively, evaluated with an ASSESS® peak flow meter), and respiratory impedance (assessed with MostGraph®) were measured before and after a minimum of one year of Tio-Res 5 µg/day administration. Sixteen symptomatic, never-smoking asthmatics, aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA, were analyzed. All patients were female (mean age, 81.6 years). Tio-Res led to statistically significant improvements in the total ACT score (19.9 to 23.6), FVC and FEV1 (1.97 to 2.14 L and 1.13 to 1.23 L, respectively), and mPEF and ePEF (229.9 to 253.8 L/min and 259.8 to 277.4 L/min, respectively). Tio-Res also resulted in statistically significant improvements in respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), R5-R20, low-frequency reactant indices at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area (ALX). Our retrospective study suggests that Tio-Res improves symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA.

PRS6 Impact of Omalizumab on Emergency-Department Visits, Hospitalizations and Corticosteroid Use in Patients with Uncontrolled Asthma Using High-Dose Inhaled Corticosteroids

This study evaluated the impact of omalizumab on emergency-department (ED) visits, hospitalizations and corticosteroid use among uncontrolled asthma patients using high-dose inhaled corticosteroids (ICS) prior to initiating omalizumab. Health insurance claims from the MarketScan database (2002Q1-2009Q1) were analyzed. Patients with ≥12 months of continuous insurance coverage prior to and after the first omalizumab dispensing, ≥8 weeks of high-dose ICS use, ≥8 weeks of long-acting beta2-agonist (LABA) use, and uncontrolled asthma at baseline were included. A retrospective analysis was conducted to quantify the impact of omalizumab on resource use by comparing ED visits, hospitalizations, and corticosteroid use one year before and after omalizumab initiation. A one-year period was chosen to cover any potential seasonality impacts. A total of 644 patients (mean age: 49.9; female: 59.2%) formed the study population. Omalizumab was associated with a 48.6% reduction in the proportion of patients with ≥1 asthma-related ED visits (pre vs. post-omalizumab period: 21.4% vs. 11.0%, P<0.001) and 40.8% reduction in asthma-related hospitalizations (25.0% vs. 14.8%, respectively, P<0.001). Compared to the pre-omalizumab period, the use of ICS decreased significantly after omalizumab initiation (7.8 vs. 6.5 dispensings, P<0.001; 41.9% of patients had a reduction in ICS use). A similar reduction in oral corticosteroid use was observed (5.0 vs. 3.6 dispensings, P<.001; 53.3% of patients had a reduction in oral corticosteroid use). The results of the current study showed that omalizumab treatment initiation was associated with statistically significant reductions in ED visits, hospitalizations and corticosteroid use.

Impact of omalizumab on emergency-department visits, hospitalizations, and corticosteroid use among patients with uncontrolled asthma

Omalizumab is a monoclonal antibody indicated for moderate to severe allergic asthma patients with inadequately controlled symptoms. To evaluate the impact of omalizumab on emergency department (ED) visits, hospitalizations, and corticosteroid use among patients with uncontrolled asthma using high-dose inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA). Health insurance claims from the MarketScan database (2002Q1-2009Q1) were analyzed. Patients with 12 months or more of continuous insurance coverage before and after the first omalizumab dispensing, 8 or more weeks of high-dose ICS use, 8 or more weeks of LABA use, and uncontrolled asthma at baseline were included. A retrospective analysis was conducted to quantify the impact of omalizumab on resource use by comparing ED visits, hospitalizations, and corticosteroid use 1 year before and after omalizumab initiation. A 1-year period was chosen to cover any potential seasonality impacts. In total, 644 patients (mean age, 49.9; female, 59.2%) formed the study population. Omalizumab was associated with a 48.6% reduction in the proportion of patients with 1 or more asthma-related ED visits (pre vs post-omalizumab period: 21.4% vs 11.0%; P < .001) and a 40.8% reduction in asthma-related hospitalizations (25.0% vs 14.8%, respectively, P < .001). Compared with the pre-omalizumab period, the use of ICS decreased significantly after omalizumab initiation (7.8 vs 6.5 dispensings, P < .001; 41.9% of patients had a reduction in ICS use). A similar reduction in oral corticosteroid use was observed (5.0 vs 3.6 dispensings, P < .001; 53.3% of patients had a reduction in oral corticosteroid use). The current analysis showed that omalizumab treatment initiation was associated with significant reductions in ED visits, hospitalizations, and corticosteroid use.

Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?

There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤ 2,000 μg · day(-1) fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting β(2)-agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous β(2)-agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.

Use of High-Dose Inhaled Corticosteroids is Associated With Pulmonary Tuberculosis in Patients With Chronic Obstructive Pulmonary Disease

The use of high-dose inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) has recently been shown to increase the incidence of pneumonia. However, to our knowledge, the impact of high-dose ICS on pulmonary tuberculosis (TB) has never been investigated. To study that impact, we conducted a retrospective study including patients aged more than 40 years old with irreversible airflow limitation between August 2000 and July 2008 in a medical center in Taiwan. Of the 36,684 patients who underwent pulmonary function testing, we included 554 patients. Among them, patients using high-dose ICS (equivalent to >500 microg/d of fluticasone) were more likely to have more severe COPD and receive oral corticosteroids than those using medium-dose, low-dose, or no ICS. Sixteen (3%) patients developed active pulmonary TB within a follow-up of 25,544 person-months. Multivariate Cox regression analysis revealed that the use of high-dose ICS, the use of 10 mg or more of prednisolone per day, and prior pulmonary TB were independent risk factors for the development of active pulmonary TB. Chest radiography and sputum smear/culture for Mycobacterium tuberculosis should be performed before initiating high-dose ICS and regularly thereafter.

Measuring exacerbations in obstructive lung disease

Using hospitalization always has been seen as a solid measurement for exacerbation in pharmacoepidemiology, but might lead to an underestimation of disease exacerbation because of a trend towards outpatient care. The aim of this study was to quantify the incidence of different exacerbation markers in obstructive lung disease and to identify predictors for these exacerbation markers. We conducted a cohort study using the PHARMO record linkage system, including demographic details and complete medication histories of more than two million community-dwelling residents in the Netherlands from 1985 onwards. Eligible patients were adult users of inhaled corticosteroids (ICS). Outcome parameters were hospitalization and short courses of systemic corticosteroids. Patients were allowed to have multiple exacerbations during follow-up. We identified 5327 patients. During follow-up, 8635 exacerbations occurred in 2332 patients with a trend in time towards treating exacerbations out of the hospital (p-value 0.003). Of all patients with exacerbations, 73% was not hospitalized during follow-up. Exacerbations were associated with high-dose ICS use (adjusted RR 1.4; 95% CI 1.2-1.7) and chronic systemic corticosteroid use (adjusted RR 1.9; 95%CI 1.6-2.2). Using hospitalization only as exacerbation marker leads to underestimating the exacerbation rate, because of exacerbation treatment out of the hospital. Patients with obstructive lung disease using chronic systemic corticosteroids or high-dose ICS use are more prone to exacerbations. This implies that these patients should be monitored carefully to prevent recurrent exacerbations which are detrimental for their prognosis and quality of life.

Risk of glaucoma in elderly patients treated with inhaled corticosteroids for chronic airflow obstruction

Background Topical and systemic corticosteroids are well known to raise intra-ocular pressure while the effect of inhaled corticosteroids (ICS) on the risk of glaucoma remains uncertain. We sought to determine the risk of new onset ocular hypertension or glaucoma requiring treatment, associated with the use of ICS in elderly patients treated for airways disease. Methods We carried out a nested case–control study using the databases from the Québec provincial health insurance plan. A cohort of patients receiving respiratory medications was formed among all subjects 66 years of age and older. Cases were subjects in whom treatment for glaucoma was initiated between January 1, 1988 and December 31, 2003 after a first ever visit to an ophthalmologist within the preceding 90 days. Age-matched controls were selected among individuals who also visited an ophthalmologist for the first time within 90 days of the case's treatment date and did not receive a treatment for glaucoma. Results A total of 2291 cases were identified. For comparison, a total of 13,445 age-matched controls were selected. The mean age was (75 ± 4.2 years). The adjusted rate ratio for glaucoma was 1.05 (95% CI 0.91–1.20) with ICS use in the preceding 30 days. There was no dose-related effect of ICS on the risk of glaucoma or raised intra-ocular pressure requiring treatment. Continuous use of high-dose ICS for 3 of more months was not associated with an increased risk of glaucoma. Conclusion In a large cohort of elderly patients treated for airways disease, we found that current use and continuous use of high-dose ICS did not result in an increased risk of glaucoma or raised intra-ocular pressure requiring treatment.

Effects of corticosteroid use on readmission in obstructive lung disease

Obstructive lung disease is a leading cause of morbidity and mortality worldwide. Some patients are readmitted, but currently predicting parameters for identifying these patients are lacking. The aim of this study was to quantify the incidence of readmission in chronic obstructive lung disease and to identify determinants for hospital readmission. We conducted a cohort study using the PHARMO record linkage system, including demographic details and complete medication histories of more than two million community-dwelling residents in the Netherlands from 1985 onwards. Eligible patients were adult users of inhaled corticosteroids (ICS) with an admission for obstructive lung disease. The outcome parameter was readmission within a follow-up period of one year. We identified 605 ICS users with an admission for chronic obstructive lung disease, 132 of these patients were readmitted. Readmission was associated with a high Chronic Disease Score (adjusted HR 2.4; 95% CI 1.1-5.3). Patients using short courses of systemic corticosteroids only (adjusted HR 0.5; 95% CI 0.4-0.8) or combined with antibiotics (adjusted HR 0.4; 95% CI 0.2-0.6) were at decreased risk of readmission. The effect of high-dose ICS use varied over time. Treatment of exacerbations out of the hospital was associated with a decreased risk of readmission, while patients with multiple chronic diseases are at increased risk of readmission for obstructive lung disease. These patients should be educated and should be invited to consultation more often to be able to detect exacerbation in an early phase and start treatment as early as possible.

Facing the challenge of unmet needs in asthma

Background As the prevalence of asthma rises, new treatment options are becoming available; however, despite these advances, asthma management continues to be suboptimal in many patients. Objectives To examine asthma control levels, as evaluated by the occurrence of asthma exacerbations (worsening symptoms, rescue medication use, and emergency department visits or hospitalizations), attained using current treatment methods and to assess the effectiveness of treatment with inhaled corticosteroids (ICSs) alone or combined with long-acting β 2 -agonists (LABAs). Methods Selected studies evaluating the effects of using ICSs alone or combined with LABAs on asthma control were reviewed. Results Most patients with asthma experienced 1 or more exacerbations per year. Findings from the reviewed studies indicate that aiming for total asthma control by increasing the dose of the administered ICS and adding a LABA to a higher dose of an ICS can reduce the proportion of patients experiencing exacerbations to 5%. These findings suggest that prolonged use of high-dose ICSs may offer beneficial results regarding long-term treatment outcomes. However, with increased use at higher doses, the systemic and oropharyngeal safety of ICSs needs to be carefully considered. Conclusions Therapy with ICSs alone or combined with LABAs is effective for the treatment of asthma; however, current prescribing patterns may not optimize the potential of these therapies. A reexamination of treatment regimens and goals for asthma therapy is necessary to improve outcomes for patients.

Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients?

Despite absence of clear proof of efficacy, the use of inhaled corticosteroids (ICS) is widespread in cystic fibrosis (CF) patients. Therefore, the effect of ICS on lung function and other clinical variables was studied in 27 prepubertal CF children with mild to moderate lung disease. In a prospective double-blind case-controlled study, fluticasone propionate 500 microg or placebo were administered twice daily during 12 months. The mean (standard error of the mean, SEM) patient age was 8.2 (0.6) years in the placebo group and 9.0 (0.5) years in the fluticasone group. The mean (SEM) forced expiratory volume in 1 s (FEV(1)) was 91% (4%) in the placebo group and 86% (4%) in the fluticasone group. There was no statistically significant difference in the evolution of lung function and the number of respiratory exacerbations between groups. However, longitudinal growth in fluticasone patients was significantly slower than in placebo patients: 3.96 (0.29) cm versus 5.49 (0.38) cm [p<0.005, analysis of variance (ANOVA)] over the 12-month study duration. This resulted in a significant change in height standard deviation score (SDS) of -0.38 (0.09) in the fluticasone group versus -0.01 (0.07) in the placebo group (p<0.003, ANOVA). No catch-up growth was noted 1-2 years after discontinuation of inhaled steroids. The use of high-dose ICS in CF patients with mild lung disease may lead to persistent growth impairment.

The Role of Omalizumab in the Treatment of Severe Allergic Asthma

BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.OBJECTIVE: To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.METHODS: A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.RESULTS: Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumabtreated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

The Role of Omalizumab in the Treatment of Severe Allergic Asthma

A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada. To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada. A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use. Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or four-week intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment. Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

High dose versus low dose inhaled corticosteroid as initial starting dose for asthma in adults and children.

Inhaled corticosteroids (ICS) form the basis of maintenance therapy in asthma and their efficacy is well established. However, the optimal starting dose of ICS is not clearly established. Recent reviews demonstrate a relatively flat efficacy curve for ICS and increasing side effects with increasing ICS doses. High doses are frequently prescribed and there are now reports of significant side effects occurring with high dose ICS use. These issues demonstrate the need to establish the optimal starting dose of ICS in asthma. To establish the optimal starting dose of ICS by evaluating the efficacy of initial high dose ICS with low dose ICS in subjects with asthma, not currently on ICS. We searched the Cochrane Airways Group trials register and reference lists of articles. Date of last search: January 2003 Randomised controlled trials of two different doses of the same ICS in adults and children with asthma with no concomitant ICS or OCS. Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: step down vs constant dose ICS (n=7); high vs moderate (n=11); high vs low (n=9); moderate vs low (n=11); fold change in dose (all studies). 31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV(1) ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF l/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06 ). Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS. For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down-titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma.

Fracture risk associated with inhaled corticosteroid use in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are frequently treated with inhaled corticosteroids (ICS). However, the impact of ICS use on fracture risk remains unclear in these patients. This nested case-control study examines the association between ICS use and nonvertebral fractures in Veterans Affairs patients with COPD. From a cohort of 40,157 patients with a COPD diagnosis between October 1, 1998 and September 30, 1999, and that used services in the preceding 12-month period but did not have a COPD diagnosis, 1,708 cases with nonvertebral fractures were identified and matched to 6,817 control patients. Patients were 94% male, and average age was 62.7 years. ICS exposure was identified through prescription records and converted to beclamethasone equivalents. In conditional logistic regression models, exposure to ICS at any time during follow-up was not associated with an increased fracture risk (adjusted odds ratio = 0.97; 95% confidence interval, 0.84-1.11). However, current high-dose ICS users (> or = 700 microg per day) had an increased risk of fractures compared with patients with no exposure (adjusted odds ratio = 1.68; 95% confidence interval, 1.10-2.57). In patients with COPD, current use of high-dose ICS was associated with an increased risk of nonvertebral fractures.

Asthma Severity, Psychiatric Morbidity, and Quality of Life: Correlation with Inhaled Corticosteroid Dose

Objectives. Psychiatric phenomena in asthma has been debated for some time. Inhaled corticosteroids (ICS) are a significant part of treatment. We attempted to quantify the prevalence of psychiatric morbidity relative to asthma severity, quality of life (QOL), and ICS dose. Data Sources. Fifty asthmatic patients (18 ≥ X ≤ 75 years) on ICS, attending an urban clinic had asthma and ICS dose stratified by symptom severity and preparation potency. Peak flow and forced expiratory volume in 1 second (FEV1) were measured. Patients completed general QOL and disease-specific QOL questionnaires, along with psychiatric rating scales. Results. Patients (n = 50) clustered in the 40–59 year range (n = 27, 54%) and were predominantly female (n = 44, 88%) Hispanics (n = 30, 60%), with mild-moderate asthma (n = 18, 36%) and on low-dose ICS (n = 22, 44%). FEV1 ranged from 32 to 123 (mean 76.98, SE 3.01). Peak flow ranged from 210 to 590 (mean 407.83, SE 13.24). Prevalence of anxiety and depressive symptoms were higher than expected (Kendall's tau-c, n = 50, P < .01). Independently, high ICS dose and asthma severity correlated directly with all measures of psychiatric morbidity (Pearson's r 0.781, P < .01). High ICS dose correlated inversely with SF-36 Mental Component Scale (Pearson's r 0.681, P < .01) and directly with FEV1 and peak flow when age/sex adjusted (Spearman's rho: 0.660, P < .001). Conclusions. Psychiatric morbidity is more prevalent in this population and impacts negatively on QOL. Use of high-dose ICS benefited pulmonary function and “physical” QOL, yet may have negatively affected patients' mental well-being. Longitudinal follow-up, extension of sample size, and better study control would allow closer approximation of possible negative associations with ICS.